Con il patrocinio di
SOCIETÀ CHIMICA ITALIANA SEZIONE EMILIA ROMAGNA
XIX GIORNATA DELLA CHIMICA DELL’EMILIA ROMAGNA
“LA TAVOLA PERIODICA: UNO STRUMENTO
ANCORA ATTUALE”
Modena 6 Dicembre 2019
Dipartimento di Scienze Chimiche e Geologiche
Dipartimento di Scienze della Vita
Comitato Scientifico
Alberto CAVAZZINI (Università di Ferrara) - Presidente Direttivo SCI ER
Elisa BOANINI (Università di Bologna)
Barbara CACCIARI (università di Ferrara)
Roberto CORRADINI (Università di Parma)
Nicola DELLA CA' (Università di Parma)
Mariafrancesca FOCHI (Università di Bologna)
Rita MAZZONI (Università di Bologna)
Claudio MUCCHINO (Università di Parma)
Federica PELLATI (Università di Modena e Reggio Emilia)
Giorgio PELOSI (Università di Parma)
Laura PIGANI (Università di Modena e Reggio Emilia)
Maurizio REMELLI (Università di Ferrara)
Michela ROSINI (Università di Bologna)
Comitato Organizzatore
Federica PELLATI (Dipartimento di Scienze della Vita)
Laura PIGANI (Dipartimento di Scienze Chimiche e Geologiche)
Programma
09:00-09:30 Registrazione, allestimento poster e caffè di benvenuto
09:30-10:00 Apertura dei lavori
I Sessione
10:00-11:20 Comunicazioni Orali dei Dottorandi
10:00-10:20 O1 Bellotti Denise (UNIFE) “Zn(II) and Cu(II) interaction with ZinT protein: finding a correlation between coordination chemistry and pathogenic activity”
10:20-10:40
O2 Menichetti Arianna (UNIBO) “Novel gelatin films modified by quercetin for biomedical applications”
10:40-11:00
O3 Nicolini Alessio (UNIMORE) “Extended Metal Atom Chains (EMACS) as magnetic nanostructures: synthesis and magnetic behavior”
11.00-11:20 O4 Orsoni Nicolò (UNIPR) “Functionalized riboflavin and its ruthenium(II) arene complex: synthesis, characterisation and photoactivation studies”
11:20-12:30 Comunicazioni Flash dei Dottorandi
F1 Albertini Claudia (UNIBO) “Ibuprofen-cromolyn co-drugs as polypharmacological tools for Alzheimer disease”
F2 Brancolini Gianluca (UNIBO) “Recovery and recycling of carbon fibers and their use as raw material for a new production of sustainable composites with a "cradle to cradle" approach”
F3 Di Filippo Maria Francesca (UNIBO) “Functional properties of chitosan films modified by snail mucus extract”
F4 Faccani Lara (UNIPR) “Ceramised textile for water remediation”
F5 Illuminati Davide (UNIFE) “Synthesis of p-substituted DMP-like analogues and their application in NOC(1-13)-NH2“
F6 Maletti Laura (UNIMORE) “Valorization of agri-food residues from industrial processes”
F7 Musella Elisa (UNIBO) “Electrochemical approach for the production of layered double hydroxides with a well-defined Co/Me(III) ratio for oxygen evolution reaction”
F8 Tinivella Annachiara (UNIMORE) “An integrated in silico drug repurposing workflow to identify novel potent Carbonic Anhydrase inhibitors”
F9 Vergine Giulia (UNIFE) “Method development for the speciation analysis of organotin compounds by HPLC-ICP/MS”
F10 Voronov Aleksandr (UNIPR) “Palladium-catalyzed synthesis of chiral hydantoins”
12:30-14:30 Buffet lunch – Sessione Poster
II Sessione
LA TAVOLA PERIODICA: UNO STRUMENTO ANCORA ATTUALE
14:30-15:00 Prof. Roberto Cammi (UNIPR)
“Configurazione Elettronica ed Elettronegatività degli Atomi sotto Alta Pressione: una Riscrittura della Tavola Periodica degli Elementi”
15:00-15:30 Dr. Lotte Lens (Università Johannes Gutenberg,Mainz)
“Superheavy Elements: exploring the limits of the periodic table”
15:30-16:00 Prof. Gianantonio Battistuzzi (UNIMORE)
“Elementi inorganici e biologia: un ossimoro vitale”
16:00-16:30 Premiazioni e Chiusura dei lavori
PRESENTAZIONI ORALI
O1 Bellotti Denise UNIFE
O2 Menichetti Arianna UNIBO
O3 Nicolini Alessio UNIMORE
O4 Orsoni Nicolò UNIFE
PRESENTAZIONI FLASH
F1 Albertini Claudia UNIBO
F2 Brancolini Gianluca UNIBO
F3 Di Filippo Maria Francesca UNIBO
F4 Faccani Lara UNIPR
F5 Illuminati Davide UNIFE
F6 Maletti Laura UNIMORE
F7 Musella Elisa UNIBO
F8 Tinivella Annachiara UNIMORE
F9 Vergine Giulia UNIFE
F10 Voronov Aleksandr UNIPR
PRESENTAZIONI POSTER
P1 Ahmad Mohamad UNIMORE
P2 Anceschi Lisa UNIMORE
P3 Bardi Brunella UNIFE
P4 Basagni Filippo UNIBO
P5 Belletti Giada UNIFE
P6 Bisag Giorgiana Denisa UNIBO
P7 Bonfant Giulia UNIFE
P8 Botti Giada UNIFE
P9 Brandolese Arianna UNIFE
P10 Brusa Irene UNIBO
P11 Buffagni Mirko UNIMORE
P12 Cabrelle Chiara UNIBO
P13 Campeti Jessica UNIBO
P14 Cesa Elena UNIFE
P15 Chaouch Mohamed Aymen UNIMORE
P16 Chenet Tatiana UNIFE
P17 Cristoni Camilla UNIMORE
P18 Da Ros Federica UNIMORE
P19 Dai Yasi UNIBO
P20 De Luca Chiara UNIFE
P21 De Ventura Tiziano UNIFE
P22 De Zio Simona UNIBO
P23 Dini Valentina Antonia UNIBO
P24 Fabbri Martina UNIFE
P25 Gentili Silvia UNIFE
P26 Giani Niccolò UNIBO
P27 Giordani Martina UNIMORE
P28 Gullo Maria Chiara UNIFE
P29 Hallan Supandeep Singh UNIFE
P30 Imperato Manuel UNIMORE
P31 Introvigne Maria Luisa UNIMORE
P32 Konchie Simo Claude Ulrich UNIMORE
P33 Lancellotti Lidia UNIMORE
P34 Li Min UNIBO
P35 Lievore Giulio UNIFE
P36 Lodesani Federica UNIMORE
P37 Maccaferri Emanuele UNIBO
P38 Marangon Vittorio UNIFE
P39 Marchetti Lucia UNIMORE
P40 Marchini Edoardo UNIFE
P41 Moro Miriam UNIBO
P42 Mugnaini Luca UNIBO
P43 Niorettini Alessandro UNIFE
P44 Oddone Natalia UNIMORE
P45 Oddone Natalia UNIMORE
P46 Ottonelli Ilaria UNIMORE
P47 Pedrazzani Riccardo UNIBO
P48 Phan Huu Dang Khoa Andrea UNIFE
P49 Pinheiro Pedro UNIBO
P50 Prandi Francesco UNIBO
P51 Ragazzini Ilaria UNIBO
P52 Romito Filippo UNIMORE
P53 Rubini Katia UNIBO
P54 Salerno Alessandra UNIBO
P55 Seghetti Francesca UNIBO
P56 Serafini Martina UNIBO
P57 Serafino Andrea UNIFE
P58 Setti Leonardo UNIMORE
P59 Sguizzato Maddalena UNIFE
P60 Shuangying Wei UNIFE
P61 Silingardi Francesca UNIBO
P62 Tacchi Francesca UNIBO
P63 Tagliazucchi Lorenzo UNIMORE
P64 Toporivska Yuliya UNIFE
P65 Turrin Giulia UNIFE
P66 Vardè Massimiliano UNIFE
P67 Vulcano Fabio UNIMORE
Figure 1. Proposed binding mode for the Zn(II)-ZinT
complex at pH 7.4. The figure was generated using
PyMol [5].
Zn(II) AND Cu(II) INTERACTION WITH ZinT PROTEIN:
FINDING A CORRELATION BETWEEN COORDINATION
CHEMISTRY AND PATHOGENIC ACTIVITY
Denise Bellotti,(a,b)
Magdalena Rowińska-Żyrek,(b)
Maurizio Remelli(a)
a) Department of Chemical and Pharmaceutical Sciences, University of Ferrara, via Luigi Borsari
46, 44121 Ferrara, Italy. E-mail: [email protected]
b) Faculty of Chemistry, University of Wroclaw, ul. F. Joliot-Curie 14, 50-383 Wroclaw, Poland.
ABSTRACT
The mechanism of metal trafficking at the host/pathogen interface represent a rational chance to
overcome the current drug-resistance crisis and ultimately design innovative antimicrobial agents.
Metals participate in infectious events and are fundamental for the subsistence of pathogenic
microorganisms. On the other hand, also humans (i.e. the host organisms) need metal ions to ensure
the correct performance of their biological functions: a sort of ‘tug-of-war’ is therefore established
between the host and the pathogen for the metals acquisition. As a consequence, in the attempt to
develop novel highly specific metal-based antibiotics, it is crucial to investigate not only the host-
mediated defence but also the metal-acquisition strategies put in place by pathogens [1].
Among several metal-sequestering proteins involved in these processes, we recently focused
on ZinT, a 216-amino acid protein mostly expressed by Gram-negative bacteria. ZinT undergoes
translocation to the periplasm in order to bind Zn(II) under strict zinc-limited conditions and shuttle
the metal to ZnuABC transporter [2]. The most probable metal-binding site of ZinT corresponds to
a domain containing three highly conserved histidine residues (position 167, 176 and 178) and one
aspartic acid (position 166). Additionally, ZinT possesses a highly conserved N-terminal histidine-
rich loop (HGHHXH, residues 124-129), whose role is unclear, although its participation in Zn(II)
uptake has been suggested [3,4]. The above results prompted us to deeply investigate complexation
of Cu(II) and Zn(II) – two endogenous and competing metal ions – with these domains of ZinT.
We studied the protected peptides Ac-124
HGHHSH129
-Am and Ac-166
DHIIAPRKSSHFH178
-
Am belonging to the amino acid sequence of the ZinT protein from Escherichia coli, and Ac-124
HGHHAH129
-Am and Ac-
166DHIIAPRKSAHFH
178-Am from the ZinT expressed by Salmonella
enterica. The characterization of the complexes has been achieved by means of mass spectrometry,
potentiometry, UV-Vis spectrophotometry,
circular dichroism (CD) and electronic
paramagnetic resonance (EPR).
The preliminary results show that all
the investigated peptides are efficient ligands
for the considered metal ions and are able to
form stable mono-nuclear complexes where
the histidine residues and, if present, the
aspartic acid participate in the metal
coordination (Figure 1). We ultimately
compared ZinT with some human-defence
mediators, e.g. the antimicrobial peptide
Calcitermin [6], to evaluate the metal
effectiveness in the expression of the
pathogenic/antimicrobial activity by the
studied systems.
O1
REFERENCES
[1] P. Chandrangsu, C. Rensing, J. D. Helmann, Nat. Rev. Microbiol. 15(6) (2017), 338–350.
[2] A. Ilari, F. Alaleona, G. Tria, P. Petrarca, A. Battistoni, C. Zamparelli, Biochim. Biophys. Acta. 1840(1) (2013)
535–544.
[3] P. Petrarca, S. Ammendola, P. Pasquali, A. Battistoni, J. Bacteriol. 192(6), (2010) 1553–1564.
[4] J. Chen, L. Wang, F. Shang, Y. Dong, N.-C. Ha, K.H. Nam, C. Quan, Y. Xu, Biochem. Biophys. Res. Commun.
500(2), (2018) 139–144.
[5] The PyMOL Molecular Graphics System, Version 1.8, Schrödinger, LLCD.
[6] Bellotti, M. Toniolo, D. Dudek, A. Mikolajczyk, R. Guerrini, A. Matera-Witkiewicz, M. Remelli, and M. Rowinska-
Zyrek, Dalton Trans. 48(36), (2109) 13740–13752.
NOVEL GELATIN FILMS MODIFIED BY QUERCETIN FOR
BIOMEDICAL APPLICATIONS
Arianna Menichetti, Katia Rubini, Marco Montalti, Elisa Boanini, Adriana Bigi
Dipartimento di Chimica “Ciamician”, Università di Bologna, via Selmi, 2, Bologna
ABSTRACT
Nowadays, a great interest is focused on antioxidation ability which is one of the key properties for
the reduction of oxidative stress-related chronic diseases and age-related disorders such as
cardiovascular diseases, carcinogenesis and neurodegeneration [1]. Flavonoids are well known to be
beneficial for health, due to their antioxidant activity. Unfortunately, these small molecules are
subject to chemical instability due to pH and temperature variations and exposure to oxygen and
light [2]. As a consequence, the embedding of these kind of molecules in a support can lead to a
more focused and controlled release into the human body. In order to achieve this purpose, in this
work, a flavonoid (quercetin) was embedded into gelatin films in order to control its release for
biomedical applications.
Gelatin was chosen as a substrate because of its biodegradability, biocompatibility and
nonimmunogenicity, which permits its wide use both in pharmaceutical industry and biomedical
field [3]. Two main different classes of gelatin films were prepared starting respectively from
DMSO or H2O/EtOH as solvents and two different quercetin embedding techniques were explored.
The presence of quercetin significantly affected the degree
of swelling and the mechanical properties the films, also as a
function of embedding technique. The different behaviours
in thermal stability found by differential scanning
calorimetric investigation are supported by X-ray diffraction
results.
The quercetin-gelatin interaction in the films was studied by
means of fluorescence microscopy (Figure 1) and
fluorescence lifetime measurements. In particular, a static
quenching of gelatin fluorescence could be observed in each
type of film but a different organization of flavonoid
molecules in the film depending on the embedding method
was noticed. Absorption spectroscopy was used to quantify
quercetin in each film and to follow the release of quercetin
in PBS. Release rate of quercetin resulted very slow,
denoting a very strong stability of the quercetin and the
gelatin film itself, given by the interaction between the two
components.
In conclusion, novel gelatin-quercetin films have been
obtained with different preparation and embedding techniques. The presence of quercetin gives
novel properties to the gelatin films, making them more effective and suitable for biomedical and
pharmaceutic applications.
REFERENCES [1] Quideau S., Deffieux D., Douat-Casassus C., and Pouységu L., Plant polyphenols: chemical properties, biological
activities, and synthesis, Angew. Chem. Int. Ed., 2011, 50, 586 – 621
[2] Yang T., Yang H., Fan Y., Li B., Hou H., Interactions of quercetin, curcumin, epigallocatechin gallate and folic
acid with gelatin, Int. J. Biol. Macromol., 2018, 118, 124–131
[3] Boanini E., Rubini K., Panzavolta S., Bigi A., Chemico-physical characterization of gelatin films modified with
oxidized alginate, Acta Biomater., 2010, 6, 333–338
Figure 1. Fluorescence microscope image of
aggregated quercetin embedded in a gelatin
film.
O2
EXTENDED METAL ATOM CHAINS (EMACS) AS MAGNETIC
NANOSTRUCTURES: SYNTHESIS AND MAGNETIC BEHAVIOR
Alessio Nicolini(a,b)*, Rita Galavotti(a), Anne-Laure Barra(c), Marco Borsari(a), Matteo
Caleffi(a,b), Guangpu Luo(d), Ghenadie Novitchi(c), Kyungwha Park(d), Antonio Ranieri(e), Luca
Rigamonti(a), Fabrizio Roncaglia(a), Cyrille Train(c), and Andrea Cornia(a)
a) Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia &
INSTM, I-41125 Modena, Italy. b) Department of Physics, Informatics and Mathematics,
University of Modena and Reggio Emilia, I-41125 Modena, Italy. c) Laboratoire National des
Champs Magnetiques Intenses-CNRS, Universite Grenoble-Alpes, F-38042 Grenoble Cedex 9,
France. d) Department of Physics, Virginia Tech, Blacksburg, Virginia 24061, United States. e)
Department of Life Sciences, University of Modena and Reggio Emilia, I-41125 Modena, Italy.
*Email: [email protected]
ABSTRACT
Extended Metal Atom Chains (EMACs) consist in arrays of metal ions, wrapped together by
oligo--pyridylamido, or related ligands.[1-3] The arrangement of the donor atoms often promotes
the formation of metal-metal bonds.[1] EMACs have attracted renewed interest since the
pentachromium(II) complex [Cr5(tpda)4Cl2] (H2tpda = N2,N6-di(pyridin-2-yl)pyridine-2,6-diamine)
was shown to exhibit a directionally-bistable magnetic moment at low temperature (S = 2 ground
state).[4] Here, by refluxing [Fe2(Mes)4] (HMes = mesitylene), Fe4Cl8·6THF and H2tpda in toluene
and in strictly anaerobic and anhydrous conditions, we isolated crystals of the first homometallic
iron(II)-based EMAC supported by oligo--pyridylamido ligands: the tetrairon(II) complex
[Fe4(tpda)3Cl2] (1) (Fig. 1).[5] In similar conditions, also [Fe4(tpda)3Br2] (2) was isolated. The
spectroscopic and electronic properties of 1 and 2 were investigated in CH2Cl2 by UV-Vis-NIR
absorption spectroscopy, 1H-NMR spectroscopy and cyclic voltammetry. 1H-NMR showed that 1
and 2 possess D3 symmetry in CH2Cl2 solution. In both cases, the electrochemical measurements
showed four fully resolved, quasi-reversible one-electron redox processes, implying that both 1 and
2 can adopt five oxidation states in a potential window of only 0.8 V. Direct current magnetic
measurements on 1 indicate dominant ferromagnetic coupling at room temperature, although the
ground state is only weakly magnetic.[5] Based on Density Functional Theory and Angular Overlap
Model calculations, this magnetic behavior was explained as being due to two pairs of
ferromagnetically-coupled iron(II) ions (J = –21 cm–1 using JSi·Sj convention) weakly
antiferromagnetically coupled with each other.[5] Alternating-current susceptibility data revealed the
onset of slow magnetic relaxation below 2.8 K (estimated Ueff/kB = 10.1(1.3) K).[5]
To attempt activating the electronic interaction mechanism known as double-exchange, which
provides an effective source of ferromagnetic coupling in mixed valent compounds, the one-
electron chemical oxidation of 1 was carried out using ferrocenium hexafluorophosphate (1 equiv)
in CH2Cl2. The isolated product is indeed a mixed-valence species showing an intervalence
electronic absorption band around 700-750 nm, but containing one metal center less:
[FeII2FeIII(tpda)3]PF6 (3). In order to better stabilize these chain like structures, a new tripodal ligand
(4) based on three covalently linked oligo-α-
pyridylamido units was designed and synthesized
(Fig. 1). Preliminary results in the investigation
of its coordinating properties will be presented.
REFERENCES [1] J. F. Berry et al., Struct. Bonding 2010, 1-28
[2] S.-A. Hua et al., Eur. J. Inorg. Chem. 2015, 2510-2523
[3] S.-A. Hua et al., J. Chin. Chem. Soc. 2014, 9-26
[4] A. Cornia et al., Chem. Commun. 2014, 15191-15194
[5] A. Nicolini et al., Inorg. Chem. 2018, 5438-5448
Figure 1. Molecular structure of 1, viewed
approximately normal to the metal ion chain (left).
Structure of 4 (right).
O3
FUNCTIONALIZED RIBOFLAVIN AND ITS RUTHENIUM(II) ARENE COMPLEX: SYNTHESIS, CHARACTERIZATION AND
PHOTOACTIVATION STUDIES
Nicolò Orsoni(a), Álvaro Martínez (b), Luca Salassa(b), Giorgio Pelosi(a), Franco Bisceglie(a) (a) Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale, Università di Parma, Parco Area delle Scienze 17/A 43124 Parma, Italia. (b) Donostia International Physics Center, Paseo Manuel de Lardizabal 4, Donostia, 20018, Spain. ABSTRACT Visible light is an extremely useful tool to activate biologically non-active inorganic compounds into highly toxic species. An alternative technique to the classical photodynamic therapy is the so-called “photoactivated chemotherapy”. In this latter case, a biologically active compound is protected against interaction with the cell environment by a light-cleavable protecting group and unprotected by light irradiation. [1]. In the literature [2], dicationic pyridil ruthenium(II) arene complexes [(η6-arene)Ru(N,N′)(L)]2+ are well-known compounds able to release selectively their monodentate ligand (L) when excited with light, leading to the formation of extremely reactive acqueous species. In the same context, riboflavin (Rf) is an interesting molecule [3] that is able to reduce a platinum(IV) prodrug when irradiated with a blue light generating a biologically active platinum complex. The aim of this work is the functionalization of Rf able to bind to ruthenium as a monodentate ligand. The final complex presents two reactivities: the photoreduction of platinum induced by the Rf and the photodissociation of the Ru(II) arene complex. Here, we present the synthesis of the functionalized Rf and the Ru(II) arene complex and the preliminary studies of photoactivation. REFERENCES [1] Bonnet, S.; Why develop photoactivated chemotherapy? Dalton Transactions, 2018, 47, 10330. [2] Betanzos-Lara, S. et al.; Photoactivatable organometallic pyridil ruthenium(II) arene complexes. Organometallics, 2012, 31, 3466−3479. [3] Gurruchaga-Pereda J. et al.; Flavin Bioorthogonal Photocatalysis Towards Platinum Substrates, ACS Catalysis, 2019, https://doi.org/10.1021/acscatal.9b02863.
O4
IBUPROFEN-CROMOLYN CO-DRUGS AS
POLYPHARMACOLOGICAL TOOLS FOR ALZHEIMER
DISEASE
Claudia Albertini*(a)
, Maria Laura Bolognesi(a)
a) Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna,
Via Belmeloro 6, 40126, Bologna, Italy.
ABSTRACT
Alzheimer disease (AD) is the most common cause of dementia worldwide, and its incidence is
expected to increase by 2050.[1]
Nevertheless, all the currently available drugs have only a
symptomatic effect and an effective treatment represents an extremely urgent medical need. One of
the reason behind the large number of failures in AD drug discovery is probably the multifactorial
nature of this disease, that makes the classic paradigm one-target-one-drug-one disease ineffective.
Focusing on that, the most promising strategy to treat complex diseases seems to be a
polypharmacological approach.[2]
One of the long known, but still topical, pathway involved in AD
pathogenesis is neuroinflammation, as underlined from Alzheimer’s Drug Discovery Foundation. In
this respect, there is an ongoing phase 3 clinical trial involving
the co-administration of two well known anti-inflammatory
drugs, ibuprofen (IBU) and cromolyn (CR), by two different
pharmaceutical forms. IBU is administered as a tablet, while
CR as a inhaled powder formulation.[3]
Inspired by this
promising trial, the aim of this project is to obtain a synergistic
effect by the modulation of different mechanisms involved in
neuroinflammation pathway by IBU-CR co-drugs. Whit this
goal, we rationally designed and synthesized a small library of
co-drugs, single chemical entities obtained through cleavable
bonds between the starting drugs, that can be hydrolyzed in vivo
releasing the two parent compounds. In particular the new
molecules are designed in a way that they mimic 1:1 and 2:1
ratio IBU:CR co-drugs, and by linking or fusing strategies
(Figure 1).[2]
The design of the library took in consideration the possibility to improve the
druglikeness of the co-drugs compared to the two starting drugs. In this way, the negative charges
of acid groups of both IBU and CR have been masked, so that they do not hamper blood–brain
barrier permeation. Furthermore, co-drugs’ design increase their lipophilicity favoring the oral
administration of CR. In fact, inhalation powder is not the best administration way for AD patients,
because it requires a perfect coordination between sprinkle and inhalation, to be correctly adsorbed,
while people affected by AD often suffer of apraxia. In detail, the design of the 1:1 co-drugs
exploited a fusing strategy by the direct esterification of the carboxylic group of IBU with the
hydroxyl function of CR. Otherwise, the design of the 2:1 co-drugs implicated a linking strategy
between the two carboxylic groups of CR and the amine or hydroxyl function of the ethylene
glycol, ethanolamine and ethylenediamine linkers, with different metabolic stability. A preliminary
study of neurotoxicity on N2A cells has been performed on IBU, CR and their 1:1, 1:2
combinations and, as we expected, the two drugs tested alone and in combinations resulted not
toxic. Future studies will involve the evaluation of the metabolic stability of the co-drugs, the
immunomodulatory effect of the synthesized molecules compared to the IBU-CR combination, and
the study of the co-drugs’ possibility to interact with amyloid beta protein.
REFERENCES [1] https://www.alz.co.uk/research/world-report-2018
[2] M. L. Bolognesi, “Polypharmacology in a Single Drug: Multitarget Drugs”, Curr Med Chem (2013) 20:1639.
[3] https://www.alzdiscovery.org/research-and-grants/priorities
Figure 1. Design strategy
F1
RECOVERY AND RECYCLING OF CARBON FIBERS AND
THEIR USE AS RAW MATERIAL FOR A NEW PRODUCTION OF
SUSTAINABLE COMPOSITES WITH A "CRADLE TO CRADLE"
APPROACH
Gianluca Brancolini
Dipartimento di Chimica Industriale “Toso Montanari”, Università di Bologna, viale Risorgimento
4, 40136. [email protected]
ABSTRACT
In recent decades, carbon fibers reinforced polymers (CFRPs) have found widespread application in
a growing number of fields, such as automotive and aerospace because of their lightness combined
with great mechanical proprieties comparable to those ones of metals. Recently, there was a boost
in the CFRPs exploitation and consequently the demand for carbon fibers has reached 208.000
tons/year in 2020. For this reason, the problem of composites waste disposal is becoming of great
interest and hence research efforts are focusing on adequate recovery techniques for these
components to match the EU Directives. For their heterogeneous compositions, it is very difficult to
separate carbon fibers from composites polymer matrix. In particular, in thermoset CFRPs, carbon
fibers cannot easily be recovered and recycled by new melting and remoulding, hence research
efforts are focusing on techniques that allow the recovery of the high added value carbon fibers.
Previous studies [1, 2] highlighted that pyro-gasification processes allow to recovery carbon fibers
which ca be reused to produce chopped CFRPs.
In this context, the present work aims thus at optimizing the pyro-gasification process, and
demonstrating the potential of the recovered carbon fibers as secondary raw materials, validating a
process able to recycle the composite’s carbon-fibers fraction and close their Life Cycle in a Cradle-
to-Cradle approach.
The pyro-gasification process of several composite materials was simulated into a mitten with the
aim to study the kinetics of the chemistry reactions involved. Furthermore, the whole recycling
process was optimized in terms of temperature and oxidation time with the aim to obtained
recovered fibers with high mechanical proprieties.
REFERENCES
[1] L. Giorgini, T. Benelli, L. Mazzocchetti, C. Leonardi, G. Zattini, G. Minak, E. Dolcini, M. Cavazzoni, I. Montanari,
and C. Tosi. Recovery of Carbon Fibers From Cured and Uncured Carbon Fiber Reinforced Composites Wastes and
Their Use as Feedstock for a New Composite Production. Polym. Compos. 36 (2015) 1084-1095.
[2] L. Mazzocchetti, T. Benelli, E. D'Angelo, C. Leonardi, G. Zattini, L. Giorgini. Validation of carbon fibers recycling
by pyro-gasification: The influence of oxidation conditions to obtain clean fibers and promote fiber/matrix adhesion in
epoxy composites. Composites Part A 112 (2018) 504-514.
F2
FUNCTIONAL PROPERTIES OF CHITOSAN FILMS MODIFIED BY SNAIL MUCUS EXTRACT Maria Francesca Di Filippo(a), Silvia Panzavolta(a), Beatrice Albertini(b), Nadia Passerini(b), Adriana Bigi(a), Luisa Stella Dolci(b) a) Department of Chemistry ‘G. Ciamician’, University of Bologna, [email protected]; b) Department of Pharmacy and BioTechnology, University of Bologna; ABSTRACT The environmental problems caused by the continuous increase of plastic pollution have stimulated many efforts addressed to find suitable substitutes obtained from natural and renewable sources through green processes. Chitosan has been proposed as an eligible material with potential applications in many fields, including medicine, agriculture, food, textile, environment, and bioengineering, due to its excellent properties of non toxicity, biocompatibility, biodegradability, chelating capability. In particular, chitosan ability to form films has been widely exploited for food packaging, wound dressing and drug delivery applications [1]. A large number of studies have focused on modifying the composition and the properties of chitosan-based films in order to improve their performances and widen their application fields. In particular, films with improved light barrier and extra protective shield against oxidative processes were produced by incorporation of compounds of natural origin as antioxidant and/or antimicrobial agents [2]. Among natural-derived active substances, snail mucus is receiving a great deal of attention, as it has been recently proposed as an ingredient of several cosmetic (e.g. creams) and para-pharmaceutical products for the management of wound and for the treatment of chronic bronchitis [3]. In fact, snail mucus (S) is an attractive natural substance thanks to its emollient, moisturizing, protective and reparative properties. It contains bioactive substances which are responsible for its unique properties not replicable in the laboratory with synthetic chemical compounds. The aim of the present study was to explore the physicochemical properties of chitosan-based films added with snail mucus extracted from Helix Aspersa Muller (patent application n. 102019000004940). To this purpose, chitosan films at different content of snail mucus were fabricated by simple solvent casting technique. The results of this work show that snail mucus can be added to chitosan previously solubilized in acetic or lactic acid, or it can also be used directly to dissolve chitosan. Tensile tests revealed that composite films can be stretched up more than ten times with respect to pristine chitosan films, demonstrating that S addition displays a plasticizing effect on the films. Moreover, snail mucus also enhances water barrier properties and bioadhesion. Structural characterizations indicate that the interactions between snail mucus and chitosan chains involve hydrogen bonds between the hydroxyl groups of chitosan and polar groups of S. These results demonstrate that variations in composition can be utilized to modulate the properties of these materials for different potential applications as edible coating for food packaging or as composite for the biomedical field. REFERENCES [1] I. Laceta, P. Guerrero, K. de la Caba, Functional properties of chitosan-based films, Carbohydr. Polym., 93, (2013), pp. 339– 346. [2]V.G.L. Souza, A.L. Fernando, J.R.A. Pires, P.F. Rodrigues, A.A. Lopes, F.M.B. Fernandes, Physical properties of chitosan films incorporated with natural antioxidants, Ind. Crop Prod., 107, (2017), pp.565–572. [3] D.Tsoutsos, D. Kakagia, K. Tamparopoulos, The efficacy of Helix aspersa Muller extract in the healing of partial thickness burns: a novel treatment for open burn management protocols, J. Dermatol. Treat., 20, (2009), pp. 219–222.
Figure 1. Graphical abstract
F3
!"#$%&'"()*"+*&,")-.#)/$*"#)#"%"(&$*&.0))
,121)-1331456)&71251)8149456)-:753:)!;)'5<:94:6)!1279)=17>5??:2256))
'5<941).2@:7756)%1A>1)=79?56)$441),B5?1)!9?@1;)
!"#$#%#&'($')*$+,-.'+'/+*,&0&1$.'(+$'2.#+3$.0$'4+3.5$*$'6!)/74'8'49:;<''
=$.'>3.,.3&0&'?@'A'@BCDB'E.+,-.'6:F;'<'$"#+*G$"#+*H*,3H$#'
)
$='*#$!*)40+.,'I.#+3'$"'+""+,#$.0'J&3'0$J+H'K%5.,'L+.0#L'.,('"%3M$M.0'"#3$*#0N'(+O+,('&,'I.#+3'".J+#N'.,('.M.$0.P$0$#N'J&3'
+,+31N' O3&(%*#$&,' .,(' #L+' 1+,+3.0' +*&,&5$*' (+M+0&O5+,#H' E&3' #L+"+' 3+."&,"<' +,"%3$,1' .M.$0.P$0$#N' .,('"%"#.$,.P0+'5.,.1+5+,#'&J'I.#+3'.,('".,$#.#$&,'P+*.5+'$,'QCDR'&,+'&J'DS'1&.0"'I&30('0+.(+3"'.13++('%O&,'$,'
&3(+3' #&' .*L$+M+' .' P+##+3' I&30(' PN' QCTCH' 9+I' #+*L,&0&1$+"' 5.N' J.*+' #L$"' *L.00+,1+' PN' $5O3&M$,1' #L+'
O+3J&35.,*+'&J'#3.($#$&,.0'"N"#+5"H'F5&,1' #L+5<' ,.,&#+*L,&0&1$+"'
#L.#' $,#+13.#+' #$#.,$%5' ($&U$(+'
6/$VQ;' ,.,&O.3#$*0+"' 69W";' $,'
J$0#+3$,1X.("&3P$,1' 5+5P3.,+"<'O3&M+'M+3N'+JJ$*$+,#'$,'#L+'.(M.,*+('
&U$(.#$&,'#3+.#5+,#'&J'O&00%#.,#"H'!,'
O.3#$*%0.3<' /$VQ' 9W"' ($"O0.N'OL&#&*.#.0N#$*' .*#$M$#N' %O&,'
+UO&"%3+' #&' Y=' 0$1L#<' I$#L' #L+'
J&35.#$&,'&J'"%O+38&U$(.,#'3.($*.0"'IL+,' $,' *&,#.*#' I$#L' &UN1+,' .,('
I.#+3'6E$1%3+'D8F;H'!,'#L$"'"#%(N'I+'
*&.#+('*&55+3*$.0'J.P3$*'I$#L'/$VQ'
9W"'PN'+UO0&$#$,1'#L+'L$1L'.JJ$,$#N'&J' 5+#.0' &U$(+' 9W"' J&3' ,.#%3.0'
LN(3&OL$0$*'J$P3+"<'%"$,1'.'($O8O.(8
*%3$,1' O3&*+""' "&' ."' #&' *3+.#+',.,&"#3%*#%3+(' *&.#$,1"' .P0+' #&'
(+13.(+' O&00%#.,#"' $,' I.#+3H' /L+'
1&&(' "#.P$0$#N' &J' #L+' (+O&"$#+('
*&.#$,1'&,'$,+3#'*&##&,'"%OO&3#'I."'.03+.(N'$,M+"#$1.#+('$,'.'O3+M$&%"'I&3ZH'W&"#8O%3$J$*.#$&,'#3+.#5+,#"'.3+',&#'3+[%$3+(H'\D]\Q]H'^+13.(.#$&,'#+"#"'I+3+'*.33$+('&%#'%"$,1'#L+':L&(.5$,+'_'"N,#L+#$*'(N+'6C<CCTR'1X`;''."'.'
5&(+0'&J'&31.,$*'#3.*+'O&00%#.,#H':L&(.5$,+'_'$5O.3#"'.'(++O'5.1+,#.'L%+'6.P"&3P.,*+'O+.Z'.#'RR@',5;'#&'
$#"'I.#+3' "&0%#$&,"<'5.Z$,1' $#"'*&,*+,#3.#$&,'+."N' #&'[%.,#$JN'PN'Y=8=!)'"O+*#3&"*&ONH'7UO+3$5+,#"'I+3+'*.33$+('&%#'$,'.'O3+8O$0&#'O0.,#'6?`'M&0%5+<'#L3++'$,#+3*L.,1+.P0+'0$1L#'"&%3*+"<'#I& $,#+3*L.,1+.P0+'O0."#$*'
"[%.3+' J3.5+' J.P3$*' L&0(+3"<' #+5O+3.#%3+' *&,#3&0<' .,(' .' O+3$"#.0#$*' O%5O' +,"%3$,1' J&3*+(' J0&I<' E$1H' D8_;H'
^$JJ+3+,#' +UO+3$5+,#.0' *&,($#$&,"' $,*0%(+(a' #L3++' ($JJ+3+,#0N8*&0&%3+(' J.P3$*"' 6DCCb' *&##&,<' *&##&,' .,('"N,#L+#$*'J$P3+"<'.0"&'($JJ+3$,1'PN'#L$*Z,+""'.,('*&5O&"$#$&,;c'#I&'#NO+"'&J'0$1L#'"&%3*+'6IL$#+'.,('Y='0$1L#;c'
#I&'#NO+"'&J'OL&#&*.#.0N"#'6/$VQ'9W"'.0&,+'.,('/$VQ'G')$VQ'DaT'9W";<'.,('#L3++'I&3Z$,1'#+5O+3.#%3+"'6DRd4<'
Q?d4<'TBd4;<'IL$*L'.00&I+('$(+,#$JN$,1' #L+'P+"#'(+"$1,'&O#$&,H'4&,"$"#+,#'I$#L' #L+'*.#.0N#$*'.OO3&.*L<' #L+'
O+3J&35.,*+'I."'+M.0%.#+('$,'#+35"'&J'#L+'/%3,8VM+3'E3+[%+,*N'6/VE;a'
!
"#$ %&'(!')!*+',-./ 01*0+2&03/4(!/2&05
&'(!')!.4/4(67/'
IL+3+'5&0+"'&J'*.#.0N"#'.3+'*.0*%0.#+('."'$,$#$.0'*&,*+,#3.#$&,'#$5+"'+JJ$*$+,*N<'+UO+3$5+,#.0'#$5+'$"'
$,'"+*&,("<'.,('5&0'&J'*.#.0N"#'$"'#L+'.5&%,#'&J'9W"'(+O&"$#+('&,'#L+'+UO&"+('.3+.'&J'J.P3$*H':+.*#$&,'
+JJ$*$+,*N'$"'(+J$,+('."'#L+'3.#$&'P+#I++,'#L+'.P"&3P.,*+'.#'#$5+'#'.,('#L.#'.#'#$5+'CH'':+"%0#"'"L&I,'$,'E$1%3+'D'4'$,($*.#+'#L+'DCCb'*&##&,'J.P3$*'*&.#+('I$#L'/$VQ'G')$VQ'DaT'9W"'%,(+3'IL$#+'0$1L#'.#'
/eQ?d4' ."' #L+' P+"#' (+"$1,' "#3.#+1NH'/L+' *&##&,' J.P3$*' $"' [%$#+' #L$,' .,(' P$,("' .' "5.00' .5&%,#' &J'
*.#.0N"#<'+,&%1L<'L&I+M+3<'#&'(+13.(+'.00':L&(.5$,+'_'$,'?'L&%3"H'/L+'O3+"+,*+'&J'"$0$*.'$,*3+."+"'
#L+' OL&#&*.#.0N#$*' +JJ$*$+,*N' &J' /$VQ' P+*.%"+' "$0$*.' L$,(+3' #L+' J&35.#$&,' &J' KQVQ' I$#L' 3.($*.0"'
3+*&5P$,.#$&,'\T]H'/L+'IL$#+'0$1L#'%"+('$,'#L+"+'+UO+3$5+,#"'J+.#%3+"'.'5.$,'+5$""$&,'O+.Z'.#'@RQ',5<'
-5AB2:)C;)F;')%O+38&U$(.,#'3.($*.0"'J&35.#$&,'5+*L.,$"5'_;'W3+8O$0&#'"*.0+'
OL&#&*.#.0N#$*'3+.*#&3'4;'/VE'13.OL'&J'+UO+3$5+,#.0'3+"%0#"H')
!" #$
%&" '%(
%& (&%
!"##$%&'%(
)*%&
+!,*-./0.*12
3453 +,*61*3/02
7892
)83
(80!2:8,20/53-
+0/-.*12-4338,.2
:8,21!,/5*;!<
.!9.*0!
=> ?>
@>
AB
!938-4,!
)*))+,))
-*))+.)/
/*))+.)/
0*))+.)/
1*))+.)/
2*))+.)3
2*-)+.)3
2*/)+.)3
2*0)+.)3
2*1)+.)3
)%C2D-!12"E2 >
)!9.*0!2-47-.,/.!-
?!-.21#8*1!F2EGGH218..862:/7,*1218/.!<2I*.#22
)*%&2J2K*%& EFL M+- 46<!,
AB2D0!:.N2)OLP'@>2Q#2D,*R#.N2)O&P'@>20*R#.
+#8.81/./0S-.2
.S3!
)!53!,/.4,!2186.,802
F4
M+3N'*0&"+'#&'Y='3+1$&,<'0$Z+0N'+,&%1L'#&'.*#$M.#+'/$VQ'<'+U#+,($,1'#L+'3.,1+'&J'.OO0$*.P$0$#N'#&'5&3+'
0&I8*&"#'.,('+*&8J3$+,(0N'0$1L#'"&%3*+"'"%*L'."'J0%&3+"*+,#'0.5O'.,('"&0.3'0$1L#H'
'
#"-"#"0!"'))
\D]'4&"#.H'FH`H'<'V3#+00$')H'<'_0&"$'2H'<'F0P&,+##$')H'<'=.**.3$'FH'<'^&,($'2H'f/$VQ'P."+('OL&#&*.#.0N#$*'*&.#$,1"a'J3&5'
,.,&"#3%*#%3+'#&'J%,*#$&,.0'O3&O+3#$+"g'4L+5$*.0'7,1$,++3$,1'h&3,.0H'QCDT'
\Q]'V3#+00$')H'<'_0&"$'2H'<'F0P&,+##$')H'<'=.**.3$'FH'<'^&,($'2H'<'4&"#.'FH`H'f/$VQ'P."+(',.,&8OL&#&*.#.0N"$"'$55&P$0$-+('
&,'*+00%"+'"%P"#3.#+"g'h&%3,.0'&J'WL&#&*L+5$"#3N'.,('WL&#&P$&0&1N'Fa'4L+5$"#3NH'QCDT'
\T]'i.Z%5.'+#'.0H'f7JJ+*#"'&J'"$0$*.'*&.#$,1'&,'OL&#&*.#.0N#$*'3+.*#$&,"'&J'.,.#."+'#$#.,$%5'($&U$(+'"#%($+('PN'[%.,#$#.#$M+'
(+#+*#$&,'&J'3+.*#$M+'&UN1+,'"O+*$+"g'FOO0$+('4.#.0N"#'_a'7,M$3&,5+,#.0H'QCDT'
SYNTHESIS OF P-SUBSTITUTED DMP-LIKE ANALOGUES AND
THEIR APPLICATION IN NOC(1-13)-NH2
Davide Illuminati(a), Anna Fantinati(a), Salvatore Pacifico(a), Delia Preti(a), Remo Guerrini(a),
Claudio Trapella(a)
a) Department of Chemical and Pharmaceutical Sciences, University of Ferrara, via Fossato di
Mortara 17, Ferrara 44121, Italy.
ABSTRACT
Nociceptin (N/OFQ peptide) is a neuropeptide involved in several biological functions, such as pain
modulation, anxiety, learning, memory, food intake, reward pathways and tolerance development.
The N/OFQ system is involved in the inhibition of tachykinergic bronchoconstriction through the
activation of the NOP receptor; even though it is classified as endogenous opioid receptor it does
not bind the other classical opiates.
Once it was demonstrated the importance of non-natural aromatic amino acids as dimethyl-tyrosine
(Dmt) and dimethyl-phenylalanine (Dmp), instead of Tyr1 and/or Phe1,4 in the message domain of
opioid peptides to enhance their biological activity or to modulate their receptor selectivity, the
interest about the synthesis of non-natural aromatic amino acids has been increased.[1]
It is already known, from literature, that Phe4 is mandatory for NOP activation, and the presence of
EWG groups increase the biological activity of the peptide, while Phe1 seemed to be important but
not mandatory for the explication of biological activity. It was discovered that Dmp could represent
a valid surrogate for Phe1,4, due to the similarity to Dmt. It seemed that Dmp1 should maintain the
same receptor selectivity of N/OFQ while Dmp4 could be detrimental for NOP, reducing its binding
receptor affinity. [2,3]
The activity research was focused on the synthesis of 3 different non-natural amino acids Dmp-like,
characterized by the presence of 2’;6’ methyl functions and a para-EWG group in the aromatic ring
of Phe4.
It was possible to obtain the Fmoc-protected amino acids (pF)Dmp; (pNO2)Dmp and Dmp
derivatives through a C-H alkylation Pd catalysed synthetical pathway recently published to obtain
Dmt in good yield, starting from the natural amino acid Tyr and avoiding racemization processes.[4]
It was necessary to modify and work up the synthesis published by X.Wang et al., to reach the
desired products in permissive conditions for the C-H di-methylation reaction.
Once obtained the desired products, they
were ready to be inserted, through SPPS
in NC(1-13)-NH2, the shortest fragment
of N/OFQ with the same biological
activity of the parent peptide, comparing
their affinity binding receptor
differences.
REFERENCES [1] S.D.Bryant; Y.Jinsmaa; S.Salvadori; Y.Okada; L.H.Lazarus; Dmt and opioid peptides: a potent alliance,
Biopolymers (PeptideScience); (2003) 71,86–102
[2] R.Guerrini; G.Calò et al.; Address and Message Sequences for the Nociceptin Receptor: a structure-activity study of
Nociceptin(1-13)-peptide amide; J.Med. Chem.; 1997, 40, 1789-1793
[3] R.Guerrini; G.Calò et al.; Structure-activity of the Phe4 residue of Nociceptin(1-13)-NH2: identification of highly
potent agonists of the N/OFQ receptor; J. Med. Chem.; 2001, 44, 3956-3964
[4] X. Wang; S. Niu; L. Xu; C. Zhang; L. Meng et. al.; Pd-Catalyzed dimethylation of Tyrosine-derived Picolinamide
for synthesis of (S)-N-Boc-2,6-dimethyltyrosine and its analogues; Org. Lett.; 2017, 19: 246-249
Figure 1. (pF)-Dmp; (pNO2)Dmp; Dmp synthesized from (pNO2)Phe
F5
VALORIZATION OF AGRI-FOOD RESIDUES FROM INDUSTRIAL
PROCESSES Laura Maletti(a), Veronica D’Eusanio(b), Lidia Lancellotti(c), Lisa Lancellotti(d), Lorenzo Tassi(e)
(a) Laura Maletti, Department of Chemical and Geological Sciences, University of Modena and
Reggio Emilia, via G. Campi 103, 41125 Modena, Italy, Email: [email protected]
(b) Veronica D’Eusanio, Department of Chemical and Geological Sciences, University of
Modena and Reggio Emilia, via G. Campi 103, 41125 Modena, Italy
(c) Lidia Lancellotti, Department of Chemical and Geological Sciences, University of Modena
and Reggio Emilia, via G. Campi 103, 41125 Modena, Italy, Email:
(d) Lisa Lancellotti, Department of Chemical and Geological Sciences, University of Modena
and Reggio Emilia, via G. Campi 103, 41125 Modena, Italy, Email:
(e) Lorenzo Tassi, Department of Chemical and Geological Sciences, University of Modena and
Reggio Emilia, via G. Campi 103, 41125 Modena, Italy, Email: [email protected]
ABSTRACT
In these last years, more and more attention has been paid to the possibilities that allow the use of
agricultural waste and by-products coming from the agro-food primary productions to obtain high
added value fractions such as polysaccharides fibers, vegetable fats, biopharmacologically active
compounds, nutraceutical ingredients and cosmeceutical products. Finally, the residual matter post-
extraction may be suitable for energy recovery, in order to limit some problems related to the waste
disposal and the waste of raw materials [1]. This is a very actual topic which perfectly matches with
the concept of green economy, circular economy and bioeconomy, where all the activities are
organized so that the waste materials of someone become resources for someone else.
The basic idea is the exploitation of the transformation cycles that underlie the biorefinery concept,
that is the effective conversion of biomasses, in a way as sustainable as possible, to obtain “precious”
products of commercial interest, starting from apparently poor materials which typically are available
in large amounts.
In particular, this study is focused on the separation, extraction, purification and characterization of
some fractions obtained from agronomic residues of Cucurbitaceae and other waste materials, by
applying research methodologies and techniques such as matrices conditioning, effective splitting up
processes and several instrumental analytical techniques to isolate and characterize as completely and
accurately as possible the fractions and sub-fractions obtained [2,3], from the chemical, compositional
and morphological point of view. Furthermore, some technological tests have also been applied to
some of our products to have a more complete idea of their behavior [4,5] in order to evaluate in
which technological application they may be used.
The above mentioned procedures allowed us to obtain different types of fibers from the pulp and the
rind of the different melon and watermelon varieties that have been studied. In addition, germplasm
oil, protein-starch and pigments from the seeds have been isolated, all fractions which may have
different applications in various industrial fields, in particular being noticed as additives in the food
and feed industries.
F6
References
[1] L. Maletti, C. Baraldi, G. Foca, A. Marchetti, F. Roncaglia, S. Sighinolfi, L. Tassi: Red-Horse chestnuts seeds of
Aesculus X Carnea: a ney way for health and food design?, chpt book in “Nuts and seeds in Health and disease prevention
- Second edition”, V.R. Preedy and R.R. Watson (Ed.s), Elsevier, in press.
[2] A. Ciurzynska, A. Lenart, K. J. Greda: Effect of pre-treatment conditions on content and activity of water and colour
of freeze-dried pumpkin, Food and Science Technology, 59 (2014) 1075-1081.
[3] F. M. Vella, D. Cautela, B. Laratta: Characterization of Polyphenolic Compounds in Cantaloupe Melon By-Products,
mdpi Journal, Foods 8 (2019) 196-204.
[4] T.L. Traynham, D. J. Myers, A.L. Carriquiry, L.A. Johnson: Evaluation of Water Holding Capacity for wheat soy flour
blends, J. Am. Oil Chem. Soc. 155 (2007) 84-151.
[5] J.E. Eastman, C.O. Moore: Cold water soluble granular starch for gelled food compositions. US Patent, 1984,
4,465,702.
ELECTROCHEMICAL APPROACH FOR THE PRODUCTION OF
LAYERED DOUBLE HYDROXIDES WITH A WELL-DEFINED
CO/ME(III) RATIO FOR OXYGEN EVOLUTION REACTION
Elisa Musella(a)
, Isacco Gualandi(a)
, Erika Scavetta(a)
, Massimo Gazzano(b)
, Arianna Rivalta(a)
,
Elisabetta Venuti(a)
, Meganne Christian(c)
, Vittorio Morandi(c)
, and Domenica Tonelli(a)
a) Dipartimento di Chimica Industriale ‘Toso Montanari’, Università di Bologna, Viale
Risorgimento 4, 40136 Bologna, Italy
b) Istituto per la sintesi organica e la fotoreattività, Consiglio Nazionale delle Ricerche, via Gobetti
101, 40129 Bologna, Italy
c) Istituto per la microelettronica e microsistemi, Consiglio Nazionale delle Ricerche, via Gobetti
101, 40129 Bologna, Italy
ABSTRACT
The increasing global energy demand on energy grows and renewable resources are the only
possible tools to rely for the future. The most relevant problem is that they tend to be intermittent
and unpredictable. [1] As a result, there will be an increasing need to store this energy for times
when the sun is not shining, and the wind is not blowing. Water electrolysis has drawn a lot of
attention to store energy from renewables. In this scenario, layered double hydroxides (LDHs)
containing redox active metals are promising materials. Cobalt based LDHs catalysts with iron and
aluminum in different molar ratio ranging from 1:1 until 4:1 were synthesized by a newly
developed electrochemical potentiodynamic method, for the first time [2]. The obtained catalysts
were characterized by a comprehensive combination of techniques and were evaluated for the
oxygen evolution reaction (OER) on classically used rotating disk electrodes and on a stationary
system. In all cases studied, an optimal Fe and Al content was highlighted and the performances
resulted highly competitive. [3]
Figure 1. Sketch of the proposed work.
REFERENCES [1] I. Roger, M. A. Shipman and M.D. Symes, Nat. Rev. Chem. 1 (2017) art. no. 003.
[2] E. Musella, I. Gualandi, E. Scavetta, A. Rivalta, E. Venuti, M. Christian, V. Morandi, A. Mullaliu, M. Giorgetti, and
D. Tonelli, J. Mater. Chem. A, 7 (2019) 11241–11249.
[3] E. Musella, I. Gualandi, E. Scavetta, M. Gazzano, A. Rivalta, E. Venuti, M. Christian, V. Morandi, and D. Tonelli
accepted manuscript in Chem. – Eur. J. (DOI: 10.1002/chem.201903288)
F7
AN INTEGRATED IN SILICO DRUG REPURPOSING
WORKFLOW TO IDENTIFY NOVEL POTENT CARBONIC
ANHYDRASE INHIBITORS
Annachiara Tinivella(a,b)
, Anna Laura Benatti(a)
, Luca Pinzi(a)
, Giulio Rastelli (a)
(a) Department of Life Sciences, University of Modena and Reggio Emilia, Via Giuseppe Campi
103, 41125, Modena, Italy.
(b) Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia,
via Giuseppe Campi, 287, 41125, Modena, Italy
E-mail: [email protected]
ABSTRACT
Drug repurposing, i.e. the identification of novel therapeutic uses for already marketed
drugs, is an established alternative to traditional drug discovery [1]. Drug repurposing allows for the
efficient exploitation of molecules that in most cases already possess optimized drug-like
properties, as well as satisfactory pharmacokinetic characteristics and toxicity profiles. In recent
years, computational strategies have been successfully applied for the design of repurposing
campaigns, allowing to exploit the ever-increasing amount of biological, structural and bioactivity
data available to the public [2].
In this study, we developed an integrated in silico protocol to identify novel uses for a
library of previously identified molecules bearing the hexahydrocyclopenta[c]quinoline scaffold [3].
In particular, we first applied ligand-based (3D shape-based screening) approaches to
thoroughly exploit three public repositories of pharmaceutical interest, namely the DrugBank, PDB
and ChEMBL databases. From these analyses we could identify a list of promising targets to be
further validated by structure-based methods, i.e. molecular docking to selected protein
conformations. Based on the in silico findings, human Carbonic Anhydrases (hCAs) emerged as
promising biological targets for one of the investigated compounds.
In collaboration with the group of Professor Supuran (University of Florence), we tested the
candidate compound on selected therapeutically relevant hCAs (isoforms I, II, IX and XII).
Remarkably, the candidate compound resulted to be a low nanomolar hCA II inhibitor with a
marked selectivity against the other investigated isoforms. Moreover, we also obtained an X-ray
crystal structure of the newly identified inhibitor in the active site of hCA II.
Further design based on the hexahydrocyclopenta[c]quinoline scaffold is currently in
progress, based on the in silico and experimental data collected so far.
REFERENCES [1] Ashburn, T. T.; Thor, K. B. Nature Reviews Drug Discovery 2004, 8(3), 673–683.
[2] March-Vila, E.; Pinzi, L.; Sturm, N.; Tinivella, A.; Engkvist, O.; Chen, H.; Rastelli, G. Front Pharmacol 2017, 8,
298.
[3] Carlino, L.; Christodoulou, M. S.; Restelli, V.; Caporuscio, F.; Foschi, F.; Semrau, M. S.; Costanzi, E.; Tinivella,
A.; Pinzi, L.; Lo Presti, L.; Battistuta, R.; Storici, P.; Broggini M.; Passarella, D.; Rastelli, G. ChemMedChem 2018,
13(24), 2627–34.
F8
METHOD DEVELOPMENT FOR THE SPECIATION ANALYSIS
OF ORGANOTIN COMPOUNDS BY HPLC-ICP/MS
Giulia Vergine*, Valentina Costa, Elena Sarti, Alberto Cavazzini, Luisa Pasti
Department of Chemical and Pharmaceutical Sciences, via Luigi Borsari, 46, 44121, Ferrara
*Email: [email protected]
ABSTRACT
Organotin compounds (OTCs) are well known global pollutants. Depending on the nature and the
number of the organic groups bound to the Sn cation, some organotins show specific toxic effects to
different organisms, even at very low concentration levels. They are considered endocrine
disruptors, as responsible for genetic, reproductive and metabolic disorders[1] and because of their
persistence, OTCs presence and bioaccumulation in living organisms is still a current issue[2]. The
Ministerial Decree n°260/2010 sets the environmental quality standard EQS for TBT compounds in
marine sediments at 5µg/kg dw. Therefore, analytical methods in compliance with the EQS
proposed to protect the aquatic environment and human beings are needed.
The current method adopted by national and international protection agencies consists in different
sequential steps, after sample lyophilization and homogenization, such as extraction, derivatization
with Grignard reagent, clean up and, finally, GC/MS determination[3].
Since low yields of derivatization and losses of analytes can easily occur during all this complex
sample preparation procedure, leading to an underestimation of OTCs content in environmental
samples, more accurate and sensitive analytical methods need to be improved in order to be able to
detect these compounds in complex matrices, such as sediments and biota.
The aim of this study was the development of a method for the speciation of TBT and its
degradation products, dibutyltin (DBT) and monobutyltin (MTB), by liquid chromatography
coupled to inductively coupled plasma mass spectrometry (HPLC-ICP-MS). In order to optimize
the method conditions, the influence of the percentage of organic modifier (methanol), the content
of acetic acid and tropolone as complexing agent in the mobile phase was studied. The developed
sensitive method allowed the separation of the three organotin compounds in less than 10 minutes.
In addition, methods based on HPLC-ICP/MS can significantly simplify sample preparation step
avoiding derivatization.
REFERENCES [1] R.F. Cole et al., Trends in Environmental Analytical Chemistry 8 (2015) 1–11
[2] T. Fortibuoni et al., Environ. Sci. Technol. 2013, 47, 3370−3377
[3] R. Morabito, Metodologie analitiche di riferimento - Appendice 1, ICRAM (2001)
F9
PALLADIUM-CATALYZED SYNTHESIS OF CHIRAL HYDANTOINS
Aleksandr Voronov, Nicola Della Ca’
Department of Chemical Sciences, Life Sciences and Environmental Sustainability University of Parma, Parco Area delle Scienze, 17A, 43124, Parma, Italy
ASTRACT Hydantoins are a class of important five-membered heterocycles involved in biological processes and frequently found in a number of pharmaceuticals and cosmetic products. As a result, many procedures have been developed for the construction of these compounds over the past decades [1]. The carbonylation strategy represents an attractive route since it may enable the synthesis of chiral hydantoins starting from α-amino acid derivatives. However, the reported carbonilation protocols often require the use of toxic reagents such as phosgene, triphosgene [2] or high pressures of carbon monoxide [3]. Palladium-catalyzed carbonylation reactions continue to play a leading role in the synthesis of carbonyl-containing chemicals both on laboratory and industrial scale.[4] We now disclose a new palladium-catalyzed carbonylative approach to access chiral hydantoins from α-amino amides under mild reaction conditions. The optimized reaction conditions feature the use of palladium (II) acetate as catalyst (10 mol%), copper (II) acetate as oxidant (1 equivalent) and glacial acetic acid as solvent, under 1 atmosphere of the CO/air mixture in 3:1 ratio (Figure 1). During the optimization study we managed to exclude the formation of symmetrical urea (from two molecules of the starting α-amino amide) that can be easily obtained under different carbonylation conditions [5]. The major byproduct comes from the acetylation of the primary amino group of the substrate due to highly acidic medium employed. Hydantoins were obtained in good yields (62-82%) and the chirality of the starting α-amino amides was conserved in the final products.
R1
NH2
NH
OR2
CO/air (3:1, 1 atm)R1
O
HNN
O
R2Pd(OAc)2, Cu(OAc)
2
AcOH, 80 °C, 6 h
R1
NHAcNH
OR2
+
14 examples(62-82%)
Figure 1. Palladium-catalyzed carbonylative approach to chiral hydantoins.
REFERENCES [1] Konnert, L.; Lamaty, F.; Martinez, J.; Colacino, E. Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold. Chem. Rev. 2017, 117, 13757−13809.
[2] Zhang, D.; Xing, X.; Cuny, G. D. Synthesis of Hydantoins from Enantiomerically Pure α-Amino Amides without Epimerization. J. Org. Chem. 2006, 71, 1750−1753.
[3] Dumbris, S. M.; Diaz, D. J.; McElwee-White, L. Preparation of Hydantoins by Catalytic Oxidative carbonylation of α-Amino Amides. J. Org. Chem. 2009, 74, 8862−8865.
[4] Shen, C.; Wu, X.-F. Palladium-Catalyzed Carbonylative Multicomponent Reactions. Chem. Eur. J. 2017, 23, 2973–2987.
[5] Gabriele, B.; Salerno, G.; Mancuso, R.; Costa, M. Efficient Synthesis of Ureas by Direct Palladium-Catalyzed Oxidative Carbonylation of Amines. J. Org. Chem. 2004, 69, 4741–4750.
F10
A PROPOSAL FOR EXPLORING LOCAL SPATIAL FEATURES
IN HYPERSPECTRAL IMAGES
Mohamad Ahmad1,3
, Raffaele Vitale1,2
, Cyril Ruckebusch1, Marina Cocchi
3
1 Université de Lille Sciences et Technologies, LASIR CNRS, F-59000 Lille, France
2 KU-Leuven, Department of Chemistry, Molecular Imaging and Photonics Unit, Celestijnenlaan
200F, B-3001 Leuven, Belgium 3Dipartimento di Scienze Chimiche e Geologiche, Università di Modena e Reggio Emilia, Via
Campi 103, 41125 Modena, Italia
ABSTRACT
We propose a methodological framework to extract characteristic images based on their spatial
features in hyperspectral imaging data, while establishing a link to the spectral wavelengths where
this spatial information is highlighted. The approach relies on the 2D Wavelet Transform (by using
the stationary wavelet transform implementation, 2D-SWT) capability of capturing distinct spatial
features in disjoint subspaces (different sub-images at each spectral channel). The proposed
methodology is composed of two main steps. First, it utilises 2D-SWT to highlight spatial features,
decomposing each image (without unfolding) constituting the hyperspectral data-cube with a
selected wavelet filter up to the maximum decomposition level (fig. 1.2). Then, the most distinct
features are determined by computing descriptors (such as contrast or homogeneity) on the grey-
level co-occurrence matrices gathered by each sub-image obtained by 2D-SWT (per spectral
channel) (fig. 1.3). In this way, spatial/spectral information can be rearranged in a two dimensional
data matrix, with the descriptors as rows and the spectral wavelengths as columns (fig. 1.4).
This data can be investigated by different multivariate analysis tools to analyse the characteristic
spatial features and their variability along the spectral channels, taking into account the correlation
structure among spectral wavelengths.
Figure 1: Illustration of descriptor matrix framework
P1
PREPARATION OF OILS FROM DRUG-TYPE CANNABIS
SATIVA L. AND EVALUATION OF THE PROFILE IN
CANNABINOIDS AND TERPENES
Lisa Anceschi
(a),(b), Virginia Brighenti
(a),Manuela Licata
(c), Marco Ternelli
(d), Federica
Pellati(a)
a Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103,
41125, Modena, Italy. b Doctorate School in Clinical and Experimental Medicine (CEM), University of Modena and
Reggio Emilia, 41125 Modena, Italy. [email protected] c
Forensic Toxicology Laboratory; Department of Biomedical, Metabolic and Neural Sciences,
University of Modena and Reggio Emilia, Via del Pozzo, 71, 41124, Modena, Italy. d Farmacia Ternelli Dr. Maurizio, Bibbiano, RE, Italy.
ABSTRACT
Cannabis sativa L. is an annual cycle herbaceous plant belonging to Cannabaceae family. It has
been used as a medicinal plant since ancient times [1]. During the maturation, the female flower
gradually becomes covered with trichomes, which represent the sites of accumulation of secondary
metabolites. The main classes of compounds present in Cannabis sativa L. are cannabinoids and
terpenes. Among cannabinoids, the main ones are Δ9-tetrahydrocannabinolic acid (Δ
9-THCA),
cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA), which are decarboxylated to their
neutral forms under the action of light and heat. Terpenes consist of multiples of isoprenic units [2],
[3]. This work was aimed at the development of an efficient method for the production of
therapeutic Cannabis oils rich both in cannabinoids and terpenes to promote the so called
“entourage effect”, in collaboration with Dr. Marco Ternelli of the Pharmacy of Bibbiano (RE) and
Dr. Manuela Licata of the Forensic Toxicology Laboratory in Modena. A variety of drug-type
Cannabis sativa L. plant material, widely used in the pharmaceutical field, was selected for the
characterization of cannabinoids and terpenes present in the dry inflorescences. Then oils were
prepared according to different protocols described in the literature and, subsequently, by
optimizing the conditions using dynamic maceration, steam distillation and microwave assisted
extraction of the essential oil. The cannabinoids content in the oils was determined by HPLC-ESI-
MS/MS, and terpenes profiling was performed by HS-SPME-GS-MS and FID. Some of the oils
were characterized by a high terpene component and a good cannabinoids content, thanks to the
efficacy of the preparation process. The extractive methods developed through modifications of the
known protocols will find application in the preparation of high quality Cannabis oils to be used in
the pharmaceutical field.
REFERENCES
[1] R. Mechoulam, L. O. Hanuš, R. Pertwee, and A. C. Howlett, Nature Reviews Neuroscience, vol. 15, no. 11. pp.
757–764, 2014.
[2] G. Appendino, G. Chianese, O. Taglialatela-Scafati, Current Medicinal Chemistry, vol. 18, no. 7, pp. 1085–
1099, Mar. 2011.
[3] B. De Backer, B. Debrus, P. Lebrun, L. Theunis, N. Dubois, L. Decock, A. Verstraete, P. Hubert, C. Charlier,
Journal of Chromatography B, vol. 877, no. 32, pp. 4115–4124, Dec. 2009.
P2
A CALIX[4]ARENE-BASED MOLECULAR THERMOMETER
EXPLOITING FLUORESCENCE ENERGY TRANSFER
Brunella Bardi*, Irene Tosi, Federica Faroldi, Laura Baldini, Francesco Sansone, Cristina
Sissa, Francesca Terenziani
Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale, Università di Parma,
Parco Area delle Scienze 17/A, 43124 Parma, Italy
ABSTRACT
Temperature is a fundamental parameter in physical, chemical and biochemical processes.
Monitoring and mapping temperature at the nanoscale is essential in nanotechnology and
nanomedicine, pushing forward the field of nanothermometry. So far, many approaches have been
developed in order to engineer molecular thermometers with suitable sensitivity and sub-
micrometric resolution, many of them relying on fluorescent probes having temperature-dependent
emission [1]. Here, we report on a ratiometric molecular thermometer exploiting the occurrence of
resonance energy transfer (RET) between Coumarin 343, acting as the energy donor, and 7-
nitrobenz-2-oxa-1,3-diazol-4-yl (NBD), acting as the energy acceptor, anchored at the upper rim of
a cone calix[4]arene scaffold [2]. This system works as a robust and reversible ratiometric
temperature sensor over a 60°C-wide temperature range. Extensive spectroscopic study unraveled
the operating principle of the
sensor, relying on the
conformational variations of the
macrocycle induced by
temperature, affecting
interchromophore distances and
thus modifying RET efficiency
(Figure 1). To the best of our
knowledge, this is the first
example of nanothermometer
exploiting the conformational
variations of a calix[4]arene
macrocycle as the driving force,
proofing a new effective strategy
in the design of RET-based
thermometers.
REFERENCES [1] M. Quintanilla and L. M. Liz-Marzán, Nano Today, 2018, 19, 126–145
[2] B. Bardi, I. Tosi, F. Faroldi, L. Baldini, F. Sansone, C. Sissa, F. Terenziani, Chem. Commun., 2019, 55, 8098-8110
Figure 1. Working mechanism of the calix[4]arene-based
nanothermometer. At low temperatures the calix[4]arene scaffold adopts a
“closed” conformation bringing the chromophores at short distance,
promoting efficient RET; at higher temperatures the “open” conformation
is favored, moving the chromophores far apart and thus decreasing RET
efficiency.
P3
MERGING MEMANTINE AND FERULIC ACID TO PROBE
CONNECTIONS BETWEEN NMDA RECEPTORS, OXIDATIVE
STRESS AND AMYLOID-β PEPTIDE IN ALZHEIMER’S DISEASE
Basagni F.(a)
, Simoni E.(a)
, Caporaso R.(a)
, Abu I.F.(b)
, Catanzaro M.(c)
, Fagiani F.(c)
, Fusco
F.(d)
, Masuzzo S.(d)
, Albani D.(d)
, Lanni C.(c)
, Mellor I.R.(b)
, Minarini A.(a)
and Rosini M.(a)
(a) Department of Pharmacy and Biotechnology, Alma Mater Studiorum – University of Bologna,
Via Belmeloro 6, 40126 Bologna (IT) (b)
School of Life Sciences, University of Nottingham, University Park, Nottingham, NG72RD (UK) (c)
Department of Drug Sciences (Pharmacology Section), University of Pavia, V.le Taramelli 14,
27100 Pavia (IT) (d)
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via La Masa 19, 20156 Milan (IT)
ABSTRACT
Loss of synaptic function is closely related to cognitive impairment in Alzheimer’s disease (AD),
albeit the mechanism of synaptic damage remains incompletely understood. N-methyl-D-aspartate
(NMDA) receptors (NMDAR) play a pivotal role for synaptic plasticity in the healthy brain. The
localization of NMDAR seems to affect their biological activities, with synaptic NMDAR
contributing to cell survival and plasticity, while extrasynaptic NMDAR preferentially activating
apoptotic signaling cascades.1 Memantine is an uncompetitive NMDAR antagonist approved by
FDA to treat moderate-severe AD patients. It acts as an open-channel blocker with a relatively
rapid off-rate from the channel. Due to this peculiar kinetics, memantine mainly enters the channel
in conditions of excessive and prolonged glutamate exposure, preferentially acting on
extrasynaptic/tonically-activated NMDAR over synaptic/phasically-activated NMDAR.2
In the light of the above, we considered memantine as a driving force which could specifically
convey bioactive payloads at glutamatergic extrasynaptic sites, where NMDAR have been proposed
to trigger neurotoxic events
mediated by amyloid β peptide
(Aβ) and oxidative stress. To this
aim, we applied a multifunctional
approach by conjugating
memantine to ferulic acid (FA),
which is known to protect the
brain from Aβ neurotoxicity and
neuronal death caused by ROS3
(Fig. 1).
Electrophysiological studies have shown that the new molecules behave, like memantine, as open-
channel blockers of NMDAR, albeit with lower efficacy with respect to the reference compound.
Furthermore, the most promising compound exerts antioxidant properties both directly and
indirectly through the activation of Nrf-2 pathway in SH-SY5Y cells, and the ability to modulate
Aβ production, as revealed by the observed increase of the non-amyloidogenic sAPPα in H4-sw
cells.
REFERENCES
[1] Lipton, S. A. Nat. Rev. Drug Discov., 2006, 5, 160–170.
[2] Le, D. A. & Lipton, S. A. Drugs Aging, 2001, 18, 717–24.
[3] Benchekroun M. et al., J. Med. Chem., 2016, 59 (21), 9967–9973.
Figure 1. Multifunctional approach: memantine-ferulic acid
conjugates to investigate AD pathogenetic network.
P4
PLA WATER BASED COATINGS FOR RECYCLABLE AND
BIODEGRADABLE FLEXIBLE PACKAGING PAPER
MATERIALS
G. Belletti(a)
, V. Saez Talens(b)
, A. Guillem Ortiz(b)
, A. Aragón Gutiérrez(b)
, L. Crowther-
Alwyn (c)
, L. Ricci(d)
, M. Bertoldo(a,d)
a) Istituto per la Sintesi Organica e la Fotoreattività del Consiglio Nazionale delle Ricerche (ISOF-
CNR)
Via P. Gobetti 101, 40129 Bologna (Italy). e-mail: [email protected]
b) Instituto Tecnológico del Embalaje, Transporte y Logística (ITENE), C/ Albert Einstein, 1,
46980 Paterna, Valencia (Spain)
c) Centre Technique du Papier (CTP), Domaine Universitaire CS 90251, 38044 Grenoble Cedex
(France)
d) Istituto per i Processi Chimico-Fisici del Consiglio Nazionale delle Ricerche (IPCF-CNR), Area
della Ricerca, Via G.Moruzzi 1, I-56124 Pisa, Italy
Paper-based materials are commonly used in flexible packaging being light-weight, durable, easy to
print, bio-based and easily recyclable. Additional layers, usually made of fossil oil derived polymers
and alluminium foils, are often combined with cellulosic-material to provide all the properties
required for the final application such as barrier to oxygen, moisture, aromas and contaminants,
sealability and bending resistance and good grip control. Due to the large volume and the short
circulating time of food packaging materials used currently in the world and in Europe many efforts
are nowadays devoted to develop innovative solutions that avoid disposal and pollution. In this
framework, in 2017 the Bio Based Industries Joint Undertaking founded SHERPACK’s project
under the European Union’s Horizon 2020 research and innovation programme. SHERPACK’s
ambition is to develop a renewable, biodegradable and recyclable flexible paper-based packaging
material for food that has to be easily converted by heat-sealing and folding. The target product
must have improved stiffness and grip resistance with respect to traditional paper in order to replace
materials such as plastics or aluminum foil currently used on the market. To reach these goals,
SHERPACK relies on three major innovations: wet-lamination of a thin layer of fiber specialty on
the cellulosic substrate, specific formulation and printing of a polysaccharide grid to improve the
grip and stiffness, formulation and coating of a biodegradable polymer waterborne emulsion.
When combining polymers with paper, water coating process is preferred over lamination and
extrusion allowing low thickness and thus overall low cost and reduced material consumption.
Hence, a brand new green process was developed to obtain a waterborne poly(lactic acid) (PLA)
formulation. This coating, once applied on paper will provide heat sealability and barrier to water
vapor. The procedure to obtain the PLA formulation involves blending with a high shear mixer a
PLA solution in a nontoxic organic solvent and a water phase containing a polysaccharide, which
acts as stabilizing agent. Emulsion stability over time was assessed by dynamic light scattering
analysis, whilst the phase morphology of the dried formulation was studied by SEM microscopy.
The process was successfully scaled up to produce nearly 200 ml of emulsion that was exploited to
make preliminary coating tests on paper. The coated paper showed promising properties, exhibiting
a cobb index value of 2 g/m2
(water, 60s).
P5
CENTRAL-TO-AXIAL CHIRALITY CONVERSION APPROACH
DESIGNED ON ORGANOCATALYTIC ENANTIOSELECTIVE
CYCLOADDITIONS
Giorgiana Denisa Bisag, a)
Daniel Pecorari, a)
Andrea Mazzanti, a)
Luca Bernardi, a)
Mariafrancesca Fochi, a)
Giorgio Bencivenni, a)
Giulio Bertuzzi, a)
Vasco Corti a)
a) Department of Industrial Chemistry “Toso Montanari” Alma Mater Studiorum – University of
Bologna. Viale del Risorgimento 4, 40136 Bologna, Italy.
Email: [email protected]
ABSTRACT
The central to axial chirality conversion approach consists, first of all, in the synthesis of
enantioenriched molecules displaying central chirality, and then in the conversion of the central
chirality into axial chirality thanks to oxidation or elimination reactions, leading to the
corresponding atropisomeric sistems. This methodology was theorized for the first time in 1955 by
Berson1 and later demonstrated by Meyers
2 and others.
3
Following this principle, we developed the first stereoselective synthesis of enantioenriched axially
chiral indole–quinoline systems.4 The strategy takes advantage of an organocatalytic
enantioselective Povarov cycloaddition between 3-alkenylindoles and N-arylimines, followed by an
oxidative central-to-axial chirality conversion process. It allows the obtainment of previously
unreported axially chiral indole-quinoline biaryls. The methodology is also implemented for the
design and the preparation of challenging compounds exhibiting two chirality axes.
The tetrahydroquinoline scaffolds are synthetized exploiting an acid catalyzed inverse-electron-
demand [4 + 2] cycloaddition. This cycloaddition consists in the reaction between an N-arylimine
and a hindered 3-alkenylindole. The Povarov cycloaddition is promoted by the chiral acid (R)-
TRIP, able to deliver enantioenriched tetrahydroquinolines in excellent yields, stereo- and
enantioselectivities. The tetrahydroquinoline scaffolds obtained in this way are subsequently
oxidized to atropisomeric indolylquinolines with retention of the chiral information imparted in the
Povarov reaction.
Figure 1. Combining organocatalytic enantioselective Povarov cycloadditions with the central-to-axial chirality
conversion concept
REFERENCES [1] J. A. Berson, E. Brown, J. Am. Chem. Soc. 1955, 77, 450
[2] A. I. Meyers, D. G.Wettlaufer, J. Am. Chem. Soc. 1984, 106, 1135
[3] Angew. Chem. Int. Ed.2016,55, 1401
[4] G. D. Bisag, D. Pecorari, A. Mazzanti, L. Bernardi, M. Fochi, G. Bencivenni, G. Bertuzzi, V. Corti. Chem. Eur. J.
2019. DOI: 10.1002/chem.201904213
P6
HOW HALOGEN BONDS PROMOTE SUPRAMOLECULAR
ASSEMBLIES IN SILVER HALO-
PHENYL(BISPYRAZOLYL)METHANE COMPLEXES IN
DIFFERENT SOLVENT SYSTEMS
Giulia Bonfant(a), Davide Balestri(a), Marianna Vescovi(a), Matteo Melegari(a),
Luciano Marchiò (a) a SCVSA department: Chemistry Unit, University of Parma, Parma, Italy. [email protected]
ABSTRACT
The halogen bond is a weak interaction that in recent years has become increasingly important in
the field of crystal engineering. This weak interaction is highly directional due to the presence of a
sigma-hole, on the opposite side of the R-X sigma bond. This positive-potential zone is evident in
atoms such as bromine and iodine, characterized by low electronegativity and high
polarizability.[1,2] Here we report a new class of ligands based on the bis(3,5-
dimethylpyrazolyl)methane scaffold having a phenyl group functionalized with a halogen atom (X=
I, Br) in para or meta positions. The halogen atom is essential to introduce a potential halogen-bond
donor site in the supramolecular system formed with Ag(I) salts. Two different Ag(I) salts were
chosen: AgPF6, which has a non-
coordinating counter-ion and AgCF3SO3,
which has a potentially coordinating
counter-ion. These mono-charged cationic
complexes present a mononuclear
structure with a 1:2 metal-ligand ratio,
namely [Ag(L4X)2]+. In all compounds,
the presence of halogen bonds in the
crystalline structure was confirmed by X-
ray diffraction on single crystals.
Interestingly, the solvent of crystallization
influences the crystal packing. In
particular, [Ag(L4I)2]PF6 gives rises to
three solvates in DCE/Hex, DCM/Hex and
THF/Hex, respectively. Likewise,
[Ag(L4I)2]CF3SO3 presents two solvates
when crystallized in DCM/Hex and
THF/Hex, respectively. The complexes
[Ag(L4I)2]PF6 and [Ag(L4I)2]CF3SO3
crystallized from THF/Hexane are
characterized by the presence of three different phases. The evolution from Phase 1 (a potentially
porous material with honeycomb structure characterized by hexagonal 1D channels comprising
56% of the unit cell volume) to Phase 3 occurs by the stepwise decrease of crystallization solvent.
REFERENCES [1] B. Li, S. Zang, L. Wang, T. C. W. Mak, C. Chem. Rev. 2016, 308, 1-21.
[2] I. Bassanetti, C. Atzeri, D. A. Tinonin, L. Marchiò, Cryst. Growth Des. 2016, 16, 3543-3552.
Figure 1. Solvates and different phases of [Ag(L4X)2]+
complexes reported in this work.
P7
NEW STRATEGIES TO OVERCOME POOR ORAL
BIOAVAILABILITY OF DRUGS BY INCREASING THEIR
WATER SOLUBILITY
Giada Botti, Denise Bellotti, Alessandro Dalpiaz, Maurizio Remelli, Remo Guerrini Department of Chemical and Pharmaceutical Sciences, University of Ferrara, via Fossato di Mortara 19,
44121 Ferrara, Italy. [email protected], [email protected]
ABSTRACT
The oral administration of drugs can induce poor therapeutic effects if they are unable to reach the
bloodstream from the intestinal lumen. The poor oral bioavailability of drugs can be associated to
their poor dissolution rate in physiologic fluids. Indeed, great amount of drugs are lipophilic, showing
high ability to permeate across the intestinal barrier, but their very poor dissolution in water sensibly
reduces their oral bioavailability.
Deferoxamine is an iron-chelant drug, used in severe forms of Thalassemia, characterized by very
poor water solubility and short in vivo half-life. As a consequence, the administration of this drug
requires the intravenous way with high frequency, inducing the low compliance of patients.
Taking into account that the clusterization can help the dissolution of drugs and protect them from
the metabolism, and that can be apply to this drug too1, I have contributed to design a strategy in order
to synthetize one omodimer and two omotetramers of
deferoxamine (Figure 1). According to this strategy,
the drug can be conjugated, through linkers, to cores
such as the PWTs (Peptide Welding Technology),
currently known to increase the dissolution of some
peptides and to reduce their metabolism in the
bloodstream, extending their half-time and allowing
less administrations2. Preliminary results indicate that
the omodimer an omotetramers of deferoxamine
obtained with this strategy allow to sensibly increase
its dissolution in aqueous medium and to reduce its
metabolism in the bloodstream, allowing to extend its
half-life and to maintain its chelating properties.
Another way to avoid the poor water dissolution of
lipophilic drugs is the formulation of pharmaceutical
co-crystals, known to potentially induce an increase of
their dissolution rate in water with consequent
enhancement of oral bioavailability. Very recently it has been demonstrated that co-crystals can also
modulate the permeation of drugs across the intestinal barriers3. These aspects will be accurately
studied in vitro by using intestinal cells monolayers, in order to verify if co-crystals can be considered
as a simple mixture of compounds or a new pharmaceutical and pharmacological entities.
REFERENCES
[1] Z. Liu, T.-M. Lin, M. Purro, and M. P. Xiong. “Enzymatically Biodegradable Polyrotaxane-Deferoxamine
Conjugates for Iron Chelation”, ACS Appl. Mater. Interfaces, 2016, 8, 25788-25797.
[2] R. Guerrini, E. Marzola, C. Trapella, M. Pelà, S. Molinari, M.C. Cerlesi, D. Malfacini, A. Rizzi, S. Salvadori, G.
Calò. “A novel and facile synthesis of tetra branched derivatives of no-ciceptin/orphanin FQ”, Bioorg. Med. Chem.
2014, 22(14), 3703-3712.
[3] A. Dalpiaz, V. Ferretti, G. Botti, B. Pavan, “Drug Release from Pharmaceutical Co-Crystals: Are Therapeutic and
Safety Properties of Active Pharmaceutical Substances Retained?”, Curr Drug Deliv. 2019;16(6):486-489.
Figure 1. Representation of an omotetramer: the
grey dots represent the PWT1 (Lys-Lys-Lys),
the red ones the Deferoxamine and the blue-
green the linkers.
P8
N-HETEROCYCLIC CARBENE (NHC) CATALYSIS IN
CHALLENGING KINETIC RESOLUTION PROCESSES OF
BIGINELLI COMPOUNDS
Arianna Brandolese(a)
, Olga Bortolini (a)
, Alessandro Massi (a)
aDepartment of Chemical and Pharmaceutical Sciences, University of Ferrara, via L. Borsari 46,
44121 Ferrara, Italy
e-mail: [email protected]
ABSTRACT
N-Heterocyclic carbenes (NHCs) have been used as powerful organocatalysts for a large number
of asymmetric and non-asymmetric transformations.1 In particular, they have been employed for the
synthesis of a variety of optically enriched functionalized molecules through, for example, kinetic
resolution processes. Kinetic resolution, in fact, constitutes a useful method in asymmetric
synthesis, representing one of the most widely used industrial procedure for the preparation of
chiral compounds.2
Herein, we report the first example of N-heterocyclic carbene-organocatalyzed kinetic resolution
of biologically active Biginelli compounds. Dihydropyrimidones (DHPMs), well known as Biginelli
products, can be simply synthetized through an efficient multicomponent reaction using highly
accessible aldehydes, active methylene compounds and (thio)ureas in acidic medium.3 In recent
years, DHPMs have attracted considerable attention, thanks to their several biological and
pharmaceutical applications. Optically active DHPMs represent challenging synthetic targets
accessible through direct asymmetric synthesis or chemical resolution processes.4
The aim of this study was to carry out a stereoselective N-3 acylation of racemic DHPMs. The
reaction promoted by chiral NHCs in oxidative conditions led to optically active N-3 acylated
products (Figure 1). Reaction conditions were optimized to reach satisfactory level of conversion
(up to 80%) and stereoselectivity (up to 84:16 er).
To the best of our knowledge, this work represents the first example of kinetic resolution of
amides and in the future could be extended to other biologically relevant amide-based compounds.
REFERENCES [1] De Risi, C.; Bortolini, O.; Di Carmine, G.; Ragno, D.; Massi, A. Synthesis 2019, 51, 1871–1891, and references
therein.
[2] Nagarajaiah, H; Mukhopadhyay, A.; Moorthy, J. N. Tetrahedron Letters 2016, 57, 5135–5149.
[3] Heravi, M. M.; Moradi, R.; Mohammadkhani, L.; Moradi, B. Molecular Diversity 2018, 22, 751–767.
[4] Wang, Z.; Pan, D.; Li, T.; Jin, Z. Chem. Asian J. 2018, 13, 2149–2163.
Figure 1. N-3 acylation of DHPMs.
P9
HIT OPTIMIZATION FOR THE DEVELOPMENT OF NOVEL
RNF5 INHIBITORS AS THERAPEUTIC STRATEGY IN CYSTIC
FIBROSIS
Irene Brusa,(a, b)
Dario Gioia,(b)
Elvira Sondo,(c)
Marinella Roberti,(a)
Nicoletta Pedemonte,(c)
and Andrea Cavalli.(a, b)
a) Department of Pharmacy and Biotechnology, University of Bologna Alma Mater Studiorum, Via
Belmeloro 6, 40126 Bologna, Italy.
b) Computational & Chemical Biology, Istituto Italiano di Tecnologia, Via Morego 30, 16163,
Genova, Italy.
c) U.O.C. Genetica Medica, Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, Genova 16147,
Italy.
E-mail: [email protected]
ABSTRACT
In cystic fibrosis (CF), deletion of phenylalanine 508 (F508del) in the CFTR anion channel is
associated to misfolding and premature degradation of the mutant protein [1]. RNF5 is an ubiquitin-
ligase promoting F508del-CFTR degradation. Recently, our group reported that genetically
suppressing in vivo RNF5 increases CFTR activity in intestinal epithelial cells, thus validating
RNF5 as drug target for FC. Therefore, through computational methods, we discovered inh-2, a
drug-like small molecule that inhibits RNF5 (Fig. 1 – a), thus decreasing ubiquitylation of mutant
CFTR and causing stabilization of the mature form of CFTR [2].
Therein, we focused on the design and synthesis of a large library of inh-2 analogues, with the
purpose of providing evidence to support RNF5 druggability. The new derivatives were synthetised
leaving the central 1,2,4-thiadiazol-5-ylidene core unchanged, while exploring different functional
groups in the N-4-benzyl region (Fig. 1 - b). At the same time, in vitro experiments were carried out
to investigate the activity of the new analogues. Finally, the obtained data were used to perform
structure-activity relationship studies (SAR), thus validating the 1,2,4-thiadiazolylidene scaffold as
a versatile architecture for the identification of RNF5 inhibitors useful to attenuate CF pathological
phenotypes.
Figure 1: a) inh-2 structure; b) synthetized inh-2 analogues.
REFERENCES
[1] K. Du, M. Sharma, and G.L. Lukacs, Nat. Struct. Mol. Biol. 12 (2005) 17-25.
[2] E. Sondo, F. Falchi, E. Caci, L. Ferrera, E. Giacomini, E. Pesce, V. Tomati, S.M. Bertozzi, L. Goldoni, A. Armirotti,
R. Ravazzolo, A. Cavalli, and N. Pedemonte, Cel. Chem. Biol. 25 (2018) 891-905.
P10
ANOMALOUS GELATION DURING THE ATRP OF STYRENE Mirko Buffagni(a), Niccolò Braidi(a), Francesca Parenti(a), Aldo Longo(b), Angelo Ferrando(b), Franco Ghelfi(a) a) Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Via G. Campi 103, 41125 Modena, Italy. E-mail: [email protected] b) "Claudio Buonerba" Research Center, Versalis (Eni) S.p.A., Via G. Taliercio 14, 46100 Mantova, Italy. E-mail: [email protected] ABSTRACT Atom transfer radical polymerization (ATRP) is a type of reversible deactivation radical polymerization, first described in 1995.[1–2] ATRP allows the synthesis of polymers with low dispersities (Đ < 1.1) and the preparation of controlled molecular architectures, giving birth to new advanced materials. ATRP is controlled by an equilibrium between halogenated dormant species (P n–X) and growing radicals (Pn·) (Scheme 1). The dormant species periodically react with a transition metal complex in its lower oxidation state (Mtm/L) to form the growing radicals, which can be deactivated by reaction with the oxidized transition metal complex (X–Mtm+1/L). The control of ATRP is ensured by keeping the equilibrium towards the dormant species, avoiding a high concentration of radicals and subsequent termination reactions (dashed arrow).
Our research group developed a type of activators regenerated by electron transfer (ARGET) ATRP process, highlighted in Scheme 2. ARGET systems exploit a chemical reducing agent to generate in situ the activator from the deactivator.[3] In our system, the reducing agent is ascorbic acid (AA) and Na2CO3 is added to activate AA and to counteract the acidity. The bifunctional initiator (X–R–X) generates a polymer with two halogenated chain ends. The monomer is styrene, the transition metal is copper and the ligand is tris(2-pyridylmethyl)amine (TPMA). Lastly, the solvent is a mixture of ethyl acetate (EtOAc) and ethanol (EtOH).
In specific conditions of reagents concentration and temperature, the reaction system evolved to a jelly-like consistency, without the addition of any crosslinker or gelling agent. The surprising discovery was patented.[4] The gelation can be explained with chain transfer processes or the formation of new double bonds via dehydrohalogenation of the initiator or the polymer chain, which can both give crosslinks and then gelation. However, these hypotheses were disproved by various scientific experiments and at this time the only plausible explanation for the phenomenon is the formation of an olympic network, a mechanically-interlocked architecture composed by interpenetrated macrocyclic polymer chains.
Scheme 1. ATRP equilibrium. Scheme 2. ARGET ATRP process studied by our research group (X = Cl, Br).
REFERENCES [1] Wang J. S., Matyjaszewski K. J. Am. Chem. Soc. 1995, 177, 5614–5615. [2] Kato M., Kamigaito M., Sawamoto M., Higashimura T. Macromolecules 1995, 28, 1721–1723. [3] Jakubowski W., Min K., Matyjaszewski K. Macromolecules 2006, 39, 39–45 [4] Ghelfi F., Ferrando A., Longo A., Buffagni M. WO2019215626 2019.
P11
NETWORK-BASED APPROACHES TO MAP STRUCTURE
ACTIVITY RELATIONSHIP (SAR) INTO BIOACTIVE
CHEMICAL SPACES
Chiara Cabrelle, Maurizio Recanatini
Department of Pharmacy and Biotechnology, Alma Mater Studiorum – University of Bologna, Via
Belmeloro 6, I-40126 Bologna, Italy
ABSTRACT
Chemical space is an attractive concept used to describe how compounds spread throughout a
reference space giving rise to a molecular landscape. In medicinal chemistry, it is interesting to
study the chemical space populated by compounds with relevant biological activities. Chemical
space descriptions could be modelled by coordinate-based or coordinate-free representations. In
the latter the reference space is represented by a hardly interpretable similarity matrix (numerical).
However, the use of networks to visually interpret chemical space allows one to overcome this
drawback. The analysis of network properties and topology of chemical space networks (CSN)
offers meaningful insights into SAR investigation1.
The aim of this work was to provide a global and easy representation of SAR of two datasets of
target-specific compounds applying network-based methods.
We first designed the threshold chemical space networks
(THR-CSN, Figure 1), in which nodes represent
compounds and edges represent pairwise molecular
similarity relationships above a pre-defined threshold. In
order to show the variation of similarity values, the edges
were weighted. To assess chemical structure similarity, we
generated a matrix using Tanimoto coefficient (Tc) as
similarity measure of fingerprint descriptors (i.e. MACCS,
ECFP, and so on).
Then, we displayed biological activities in the network
coloring the nodes using a color range from red (lowest
potency) over yellow to green (highest potency).
In conclusion, this pipeline provides a global perspective
of the CSN of the two investigated datasets and the
network analysis might give us the possibility to calculate
indicators of SAR information content, useful for guiding
through analogue library design.
REFERENCES [1] Zhang, B.; Vogt, M.; Maggiora, G. M.; & Bajorath, J. Comparison of bioactive chemical space networks generated
using substructure-and fingerprint-based measures of molecular similarity. J Comput Aided Mol Des 2015, 29, 595-608.
Figure 1. Exemplary THR-CSN.
P12
NYLON 6,6 NANOFIBERS: ELECTROSPINNING AND
EVALUATION OF THE BEADS EFFECT ON THE
STRENGTHENING OF LAMINATED COMPOSITES
Jessica Campeti(a)
, Emanuele Maccaferri(b)
, Laura Mazzocchetti(b)
, Loris Giorgini(b)
, Andrea
Zucchelli(c)
(a) Centro Interdipartimentale di Ricerca Industriale su Meccanica Avanzata e Materiali, Via
Einstein 8, Faenza (RA). e-mail: [email protected]
(b) Dipartimento di Chimica Industriale “Toso Montanari”, Università di Bologna, Viale del
Risorgimento 4, Bologna
(c) Dipartimento di Ingegneria Industriale, Università di Bologna, Viale del Risorgimento 2,
Bologna
ABSTRACT
Carbon Fiber Reinforced Polymers (CFRP) are characterized by excellent mechanical properties and
low density. Usually, these materials are used for application in automotive and aerospace sectors.
Laminated CFRP are obtained from stacking of prepregs (carbon fiber fabric pre-impregnated with
resin) and then cured at high temperature.
One of the main problems affecting laminated composites is delamination, i.e. the separation of the
different constituent layers caused by the formation of micro-cracks in the interlaminar region. In fact,
in this area, only the matrix is present, that has poor mechanical properties. Once triggered, the micro-
cracks propagate and grow in dimension until structural failure of the object. There are several ways
to increase the interlaminar fracture toughness of the composite and its mechanical properties. For
instance, it is possible to use liquid rubber for toughening the matrix. Another way is the interleaving
of films or nanofibrous membranes between the composite plies during the lamination. Such
membranes, produced via electrospinning, are more convenient than films because they are easy to
integrate thanks to their high porosity and they don’t increase the composite’s weight and thickness.
Assuming that the reinforcing effect might arise from intrinsic nanofibers characteristics and from
bridging effect (ability of the nanofibrous mat to slow down the crack propagation), in this work it has
been taken into consideration the hypothesis that the controlled formation of beads in the fibrous
membranes (usually considered as defects) could positively affect the interlaminar strength. This idea
stems from a study by Greenfeld et. al(1)
that implemented beaded fibers (not nanometric) as
reinforcing system for composite materials. They
observed that beads intermittently placed (Figure
1) on a glass fiber, increase fiber anchoring to the
matrix, and can potentially dissipate energy by
deforming the matrix during failure. Similarly,
nanofibers with beads could oppose against crack
propagation. Nylon 6,6 nanofibers were thus produced searching the conditions that could cause
beads formation. Parameters that generally give beads in electrospun fibers were set: bad solvent
system, low concentration of polymeric solution, small voltage during electrospinning process.
After a large number of tests carried out to obtain the desired beaded morphology, two membranes,
characterized by different morphologies from the classical ones (homogeneous and threadlike), have
been selected: one membrane containing a combine of nanofibers, beaded nanofibers and nano-drops;
the other one having some “welded” nanofibers probably caused by an incomplete solvent
evaporation during the electrospinning process. The produced nanofibrous mats have been
morphologically (SEM analysis) and thermally (DSC analysis) characterized. DCB test were then
carried out to evaluate the effectiveness of such membranes as a reinforcement in laminated
composites and it was found an improvement against delamination. This work is just a preliminary
study about the potentiality of beaded nanofibers on the strengthening of laminated composites and
further studies will be needed.
Figure 1: Example of fiber with beads(1)
P13
REFERENCES
1. Greenfeld, I., Zhang, W., Sui, X. M. & Wagner, H. D. Intermittent beading in fiber composites. Compos. Sci.
Technol. 160, 21–31 (2018)
APPLICAZIONE “SAFE BY DESIGN” ALLA
FOTOSTABILIZZAZIONE DI TiO2 E ZnO CON COMPOSTI A
STRUTTURA FENOLICA
Elena Cesa, Stefano Manfredini, Anna Baldisserotto, Mattia Battistin Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara, via Luigi Borsari, 46
ABSTRACT
La pelle rappresenta l’organo più grande del corpo umano ed è nostro compito garantirne l’omeostasi
attraverso un’adeguata protezione dalle aggressioni esterne, tra cui inquinamento ambientale e
radiazioni UV. In questo scenario la fotoprotezione rappresenta la principale strategia preventiva contro
photoaging e tumore alla pelle. Non a caso, i filtri solari sono tra i cosmetici più studiati, in cui la
combinazione di efficacia, gradevolezza e sicurezza d’uso rappresenta una priorità. Infatti lo stesso
filtro solare è soggetto all’azione dei raggi UV, trasformandosi in fonte di radicali liberi e minaccia per
l’integrità cutanea.
Una possibile idea risolutiva, promossa in questa ricerca, consiste nel funzionalizzare filtri fisici, quali
TiO2 e ZnO, con molecole in grado di apportare un effetto SPF Boosters ed allettanti attività
antiossidanti; al fine di ottenere un composto multifunzionale. In particolare si sono impiegati composti
naturali a struttura fenolica, quali Acido Ellagico ed Acido Ferulico, indagando parallelamente
l’influenza dimensionale degli ossidi metallici impiegati, sottoforma di particelle fini (120-200nm) o
particelle nano strutturate (1-100 nm). L’obbiettivo del progetto è la valutazione delle capacità
fotoprotettiva e fotocatalitiche degli addotti, a confronto con TiO2 e ZnO in forma libera.
Inizialmente viene svolta la funzionalizzazione degli ossidi metallici, purificazione e caratterizzazione
dell’addotto per individuare i gruppi funzionali coinvolti nell’addizione e la % di ossido metallico
coordinato. Poi segue una fase di formulazione e valutazione delle proprietà dei prototipi, confrontati
con i rispettivi componenti in forma libera o sotto forma di miscela fisica.
Dai risultati ottenuti mediante determinazione UV indirettta, la funzionalizzazione avviene per il 10%,
con differenze minime e non statisticamente significative tra la forma nano e non nano. Tramite
spettroscopia IR si studia la struttura degli addotti: nell’Acido Ferulico la coordinazione interessa sia il
gruppo fenolico che il gruppo carbossilico mentre nell’Acido Ellagico partecipa unicamente la
funzionalità catecolica.
Per l’attività fotoprotettiva espressa come SPF in vitro, sono stati impiegati due metodi differenti:
Diffey-Robson, svolto presso il Laboratorio di Ricerca e Sviluppo di Kalis srl, e la normativa ISO
24443:2012, applicata ad Ambrosialab srl. In questo caso la reazione di addizione non si dimostra
particolarmente vantaggiosa in termini di fotoprotezione, ma eccellenti sono i risultati ottenuti
dall’indagine fotocatalitica. Quest’ultima è stata determinata mediante analisi UV della
fotodegradazione di Blu acido 9 in presenza del filtro fisico. Per tale proprietà i risultati sono stati
eccellenti: tutti gli addotti si dimostrano privi di attività fotocatalitica (ridotta fotodegradazione del
colorante), differentemente dai campioni costituiti dal solo ossido metallico nano o non nano.
In conclusione i trattamenti di “copertura” di TiO2 e ZnO si rilevano strategie efficaci per un approccio
“safe by design” nel ridurre la svantaggiosa fotoreattività dei filtri fisici. Ciò si traduce in una maggior
sicurezza d’uso del prodotto solare oltre ad una prolungata fotoprotezione e stabilità della formulazione.
REFERENCES [1]Threes G Smijs and Stanislav Pavel, “Titanium dioxide and zinc oxide nanoparticles in sunscreens: focus on their safety
and effectiveness”, Dove medical Press, Nanotechnology, Science and Applications 2011:4 95–112. [2]Shinya Higashimoto, Takuya Nishi, Miki Yasukawa, Masashi Azuma, Yoshihisa Sakata, Hisayoshi Kobayashi,
“Photocatalysis of titanium dioxide modified by catechol-type interfacial surface complexes (ISC) with different substituted
groups”, Journal of Catalysis 329 (2015) 286-290.
P14
CHEMICAL COMPOSITION AND ANTIOXIDANT ACTIVITY OF
BIOACTIVE COMPOUNDS IN PRUNES
(PRUNUS DOMESTICA L.) WASTE PRODUCT
Mohamed Aymen Chaouch, Stefania Benvenuti
Department of Life Sciences, University of Modena and Reggio Emilia,
Via G. Campi 103, 41125 Modena, Italy
ABSTRACT
Fruits have always been one of the essential elements for a balanced diet and are known for
their role in the maintenance of the vital functions of the human organism. They are often
considered "functional foods" due to their rich content of various micronutrients such as phenolic
compounds, carbohydrates, minerals, vitamins, etc. Thus, having different colors, tastes and very
attractive aromas, fruits could be consumed fresh or as processed products1.
Thus, noting that fruits aren’t only consumed in their fresh status, they undergo several
transformations that lead to the emergence of a wide range of by-products and wastes including
fruit pulp, skins and seeds. These by-products are easily degradable and highly unstable that needs
to be processed quickly. They have generally high energy value thanks to digestible pectins and
sugars. In order to valorise and to avoid environmental problems due to these by-products, the fruits
processing industry often faces several solutions such as their application as animal feeds,
composting agents, bio-adsorbents for residual waters treatment, and to produce energy and to
recovery bioactive constituents2.
The European plum (Prunus domestica L.) is one of the first domesticated fruits by humans.
It belongs to the genus Prunus of the family Rosaceae that includes also apple, cherry, pear, peach,
and several berry crops. Its fruits could be consumed fresh, dried or prepared as jams, compotes and
preserves. Thus, this study aims to the characterisation of bioactive compounds present in Prunus
domestica L. by-product, as well as the evaluation of its antioxidant capacity. For that, phenolic
compounds and sugars were isolated with 80% aqueous ethanol and water, respectively.
The analysis of extracted samples by different assays
(Folin-Ciocalteu assay, Aluminum chlorate assay, Fehling’s
assay, Enzymatic assay, HPLC-RI and ICPMS) revealed
that prune waste product is still rich in phenolic compounds
(2.35-4.07 mg GAE/g FW), flavonoids (0.023-0.125 mg
QE/g FW), sugars (0.93 - 1.45 g/100g FW), sorbitol (3.96
g/100g FW) and some metals (K, Ca, Mg…). Furthermore,
ESI-MS and MS2 analysis showed that ethanolic extract is
mainly composed by caffeoylquinic acid isomers, cyanidin
and quercetin. DPPH assay reported a significant
antioxidant capacity of prune byproduct (121.67 - 294.09
mg AAE/100g) compared to plum fruits (10.38 - 972.74 mg
AAE/100g).
In the light of all above, the objective of further analysis
will be the application of prune by-product into new
formulations in order to obtain beneficial nutraceutical
derivatives.
This research was supported by MonteRè, Cooperativa Modenese essiccazione frutta, S. Maria di Mugnano, for the
enhancement of by-products of the processing chain.
REFERENCES:
Figure 1. Prunes (dried plums)
P15
[1] M. B. Soquetta, L. M. Terra and C. P. Bastos. CyTA-Journal of Food, 2018, 16 (1), 400-412.
[2] M. Faustino, M. Veiga, P. Sousa, E. M. Costa, S. Silva & M. Pintado. Molecules, 2019, 24 (6), 1056-1089.
LA-ICP-MS LINE SCAN AND ELEMENT IMAGING ANALYSES
FOR THE INVESTIGATION OF METAL UPTAKE AND
DIFFUSION ON SCALLOP SHELLS FROM AQUEOUS
SOLUTIONS
Tatiana Chenet(a)
, Gunnar Schwarz(b)
, Marcel Burger(b)
, Bodo Hattendorf(b)
, Detlef
Günther(b)
, Andrea Baldi(a)
, Alberto Cavazzini(a)
, Luisa Pasti(a)
(a)
Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Via Borsari, 46 -
44121 Ferrara, Italy, [email protected] (b)
Laboratory of Inorganic Chemistry, ETH Zürich, Vladimir-Prelog-Weg, 1 - 8093 Zürich,
Switzerland
ABSTRACT
Mollusk shells are formed by a biologically controlled mineralization that leads to the formation of
superimposed CaCO3 layers. This process takes place in a confined space between the mantle and
the protective organic layer [1].
Intensive shellfish production leads to the formation of large amounts of pre-consumer and post-
consumer residues, mainly composed of shells. The
improper disposal of this particular material results in a
waste of natural resources, but also can raise
environmental issues.
The reuse of this material as adsorbent could potentially
be a cost-effective approach for the removal of heavy
metals in water remediation technologies.
Heavy metals are common pollutants found in natural
waters, especially nearby mining sites and metalworking
industries. In particular, cadmium represents a
contaminant of major interest because of its toxicity even
at low concentrations: it substitutes calcium and zinc in
biological processes leading to the alteration of cellular
metabolism [2].
In this study we investigated the adsorption and diffusion
of cadmium through the shell layers using laser ablation
(LA-ICP-MS), a well-established technique that provides flexibility to perform spatially resolved
analyses at the µm scale and also bulk analyses in short time with minimal sample preparation
needed [3].
Line scans and elemental imaging analyses were carried out with an ArF Eximer laser system
operating at a wavelength of 193 nm, coupled to an ICP-TOFMS (Tofwerk, Thun, Switzerland) at
ETH Zürich.
Both line scans and element images showed that cadmium is adsorbed mainly on the outer layers
with little diffusion towards the shell interior.
REFERENCES [1] F. Marin, N. Le Roy, B. Marie. The formation and mineralization of mollusc shell. Frontiers in Bioscience S4
(2012) 1099-1125.
[2] M. Remelli, V. M. Nurchi, J. I. Lachowicz, S. Medici, M. A. Zoroddu, M. Peana. Competition between Cd(II) and
other divalent transition metal ions during complex formation with amino acids, peptides, and chelating agents.
Coordination Chemistry Reviews 327-328 (2016) 55-69.
[3] D. Günther, B. Hattendorf. Solid sample analysis using laser ablation inductively coupled plasma mass
spectrometry. Trends in Analytical Chemistry 24 (2005) 255-265.
Figure 1. Scallop shells
P16
ELECTROANALYTICAL DETERMINATION OF CANNABIDIOL
AND TRANS-Δ9-TETRAHYDROCANNABINOL IN AQUEOUS
SOLUTIONS USING AMPEROMETRIC SENSORS
C. Cristoni1, L. Pigani
1, D.López-Iglesias
2, C.Zanardi
1, F. Vulcano
1
1 Dipartimento di Scienze Chimiche e Geologiche, Università di Modena e Reggio Emilia, Via
Campi 103, Modena Italy 2 Department of Analytical Chemistry, University of Cadiz, Cadiz, Spain
ABSTRACT
Cannabinoids are terpenophenolic compounds extensively investigated due to their pharmacological
properties. They can be classified in three main groups: endocannabinoids, phytocannabinoids and
synthetic cannabinoids. Phytocannabinoids are known for the psychoactivity of the trans-Δ9-
tetrahydrocannabinol (Δ9-THC, Figure 1), one of the most active cannabinoids. By contrast,
cannabidiol (CBD, Figure 1), constitutes the major non-psychoactive cannabinoid of the plant.
Several therapeutic properties can be attributed to this compound, such as anti-inflammatory,
analgesic and neuroprotective, among others.
Figure 1. Molecular structures of Δ9-THC, CBD and CBN.
Cannabinoids in real samples are determined by chromatographic techniques, which carry
drawbacks like non-portable instrumentation and a long analysis time. Electrochemical sensors have
come into view as excellent alternatives to chromatographic techniques, thanks to the low cost of
the instrumentation, the possibility to miniaturize the measuring device and the simplicity of use.
Δ9-THC, CBD and CBN are electroactive, due to the irreversible oxidation of the phenol group;
thus, a study of their electrochemical behaviour represents an interesting topic of research in view
of the development of an electrochemical method for their fast detection.
Of the many electrodic materials available, the chosen one is a specific silicon oxide-based
graphitic material, SonogelCarbon, containing a conducting polymer, poly-(3,4-
ethylenedioxythiophene) (PEDOT)[1]
. The so-called SNGC-PEDOT electrodes have been tested for
the electrochemical determination of CBD, CBN and Δ9-THC from an aqueous/ethanol mixture,
showing better performances with than other electrodic materials conventionally employed in
electroanalysis, such as platinum and glassy-carbon, and more consistent responses than other
PEDOT electrodes containing gold nanoparticles (PEDOT-NpAu).Another type of electrode was
considered, SPE (screen printed electrode) functionalised with PEDOT. This type of electrode can
be dispensable due to its low production cost, and it requires a very low volume of solution, all of
these qualities make them very interesting for quick, in situ analysis.
The analytical parameters obtained, in terms of sensitivity, limits of detection and quantification for
both SNGC-PEDOT and SPE- PEDOT are comparable to those obtained for other electrochemical
sensors. Furthermore, the possibility to easily renew the electrode surface by a simple and fast
polishing method, for the first, and disposability for the second, constitute valuable features of the
proposed sensors. Based on the experimental results, the two electrochemical methods studied can
both become a valuable instrument for the determination of these cannabinoids.
REFERENCES [1] López-Iglesias, D.; García-Guzmán, J. J.; Bellido-Milla, D.; Naranjo-Rodríguez, I.; Palacios-
Santander, J. M.; Cubillana-Aguilera, L. J., Electrochem. Soc., 2018, 165, B906.
P17
TAILORING POLYMERIC NANOPARTICLES FOR BLOOD-BRAIN BARRIER CROSSING AND GLIOBLASTOMA
TARGETING
Federica Da Rosa, Jason Thomas Duskeya, Giovanni Tosia, Barbara Ruozia, Natalia Oddonea, Andreas Grabruckerb, Maria Vandellia, Flavio Fornia a Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy b Department of Biological Sciences, University of Limerick, Limerick, Ireland *e-mail: [email protected]
Glioblastoma Multiforme (GBM), is the most common adult malignant brain tumor with poor prognosis and low patient survival rates [1]. Due to the limited drug access to the central nervous system, which is restricted by the blood-brain barrier (BBB), brain diseases such as GBM are among the most difficult to treat [2]. Thus, in order to have a chance to obtain a therapeutic effect in the brain, targeted nanomedicines could be employed. Nanoparticles based on poly(lactic-co-glycolic acid)(PLGA) functionalized with specific ligands, could be promising drug delivery systems for crossing the BBB and specifically targeting GBM. For this purpose, PLGA NPs superficially modified with the peptide ligands g7, shown to be able to trigger BBB transport and A6, known ligand able to link CD44 receptors over-expressed in GBM cells, were formulated.
Different PLGA NPs, fluorescent due to the presence of PLGA-conjugated dye Cy5, were prepared with either a mixture of PLGA alone, PLGA with g7 or PLGA with A6 and fully characterized. NPs with the highest amount of ligands were employed to perform viability studies on the C6 GBM cell line. Finally, cell uptake and localization studies were carried out with all the formulations.
The viability studies showed that all NP formulations display a certain level of citotoxicity within the first 48h at a very high concentration (<[2 mg/ml]); however, all cells after this period have shown recovery of cell viability and health leading to normal growth. Furthermore, preliminary studies on cell uptake and localization seem to confirm that the NPs reach endosomes and nucleus.
The g7 and A6 PLGA NPs have been successfully formulated into stable and biologically compatible NPs. Quantification of colocalization with the early endosome will give more insight into the mode up uptake and further in vivo studies will confirm their effectiveness in targeting both BBB and GBM cells.
REFERENCES:
[1] Xiea B, Zhanga L, Hua W, Fanc M, Jiangc N, Duand Y, Jingc D, Xiaoe W, Fragosoc R.C, Lame K.S, Suna L, Li J.J, Dual blockage of STAT3 and ERK1/2 eliminates radioresistant GBM cells, Redox Biology, 2019
[2] Cai Q, Wang L, Deng G, Liu J, Chen Q, Chen Z, Systemic delivery to central nervous system by engineered PLGA nanoparticles, Am J Transl Res, 2016; issue: 749-764
AKNOWLEDGMENTS: supported by MAECI grant (PI Tosi, Nanomedicine for BBB-crossing in CNS oncologic pathologies), Emilia Romagna Region grant (Step-by-step screening: RCUP E56C18002000002) and DSV FAR Grant for Mobility (J.T.D.).
P18
THE LOW LYING DOUBLE-EXCITON STATE OF CONJUGATED DIRADICALS INCLUDING OLIGOACENES AND
CYCLACENS: A COMPUTATIONAL INVESTIGATION Sofia Canola (a), Yasi Dai (a) and Fabrizia Negri (a), (b)
a). Dipartimento di Chimica “Giacomo Ciamician”, Università di Bologna, 40126 Bologna, Italy b). INSTM UdR Bologna, Italy
Conjugated diradicals with a singlet ground state have received remarkable attention owing to their potential applications in optoelectronic devices.[1] A distinctive character of these systems is the location of the double-exciton state, a low lying excited state dominated by the doubly excited H,H®L,L configuration, which may influence optical and other photophysical properties. In this contribution we investigate this specific excited state, for a series of recently synthesized conjugated diradicals and also for oligoacenes and cyclacenes. The simplest quantum-chemical model to describe a diradical includes two electrons in two orbitals (2e-2o). The double-exciton state emerges as one of the two singlet excited states from a full configuration interaction (CI) within the 2e-2o model. A reliable prediction of its excitation energy is however challenging because of correlation effects and generally MCSCF + CASPT2 or similarly correlated methods are required. However, double excitations can be recovered from TDDFT calculations also with the spin-flip (SF) scheme [2] and, for systems with well localized Broken Symmetry (BS) frontier molecular orbitals (FMOs), TDUDFT calculations can be used to predict the excitation energy of the double-exciton state since this excited state is described in terms of singly excited configurations.[3] The results of the calculations indicate the presence of a low lying double exciton state for all the investigated systems, in particular for long oligoacenes displaying large diradical character (y0) and cyclacenes formed with an even number of fused rings. The quality of computed results is assessed considering diradical and multiradical (NFOD) descriptors, and the excited state wavefunction composition for the investigated systems. REFERENCES [1] Hu, X.; Wang, W.; Wang, D.; Zheng, Y., J. Mater. Chem. C 2018, 6, 11232 -11242. [2] Shao, Y.; Head-Gordon, M.; Krylov, A. I., J. Chem. Phys. 2003, 118, 4807-4818. [3] Canola, S.; Casado, J.; Negri, F., Phys. Chem. Chem. Phys. 2018, 20, 24227-24238; Canola, S.; Dai, Y.; Negri, F., submitted.
Figure 1. BS FMOs of 6-Cyclacene. Linear combination of the BS orbitals in terms of closed-shell (CS) orbitals, along with y0
(PUB3LYP/6-31G*) and NFOD (TPSS/def2-TZVP, Tel =5000K) are presented.
P19
FROM PREPARATIVE BATCH CHROMATOGRAPHY TO A 2-
COLUMN MULTICOLUMN COUNTERCURRENT SOLVENT
GRADIENT PURIFICATION PROCESS FOR A PEPTIDE
PURIFICATION
Chiara De Luca(a)
, Sebastian Vogg(b)
, Martina Catani(a)
, Marco Macis(c)
, Antonio Ricci(c)
,
Massimo Morbidelli(b)
, and Alberto Cavazzini(a)
(a) Dept. of Chemistry and Pharmaceutical Sciences, Università degli Studi di Ferrara, Via Borsari
46, 44121, Ferrara, Italy
(b) Dept. of Chemistry and applied Biosciences, ETH Zurich, 8093, Zurich, Switzerland
(c) Fresenius Kabi iPSUM, Via San Leonardo 23, 45010, Villadose (RO), Italy
ABSTRACT
Many peptides used for pharmaceutical applications are synthesized through Solid Phase Synthesis.
The crude peptide mixture usually contains many impurities chemically very similar to the peptide.
Reversed phase preparative chromatography is the preferred choice for downstream purification.
However, the separation can be very difficult because of the similar adsorption behavior that the
peptide and impurities have with the solid phase. This results in peak overlapping which implicates
some regions not fulfilling the strict purity constraints. To obtain a pool with higher purity, the
product collection window must be narrowed, causing a reduction in the product yield. On the
contrary, if a higher recovery is required, the collection window is broadened, and this leads to
much lower purities. This purity-recovery trade-off is a limit intrinsic to batch chromatography
[1,2]. Continuous chromatographic techniques constitute a recent alternative to batch processes,
because they allow to internally recycle impure front and tail of the main peak and therefore to
increase recovery [3].
This works investigates the possibility of overcoming the purity-yield trade-off through 2-column
MCSGP process, a semi-continuous countercurrent chromatographic technique, where two columns
work alternatively in interconnected or batch mode. While in the first column the gradient method is
performed, the overlapping fractions eluting are recycled into the second column, which is also
filled with fresh feed during the collection of product pool from the first column. These operations
permit to increase the recovery of the peptide, keeping a very high purity. After these tasks are
accomplished, columns exchange position, and half a cycle is completed. Usually, during an
MCSGP run, 4 to 6 cycles are carried out [2]. The performances of the MCSGP run can be modified
depending on the times chosen for the recycling and collection (called switching times because the
countercurrent movement of the stationary phase is simulated through the switching of the inlet and
outlet valves).
The work started with the determination of batch conditions where the region of the main peak with
a purity fulfilling the imposed specifications is as large as possible. From the Pareto (recovery vs
purity) curve related to this batch chromatogram, a first group of trial values has been established to
set up the MCSGP switching times. The results obtained for the pools collected during the MCSGP
run have been compared with those of the batch. By adjusting the times of recycling and collection
windows, the purity and recovery of the pools as well as the productivity of the method have been
significantly modified to improve the performances of the MCSGP with respect to the batch.
REFERENCES [1] T. Mueller-Spaeth, G. Stroelhein, O. Lyngberg, and D. Maclean, Chemistry Today, 31 (2013) 56-60
[2] F. Steinebach, N. Ulmer, L. Decker, L. Aumann, and M. Morbidelli, J. Chrom. A, 1492 (2017) 19-26
[3] S. Vogg, N. Ulmer, J. Souquet, H. Broly and M. Morbidelli, Biotech. J., 14 (2019)
P20
PREPARATION AND REACTIVITY OF BENZOSSAZINDIONIC AND 2-AMINO-BENZOSSAZYNIC NUCLEI
De Ventura Tiziano a),Zanirato Vinicio(a), Delia Preti(a), Salvatore Pacifico(a), Giulia Turrin(a),
Anna Fantinati(a), Valentina Albanese(a),) and Claudio Trapella(a).
a) Department of Chemical and Pharmaceutical Sciences, Via Fossato di Mortara, 17, University
of Ferrara, 44121 Ferrara, Italy
ABSTRACT
NLRP3-inflammasoma is a multi-protein complex capable by a cysteine-protease action of allowing
the maturation of pro-IL-1ß in IL-1ß which is rapidly secreted out of the cell. In the microenvironment
of some tumors, IL-1ß appears to be over-expressed thus indicating an irregular activity of the
inflammasoma.1
The research work developed aimed to identify efficient and flexible synthetic strategies for the
preparation of compounds with therapeutic potential on IL-1ß NLRP3-inflammasoma-dependent
pathologies. Starting from the compound MCC950, a diaryl sulfonyl urea which shows an inhibitory
activity of IL-1ß LPS release induced in a specific and dose-dependent manner on NLRP3-
INFLAMMASOMA2, structural variations were made on the ureidic functionality of s-indacenamino
nucleus. As a first objective we have made changes to the N-aryl nucleus orienting the synthesis
towards obtaining sulfonylureas that had a more cluttered and functionalized as-indacenamine
nucleus. For this purpose we have chosen to use the ethyl ester of a derivative of the symmetrically
condensed anthranilic acid with two cyclopentanic rings (1) [Figure 1]. The classical chemical
manipulations of the ester group have allowed the introduction of apolar substituents in ortho position
of amino functionality on the as-indacenamine nucleus. Alternatively, by proceeding with the
saponification of the ethyl ester we were able to prepare an analogue of anthranilic acid which, by
reaction with triphosgene or with cyanogen bromide, supplied the benzoxazindionic and 2-amino-
benzoxazine nuclei respectively symmetrically condensed to two cyclopentanic aliphatic rings.
The first nucleus, sensitive to different nucleophiles, proved to be very interesting as it allowed us to
prepare both ortho-substituted as-indacenamines with polar functional groups, and stable N-
aroylsulfonamides, or mixed imides. The new functional group substituted at the two ends with two
aromatic nuclei could be considered as a convenient structural simplification of the chemically labile
diarylsulfonylureas.
Furthermore, we hypothesized that the opening of the oxazinonic ring by addition of nucleophilic
species to the carbonyl of 2-sulfonamide benzoxazinones would have provided the corresponding
sulfonylureas in an alternative way. The idea was to prepare potentially usable molecules as masked
forms of the labile sulphonylureidic group.
MCC950
NH
NH
O
SO
O
O
HO
NH2
CO2Et
trifo
sgene
Grigard
ON
NH2
O
ON
NH
O
SO O
Ar H2O
OHN
O
O
Nu
NH2
R1
R1=OH
1
REFERENCES [1].Koizumi, Y.; Toma, C.; Higa, N.; Nohara, T.; Nakasone, N.; Suzuki, T.
Inflammasome activation via intracellular NLRs triggered by bacterial infection. Cell Microbiol.
2012, 14, 149- 154. (risposta infiammatoria)[2].Chen, G. Y., Nuñez, G. Sterile inflammation:
sensing and reacting to damage. Nat. Rev. Immunol. 201037.
Figure 1
P21
ELECTROCHEMICAL MICRO-BIOSENSORS FOR SPATIALLY
RESOLVED STUDIES OF METABOLITES
Simona De Zio, Marco Malferrari, Stefania Rapino
Department of Chemistry Giacomo Ciamician, University of Bologna, via Selmi 2, 40126.
Mail contact: [email protected]
ABSTRACT
The disentangling of the mechanisms at the basis of cancer development and proliferation are
fundamental in cancer research. The development of new tools and analysis techniques could enable
the access to important information related to the state of the disease.
Scanning electrochemical microscopy (SECM) is a technique able to investigate the functionality of
cells and their surroundings with high spatial and temporal resolution. SECM uses
ultramicroelectrodes as probes to obtain not only images related to cellular topography but also to
metabolic activity [1].
Glucose microbiosensors, developed modifying platinum electrodes with enzymatic
functionalization[2], can be used as probes of the SECM to measure the concentration of glucose, a
metabolite that is used in higher amount by tumor cells, in ex vivo tissues with high sensitivity. The
study of tumor tissues by quantifying the metabolite content of the tumor microenvironment (like
glucose and lactate), infact, can represent an effective tool to identify the type of tumor, its
aggressiveness and possible response to therapies.
The micro-biosensor was coated to protect the enzymatic active layer by the mechanical stress
caused by the penetration in the tissues. The sensors were tested in matrices mechanically similar to
those of human tissue: calibration curves recorded before and after the mechanical tests
demonstrated the proficiency of the covering method.
The electrochemical microbiosensor was used to characterize different points of a ex vivo tissue
measuring the local concentration of glucose with a micrometric resolution.
REFERENCES
[1] Tzu-En Lin, Stefania Rapino, Hubert H.Girault and Andreas Lesch, Electrochemical Imaging of cells and
tissues, Chem. Sci. 2018, 9,4546-4554.
[2] Alice Soldà, Giovanni Valenti, Massimo Marcaccio, Marco Giorgio, Pier Giuseppe Pelicci, Francesco Paolucci
and Stefania Rapino, Glucose and Lactate Miniaturized Biosensors for SECM-Based High-Spatial Resolution
Analysis: A Comparative Study; ACS Sens.; 2017; 2; 1310-131.
P22
THERMALLY REVERSIBLE ELECTROSPUN NANOFIBERS
BASED ON DYNAMIC COVALENT NETWORKS
Valentina Antonia Dini(a), Aldo Altomare(b), Rodrigo Araya-Hermosilla(c), Maria Letizia
Focarete(a), Francesco Picchioni(d), Chiara Gualandi(a)
a) Department of Chemistry “Giacomo Ciamician”, Alma Mater Studiorum – University of
Bologna, Bologna, Italy ([email protected]; [email protected];
[email protected]), b) Zernike Institute for Advanced Materials, University of Groningen, The
Netherlands ([email protected]), c) Programa Institucional de Fomento a la Investigación,
Desarrollo e Innovación, Universidad Tecnológica Metropolitana, Chile ([email protected]),
d) Department of Chemical Engineering, University of Groningen, The Netherlands
ABSTRACT
Electrospinning (ES) is an attractive, simple and versatile method for producing continuous micro-
and nanoscale fibers for a wide range of applications (e.g. filtration, sensors, catalytic systems,
structural composites and in biomedical field). ES is typically applied to polymer solutions, thus
thermoplastic polymers can be easily processed into fibers, while electrospinning of thermosets is
highly challenging, being the latter intrinsically insoluble. However, thermosets have in many
aspects better properties than thermoplastics [1], including excellent mechanical properties,
insolubility and infusibility, thanks to the presence of covalent crosslinks that generate an infinite
3D molecular network that, however, prevents polymer recyclability and processability. In recent
years thermosetting polymers constituted by thermoreversible covalent bonds have been studied, in
particular the systems based on the cycloaddition reaction [4 + 2] of Diels-Alder (DA). Here,
starting from a diene and a dienophile (substituted alkene), a cyclic adduct can be generated and
easily retransformed into the initial components thanks to a temperature variation (Figure 1) [2].
In this work a polyketone modified with furan pendant
groups and bismaleimide, capable to form and break
Diels-Alder adducts using heat as external stimulus was
used. Electrospinning conditions were optimized to
produce continuous fibers that were thoroughly
characterized by means of different techniques, such as
TGA, DSC and SEM, and crosslinking degree was
evaluated by gel content measurements. Moreover, fibers
of the thermally reversible polyketone with another
polymer, either polycaprolactone or a acrylonitrile-
butadiene copolymer, were prepared to improve fiber
toughness. Fibers were also loaded with CNTs, that were
proven to chemically react with the polyketone [3], with the aim of modifying their electrical and
mechanical properties.
Electrospun fibers of thermoreversible thermosets were successfully produced. We also
demonstrated that the versatility of the technology allows to combine this dynamic covalent
network with other polymers and fillers. Further studies will be necessary to verify whether it is
possible to obtain conductive nanofibers that maintain the properties of thermoreversibility that
characterize the polymer used.
REFERENCES [1]G. Gibson, “Epoxy Resins,” in Brydson’s Plastics Materials: Eighth Edition, 2016, pp. 773–797.
[2]Y. Zhang, A. A. Broekhuis, and F. Picchioni, “Thermally self-healing polymeric materials: The next step to
recycling thermoset polymers?,” Macromolecules, vol. 42, no. 6, pp. 1906–1912, 2009.
[3]R. Araya-Hermosilla et al., “Electrically-responsive reversible Polyketone/MWCNT network through Diels-Alder
chemistry,” Polymers (Basel)., vol. 10, no. 10, p. 1076, Sep. 2018.
Figure 1. Diels-Alder and retro-Diels-Alder
cycloaddition scheme.
P23
DISCOVERY OF NOVEL SPIROCYCLES AS INHIBITORS OF
THE MITOCHONDRIAL PERMEABILITY TRANSITION PORE
M. Fabbri1, G. Morciano
2,3, S. Pacifico
1, G. Turrin
1, T. De Ventura
1, A. Fantinati
1, V.
Albanese1, S. Missiroli
2, C. Giorgi
2, P. Pinton
2, R. Guerrini
1, C. Trapella
1, D. Preti
1.
1Department of Chemical and Pharmaceutical Sciences of the University of Ferrara, Ferrara, Italy;
2Department of Morphology, Surgery and Experimental Medicine of the University of Ferrara,
Ferrara, Italy; 3Maria Cecilia Hospital GVM Care & Research, Ravenna, Italy.
ABSTRACT
Acute myocardial infarction (MI) is a major cause of death worldwide and experimental studies
have shown that nearly 50% of the final infarct size is due to the so-called reperfusion injury (RI),
an elusive phenomenon that remains resistant to treatment.1 Recent cardiology research
investigations have demonstrated that the opening of a large pore in the mitochondrial membrane,
namely the mitochondrial permeability transition pore (mPTP), plays a key contribution in the final
step of RI and is responsible for mitochondrial and cardiomyocyte death.2,3
We recently reported
the discovery, optimization, and structure−activity relationship (SAR) studies of the first
small-molecules able to target the c subunit of the F1/FO-ATP synthase complex thus inhibiting
mPTP opening.4 This first series of molecules is characterized by a 1,3,8-triazaspiro[4.5]decane
scaffold that has been designed starting from the more complex structure of Oligomycin A. The
most promising inhibitor (10, Figure 1) showed beneficial effects in an ex vivo model of MI. A
second series of small-molecules, containing an isatine core, was subsequently identified. One of
these (GT8) exhibited good inhibitory activity on the target mPTP.
Based on these preliminary results we have recently explored new isatine-based spirocycles in order
to identify clinically useful mPTP inhibitors (unpublished results). These compounds have been
obtained appliying a synthetic approach similar to that previously used for 10 that was optimizated
because of the particular chemical behaviour of the isatine scaffold. One of the resulting compounds
(6) was then tested in HeLa cells throught
calcein-Co2+
protocol5. This assay revealed
that 6 behaved as weak but promising
mPTP inhibitor. Considering these
evidences, future perspectives will be
focused on the synthesis of analogs of
compound 6 introducing various chemical
substituents on the indole core (-R, Fig. 1),
the N1’
benzyl moiety (-R1) or the N3
phenyl ring. By this means, we will obtain
useful information for elaborating a
complete SAR study and improving the
potency of 6.
REFERENCES [1] R. Ferrari et al. Reperfusion damage - a story of success, failure, and hope. Circ. J. 2017, 81, 131.
[2] G. Morciano et al. Mechanistic Role of mPTP in Ischemia-Reperfusion Injury. Adv. Exp. Med. Biol. 2017, 982, 169.
[3] T. Briston et al. Mitochondrial Permeability Transition: A Molecular Lesion with Multiple Drug Targets, Trends
Pharmacol. Sci. 2019, 40, 50.
[4] D. Preti, G. Morciano et al. Discovery of Novel 1,3,8-Triazaspiro[4.5]decane Derivatives that Target the c Subunit
of F1/FO-Adenosine Triphosphate (ATP) Synthase for the Treatment of Reperfusion Damage in Myocardial Infarction, J.
Med. Chem, 2018, 61, 7131.
[5] M. Bonora et al. Comprehensive analysis of mitochondrial permeability trantition pore activity in living cells using
fluorescence-imaging-based techniques, Nature Protocols, 2016, 11, 1067.
P24
COPPER BINDING TO R1 AND R3 FRAGMENTS OF TAU
PROTEIN
Silvia Gentili(a), Matteo Tegoni(a), Denise Bellotti(b), Chiara Bacchella(c), Alice Mazza(a),
Maurizio Remelli(b), Simone Dell’Acqua(c), Luigi Casella(c), Daniela Valensin(d)
a) Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma,
Parco Area delle Scienze 11/a, 43124 Parma, Italy
b) Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Via Luigi Borsari
46, 44121 Ferrara, Italy
c) Department of Chemistry, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy
d) Department of Biotechnology, Chemistry and Pharmacy, University of Siena, via Aldo Moro 2,
53100 Siena, Italy
ABSTRACT
Tau is a 441-mer peptide present in significant amounts in neurons, where it contributes to the
stabilization of microtubules. Insoluble amyloid aggregates of tau are associated with over 20
neurological disorders known as tauopathies, among which is Parkinson.[1] In neurons, tau binds
tubulin through its microtubule binding domain which comprises four repeats (R1-R4)
characterized by the presence of histidine residues. These regions are potential binding sites for
metal ions.[2] The elucidation of the binding capacities toward metal ions, especially those redox
active such as copper(II), may shed light on the biomolecular processes that underlie the
progression of tauopathies.[3] In this contribution we examine the stability of Cu(II) and Cu(I)
adducts with two peptide fragments which are encompassed in the R1 and R3 repeats of tau (Fig.
1).
R1 (HL):
Ac-257VKSKIGSTENLKHQGGG273-NH2
R3 (L):
Ac-323GSLGNIHHKPGGG335-NH2
Copper(II) binding to R1 (HL) starts at pH 4. The relevant species at pH 7.4 is [CuLH]2+, where the
imidazole ring, two amidic nitrogen atoms, and a water molecule occupy the equatorial
coordination positions of copper(II). As for the R3 peptide, at pH 7.4 [CuL]2+ and [CuLH-1]+ are the
two most abundant species (in a ratio of ca. 1:2). In the case of [CuL]2+, the two imidazole groups
of R3 and one deprotonated amidic nitrogen atom are bound to the equatorial plane. In [CuLH-1]+, a
further amidic nitrogen bounds the metal ion in the equatorial plane, most likely pushing one
imidazole group to the axial position.
Copper(I) adducts with the R1 and R3 tau fragments were investigated via spectrophotometric
competition titrations with the metallochromic ligand ferrozine (Fz).[4] The chromophoric complex
[CuI(Fz)2]3- (having two characteristic absorption bands at 470 nm and 600 nm) is formed by
titrating a Cu(I) solution with ferrozine. The back titration of this solution with the R1 and R3
fragments, led to a decrease in the absorbance values (Fig. 2).
Figure 1. Left. Sequences of the R1 and R3 peptides. Center. Distribution diagram of the Cu(II)/R1 system (CCu = 470
µM, L:Cu = 1.5, charges omitted). Right. Proposed structure of the species [CuLH]2+ (HL = R1).
P25
A significative change in the absorbance, which decreases of almost 0.40 units, is observed upon
the addition of R3 to [CuI(Fz)2]3-. On the contrary, in the case of the R1 peptide, the absorbance
decrease of only 0.20 units can be fully accounted by dilution effects. Data treatment using
HypSpect program yields a log β value of 10.1(2) for the Cu(I)-R3 complex, while for the back
titration of [CuI(Fz)2]3- with R1 it confirms the absence of significant interactions of Cu(I) with R1.
NMR data suggest that the binding of Cu(I) to R3 occurs at the tandem HH site, as it occurs for
Cu(II).
The redox behavior of these complexes will be discussed in terms of their speciation. Also, an
insight of the role of the copper adducts with R1 and R3 in catecholase activity will be given.
REFERENCES [1] M. Goedert, D. S. Eisenberg, R. A. Crowther, Annu. Rev. Neurosci. 2017, 40, 189-210.
[2] M. G. Savelieff, S. Lee, Y. Liu, M. H. Lim, ACS Chem. Biol. 2013, 8, 856-865.
[3] A. Soragni, B. Zambelli, M. D. Mukrasch, J. Biernat, S. Jeganathan, C. Griesinger, S. Ciurli, E. Mandelkow, M.
[3] Zweckstetter, Biochemistry 2008, 47, 10841-51.
[4] Z. Xiao, L. Gottschlich, R. Meulen, S. R. Udagedara, A. G. Wedd, Metallomics, 2013, 5, 501-513.
ACKNOWLEDGEMENTS The authors acknowledge MIUR for financial support through the project "Metal ions, dopamine, and oxidative stress in
Parkinson's disease” (PRIN 2015T778JW).
Figure 2. Left. Absorption spectra for the titration of Cu(I) with Fz (CCu = 55 µM, Fz:Cu = 2:1, CASC = 10 mM).
Center. Absorption spectra for the titration of [CuI(Fz)2]3- with R3 (CCu = 55 µM, R3:Cu = 0-4.77:1, CASC = 10 mM).
Right. Plot of absorbance values at 600 nm as a function of the equivalents of R1 and R3 added to [CuI(Fz)2]3- (open
circles: observed; filled circles: calculated).
RECYCLED CARBON FIBERS IN ADDITIVE MANUFACTURING
Niccolò Giani(a)(b)
, Francesco Picchioni (b)
, Tiziana Benelli (a)
a) Dipartimento di chimica industrial, Università di Bologna (NG: [email protected])
b) Faculty of Science and Engineering (FSE), University of Groningen (Netherland)
Carbon fibers (CFs) are used in an increasing number of applications, such as automotive,
aerospace and defence, wind turbines and sport due to optimal mechanical properties and light
weight compared to conventional material. Over 97% of the carbon fibers are used as reinforcement
in composite materials (CFRCs) and, recently, there has been an intensification in the use of
CFRCs; moreover, a further expansion is expected to reach a demand of 208,000 tons in 2020.
Such increase in the use of CFRCs will result in an increase of waste deriving both from the
production processes (offcuts of prepregs and cured composites) and the end of life products. This
trend has raised the interest in technologies for the recycling of CFRCs in order to obtain a positive
environmental and economic impact.
In this context, the researches have been focused to the re-evaluation of recycled CFs (rCFs) and
their implementation in new applications, using them as reinforcement in thermoplastic material
suitable for 3D printing.
Thus, the purpose of this work is to evaluate if rCFs can replace virgin CFs (vCF) applied to 3D
printing materials. In particular, two thermoplastic matrices commonly used for 3D printing have
been studied: poly-lactic acid (PLA) and polypropylene (PP).
PLA is a biodegradable and totally bio-based polymer, and it shows a polar structure that could
bring a good interaction with an oxygen-rich surface of rCFs. PP, instead, due to a totally apolar
structure, shouldn’t interact with the oxidized groups of rCFs. For this reason, polypropylene-g-
maleic anhydride has been used as compatibilizer in PP composites, in order to improve the
interaction on the interface between rCFs and PP matrix.
The chopped fibers have been added to polymeric matrix in a twin-screw mixer, obtaining a
massive blended material. Then, the compounded material has to be ground in order to be extruded.
The extrusion has been carried out on a twin-
screw extruder and represents the last step to get
the 3D printing filament. Thus, most of efforts
have been spent to determine the optimal
extrusion parameters (screw speed, 5 heating
zones temperature, post-extrusion traction). The
rCFs content and their distribution along the
filament (dispersion homogeneity), have been
evaluated by a degradation test which has been
designed to degrade only the polymeric matrix
and leave CFs undamaged. The CFs content
resulted very close to the target value (5 %wt) for
both PLA/rCF (4.3%wt) and PLA/vCF (4,8
%wt).
The mechanical properties of PLA/CFs filament
have been studied by dynamical mechanical
analysis (DMA). The addition of CFs leads to a
stiffening of the material: the elastic modulus EI raises from 2500 MPa (neat PLA) to 5700 MPa
(PLA/rCFs) and 6300 MPa (PLA/vCFs).
Moreover, mechanical properties of rCFs and vCFs have been compared by tensile tests of 3D
printed dog-bone specimens (Figure 1). The breaking strain decreases with the addition of CFs in
PLA matrix proving the brittleness effect of CFs loading. It is worth nothing the better breaking
behaviour of PLA/rCFs with respect to PLA/vCFs, both as breaking load (60.7 MPa vs. 59.0 MPa)
than as breaking strain (8.0 % vs. 6.4 %). These results are really promising, demonstrating the
effectiveness of rCFs as reinforcing materials.
Figure 1. up)3D printed dog-bone specimens used for
tensile test. Down) Tensile test plot of neat PLA (red curve),
PLA/rCFs (yellow curve) and PLA/vCFs (blue curve)
P26
ULTRASENSITIVE NON-ELECTROCHEMICALNEURO-
INPIRED SENSOR FOR DOPAMINE
Martina Giordani(a)
, Matteo Sensi(b)
, Marcello Berto(a)
, Fabio Biscarini(b,c)
a) dipartimento di scienze Biomediche, Metaboliche e Neuroscienze, Via Campi 287, Modena,
Università di Modena e Reggio Emilia ([email protected]); b) Dipartimento di Scienze
della Vita, Via Campi 287, Modena, Università di Modena e Reggio Emilia; c) Center for
Translational Neurophysiology of Speech and Communication, Via Fossato di Mortara17-19, IIT
Ferrara.
ABSTRACT
We present an ultra-sensitive and selective sensor for dopamine (DA) by means of a neuro-
inspired device platform without the need of a specific recognition moiety is demonstrated.
DA is a neurotransmitter of catecholamines family that controls functions of cardiovascular, renal,
hormonal and central nervous systems. DA deficit is a hallmark of Parkinson’s disease (PD), due
to the degeneration of dopaminergic neurons in substantia nigra pars compacta.
The sensor is a whole organic device featuring two electrodes made of poly(3,4-
ethylenedioxythiophene):polystyrene sulfonate – PEDOT:PSS – directly patterned through laser
ablation on a polydymethylsiloxane – PDMS – flexible substrate. One electrode is pulsed with a
train of voltage square waves (-200 mV with a frequency of 500 Hz for 1s), to mimic the pre-
synaptic neuron behavior, while the other is used to record the displacement current, mimicking the
post-synaptic neuron. The current response exhibits the features of synaptic Short-Term Plasticity
(STP) with facilitating or depressing response according to the stimulus frequency. We found that
the resulting current decreases with a characteristic time, τSTP , depending on DA concentration in
solution. The sensor detects [DA] down to 1 pM range. We assess the sensor also in the presence
of several moieties physiologically present in cerebrospinal fluid or extracellular fluids, i.e. ascorbic
acid, uric acid, 3-methoxytyramine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, serotonin,
epinephrine and norepinephrine. Our detection strategy successfully discriminates DA from the
other analytes in model solutions (i.e. Phosphate Saline Buffer). The sensor appears still more
sensitive to DA than to the others, even in presence of moieties with similar chemical structures.
The synapse appears ultrasensitive to DA (from physiological to pathological concentrations) and
selective thanks to the interaction mechanism with PEDOT:PSS. DFT calculations on
PEDOT:PSS/metabolite clusters hint to a correlation between the STP response and stronger non-
covalent interactions between DA and PEDOT:PSS, specifically electrostatic and hydrogen
bonding of DA ammonium end group with sulfonate.
The whole organic synapse, being biocompatible, soft and flexible, is attractive for implantable
devices aimed to real-time monitoring of DA concentration in bodily fluids, to be used as a
diagnostic tool, for instance, in chronic neurodegenerative diseases such as Parkinson’s disease.
REFERENCES [1] Giordani et al., PROC. of SPIE, 2016, vol. 9944
[2] Giordani et al., ACS Sens., 2017, 2, 1756-1760
P27
SELECTIVE LIGANDS FOR MINOR ACTINIDES EXTRACTION
M. Chiara Gullo(a)
, A. Ossola(b)
, E. Mossini(b)
, A. Arduini(a)
, F. Sansone(a)
, S. Scaravaggi(b)
, N.
Boubals(c)
, M.C. Charbonnel(c)
, M. Mariani(b)
, E. Macerata(b)
, A. Casnati(a)
a) , Department of Chemistry, Life Sciences and Environmental Sustainability,
43124 Parma, Italy
b) Politecnico di Milano, Department of Energy, Nuclear Engineering Division, 20133 Milano, Italy
c) Institution French Alternative Energies and Atomic Energy Commission, CEA Marcoule,
Nuclear Energy Division, Research Department of Mining and Fuel Recycling ProCesses, DMRC,
BP 17171, F-30207, Bagnols sur Cèze, France
e-mail: [email protected]
One of the most important scientific, and social challenges that humanity faces today is to manage
the huge amount of nuclear wastes accumulated in the last 70 years and to make exploitation of
nuclear energy as sustainable as possible [1]. Currently, the PUREX process is used worldwide to
recover Pu and U from the spent fuel while the rest of the waste contains the minor actinides (MAs)
that account for most of the long-term radiotoxicity of radioactive wastes [2]. Interestingly the
recovery of MAs and their separation from Lanthanides would allow to re-use them in novel
nuclear fuels thus closing the Nuclear Fuel Cycle. Soft-donor ligands are known to interact more
strongly with trivalent actinide ions, An (III), rather than with trivalent lanthanide ions, Ln (III). In
the last few years we have been exploring different chelating units based on nitrogen ligands and
fou h h “cl ck ” py -bis-triazole unit is rather effective and selective in An/Ln
extraction from simulated nuclear wastes. We herein report the synthesis of both hydrophilic and
lipophilic ligands based on pyridine-bis-triazole unit (Fig. 1), showing their ability to effectively
and selectively separate An from Ln even at very high nitric acid concentration and in the presence
of other fission products. We will focus on the synthesis of these ligands, the study of their
complexation and extracting properties, and their resistance to the strong conditions imposed by the
industrial processes. In parallel, we seek for the synthesis and the study of the possible degradation
products identified upon radiolysis of the ligands. In this way we will be able to test the efficiency
and feasibility of the entire separation process.
Figure 1. The hydrophilic (left) and lipophilic (right) versions of the pyridine-bis-triazole ligands studied.
References [1] M. J. Hudson., L. Harwood, M., D. M. Laventine, F. W. Lewis, Inorg. Chem. 2013, 52, 3414−3428.
[2] E. Macerata, E. Mossini, S. Scaravaggi, M. Mariani, A. Mele,W. Panzeri, N. Boubals, L. Berthon, M.C.
Charbonnel, F. Sansone, A. Arduini, A. Casnati, J. Am. Chem. Soc. 2016, 138, 7232−7235.
[3] C. Wagner, E. Mossini, E. Macerata, M. Mariani, A. Arduini, A. Casnati, A. Geist, P. J. Panak, Inorg.
Chem. 2017, 56, 2135−2144.
P28
LIPOSOMES FOR THE DELIVERY OF LasR QUORUM-SENSING
INHIBITORS: A PREFORMULATORY STUDY
Supandeep Singh Hallan1, Maddalena Sguizzato
1, Elisabetta Esposito
1 and Rita Cortesi
1,*
1 Department of Chemical and Pharmaceutical Sciences (SCF), University of Ferrara, Ferrara, Italy
P. aeruginosa is a gram-negative bacterium that especially infects subjects with a weakened immune
system. Cystic fibrosis (CF) patients exhibit increased susceptibility to P. aeruginosa lung infections.
Since P. aeruginosa is a ubiquitous bacterium, exposure to this pathogen in the hospital setting results
to be frequent. CF patients most frequently succumb to a chronic infection of the lungs with P.
aeruginosa. Chronic infection can be defined as an infection, which persists in spite of therapy, and in
spite of the host’s immune and inflammatory response. Quorum sensing (QS) is one of the main
defense mechanism adopted by P. aeruginosa is represented by biofilm formation, which allows the
bacteria to avoid both the host immune system and antibiotics effect. QS is a mechanism of gene
regulation sensitive to a population density that enables host colonization contrasting the immune
surveillance through biofilm formation and the expression of virulence factors via the production of
self-generated extracellular signal molecules. P. aeruginosa is characterized by two QS systems, Las
and Rhl. Las system is controlled by the transcriptional activator LasR and the autoinducer synthase
enzyme LasI [1]. Recently, in our department a novel synthetic QS inhibitor based on a
cyclopentilamine have been synthesized.
In order to ameliorate the activity of Las QS inhibitors, we investigated the possibility to use
liposomes for their targeting. Particularly, this study focuses on a preformulatory study to select the
best liposome composition for in vitro in vivo test.
Liposomes have been prepared by direct hydration method contain 25 mg/ml lipid phase, including
Phosphatidyl Choline: Cholesterol: Charged surfactant in mixture (2:1:1, mol/mol/mol), the film was
hydrated by HPLC.H2O. Cationic liposomes were prepared with Didecyldimethylammonium
chloride (DDAC), Di isobutyl phenoxy ethyl dimethyl benzyl ammonium chloride (DEBDA) and
Octadecylamine (OD). While, anionic liposomes with Dicetyl phosphate (DCP) and extruded
through polycarbonate filters with 200 nm pore size at a nitrogen pressure of 10–20 bars using an
extruder (Lipex Biomembranes, Vancouver, Canada). The vesicles were collected and re-injected
five times.
A remarkable reduction in biofilm formation without inducing significant toxicity to A549
(pulmonary line) has been observed only in the case of C-LP-OD. Therefore, C-LP-OD has been
chosen for further loading of inhibitors. Moreover, Higher diameter has been recorded in case of
loaded liposomes (223.6 ± 1.88 nm) with respect to unloaded liposomes (205.7 ± 1.63 nm ) indicates
the successful loading of inhibitors with the yield 83.26 ± 5.87.
In conclusion, Las QS inhibitors have been loaded successfully to the liposomes, with reduction of
biofilm formation without affecting the cell viability, demonstrated that the liposomes here proposed
an interesting starting point for a future use.
REFERENCES [1] Z. Rukavina, Ž. Vanic. Pharmaceutics 2016, 8, 18; doi:10.3390/pharmaceutics8020018
P29
EFFECT OF COMPRESSION MOLDING PARAMETERS ON
GRAPHITE/EPOXY COMPOSITE BIPOLAR PLATES
Fabrizio Roncaglia(a), Alessandro Di Bona(b), Manuel Imperato(a), Roberto Biagi(c),
Marcello Romagnoli(d), Adele Mucci(a). a Dip. di Scienze Chimiche e Geologiche, UniMORE, Via Campi 103, 41125 Modena (Italy)
([email protected]) b CNR - Istituto Nanoscienze - Centro S3, via Campi 213/A, 41125 Modena (Italy) c Dip. di Scienze Fisiche, Informatiche e Matematiche, UniMORE, via Campi 213/A, 41125 Modena (Italy) d Dip. di Ingegneria "Enzo Ferrari", UniMORE, via Vivarelli 10, 41125 Modena (Italy)
ABSTRACT
Bipolar plates (BP) are the key multifunctional component in Proton Exchange Membrane Fuel Cells
(PEMFCs) which account for ~30% of the total cost [1], over 80% of the weight, and almost all of
the volume in a typical fuel cell stack [2]. BP serve multiple functions: distributing uniform gas flow,
facilitating water management, conducting current between adjacent cells, maintaining impermeable
hydrogen and oxygen barrier, providing stack structural support, and enabling heat transfer.
Therefore, the bipolar plates must meet a variety of property requirements, as shown in Table 1 [3].
Such characteristics may be obtained with a proper choice of starting materials and forming
conditions.
BP are commonly composed of pure graphite, metals or metal alloys but lately, graphite-polymer
composites have been investigated as bipolar plates materials to maximally utilize the electrical
conductivity of graphite and the mechanical strength of polymers and to exploit the benefits of smaller
size, lighter weight, easier fabrication, and reduced cost.
Recently we developed a simple but
promising graphite/epoxy composite (90
%wt of commercial graphite and 10%wt
commercial epoxy resin) able to meet the
electrical characteristics required by the US
Department of Energy (In-plane electrical
Conductivity >100 S/cm). Here we present
a study on the effect of compression
molding parameters as pressure,
temperature and time that were studied on
the same composite and analysed using a
two-level full factorial Design Of
Experiment (DOE) approach. In-plane conductivity and mechanical strength were the dependent
variables. The independent variables were controlled through a custom-made press.
REFERENCES
[1] J. P. Kopasz, T. G. Benjamin, Argonne National Laboratory - 2017 Bipolar Plate Workshop Report.
[2] R. Taherian, Journal of Power Sources, 2014, 265, 370-390.
[3] https://www.energy.gov/sites/prod/files/2017/05/f34/fcto_myrdd_fuel_cells.pdf
Table 1. U.S. DOE Technical Targets for Bipolar Plates [3]
P30
α-TRIAZOLYL-BORONIC ACIDS: A NEW CLASS OF β-LACTAMASE INHIBITORS ACTIVE AGAINST KLEBSIELLA PNEUMONIAE
CARBAPENEMASE (KPC-2) Maria Luisa Introvignea,b; Francesco Finib; Magdalena Taracilac; Robert A. Bonomoc; Emilia Casellib; Fabio Pratib. aClinical and Experimental Medicine PhD Programme, University of Modena and Reggio Emilia, Modena, Italy ([email protected]); bDepartment of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125 Modena, Italy; cDepartment of Veterans Affairs Medical Center, Cleveland, Ohio, USA. ABSTRACT Antibiotic-resistance is growing among Gram-positive and Gram-negative pathogens and most of them become multidrug-resistant (MDR) bacteria. Six of these bacteria were reported as the “ESKAPE” pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species) to emphasize that they currently cause the majority of world-wide hospital infections and “escape” the effects of antibacterial drugs1. The most clinically concerning mechanism of resistance to β-lactam antibiotics is the bacterial production of β-lactamases, a family of enzymes classified into four classes (A,B,C and D), which are able to hydrolyse the β-lactam ring. Boronic Acid Transition State Inhibitors (BATSIs) are known reversible covalent inhibitors of β-lactamases: the boronic moiety act as an electrophile which, upon attack of the nucleophilic serine, forms with the enzyme a tetrahedral adduct , mimicking the one formed with the β-lactam antibiotics. The β-lactamase is therefore ‘blocked’ and not able to hydrolyse the antibiotic. In particular, amidomethaneboronic acids I have been extensively explored as serine β-lactamases inhibitors. Seeking new boronic scaffolds for β-lactamases inhibition, we explored the substitution of the amide with a 1,2,3-triazole, a non-classical amide bioisoster. The synthesis of 4-substituted 1,2,3-triazole-1-yl-methaneboronic acids II can be easily achieved by copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, a protocol which proceeds under mild conditions, with inexpensive reagents and with high versatility, efficiency and straightforward product isolation2. In this work a series of 35 achiral α-triazolyl-boronic acids differently substituted at position 4 of the triazole were synthesised and their activity against the class A β-lactamase KPC-2 was studied. To assess the capability of the compounds to restore β-lactam susceptibility, their minimal inhibitory concentrations (MICs) were determined against a bacterial strain expressing KPC-2, using as antibiotic partner the cephalosporin Cefepime (MIC: 32 µg/ml). In general, the MIC values obtained halved at least the antibiotic concentration and in several cases MIC were lowered under the susceptibility threshold (2 µg/ml). Interestingly, some of these molecules demonstrated a good activity also against class C enzymes, offering a new boronic scaffold for wide spectrum β-lactamases inhibitors. REFERENCES (1) Tacconelli, E.; Carrara, E.; Savoldi, A.; Harbarth, S.; Mendelson, M.; Monnet ,D. L.; Pulcini, C.; Kahlmeter, G.;
Kluytmans, J.; Carmeli, Y.; Ouellette, M.; Outterson, K.; Patel ,J.; Cavaleri, M.; Cox, E. M.; Houchens, C. R.; Grayson, M. L.; Hansen, P.; Singh, N.; Theuretzbacher, U.; Magrini, N. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infc. Dis. 2018, 18 (3), 318-327.
(2) Romagnoli, C.; Caselli, E.; Prati, F. Synthesis of [(1,2,3-Triazol-1-Yl)methyl]boronic Acids through Click Chemistry: Easy Access to a Potential Scaffold for Protease Inhibitors. European J. Org. Chem. 2015, 2015 (5), 1075–1083.
P31
KINETIC CHARACTERIZATION OF NOVEL PTERIDINE-LIKE INHIBITORS OF TRYPANOSOMA BRUCEI PTR1 AND DHFR-TS
Konchie Simo Claude Ulrich (a,c), Antonio Quotadamo(a) Cecilia Pozzi(b), Stefano Mangani(b), Maria Laura Bolognesi (c), Glauco Ponterini(a), Maria Paola Costi(a)
(a) Department of Life Science, University of Modena and Reggio Emilia, It (b) Departement of Pharmaceutical Science, University of Siena, It (c) Department of Pharmaceutical Science, University of Bologna, It
Human African Tripanosomiasi (HAT, sleeping sickness) belongs to the neglected tropical deseases field (NTDs). It occurs most commonly in the setting of extreme poverty, among the rural poor and disadvantaged unrban populations like sub-saharan Africa. HAT is a protozoan parasitic disease that causes death and disability; it is caused by two subspecies of Trypanosoma brucei (Tb): Tb gambiense (endemic in central and western areas) and Tb rhodesiense ( in southern and eastern Africa). Both infections are fatal if left untreated. Tb parasitic protozoans are autotrophic for both folate and unconjugated pteridines. The parasites salvage these metabolites from their mammalian hosts and insect vectors through multiple transporters (bipterin transporters, BT and Folate transporters, FT in the Figure) essential for the metabolic process and consequently for survival. The folate metabolic process depends mainly on two enzymes: dihydrofolate folate reductase - thymidylate synthase (DHFR-TS) and pteridine reductase 1 (PTR1). DHFR is a NADPH-dependent enzyme that catalyzes the reduction of folic acid (FA) to dihydrofolate (H2F), and H2F to tetrahydrofolate (H4F). DHFR-TS is a validated and primary target of most anti-folate drugs. However, the use of traditional anti-folates targeting DHFR in trypanosomatids has been largely unsuccessful. PTR1, a short-chain dehydrogenase reductase family member and NADPH-dependent enzyme, catalyzes the conversion of biopterin to dihydrobiopterin (H2B), and then to tetrahydrobiopterin (H4B). Additionally, PTR1 can convert dhydrofolic acid (H2F) to tetrahydrofolic acid (H4F), as DHFR does (see Figure). In trypanosomatids, PTR1, which is less susceptible to traditional anti-folate inhibitors, contributes to about the 10% of the total folate parasitic metabolism. Previous studies have shown that under DHFR inhibition, PTR1 is over-expressed, thus promoting anti-folate resistance in T.brucei so PTR1 is essential for parasite survival(1). Several studies reported the successful combination of novel PTR1 and MTX, a known DHFR inhibitor, to achieve synergistic inhibition of the trypanosomatidic folate pathway and parasite killing. Methotrexate (MTX) reduction of parasite growth is potentiated when administered in combination with a PTR1 inhibitor.
The aim of this study is to investigate the TbPTR1 inhibitors effect depending on either H2B or H2F substrates in order to explain the observed in vitro anti-parasitic effect and specifically to understand the link between the inhibion effect and the substrate type associated to sub-metabolic pathways in the parasites. Secondly we assesed the same compound on DHFR-TS activity. The results are compared with the crystallographic complexes of the inhibitors with PTR1 to link the inhibition pattern with the binding mode of the inhibitor. All these information will help in the design of improved anti-PTR1 inhbitors with higher in vivo efficacy. The work was performed in collaboration with the crystallography group of the University of Siena (UniSI). Firstly we kinetically characterized all proteins under study (PTR1 and DHFR-TS) and subsequently the inhibition of MTX against TbPTR1, as positive control was assayed. MTX is a low nanoMolar PTR1 competitive inhibitor. We observed a change in the apparent inhibition constant (Kiapp) when H2B or H2F were used as substrates. Some inhibitors developed in our lab to specifically inhibit PTR1 showed a different effect. Detailed kinetic results and structural analysis of the two different substrates and to translate these effects from the molecular to the cellular level. As a concluding remark, the outcome of our experiment suggests that our novel compounds show a good potential to inhibit the parasite survival when combined with a DHFR inhibitor, by inhibiting the parasitic folate pathway with an biochemical allosteric mechanism. We may also be able to link kinetic inhibiton pattern/molecular protein-inhibitor complexes with the in vivo inhibition mechanism.
References 1. Kimuda MP, et al. Mol Basel Switz. 2019;24 2. Nare B, et al. Parasitology. 1997;114 Suppl:S101-110. 3. Linciano P. et al J Med Chem. 2019, 68, 3989-4012
P32
ORGANIC ELECTROCHEMICAL SYNTHESIS OF
HYDROVANILLOIN, A NEW BIOAVAILABLE NONTOXIC
SUBSTITUTE OF BISPHENOL A
Lidia Lancellotti(a)
, Fabrizio Roncaglia(a)
, Lorenzo Tassi(a)
, Marco Borsari(a)
a) Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, via
Campi 103,Modena, Italy
e-mail: [email protected]
ABSTRACT
Bisphenol A (BPA) is a molecule largely employed in many industrial process, it is wildly used in
the production of plastic and thermoplastic polymers (polycarbonate), together with epichlorohydrin
(ECH) is the fundamental component of the epoxy resin (DGEBA). BPA is also a xenoestrogens, a
molecule that is able to mimic the 17β-estradiol (E2) action in estrogen-dependent organs and
tissues. Recents studies have reported that BPA caused several problems in male. Some studies
have showed that low-dose treatment levels of BPA inhibit testicular steroidogenesis. It has been
necessary replace BPA with a non-toxic molecule, which can come from removable and natural
resources. Lignin has been examined as a feedstock to phenolic monomers that can be utilized in a
similar manner to petroleum-derived phenols. A variety of polymers have been prepared from lignin
including phenolformaldehyde resins, polyolefin/lignin blends, polyesters, polyurethanes, and
bioplastics. The best known sustainable phenol that came from lignin is vanillin. Vanillin is
obtained from several industrial process from natural source and petroleum derivate. The purpose of
the project is to create a non-toxic substitute of BPA and economically competitive. In our synthesis
we start from vanillin to obtain 4,4'-(ethene-1,2-diyl)bis(2-methoxyphenol) a non-toxic possible
substitute of BPA, passing thought the reaction intermediate hydrovanilloin. We used an
electrochemical synthesis to obtain hydrovanilloin, this type of synthetic pathway is a cheap and
green and we performed the pinacol coupling reaction in alkaline water solution, without the use of
toxic solvent, expensive organic mediator and noble metal or rare-heart metal. We modified the
reaction reported by Pearl paper (1952) to gain the major yield.
P33
Synthesis, Characterisation and Electrochemical study of Titanium
Hexacyanoferrate Electrode material
Min Li (a)
, Mullaliu Angelo (b)
, Giorgetti Marco (a)
(a)
Department of Industrial Chemistry “Toso Montanari”, University of Bologna, Viale
Risorgimento 4, 40136 Bologna, Italy (b)
Helmholtz Institute Ulm (HIU), Helmholtzstrasse 11, 89081, Ulm, Germany and Karlsruhe
Institute of Technology (KIT)P.O. Box 3640, 76021 Karlsruhe, Germany
ABSTRACT
Titanium Hexacyanoferrate (Na0,86Ti0,73[Fe(CN)6]·3H2O) was synthesized by simple co-
precipitation method, and the crystal structure, water content, chemical formula and an in-depth
local structural investigation at the Ti site of the as-prepared sample were characterized by PXRD,
FT-IR, TGA, MP-AES and XAS. Electrochemical tests were performed both in glass and coin cells.
The observations, based on scan rate and current behavior, show that the electrode performance is
controlled by diffusion process in aqueous electrolyte system. From cyclic voltammetry curves, we
observed redox peaks of both Fe3+/2+
and Ti4+/3+
pairs. The as-prepared sample also shown high
performance in organic electrolyte system. Compared to Li-ion batteries, the material shows high
capacity for Na-ion batteries with 74 mAh/g at C/20 rate, while Li-ion batteries only have 35
mAh/g. The specific energy value we got for Na-ion coin cell is 250 Wh/kg (based on the mass of
active material) and 122 Wh/kg for Li-ion coin cell. Both Li- and Na- half cells display high
coulombic efficiency during cyclability test, above 95%.
(a)(b)
(c)
2,0 2,2 2,4 2,6 2,8 3,0 3,2 3,4 3,6 3,8 4,0 4,2 4,4
-0,00006
-0,00003
0,00000
0,00003
0,00006
0,00009
Cu
rre
nt
(A)
Potential (V vs SCE)
0,2 mV/s 1M NaPF6 -PC
-1,0 -0,8 -0,6 -0,4 -0,2 0,0 0,2 0,4 0,6 0,8 1,0 1,2 1,4-0,0002
-0,0001
0,0000
0,0001
0,0002
0,0003
0,0004
0,0005
Cu
rre
nt
(A)
Potential (V vs SCE)
1 mV/sTiHCF_0.1M NaNO
3
Figure1 (a) Space group of Titanium Hexacyanoferrate; Cyclic voltammetry of Titanium Hexacyanoferrate in
0.1M NaNO3 electrolyte (b) and in 1M NaPF6 in PC as electrolyte (c).
REFERENCES [1] S. Adak, L. Daemen, M. Hartl, D. Williams, J. Summerhill, H. Nakotte. Thermal expansionin 3d-metal Prussian
Blue Analogs-A surveystudy. Journal of Solid State Chemistry, 2011, 184, 2854-2861.
[2]. M. Avila, L. Reguera, J. Rodrı´guez-Herna´ndez, J. Balmaseda, E. Reguera. Porous framework of
T2[Fe(CN)6]·xH2O with T ¼ Co, Ni, Cu, Zn, and H2 storage Journal of Solid State Chemistry, 2008, 181, 2899-2907.
[3]. V. D. Neff. Electrochemical oxidation and reduction of thin films of Prussian blue. J. Electrochem. Soc.,
1978,125,886.
P34
ON THE EFFECT OF MOBILE PHASE COMPOSITION AND
TEMPERATURE ON RETENTION BEHAVIOUR OF A
SYNTHETIZED BIOMOLECULE IN IP-RP-HPLC
Giulio Lievore, Chiara De Luca, Simona Felletti, Martina Catani, Alberto Cavazzini
Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy
ABSTRACT
The purification process of chemically synthetized biomolecules is a pivotal step in the
biopharmaceutical manufacturing since, during the upstream processes, carried out either with bio-
fermentation or solid phase synthesis, undesired by-products and impurities are frequently formed,
along with the target compound [1].
The downstream path consists of several stages, each of them crucial for the final product purity
and the overall procedure productivity, yield and reproducibility.
Precisely, to increase the process performance, each stage of the production requires inline
monitoring and evaluations. To this extent, liquid chromatography has long been proposed as the
major technique in terms of effectiveness and reliability.
Because the effects of temperature, organic modifier, mobile phase additives (pH, ionic strength)
and applied pressure are of primary importance for biomolecules conformation, these variables may
seriously affect the retention and peak shapes of proteins, peptides, oligonucleotides and other
species in RP-LC [2].
Aim of this study is to evaluate in detail how the impact of change in gradient conditions, mobile
phase components and temperature on retention of purified biomolecules on different stationary
phases, including octadecyl silane (ODS) and phenylhexyl stationary phase ones.
This information is essential, firstly, for the establishment of a robust, accurate and reproducible
analytical method together with the growth of a deeper awareness regarding analyte-resin
interactions, ion pairing reagent effects and temperature impact on the separation.
Phenylhexyl resins are acknowledged to retain analytes via multiple mechanisms, including π–π
interactions between the overlap of the delocalized electrons on the analyte and the stationary phase
phenyl group, or via partitioning between the mobile phase and the hydrophobic aryl-alkyl segment
of the hexyl chain [3].
When using a mobile phase buffered with either trifluoroacetic acid or ammonium acetate as ion
pairing reagent, a significant variance in eluting times and retention factors, k, was registered on the
phenylhexyl stationary phase. This may be possibly due to the development of diverse adsorption
mechanisms according to the employed ion pairing agent.
Conversely, outcomes suggest a nearly constant behaviour of the analyte on the octadecyl silane
stationary phase while modifying the ion species in the mobile phase.
Furthermore, it was observed that the influence of ion pairing reagent diminishes for both columns
by increasing column temperature.
REFERENCES
[1] Shukla, A.A. & Thömmes, J. 2010 Recent advances in large-scale production of monoclonal antibodies and related
proteins. Trends in Biotechnology, Volume 28, pag. 253-261 [2] Fekete, S., Veuthey, J.L. & Guillarme D. 2012 New trends in reversed-phase liquid chromatographic separations of
therapeutic peptides and proteins: Theory and applications. Journal of Pharmaceutical and Biomedical Analysis,
Volume 69, pag .9-27
[3] Croes, K., Steffens, A., Marchand, D.H. & Snyder L.R. 2005 Relevance of π – π and dipole–dipole interactions for
retention on cyano and phenyl columns in reversed-phase liquid chromatography. Journal of Chromatography A,
Volume 1098, pag. 123-130
P35
IONIC CONDUCTIVITY CALCULATIONS AND
RATIONALIZATION OF MIXED ALKALI ALUMINOSILICATE
GLASSES THROUGH MD SIMULATIONS
Federica Lodesani(a),*
, Maria Cristina Menziani(a)
, Hiroyuki Hijiya(b)
, Yoichi Takato(c)
, Shingo
Urata(c)
and Alfonso Pedone(a)
a) Dipartimento di Scienze Chimiche e Geologiche, Università di Modena e Reggio Emilia, via G.
Campi 103, 41125, Modena, Italia
b) Materials Integration Laboratories, AGC Inc., Yokohama, Kanagawa 221-8755, Japan
c) Innovative Technology Laboratories, AGC Inc., Yokohama, Kanagawa 221-8755, Japan
* email: [email protected]
ABSTRACT
According to the glass composition, some properties such as the chemical durability, glass
transition temperature, viscosity and the ionic conductivity can be controlled. These specific
examples depend on the ionic mobility inside a glass which can be optimized by exploiting the
mixed alkali effect (MAE) on oxide glasses, which affect some properties in a non-linear way[1]
.
Although the mixed alkaline effect for silicates have already been investigated from a molecular
dynamic (MD) point of view[2,3]
. While the simulation of the same phenomenon received less
interest in the case of mixed alkali aluminosilicate glasses, where one of the two different alkali
cations can be more prone to act as a modifier, forming non-bridging oxygens and percolation
channels, or as charge compensator of the AlO4- units present in the network. Thereby, it is
interesting to understand which is the effect of the different roles on the ionic mobility and other
properties. Furthermore, the accuracy of the atomistic simulation in reproducing the ionic
conductivity is still under investigation because it has not been computed yet.
In this contribution, we have tested classical molecular dynamics (MD) simulations using different
interatomic potential models on mixed alkali aluminosilicate glasses (Na,K) for simulating their
structure, density, glass transition temperature and ionic conductivity.
Among the tested potentials, the core-shell polarizable force field is the one which better reproduce
the available experimental properties which depend on the MAE, in particular, trends of glass
transition temperature and of ionic conductivity. In fact, the higher resistivity is shown for the
mixed alkali glass and also the effect of the temperature on conductivity of the single alkali glasses
is well controlled: higher conductivity of single Na-glass at low temperature and higher
conductivity of single K-glass at high temperature. The latter feature, which is not reproduced by
other interatomic potential models, is explained by the greater flexibility of percolation channels in
the single K-containing glass at high temperature. Additionally, in core-shell simulations the mixed
alkali effect is due to the suppression of jump events between dissimilar sites in the percolation
channels hosting both sodium and potassium, as widely described in experimental studies[4]
.
REFERENCES [1] Isard, J. O. The mixed alkali effect in glass. J. Non-Cryst. Solids 1, 235–261 (1969)
[2] Cormack, A. N., Yuan, X. & Park, B. Molecular Dynamics Simulations of Silicate Glasses and Melts. Glass Phys.
Chem. 27, 28–36 (2001)
[3] Habasaki, J., Ngai, K. L. & Hiwatari, Y. ‘Cooperativity blockage’ in the mixed alkali effect as revealed by
molecular-dynamics simulations of alkali metasilicate glass. J. Chem. Phys. 121, 925–934 (2004)
[4] Hunt, A. The mixed-alkali effect discussed within the context of percolative transport. J. Non-Cryst. Solids, 220(1),
1-16 (1997)
P36
NITRILE RUBBER ELECTROSPUN NANOFIBERS
VIA BLENDING WITH POLYCAPROLACTONE
Emanuele Maccaferri,(a)
Laura Mazzocchetti,(a)
Tiziana Benelli,(a)
Tommaso Maria Brugo,(b)
Andrea Zucchelli,(b)
Loris Giorgini (a)
a) Industrial Chemistry Department Toso Montanari, University of Bologna, Viale del
Risorgimento, 4, 40136 Bologna - Italy
b) Industrial Engineering Department, University of Bologna, Viale del Risorgimento 2, 40136
Bologna - Italy
e-mail: [email protected], [email protected], [email protected],
[email protected], [email protected], [email protected]
ABSTRACT
Rubber nanofibers production is a big challenge, due to the rubber glass transition temperature
(Tg) well below the room temperature, which prevents the retention of the nanofibrous structure
over the time, leading to the formation of bulk films. A feasible route to produce liquid rubber
(i.e. not crosslinked) nanofibers is provided by core-shell electrospinning, allowing the creation
of co-axial fibers in which the rubber is contained in a rigid polymeric shell that guarantees the
nano-structure retention. This approach, although viable, requires a more complicated setup
respect to the single-needle electrospinning, besides a low accurate and tricky control of the
core/shell polymers ratio in the nanofiber.
In the present work, we propose a simple and smart way to produce rubbery nanofibers by means of
single-needle electrospinning of NBR/PCL (nitrile butadiene rubber/polycaprolactone) blend
solutions without the need of a crosslinking step.
Polymers are well renown to commonly phase separate due to
unfavourable thermodynamics when mixed together. NBR/PCL
miscibility is prevented from a thermodynamic point of view, as
calculated according to a common approach proposed by
Hoftyzer and van Krevelen1. The unique ability of the
electrospinning process to successfully provide a NBR/PCL
blending, not possible through other processing techniques, such
as solvent casting and spin coating, is demonstrated2. The
formation of the polymeric blend has been proved by the
presence of a single Tg, as expected by the Fox equation, a
typical behaviour of materials with a single phase. Thanks to the
high degree of crystallinity of the PCL fraction (up to 71%), the
not-crosslinked rubbery nanofibers retain the nano-morphology,
as assessed via SEM analysis (Figure 1), for at least 2 years2. The mats were mechanically
characterized through tensile tests. Load values were normalized with respect to the specimen weight
instead of its section area, as commonly done, for taking into account the nanofibrous mat porosity,
allowing a more reliable elastic modulus and tensile strength evaluation2,3
. Moreover, the obtained
stress/strain data were analysed by means of a new recently proposed phenomenological model2,3
.
REFERENCES
[1] Van Krevelen, D. W.; Te Nijenhuis, K. Cohesive Properties and Solubility. In Properties of Polymers; 2009; Vol. I,
pp 189-227.
https://doi.org/10.1016/b978-0-08-054819-7.00007-8.
[2] Maccaferri, E.; Mazzocchetti, L.; Benelli, T.; Brugo, T.M.; Zucchelli, A.; Giorgini, L. Rubbery nanofibers by
co-electrospinning of almost immiscible NBR and PCL blends, Materials and Design, 2020, 186, 108210.
https://doi.org/10.1016/j.matdes.2019.108210.
[3] Maccaferri, E.; Mazzocchetti, L.; Benelli, T.; Zucchelli, A.; Giorgini, L. Morphology, Thermal, Mechanical Properties and
Ageing of Nylon 6,6/Graphene Nanofibers as Nano2 Materials. Composites Part B, 2019, 166, 120–129.
https://doi.org/10.1016/j.compositesb.2018.11.096.
Figure 1. NBR/PCL nanofibrous mat
with 60%wt of rubber (scale bar 2mm).
P37
SULFUR LOADED BY NANOMETRIC TIN AS A NEW
ELECTRODE FOR HIGH-PERFORMANCE LITHIUM/SULFUR
BATTERIES
Vittorio Marangon1 and Jusef Hassoun1,2,*
1 University of Ferrara, Department of Chemical and Pharmaceutical Sciences, Via Fossato di
Mortara 17, 44121, Ferrara, Italy.
2 National Interuniversity Consortium of Materials Science and Technology (INSTM) University of
Ferrara Research Unit, University of Ferrara, Via Fossato di Mortara, 17, 44121, Ferrara, Italy.
Corresponding author: [email protected]
ABSTRACT
We investigate herein a composite material formed by coating sulfur on nanometric tin as the
cathode for high-performances Li/S battery. The study includes structural and morphological
characterization performed by X-ray diffraction and electron microscopy, and electrochemical
investigation by meaning of voltammetry, electrochemical impedance spectroscopy, and
galvanostatic cycling in lithium cell. The data reveal an electrode reflecting the crystalline structure
of S8 and Sn, and a suitable morphology which consists of micrometric sulfur particles surrounding
a metallic core of nanometric tin. This particular configuration leads to optimal behavior in lithium
cell, with highly reversible electrochemical process evolving between 1.9 and 2.8 V vs. Li+/Li and
low polarization.
The S-Sn composite reveals a favorable electrode/electrolyte interphase having a resistance limited
to few Ω after the first activation charge/discharge cycle in Li/S cell, which allows suitable
operation with excellent rate capability and limited capacity fading. Indeed, the cell shows an
efficiency approaching 100% upon the first cycle, a maximum specific capacity of about 1200 mAh
g-1 at C/10 rate, and a still relevant capacity value of about 700 mAh g-1
at the relatively high 2C
rate, with suitable retention upon 100 charge/discharge cycles.
Figure 1. Graphical abstract showing the performances of the S-Sn 80:20 cathode at various current rates in lithium
battery and the SEM image of the S-Sn 80:20 composite powder (inset).
REFERENCES [1] V. Marangon and J. Hassoun, Sulphur Loaded by Nanometric Tin as a New Electrode for High-Performance
Lithium/Sulfur Batteries, Energy Technol., 2019, 1900081. DOI: 10.1002/ente.201900081
P38
USE OF 1H NMR TO DETECT THE PERCENTAGE OF PURE FRUIT JUICES IN BLENDS
Lucia Marchetti (a,b), Davide Bertelli (a), Federica Pellati (a)
a Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103, 41125 Modena b Doctorate School in Clinical and Experimental Medicine (CEM), University of Modena and Reggio Emilia ABSTRACT The consumption of high-nutritional-value fruit juices is increasing worldwide and, considering the large market volume, frauds and adulterations represent an ongoing problem. The most employed techniques to reveal fraud in this field, mostly GC and HPLC, aim to detect water dilution, the addition of inexpensive fruit blends to higher-value fruit juice, or the addition of pure beet sugar. These kind of techniques which involve whole-food profiling or the search for a number of compounds (targeted analysis) can be very expensive and time-consuming. Nuclear Magnetic Resonance (NMR) spectroscopy has shown many advantages over the common separative techniques. Indeed, it can detect many different compounds in one sample run, it is non-destructive, stable over time, and it requires only a limited sample preparation [1]. NMR coupled with chemometrics, is able to evaluate simultaneously, from a single dataset, a multitude of parameters related to the quality and authenticity of the product, this approach can reveal latent correlations in the data and can be useful for both qualitative and quantitative purposes [2]. Hence, this study evaluates the potential of 1H NMR combined with Partial least squares (PLS) analysis, for the determination of the relative percentage of pure fruit juices in blends. PLS modeling is a powerful multivariate statistical tool, which main objective is to eliminate multicollinearity in the set of explanatory variables (X) of a regression model, reducing the dimension of the set in such a way that the resulting subset of descriptive variables is optimal for predicting the dependent variable (Y), that represents the analyte concentrations. Apple, orange, pineapple, and pomegranate juices were selected to set up an experimental plan and then mixed in different proportions according to a central composite design (CCD). 1D NOESY experiments were choosen, in order to suppress the water signal. PLS analysis was performed using venetian-blind internal cross-validation, and the model was established using different chemometric indicators (RMSEC, RMSECV, RMSEP, R2CAL, R2CV, R2PRED). The best performing PLS model was built with five factors, explaining 94.51 and 88.62% of the total variance in X and Y, respectively. In conclusion, the present work shows the feasibility and advantages of using 1H NMR spectral data in combination with multivariate analysis to develop and optimize calibration models useful for detecting fruit juice adulteration. REFERENCES [1] M. Cuny, E. Vigneau, G. Le Gall, I. Colquhoun, M. Lees, D.N. Rutledge. Fruit juice authentication by 1H NMR spectroscopy in combination with different chemometrics tools. Anal Bioanal Chem, 2008, 390, 419–427.
P39
!" #$%$& '()*+" '$,$& (-!!" #$.$& /0!1*" 2$,$ 3#2 *4 506(7!(6- 46 *8)() 6+ ))-)) 6!9-:((68 +;< < < < < < < < < < < < < < < < < <
!=-*6(*-<9(6!0)$<#(9!+9>-5$<?$<@AB"<ACA"<DCEF@$<
<
SYNTHETICALLY MODIFIED NATURAL BETALAINS
Edoardo Marchini, Stefano Caramori, Arianna Brandolese and Alessandro Massi
University of Ferrara, Via L. Borsari, 46, 44121 Ferrara - Italy
ABSTRACT
Dye sensitized solar cells (DSSCs) are transparent and low cost1 photovoltaic devices constituted
by a wide band gap semiconductor sensitized with a
molecule able to absorb the solar light and inject one electron
into the conduction band of the semiconductor. The electron
is now able to flow in the external circuit to generate
electricity. The main interesting application of these types of
devices is the possibility to use them in indoor application
and as integration in windows and in buildings facades due
to the capacity to work properly with the diffuse light and
with no direct photons. To replace the silicon and to reduce
the environmental impact due to the fabrication and the
disposal processes, it is necessary to explore low cost
materials and Earth abundance elements.
In this contribution, we will report our search for synthetic betalains2 as sensitizer. We synthesized
a mimetic betaxanthin obtaining a comparable efficiency considering a natural extract of red
beetroot as a comparison. In order to improve the harvesting and charge separation properties we
modelled dyes with the aid of DFT and TD-DFT calculations showing the effects of the
introduction of electron donor groups on energy and topography of frontier orbitals. A first attempt
of modified betalains was obtained by careful tuning the synthetic strategies.
REFERENCES
1. B. E. Hardin, E. T. Hoke, P. B. Armstrong, J.-H. Yum, P. Comte, T. Torres, J. M. Fréchet, M. K. Nazeeruddin, M.
Grätzel and M. D. McGehee, Nature Photonics, 2009, 3, 406.
2. G. Calogero, G. Di Marco, S. Cazzanti, S. Caramori, R. Argazzi, A. Di Carlo and C. A. Bignozzi, International
journal of molecular sciences, 2010, 11, 254-267.
Figure 1. Scheme of betalain
P40
Nano-graphitic templates and hierarchical nanostructures in multi-
functional electrocatalysts for CO2 conversion
Miriam Moro(a), Giovanni Valenti(a), Tiziano Montini(b), Alessandro Boni(a), Lucia Nasi(c),
Michele Melchionna(b), Silvia Voci(a), Giovanni Bertoni(c), Marcella Bonchio(d), Paolo
Fornasiero(b), Francesco Paolucci(a) and Maurizio Prato(b)
a) Department of Chemistry “Giacomo Ciamician”, Alma Mater Studiorum - University of
Bologna, Via Selmi, 2 - 40126 Bologna, Italy.
b) University of Trieste, Dep. of Chemical Science, Center of Excellence of Nanostructured
Material (CENMAT), Trieste, Italy.
c) CNR-IMEM Institute, Parco area delle Scienze 37/A, 43124 Parma, Italy
d) University of Padova, Via F. Marzolo 1, 35131 Padova, Italy
E-mail: [email protected]
With the advancement of society, energy consumption has rapidly increased, resulting in a huge use
of fossil fuels and significant emission of CO2 into the atmosphere. To date, this trend doesn’t tend
to decrease, influencing on global warming and climate changes. To resolve this problem, the research
has focused on the development of new materials and technology capable of capturing and converting
CO2 into useful products.1 The design of new electrocatalysts that reduce CO2 in a selective and
efficient fashion is a key step for future exploitation of this technology. Among all reduction products,
formic acid is particularly attractive for its high volumetric hydrogen density, low toxicity and liquid
state, that make it a valuable hydrogen storage vector.
Here we present how the combination of different building blocks in a single nanostructure might be
a good strategy to achieve a good selectivity in the CO2 reduction process.
Combining the unique physico-chemical properties of functionalized nanomaterials (such as carbon
nanotubes and carbon nanohorns) and nanocrystalline cerium dioxide (CeO2) we revealed faradaic
efficiency for formic acid production as high as 55% at an overpotential as low as 0.02V in acid
solutions. These performances have been possible by the formation of partially reduced ceria
(Ce4+/3+O2-x), responsible of an increased CO2
adsorption and a more efficient electron transfer at
the surface.2 In the nanocomposite, where the
nanomaterials are covered by nanoparticles of
CeO2, the oxide layer is thin enough to allow
efficient charge transport through it and fast electron
transfer at the surface where CO2 is adsorbed.3
The interconnection of the various components has
been shown to be fundamental for the efficient CO2
reduction to formic acid with this new metal-free
nanocomposite and opens new possibilities in the
design of optimized electrocatalytic materials.
References
[1] B. Kumar, J. P. Brian, V. Atla, S. Kumari, K. A. Bertram, R. T. White, J. M. Spurgeon, Catalysis Today 2016, 270,
19-30
[2] T. Montini, M. Melchionna, M. Monai, P. Fornasiero, Chem. Rev. 2016, 116, 5987–6041
[3] G. Valenti, A. Boni, M. Melchionna, M. Cargnello, L. Nasi, G. Bertoni, R. J. Gorte, M. Marcaccio, S. Rapino, M.
Bonchio, et al., Nat. Commun. 2016, 7, 13549.
e-
Figure 1. Schematic CO2 reduction into formic acid
on MWCNT@CeO2
P41
STUDY ON TETRAZOLIC LIGANDS FOR ATRP APPLICATION
Luca Mugnaini (a)
, Michele Rizzi
Interdepartmental Center for Industrial Research on Advanced Applications in Mechanical
Engineering and Materials Technology, CIRI-MAM, University of Bologna, Viale Risorgimento 2,
40136 Bologna, Italy.
Corresponding author e-mail: [email protected]
ABSTRACT
Living/Controlled radical polymerization techniques have acquired, in the last years, a great
resonance in the scientific community, due to the possibility to synthesize polymers with controlled
molecular weight, low polydispersity and complex structures [1]. Between these techniques, ATRP
(Atom Transfer Radical Polymerization) is surely one of the most known and applied, due to its
versatility in the polymerization of an high number of different monomers, high tolerability of the
contaminants and possibility to obtain polymers with well-defined structures [2], making this
process applicable at industrial level. The effectiveness of an ATRP process depends on the
catalytic system [3] , consisting in a reduced metal, stable in two different reduced forms separated
by a single electron, and a ligand, which should form a stable complex in order to increase the
solubility of the reduced metal in the reaction environment. In order to increase the versatility of
ATRP, the activity of four new tetrazolic ligands [2-(2-(tertbutyl)-2H-tetrazol-5-yl)pyridine (PtZ-
tBu), 2-(2-tertbutyl)-2h-tetrazol-5-yl)quinoline (QTZ-tBu), 2-(2-methyl-2H-tetrazol-5-yl)pyridine
(PTZ-2-Me) and 2-(3-methyl-2H-tetrazol-5-yl)pyridine (PTZ-3-Me) has been studied.
These ligands were used to form stable complexes of Cu(I), which were subsequently applied in the
ATRP polymerization of methyl methacrylate in different reaction conditions.
Two different common ATRP initiators [allyl-2-chloridepropionate (ACP) and allyl-2-bromide-2-
methylpropionate (ABP)] were used with these complexes, employing different solvents (DMF,
DMSO, Toluene, THF, 1,4-dioxane) in a wide range of temperatures (70-100°C), in order to
evaluate the activity of the catalytic system in different conditions.
REFERENCES [1] W. A. Braunecker e K. Matyjaszewski, «Controlled/living radical polymerization:,» Science direct, pp. 93-146,
2006.
[2] K. Matyjaszewski e J. Spanswick, «Controlled/living radical polymerization,» materialstoday, vol. 8, pp. 26-33,
2005.
[3] KRYS, Pawel; MATYJASZEWSKI, Krzysztof. «Kinetics of atom transfer radical polymerization.» European
Polymer Journal, 2017, 89: 482-523.
P42
ELECTROREDUCTION OF CARBON DIOXIDE BY POROUS
Au-NANOSTRUCTURES PREPARED BY PULSED LASER
DEPOSITION
Alessandro Niorettini a, Serena Berardi a, Luca Mascaretti b, Beatrice Roberta Bricchi b,
Matteo Ghidelli b, Carlo Alberto Bignozzi a, Andrea Li Bassi b, Stefano Caramori a
a Dept. of Chemical and Pharmaceutical Sciences, Univ. of Ferrara, Via Luigi Borsari 46,
44121 - Ferrara, Italy
b Dept. of Energy, Politecnico di Milano, via G. Ponzio 34/3, 20133 – Milano, Italy
alessandro.niorettini@ unife.it
ABSTRACT
Burning fossil fuels to meet the ever-growing energy demand of modern society comes with
the inevitable price of releasing increasing amounts of carbon dioxide in the atmosphere.
These anthropogenic CO2 emissions contribute to greenhouse effect and to its well-known
consequences on climate.
Therefore, in order to establish a virtuous CO2 cycle, it is necessary to develop strategies
focussed on the transformation of carbon dioxide into useful products.
To this aim, one of the most pursued approaches in the scientific community is the
electrochemical reduction of CO2, using suitable metallic cathodes.[1] Furthermore, one can
envisage an electrochemical system in which the grid power is provided via the exploitation
of renewable energy.
Among the metals used as cathodes, gold has been widely used since it almost selectively
forms carbon monoxide as the main CO2 reduction product.[2] Furthermore, several reports
evidenced the importance of nanostructuring the Au-based cathodic interfaces in order to
boost CO formation over the competitive proton reduction in aqueous media.[3]
In this contribution, we will report on the preparation of two different kind of porous Au-
nanostructures, and their use as cathodes for CO2 reduction in aqueous electrolytes.[4] These
cathodic materials were synthetized by pulsed laser deposition, a versatile and easy-to-scale
technique, already implemented in industrial processes.[5] The results obtained with the
nanoporous catalysts evidenced the formation of syn-gas (CO+H2), together with smaller
amounts of formic acid, outperforming a planar gold foil used as reference.
REFERENCES [1] a) Y. Hori, Modern Aspects of Electrochemistry, no. 42, Springer, 2008, pp. 89-182; b) K. P. Kuhl, T.
Hatsukade, E. R. Cave, D. N. Abram, J. Kibsgaard, T. F. Jaramillo J. Am. Chem. Soc. 2014, 136, 14107.
[2] S. Zhao, R. Jin, R. Jin ACS Energy Lett. 2018, 3, 452; b) A. J. Welch, J. S. DuChene, G. Tagliabue, A.
Davoyan, W.-H. Cheng, H. A. Atwater ACS Appl. Energy Mater. 2019, 2, 164; c) H. Mistry, R. Reske, Z. Zeng,
Z.-J. Zhao, J. Greeley, P. Strasser, B. Roldan Cuenya J. Am. Chem. Soc. 2014, 136, 16473.
[3] a) Y. Chen, C. W. Li, M. W. Kanan J. Am. Chem. Soc. 2012, 134, 19969; b) A. S. Hall, Y. Yoon, A. Wuttig,
Y. Surendranath J. Am. Chem. Soc. 2015, 137, 14834; c) E. R. Cave, J. H. Montoya, K. P. Kuhl, D. N. Abram, T.
Hatsukade, C. Shi, C. Hahn, J. K. Norskov, T. F. Jaramillo Phys. Chem. Chem. Phys. 2017, 19, 15856.
[4] A. Niorettini, S. Berardi, L. Mascaretti, B. R. Bricchi, M. Ghidelli, C. A. Bignozzi, A. Li Bassi, S. Caramori,
manuscript in preparation.
[5] M. C. Gower Opt. Express 2000, 7, 56.
P43
ROS-RESPONSIVE “SMART” POLYMER PRODRUG: SYNTHESIS, CHARACTERIZATION AND PROOF-OF-CONCEPT
STUDY
Natalia Oddone(a), Francesca Pederzoli(a), Andreas M. Grabrucker(b, c, d), Jason T. Duskey(a), Flavio Forni(a), Maria Angela Vandelli(a), Barbara Ruozi(a), Giovanni Tosi(a)
(a)Nanotech Lab TeFarTI group, University of Modena and Reggio Emilia, Department of Life Sciences, Modena, Italy (b)Department of Biological Sciences, University of Limerick, Limerick, Ireland. (c)Bernal Institute, University of Limerick, Limerick, Ireland (d)Health Research Institute (HRI), University of Limerick, Limerick, Ireland
New approaches integrating stimuli-responsive linkers into prodrugs are currently emerging. These “smart” prodrugs can enhance the effectivity of conventional prodrugs with promising clinical applicability[1]. Oxidative stress is central to several diseases including cancer[2]. Therefore, the design of prodrugs that respond to ROS stimulus, allowing a selective drug release in this condition, is fairly encouraging. Aiming to investigate the ROS-responsiveness of prodrugs containing the ROS-cleavable moiety, Thioketal, we performed proof-of-concept studies by synthesizing ROS-responsive prodrug, namely mPEG-TK-Cy5, through exploiting fluorescent Cy5 as model “drug”. We demonstrated that, differently to non-ROS-responsive control (mPEG-Cy5), mPEG-TK-Cy5 shows a selective release of Cy5 in response to ROS in both, ROS-simulated conditions and in vitro on glioblastoma cells. Our results confirm the applicability of TK-technology in the design of ROS-responsive prodrugs, which constitutes a promising approach in cancer treatment. The translatability of this technology for other diseases treatment makes this a highly relevant and promising approach.
REFERENCES
[1] Chang M, Zhang F, Wei T, et al. Smart linkers in polymer–drug conjugates for tumor-targeted delivery. J. Drug Target. 2016; 24:475–491.
[2] Gupta MK, Meyer TA, Nelson CE, et al. Poly (PS-b-DMA) micelles for reactive oxygen species triggered drug release. J. Controlled Release. 2012; 162:591–598.
P44
SYNTHESIS, CHARACTERIZATION AND IN VITRO STUDIES OF ROS-RESPONSIVE mPEG-TK-MPH PRODRUG IN
GLIOBLASTOMA Natalia Oddone(a), Frank Boury(b), Emmanuel Garcion(b), Andreas Grabrucker(c), (d), (e), Maria del Carmen Martinez(f), Flavio Forni(a), Maria Angela Vandelli(a), Barbara Ruozi(a), Giovanni Tosi(a)
[email protected]. aNanotech Lab TeFarTI Group, University of Modena and Reggio Emilia, Department of Life Sciences, Modena, Italy. bCRCINA, INSERM, Université de Nantes, Université d’Angers, Angers, France. cDepartment of Biological Sciences, University of Limerick, Limerick, Ireland. dBernal Institute, University of Limerick, Limerick, Ireland. eHealth Research Institute (HRI), University of Limerick, Limerick, Ireland. fSOPAM, INSERM, Université de Nantes, Université d’Angers, Angers, France.
ABSTRACT
Glioblastoma (GBM), classified as malignant grade IV astrocytic tumour, is the most frequent and aggressive primary tumour of the brain. Considering that the standard GBM therapy can increase the survival expectancy in only 2.5 months, there is a need to design more effective therapies against this tumour[1]. Several Drug Delivery Systems (DDS) that improve solubility, time in blood circulation and targetability of drugs, have been demonstrated to be effective against tumours, including GBM. Nowadays, DDS that selectively respond to a given pathological feature or stimulus (e.g. GSH, pH, ROS), known as “Smart” DDS, are being developed. Since the concentration of ROS in tumours is higher than in healthy tissues, being high concentrations of ROS needed for GBM cells to grow; the design of ROS-responsive DDS for the delivery of chemotherapeutic agents against this condition, is highly promising. As Thioketal (TK)- containing linkers, have demonstrated to be biocompatible molecules that are cleaved upon ROS[2], the aim of the present work was to prepare a TK-based polymeric prodrug for the selective release of Melphalan in GBM. This prodrug, namely mPEG-TK-MPH, was synthesized by covalent conjugation of MPH to ROS-responsive mPEG-TK-COOH polymer by means of EDC/NHS coupling. A non-ROS-responsive prodrug, without TK linkages (mPEG-MPH), following a similar synthetic procedure, was also prepared and employed for comparison purposes. Both prodrugs were obtained (with high product yields) and properly characterized by means of 1H NMR and MALDI-TOF. In addition, through DLS and AFM measurements, it was demonstrated that either of the prodrugs undergo spontaneous auto- assembling into spherical nanometric structures. In vitro cytotoxicity assays performed on GBM cells (C6, U87MG and U251MG), showed that on High- ROS GBM cells (C6 and U251MG cells), mPEG-TK-MPH was significantly more cytotoxic than mPEG-MPH. On the other hand, free MPH was highly cytotoxic to all GBM cells, but also to “healthy” astrocytes cells (DI TNC1). Noteworthy, neither mPEG-MPH nor mPEG-TK-MPH, showed to be cytotoxic on astrocyte cells, which demonstrates their safety. Consequently, due to its selective cytotoxicity in High-ROS GBM cells over “healthy” cells, ROS-responsive mPEG-TK-MPH prodrug showed encouraging results as a starting point in the design of ROS-responsive DDS against GBM.
REFERENCES
P45
NANOMEDICINE FOR BRAIN TARGETING I. Ottonellia,b, G. Tosia*, N. Oddonea,b, J. T. Duskeya, A. Vilellac, S. Kovachkad, F. Spyrakisd, M. A. Vandelli a, B. Ruozia* a Nanotech Lab, Te.Far.T.I., Dept. Life Sciences, University of Modena and Reggio Emilia, Italy b Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Italy
c Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Italy d Department of Drug Science and Technology, University of Turin, Italy* Correspondence: [email protected] ABSTRACT
Central Nervous System (CNS) compartments remain one of the most difficult districts for drug delivery due to the presence of the Blood Brain Barrier (BBB) that hampers the passage of 90% of drugs. Here we describe for the first time the use of deltorphin-derived peptides (DP) and glycosylated derivatives (Glu-DP) to deliver biodegradable and biocompatible polymeric (i.e. poly-lactide-co-glycolide, PLGA) nanomedicines across the BBB. Molecular Dynamic (MD) studies to control the 3D structure of the peptide were used to analyze the favored conformation of each modified peptide (DP, and GluDP), which resulted to be 𝜶-helix-shaped. The DP and GluDP were conjugated onto PLGA using peptide coupling chemistry and formulated into nanoparticles (NPs). Physico-chemical and technological characterization of the DP-NPs and Glu-DP-NPs showed no difference in comparison with plain control PLGA NPs. When IP injected into wild-type mice, both DP- and Glu-DP-NPs were observed to cross the BBB, unlike un-targeted NPs, and furthermore Glu-DP-NPs displayed a higher BBB penetration and co-localization with astrocytes. Finding new ligands that chaperone large nanoparticulate systems through the BBB is one of the crucial challenges of nanomedicine. In this work, two deltorphin derivatives were shown to be effective in targeting brain tissues, and they could be chemically linked to the polymer PLGA with the ability to self-assemble into stable nanoparticles. Lastly and most importantly, targeted nanoparticles were shown, in vivo, to cross the BBB and to be co-localized mostly with nerons. Future experiments will help to better understand both the area/cell localization and possible treatments after CNS drug delivery. REFERENCES [1] J.T. Duskey, D. Belletti, F. Pederzoli et al. Current Strategies for the Delivery of Therapeutic Proteins and Enzymes
to Treat Brain Disorders. Int. Rev. Neurobiol., 2017, 137:1-28 [2] I. Ottonelli, J.T. Duskey, G. Tosi et al., Novel peptide-conjugated nanomedicines for brain targeting: in vivo
evidences (submitted)
P46
GOLD(I)-CATALYSED ENANTIOSELECTIVE DEAROMATIZATION OF 2-NAPHTHOLS
Riccardo Pedrazzani(a), Magda Monari(a), Marco Bandini(a) (a) University of Bologna, Chemistry Department “G. Ciamician”, Via Selmi 2, Bologna ABSTRACT
The dearomatization of organic compounds has gained interest, in many organic chemistry research groups, in the last few decades due to the possibility to transform planar ready-available chemicals in final products with high spatial and chemical complexity. In the multitude of known aromatic compounds, the ones that can undergo this kind of reactions are the hetero-aromatic rings (pyridines, indoles etc.) and the hetero-functionalized benzene rings (naphthols, phenols, etc.). In particular the dearomatization of naphthols can lead to highly functionalized polycyclic structures that are platform chemicals for further biological and pharmacological products.
Our research group has developed a new intermolecular synthetic methodology to dearomatize 2-naphthols in presence of allenamides catalysed by Ph3PAuTFA.[1] The methodology has demonstrated to be regioselective leading to the addition at carbon C1 of the naphtholic moiety and to be stereoselective for the exclusive formation of E configuration of C-C double bond.
In this work we present the synthesis of new BINOL-based chiral phosphates as counter-ions in the enantioselective dearomatization of 2-naphthols. These systems have been chosen among others for their coordinative and Lewis’ basicity properties that make them similar to the trifluoroacetate anion, which is employed in the achiral catalysis. A linear synthetic pathway is applied starting from (R)-BINOL (Fig. 1). The intermediate (R)-I plays a key role due to the possibility to obtain different silver phosphates by cross-coupling reactions. Figure 1 The counter-anions synthetized are tested in the catalytic dearomatization in the presence of JohnPhosAuCl complex. The results achieved are promising in terms of yield and enantiomeric excess (Fig. 2).
Figure 2
REFERENCES [1] J. An, L Lombardi, S. Grilli and M. Bandini, Org. Lett., 2018, 20, 7380−7383
P47
THERMALLY ACTIVATED DELAYED FLUORESCENCE:
TOWARDS HIGHLY EFFICIENT ORGANIC-LED
D. K. Andrea Phan Huu, Rama Dhali, Sangeeth Saseendran, Cristina Sissa, Francesca
Terenziani, Anna Painelli
Università degli Studi di Parma, Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità
Ambientale.
e-mail: [email protected]
ABSTRACT
One of the most promising approaches to increase the efficiency of fluorescent organic light
emitting devices (OLED) exploits the phenomenon of thermally-activated delayed fluorescence
(TADF)[1]
. Indeed, doping the fluorescent layer with TADF dyes allows to harvest the non-emissive
triplet excitons, converting them to emissive singlet excitons in a process known as reverse
intersystem crossing. Several factors affect the efficiency of a TADF emitter, including the different
nature of the involved states, their mutual interactions, conformational degrees of freedom and
environment effects. A proper understanding of how these interrelated factors affect TADF
efficiency is of paramount importance in order to improve the design of TADF emitters and of host
materials. Despite extensive theoretical work, the mechanism behind TADF is not completely
understood yet.
DMAC-TRZ is a promising TADF emitter, where an
electron donor moiety (DMAC) is connected to an
acceptor moiety (TRZ), as shown in the figure. We adopt
the essential state model (ESM) strategy to propose an
original model for this dye[2]
. The electronic ESM
Hamiltonian accounts for just for four states, two singlets
and two triplets and can be easily extended to account for
electron-vibration coupling in a fully non-adiabatic way,
and for conformational disorder due to slow torsional
degrees of freedom. Environmental effects are also
introduced in terms of electronic and orientational solvent
degrees of freedom. Specifically we exploit a novel
antiadiabatic approach to describe the coupling between
the TADF molecule and the electronic degrees of freedom
of the environment[3]
.
The proposed ESM is also easily extended to more
complex TADF dyes with a quadrupolar or octupolar structure, unveiling the effect of symmetry
breaking on key properties that lead to the TADF phenomenon. Some preliminary results on real
time dynamics of reverse intersystem crossing are also displayed.
REFERENCES [1] Uoyama, H., Goushi, K., Shizu, K., Nomura, H., Adachi, C. Highly efficient organic light-emitting diodes from
delayed fluorescence. Nature 492, 234–238 (2012)
[2] Painelli A., Amplification of NLO responses: vibronic and solvent effects in push–pull polyenes. Chemical Physics
245, 185-197 (1999)
[3] Phan Huu, D. K. A., Dhali, R., Pieroni, C., Di Maiolo, F., Sissa, C., Terenziani, F., and Painelli, A. An antiadiabatic
view of fast environmental effects on optical spectra. arXiv:1909.03398 [cond-mat.mtrl-sci] (2019)
Figure 1. PES as function of the donor-
acceptor dihedral angle. Inset: Kekulè
structure of DMAC-TRZ.
45 60 75 90 105 120 135
0.0
1.53.0
4.5
6.0
Ab
solu
te e
nerg
y (
eV
)
Dihedral angle
S1
T2
S0
T1
P48
DESIGN AND SYNTHESIS OF DONEPEZIL-DIHYDROPYRIDINE
HYBRIDS AS MULTITARGET-DIRECTED LIGANDS FOR THE
TREATMENT OF ALZHEIMER’S DISEASE
Pedro de Sena Murteira Pinheiroa,b, Carlos Alberto Manssour Fragaa,b, Maria Laura
Bolognesia,*
aDepartment of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, 40126
Bologna, Italy. bPrograma de Pós-Graduação em Farmacologia e Química Medicinal, Institute of Biomedical
Sciences, Federal University of Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil.
ABSTRACT
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases in the world
population and has become a major epidemic health problem. It is important to highlight that AD is
a multifactorial disease and consequently the development of multitarget drugs is an interesting and
promising strategy.1 Until now there are four FDA-approved drugs, tacrine, donepezil, galantamine,
and rivastigmine, for the AD treatment. These drugs improve AD symptoms through the inhibition
of acetylcholinesterase (AChE), but they are ineffective to cure the disease. This denotes a much-
needed urgency for the development of new treatments. In this way, the inhibition of AChE
represents a starting point for the creation of multitarget drugs, as it is already a clinically validated
strategy. Another strategy that appears to be promising is the calcium channel blockage, since the
overload of calcium is correlated with neuronal injury and the L-type calcium channel blockage
through the use of dihydropyridine drugs, such as Nilvadipine, was shown to be promising,
reaching a Phase III clinical trials.2 Beyond that, the combination activity of AChE inhibition and
calcium channel antagonism was already explored through the design of tacrine-dihydropyridine
analogues, which resulted in new compounds with neuroprotective activities against both calcium
overload and oxidative stress.3 In this context, we rationally designed a new series of homologous
compounds merging the dihydropyridine scaffold with the drug donepezil, creating compounds with
different linker length (Figure 1). Donepezil was selected since it is the first-choice drug for the
treatment of AD. Preliminarily, the designed compounds were evaluated through docking studies in
the crystal structure of AChE (PDB ID: 4EY7), which indicated that compounds 3 and 4 are more
promising for AChE inhibition, by having a proper link size when compared to 1 and 2.
Figure 1. Design of donepezil-dihydropyridine hybrids for the treatment of AD.
REFERENCES [1] Cavalli, A. et al. J. Med. Chem. 51, 347–372 (2008).
[2] Lawlor, B. et al. PLoS Med. 15, 9, e1002660 (2018).
[3] Marco-Contelles, J. et al. J. Med. Chem. 52, 2724–2732 (2009).
P49
GAS CHROMATOGRAPHIC DETERMINATION OF VOLATILE
AND SEMI-VOLATILE ORGANIC COMPOUNDS (VOCs AND
SVOCs) IN POLYETHYLENE AND EFFECTS OF PROCESSING
CONDITIONS
Francesco Prandi, Letterio Giannino
Dipartimento di Chimica Industriale “Toso Montanari”, Viale del Risorgimento 4, 40136
According to the most recent European directive [1]
, any organic compound with a boiling
temperature lower than 250 °C at atmospheric pressure must be considered as a volatile organic
compound (VOC). These substances can easily migrate from the matrix in which they are
contained, such as food contact materials (FCMs) or pharmaceutical blisters. A relevant problem of
polyolefins processing is the presence of volatile and semi-volatile compounds (VOCs and SVOCs)
such as linear chains alkanes (for HDPE) find in final products.
These VOCs can be detected by customers from the unpleasant smell and can be an environmental
issue.
If, during the polymer processing, there was the possibility of removing the greatest possible
quantity of pollutants, or there was the possibility of limiting their production caused by the
degradation reactions induced by the processing, a technology could be designed in order to
minimize the content of VOCs.
Since no previously standardized analytical techniques for polymeric matrix are available in
literature, we have implemented different VOCs extraction methods and gaschromatographic
analysis for quali-quantitative studies of such compounds.
In particular, GC-MS analysis were performed on HDPE samples subjected to a thermodesorption
(TDS) by analyzing the substances produced. This type of analysis is necessary for the identification
of different compounds in the polymer matrix.
In order to quantify these linear alkanes by-products, a more accurate GC-FID determination with
internal standard has been run on Microwave Assisted Extracts [2]
(MAE).
Regardless the type of extruder used, it is difficult to distinguish the effect of the various processes,
which in any case entails a lower-boiling substance content lower than the corresponding virgin
polymer.
Generally, however, a higher processing temperature, a higher degree of vacuum in the extruder,
and a longer residence time, lead to a lower content of volatile substances in the polymer.
The two HDPEs studied can be distinguished on the basis of the quantity of analytes found,
therefore the production process is mainly responsible for the amount of VOCs and SVOCs
observed.
Thus, the result is significantly important since a lower quantity of volatile substances certainly
leads to a lower migration of such materials, especially when used for food packaging.
REFERENCES
[1] Directive 2004/42/CE of the European Parliament and of the Council of 21 April 2004 on the limitation of
emissions of volatile organic compounds, EUR-Lex, Document 32004L0042
[2] Johanna Möller, Emma Strömberg, Sigbritt Karlsson, European Polymer Journal, 44, 1583–1593 (2008)
P50
PANI/AU/FE3O4 NANOCOMPOSITE MATERIALS FOR HIGH
PERFORMANCE ELECTROCHEMICAL CAPACITORS
Ilaria Ragazzinia, Barbara Ballarina, Elisa Boaninib, Maria Cristina Cassania, Luigi
Montaltoc, Paolo Menguccic, Daniele Nannia, Chiara Parisea, Daniele Rinaldic, Nicola
Sangiorgid, Alessandra Sansond
a Dept. of Industrial Chemistry "Toso Montanari", Bologna University, Via Risorgimento 4, I40136,
Bologna, Italy ([email protected])
b Dept. of Chemistry “Giacomo Ciamician”, Bologna University, Via Selmi 2, I-40126, Bologna,
Italy
c Dept. SIMAU, Università Politecnica delle Marche, via Brecce Bianche, I-60131 Ancona, Italy
d CNR - Institute of Science and Technology for Ceramics, Via Granarolo 64, I-48018, Faenza (RA),
Italy
ABSTRACT
In the present work new supercapacitor components were prepared depositing films made of
polyaniline (PANI) modified with gold/magnetite nanoparticles on flexible graphite foils. Three types
of composite materials termed PANI/Fe3O4, PANI/Au/Fe3O4 and PANI/Au/Fe3O4@Yne (where
@Yne is a propynylcarbamate group) were obtained by electrosynthesis. Galvanostatic
chargedischarge (CD) and impedance tests (EIS) were performed to verify their efficiency as
supercapacitors: for the gold-containing
electrodes PANI/Au/Fe3O4 and
PANI/Au/Fe3O4@Yne volume
capacitance (CV) values of 25861 and
22860 mF cm-3 were found in 0.5 M
H2SO4 + 0.1 M LiClO4 electrolyte at a
current density of 0.5 mA cm-2. These
values are twofold higher than those found
for PANI/Fe3O4 electrodes and threefold
greater than those for PANI alone (7846
mF cm-3). In turn PANI/Au/Fe3O4 and
PANI/Au/Fe3O4@Yne were employed to
assemble gel-state symmetric
supercapacitors. CD, EIS and longtime resistance tests were made on the new devices that displayed
energy densities of 9538 and 4533 mWh cm-3 (124 and 68 mWh cm-2) and power density values of
131 and 85 mW cm-3 (1.70 and 1.28 mW cm-2) for PANI/Au/Fe3O4 and PANI/Au/Fe3O4@Yne
respectively. To our knowledge this is the first time that AuNP–modified magnetite nanoparticles are
used in supercapacitors preparation.(1) (2)
REFERENCES
(1): Ilaria Ragazzini, Barbara Ballarin, Elisa Boanini, Maria Cristina Cassani, Luigi Montalto, Paolo
Mengucci, Daniele Nanni, Chiara Parise, Daniele Rinaldi, Nicola Sangiorgi, Alessandra Sanson,
submitted article (Electrochimica acta), 2019.
(2): Structure, morphology and magnetic properties of Au/Fe3O4 nanocomposites fabricated by a soft
aqueous route, B. Ballarin, M. C. Cassani, D. Nanni, C. Parise, D. Barreca, G. Carraro, A.
Riminucci, I. Bergenti, V. Morandi, A. Migliori,.E. Boanini, Ceram. Int., 2019, 45, 449 – 456.
Figura 1: SEM image of the composite material
P51
ADVANCES IN THE SET-UP OF A FLUORESCENCE-ANISOTROPY ASSAY FOR THE SEARCH OF NOVEL INHIBITORS OF THE TEAD-4 COMPLEXES
Filippo Romito(a), Lorenzo Tagliazucchi(a), Cecilia Pozzi (b), Stefano Mangani(b),, Ludovica Lopresti(b), Glauco Ponterini(a) Maria Paola Costi(a)
(a) Department of Life Science, University of Modena and Reggio Emilia (b) Department of Pharmaceutical Science, University of Siena, It
Background. TEAD-4 is a protein of the transcriptional enhancer factor family known as TEA (TEAD-4 = TEA domain family member 4). This is found at the end of the Hippo pathway; when activated, it shows antiproliferative and proapoptotic properties. Such a pathway is made of consecutive cytoplasmatic kinases, whose main feature is the phosphorylation, from Lats1/2, of a regulative protein known as YAP. This happens every time the Hippo pathway is activated. Should this be inactive, YAP would be able to migrate inside the nucleus, bind TEAD-4 and activate it, allowing transcription of genes regulative of cellular proliferation. This pathway is fundamental in regulating the growth of mammalian organs; a small change in this process (such as changes to the main proteins responsible for the kinasic core) leads to a failure in phosphorylation of YAP, thus allowing solid tumor formation to happen. The main objective of this study is to interfere with the interaction between YAP and TEAD to halt cancer progression[1]. YAP interacts with TEAD with three main mechanisms: a strand-strand interaction (antiparallel β-sheet), a triple α-helix with a highly conserved LXXLX motif and a twisted-coil region that comprises an Ω loop, which occupies a highly hydrophobic region[2].Therefore, TEAD-4 inhibitors represent a promising therapeutic strategy to address unmet medical needs in antiblastic medicine, above all colorectal adenocarcinoma, breast cancer and falloppian tube carcinoma. Very few inhibitors have been published and are available for drug discovery development. Objectives of the present project is the discovery and development of new TEAD binders affecting YAP-TEAD interactions showing anticancer activity. Within the project a novel HIT series was identified. The communication topic is related to TEAD recombinant protein extraction and purification and to the target-inhibitor interaction assay set-up. Results. For protein production, competent BL21 E. coli cells, were transformed with the PGEX plasmid and harvested in an adequate growth medium, then treated with isopropyl β d-1-thiogalactopyranoside to induce GST-TEAD4 transcription through lac operon activation. The protein suspension in the cell lysate obtained by sonication was submitted to an FPLC purification using GTS-HiTrap™FF, followed by cleavage by thrombin to separate the recombinant protein from the GST tag. The collected eluate was run on SDS page to evaluate the amount of tag free TEAD. Although a small amount of target protein was recovered, this was characterized and a fluorescence-ansotropy displacement assay was set-up and used on the GST-TEAD4 complex and then on the purified TEAD4, after thrombin linker hydrolysis. Conclusions and future developments. The results obtained show a higher amount of TEAD4 protein obtained, after thrombin cleavage compared with previous purification experiments. The first step to set up the displacement assay was successful as it shows a concentration dependent increase of anisotropy when the protein was added to the fluorescent inhibitor S049 in the sample cell. This
REFERENCES 1 Smith A.S., R. B Sessions et al. Antiproliferative and antimigratory effects of a novel YAP-TEAD interaction inhibitor identified using in silico molecular docking, Journal of Medicinal Chemistry, 2019; 62,3, 1291-1295 2 Elisi G. M., Santucci M, D’Arca D, Lauriola A, Marverti G, Losi L, Scalvini L, Bolognesi M. L, Mor M, Costi M.P, Repourposing of Drugs Targeting YAP-TEAD Functions, Cancers 2018 Sept 14, 10(9)
P52
indication may suggest an effective binding between the two molecules, which however will need
further experiments for confirmation and will be presented in the poster presentation.
STRONTIUM AND ZINC SUBSTITUTION IN β-TRICALCIUM PHOSPHATE
Katia Rubini
,(a) Massimo Gazzano,(b) Carlo Nervi,(c) Michele Chierotti,(c) Roberto Gobetto,(c)
Elisa Boanini, (a) and Adriana Bigi (a)
a) Department of Chemistry “Ciamician”, University of Bologna, Italy b) ISOF-CNR, Bologna, Italy c) Department of Chemistry, University of Torino, Italy [email protected] β-tricalcium phosphate (β-TCP) is one of the most common bioceramics, widely applied in bone cements and implants. It represents the stable form at temperatures lower than 1120°C. Its stability is second only to that of hydroxyapatite under most biological conditions.[1] Calcium substitution with bivalent ions seems to play an important role in the formation of hydroxyapatite and β-TCP. [2] In this paper we investigated the structural modifications induced on β-TCP structure by functionalization with two bivalent cations of great biological interest, namely strontium and zinc, in order to clarify the structural modifications induced by ionic substitution. The results of X-ray diffraction analysis indicate that zinc can substitute for calcium into β-TCP structure up to about 10 at%, whereas strontium substitution occurs up to about 80 at%. The results of Rietveld refinements indicate that Zn occupies preferentially the octahedral Ca(5) site. Furthermore Zn presence provokes a reduction of the cell parameters, a shift of the solid-state 31P NMR resonances, and a general disorder of β–TCP structure as shown by the broadening of the ATR-FTIR bands. On the contrary, the relatively small Ca(5) site is never occupied by strontium, which shows a preference for Ca(4) site, provokes an increase in cell parameters and a displacement of the phosphate vibration modes in ATR-FTIR bands, in agreement with its larger ionic radius with respect to calcium. Moreover, a relatively high content of strontium provokes a slight modification of the β-TCP structure into the more symmetric β’-TCP structure. [3] These results are due to geometrical reasons, in fact β-TCP structure can be described as a regular assembly of two kinds of columns in which Ca atoms and phosphate tetrahedra are stacked. As shown in Figure 1, the unit cell view down c-axis allows to identify A-type columns filled with Ca(4), Ca(5) and P(1) whereas B-type columns contain Ca(1), Ca(2) Ca(3) and P(2) and P(3). A-type columns are surrounded only by B-type ones. These findings provide further, more detailed, information about the influence played by ionic substitution on β-TCP structure.
REFERENCES [1] R.A. Young, W.E. Brown,in Biological Mineralization and demineralization, G.H. Nancollas, Ed., Springer-Verlag,
Berlin, 1982. [2] E. Boanini, M.Gazzano, A.Bigi, Acta Biomater. 2010, 6, 1882–1894. [3] E. Boanini, M. Gazzano, C. Nervi, M.R. Chierotti, K. Rubini, R. Gobetto, A. Bigi, J. Funct. Biomater. 2019, 10, 20;
doi:10.3390/jfb10020020
Figure1. Unit cell view down c-axis allows to identify A- and B-type columns (here Ca atoms are not present for the sake of clarity).
P53
DEVELOPMENT OF CIPROFLOXACIN-FATTY ACIDS
CONJUGATES FOR CHLAMYDIA INFECTION
Alessandra Salerno*(a)
, Antonella Marangoni (b)
, Andrea Carolina Entrocassi (c)
, Marcelo
Rodríguez Fermepin (c)
, Maria Laura Bolognesi (a)
(a)
Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Via
Belmeloro 6, 40126, Bologna, Italy. (b)
Department of Experimental, Diagnostic and Specialty Medicine,
University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. (c)
Faculty of Pharmacy and Biochemistry,
University of Buenos Aires, Junin 956, 1113, Ciudad de Buenos Aires, Argentina.
ABSTRACT Chlamydia Trachomatis (CT) is a Gram-negative bacterium responsible for one of the most common
sexually transmitted disease, especially in developing countries and among fragile populations. The disease
affects the urogenital tract and might lead to infertility, conatal infection and facilitate other virus
transmission (HIV or human papillomavirus). Most antibiotics only target the reproductive stage of CT,
while the persistent form of the bacteria, non-replicative and latent for years, is less sensitive to antibiotics
and characterized by the presence of elementary bodies (EBs). [1] Although different families of drugs are
currently in use for Chlamydia, some aspects of the treatment are still problematic: (i) the use of antibiotics,
azithromycin or doxycycline, may increase the occurrence of other contextual pathogen; (ii) the treatment of
the rectal onset of Chlamydia, is more incline to failure due to low
compliance; (iii) no antibiotics have shown any activity on the
persistent form. [2] All these elements highlight the urgency to
develop a new treatment against Chlamydia, in particular for the
persistent form and rectal infections. For this reason, in
collaboration with the University of Buenos Aires (Argentina), we
rationally designed and plan to synthesize, a series of
ciprofloxacin-fatty acids conjugates (CP-FA) combining in a single
molecule the fluoroquinolone structure with capric and lauric acid,
two lipids effective on CT. Ciprofloxacin affects CT replication
inhibiting the bacterial DNA gyrase and also acting as iron
chelator, fundamental ion for bacterial growth. On the other hand,
these fatty acids have been shown to kill the bacteria by disrupting
EB membranes.[3] Based on these evidences, we may target the
conjugate especially on the persistent form of CT. Thus, the aim of
this project is to obtain a series of single chemical entities with an
increased antimicrobial effect, obtained by a synergic activity. This
approach will be realized by directly linking the fatty acid to the
piperazine moiety of ciprofloxacin, while another strategy will
exploit a cleavable linker (e.g. glycolic acid or glycine) able to be
hydrolysed in vivo, and release the starting compounds. (Figure 1)
According to the multi-target strategy principles, targeting multiple mechanisms fundamental for the
bacteria’s life via a single molecule, would not endanger patient compliance, and could offer benefits in
slowing development of antibiotic resistance. Nevertheless, the increase of lipophilicity, thanks to the alkyl
chain, could ameliorate the chemical properties and the overall pharmacokinetics of the parent antibiotic,
allowing to reach higher intercellular concentration. [4] We also assume that the increased lipophilicity of
the CP-FA conjugates may be exploited to create rectal and topic formulations. Indeed, rectal absorption
strongly depends on the logP coefficient, and the optimal value is in accordance with the predicted logP of
our compounds. In conclusion, CP-FA conjugates have been designed to comply with current medical needs
about chlamydia and the synergic activity will be tested, thanks to the Argentinian collaboration, on different
Chlamydia strains and persistent forms, while the better lipophilicity, will help not only in bioavailability,
but also in possible rectal or topic formulation.
REFERENCES [1] Bergsson, G. et al. doi: 10.1128/AAC.42.9.2290
[2] Chrzanowska, A., et al. doi: 10.1016/j.ejmech.2019.111810
[3] Mpiga, P. et al. doi: 10.1016/j.micres.2005.04.004
[4] Vu, T.H., et al. doi: 10.1016/j.bioorg.2018.10.033
Figure 1. Conjugates design strategy
P54
CURCUMIN-BASED NEUROPROTECTIVE AGENTS
TARGETING NRF2 AND GSK-3β
Francesca Seghetti(a)
, Rita M. C. Di Martino(a)
, Letizia Pruccoli(b)
, Maria Paglione(c)
, Elia Di
Schiavi(c)
, Angela Rampa(a)
, Silvia Gobbi(a)
, Alessandra Bisi(a)
, Ana Martinez(d)
, Andrea
Tarozzi(b)
, and Federica Belluti(a)
a) Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via
Belmeloro 6, 40126-Bologna, Italy; b) Department for Life Quality Studies, Alma Mater
Studiorum-University of Bologna, Corso D'Augusto 237, 47921-Rimini, Italy; c) Institute of
Biosciences and BioResources, IBBR, Department of Biology, Agriculture and Food Science
National Research Council, CNR, Via Pietro Castellino 111, 80131-Naples, Italy; d) Centro de
Investigaciónes Biológicas, CSIC, C/Ramiro de Maeztu 9, 28040-Madrid, Spain.
ABSTRACT
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, which
pathogenesis is found to be associated with deregulation of several networked pathways involved
in neuroinflammation, oxidative stress, and mitochondrial dysfunction. Nowadays, owing to the
multifactorial character of the diseases, no effective therapies are available, thus underlying the
need for new strategies. Overexpression of the enzyme glycogen synthase kinase-3β (GSK-3β) and
downregulation of nuclear factor erythroid 2 related factor 2 (Nrf2)/ARE pathway are responsible
for a decrease in antioxidant defence effects. The involvement of GSK-3β in oxidative stress-
induced neuronal death is related to its capability to down-regulate Nrf2; this negative correlation
suggests as Nrf2 induction coupled to GSK-3β inhibition, by decreasing neuronal sensitivity to
oxidative stress, could likely represent a valuable therapeutic approach for PD cure [1]. Based on
these premises, a set of hybrid molecules were designed by combining our previously reported
curcumin-based GSK-3β inhibitors [2] with diethylfumarate (DEF) [3], a potent Nrf2 inducer. The
newly synthetized molecules showed a peculiar modulation of Nrf2 and/or GSK-3β and would
represent molecular tools to shed light on the interplay between these two interconnected targets.
REFERENCES [1] I. Gameiro, P. Michalska, G. Tenti, A. Cores, I. Buendia, A. I. Rojo, N. D. Georgakopoulos, J. M. Hernandez-
Guijo, M. T. Ramos, G. Wells, M. G. Lopez, A. Cuadrado, J. C. Menendez, R. Leon, Scientific Reports 2017, 7.
[2] R. M. C. Di Martino, A. De Simone, V. Andrisano, P. Bisignano, A. Bisi, S. Gobbi, A. Rampa, R. Fato, C.
Bergamini, D. I. Perez, A. Martinez, G. Bottegoni, A. Cavalli, F. Belluti, Journal of Medicinal Chemistry 2016, 59,
531-544.
[3] A. J. Wilson, J. K. Kerns, J. F. Callahan, C. J. Moody, Journal of Medicinal Chemistry 2013, 56, 7463-7476.
P55
TWO-TERMINAL PORTABLE DEVICE FOR DETECTING
GASEOUS AMMONIA
Martina Serafini(a), Federica Mariani(a), Erika Scavetta(a), Isacco Gualandi(a), Domenica
Tonelli(a), Francesco Basile(a)
(a) University of Bologna, viale Risorgimento, 4 [[email protected],
[email protected], [email protected], [email protected],
[email protected], [email protected]]
ABSTRACT
Due to the growing role of ammonia in the industrial area and the increasing gas emissions, it is
necessary to face the needs of protecting the environment and the health of living beings when
exposed to this chemical. To this purpose, sensitive portable devices that provide highly accurate
quantifications in situ are becoming more and more interesting1. The most commonly proposed
devices display several problems related to the high cost, complex readout electronics and high
energy consumption. This contribution describes a new sensor that is inspired by the outstanding
performances exhibited by the organic electrochemical transistors (OECTs) based on PEDOT:PSS
(poly(3,4-ethylenedioxythiophene):polystyrene sulfonate), for the detection of analytes in aqueous
solutions. A novel class of electrochemical sensors has been proposed in literature2 to detect Cl-, Br-
, I- and S2- in aqueous solutions. These devices combine the easy readout electronics, the intrinsic
signal amplification and the low energy supply typical of OECTs, with a simplified geometry that
exploits only two electrical terminals. A PEDOT:PSS film, which is
deposited between two gold tracks, is first electrochemically coated by IrO2
particles3, to provide the sensitization to pH changes. Then a solid hydrogel
is deposited by dip coating to realize an interface between the sensing
material and the surrounding environment, where ammonia gas detection
must be performed. The deposition and characterization parameters of the
synthesized particles and of the resulting composite material, together
with the correct formulation of the gel substrate for an effective solid-
gas interface are thoroughly evaluated. Moreover, the attention is focused on the optimization of the
electrochemical signal, with special regard to repeatability, reproducibility of measurements,
response time and limit of detection. As a result, the optimization of a two-terminal electrochemical
sensor for the quantification of gaseous ammonia is achieved, which, thanks to its geometry, is
particularly suited for wearable applications in the field of smart textiles.
REFERENCES 1. Van Damme, M. et al. Industrial And Agricultural Ammonia Point Sources Exposed. Nature 564, 99–103
(2018).
2. Gualandi, I. et al. Nanoparticle gated semiconducting polymer for a new generation of electrochemical sensors.
Sensors Actuators, B Chem. 273, 834–841 (2018).
3. Zhao, Y. et al. A high yield synthesis of ligand-free iridium oxide nanoparticles with high electrocatalytic
activity. J. Phys. Chem. Lett. 2, 1–3 (2011).
Figure 1. Optimized
two-terminal sensor
P56
FROM INTRA- TO INTERMOLECULAR POLYCYCLIZATION
OF DIENYNES
Andrea Serafinoa, Giovanni Maestria*
aDepartment SCVSA, University of Parma, Parco Area delle Scienze 17/A, 43124, Parma, Italy,
Photochemical reactions contribute in a significant way to the existing repertoire of carbon–carbon
bond‐forming reactions by allowing access to exceptional molecular structures that cannot be
synthesized by conventional means1. This approach allows to obtain a wide range of polycyclic
compounds from easily accessible reagents. In a previous work a series of complex tetracyclic
frameworks have been obtained from the corresponding linear dienynes2. The reaction enables the
creation of four new carbon-carbon bonds and six contiguous stereocenters. Currently ongoing
developments focus on the extension of this intramolecular reactivity to an intermolecular fashion.
(1) Chen, J.; Hu, X.; Lu, L.; Xiao, W.; “Exploration of Visible-Light Photocatalysis in Heterocycle Synthesis and
Functionalization: Reaction Design and Beyond” Acc. Chem. Res, 2016, 49 (9), 1911-1923
(2) Lanzi, M.;Santacroce, V.; Balestri, D.; Marchiò, L.; Bigi, F.; Maggi, R.; Malacria, M. and Maestri G.;
“Visible-Light Promoted Polycyclizations of Dienynes” Angew. Chem. Int., 2019, 58 (20), 6703-6707
P57
ADVANCED CHACTERIZATION TECHNIQUE FOR WINE
Leonardo Settia, Cristina Minguillónc, Giuseppe Montevecchia,b, Francesca Masinoa,b, Davide
Bertellia, Andrea Antonellia,b
aUniversità degli studi di Modena e Reggio Emilia – Dipartimento di Scienze della Vita, Via
Università 4, Modena. E-mail: [email protected], [email protected],
[email protected], [email protected], [email protected]
bCentro di ricerca interdipartimentale per il miglioramento e la valorizzazione delle risorse
biologiche agro-alimentari BIOGEST-SITEIA, Piazzale Europa 1, Reggio Emilia
cUniversitat de Barcelona, Campus de l’Alimentaciò de Torribera, Prat de la Riba, 171, 08921 Santa
Coloma de Gramenet. E-mail: [email protected]
ABSTRACT
Minor grape varieties are widespread in all Emilia-Romagna region for both white and red wines
winemaking. These varieties represent an important biodiversity source to increase the high-quality
wine production [1]. The wines produced with the ancient varieties Bertinora, Caveccia, Festasio,
Melara, Rossiola, Vernaccia del viandante, Vernaccina and Veruccese were analysed and compared
with Italian and Spanish commercial wines. The dataset was composed by 34 wine samples (20 red
and 14 white wines). The analyses for wine characterization were performed by using a 1H-NMR
analysis with a 400 MHz Bruker system at a temperature of 300 K with T2 filter. A pre-freezing
process at -80°C and an overnight lyophilization was carried out for 1 mL of each sample [2]. Then,
400 µL of D2O, 140 µL of buffer solution at pH 4.00 (sodium oxalate), and 60 µL of internal
standard, IS (TSP 5mM) were added [3]. All the spectra were processed with the MNova version
10.0 software (Mestrelab Research, Santiago de Compostela, Spain). The principal component
analysis (PCA) was carried out with the Statistica version 8.0 software (StatSoft Inc., Tulsa, OK,
USA). Beside the lyophilization, the main components of wine, such as glycerol, non-volatile acids,
and residuals of ethanol and sugars, represented the most intense signal in the spectra (3 – 5 ppm).
Nevertheless, the low signal region at 7 ppm, where all the molecules with aromatic rings
(anthocyanins and flavonoids) are present, showed appreciable differences. In particular, white
wines separated from the red wines along the PC1 component, while white wines showed
differences along the PC2 component (Figure 1). Indeed,
Vernaccina (19), Bertinora (20), Vernaccia del viandante
(23) and Melara (22) Pignoletto from Campegine winery
(33-34) showed similar characteristics. By contrast,
Pignoletto white wine from Castelfranco E. winery (1-5)
was separated completely from other white wines, such as
the Caveccia (24), Albariño (17) and Gewürtztraminer
(16). Regarding red wines, which were gathered in the
negative side of the PC1 component, Festasio (25) showed
similar characteristics to Lambrusco Reggiano (7-8),
while Veruccese (18) and Rossiola (21) were separated in
the positive side of the PC1 component.
REFERENCES [1] Mattivi, F., Zulian, C., Nicolini, G., Valenti, L., 2002. Wine, Biodiversity, Technology, and Antioxidants. Ann. N.Y.
Acad. Sci. 957, 37–56.
[2] Viggiani, L., Castiglione Morelli, M.A. 2008. Characterization of Wines by Nuclear Magnetic Resonance: A Work
Study on Wines from the Basilicata Region in Italy. J. Agric. Food Chem., 56, 8273–8279.
[3] Son, H., Hwang, G., Ahn, H., Park, W., Lee, C., Hong, Y. 2009. Characterization of wines from grape varieties
through multivariate statistical analysis of 1H NMR spectroscopic data. Food Res. Int. 42, 1483-1491.
Figure 1. Score plot of the analysed dataset.
P58
LIPID BASED NANOPARTICLES-CONTAINING
-TOCOPHEROL FOR SKIN APPLICATION
Maddalena Sguizzato1,2
, Elisabetta Esposito1*, Supandeep Singh Hallan
1, Markus Drechsler
3
Giuseppe Valacchi2 and Rita Cortesi
1,*
1 Department of Chemical and Pharmaceutical Sciences (SCF), University of Ferrara, Ferrara, Italy
2 Animal Sciences Dept., NC State University, Plants for Human Health Institute, Kannapolis, USA
3 BIMF / Soft Matter Electronmicroscopy, University of Bayreuth, Germany
Recently many antipollution dermocosmetics have been produced with the aim to defend the skin
against prolonged and repetitive daily exposure to pollutants. Nevertheless, this strategy offers a
short-term improvement of skin barrier function. In this respect there is a need for an efficacious
product, endowing skin protection from pollutants in long-term exposure, as well as for antipollution
test methods suitable for assessing product efficacy and safety [1].
This study focuses on the production of lipid nanoparticles for cutaneous antioxidant delivery.
Indeed, several molecules, such as α-tocopherol have been shown to improve skin condition and even
counteract the effects of exogenous challenges such as smoking on skin aging. Particularly this work
describes the design and development of lipid nanoparticles containing α-tocopherol as model
antioxidant agent aiming at protection of the human skin against pollutants. Namely, solid lipid
nanoparticles (SLN) and nanostructured lipid carriers (NLC) were prepared using different lipids
(tristearin, compritol, precirol or suppocire) in the presence or in the absence of caprylic/capric
triglycerides. The formulations were characterized in term of size, morphology, encapsulation
efficiency, in vitro cytotoxicity and protection against cigarette smoke.
As compared to SLN, NLC enabled a reduction on the
agglomerate formation and a control on size stability,
suggesting their suitability for antioxidant loading.
Antioxidant encapsulation efficiency was evaluated by
HPLC upon disaggregation of nanostructured lipid carriers.
The external and inner structures of
α-tocopherol-containing NLC were analyzed by cryogenic
transmission electron microscopy and x-ray spectroscopy,
respectively. Apart from suppocire, leading to formation of
spherical vesicles, the other lipids resulted in irregular
shaped nanoparticles. A doubling in the lipid phase amount
enabled to double the loading within the nanoparticles,
controlling the drug stability up to 3 months.
Tristearin based nanostructured lipid carriers loaded with
α-tocopherol were selected for ex-vivo studies since they
displayed better physico-chemical properties as compared to the other NLC compositions. Human
skin explants were treated with α-tocopherol loaded nanostructured lipid carriers and then exposed to
cigarette smoke, afterwards protein levels of the stress inducible enzyme heme oxygenase were
analyzed in skin homogenates. Interestingly, it was found that the pretreatment avoided heme
oxygenase upregulation, suggesting a protective effect of the nanoparticles.
REFERENCES [1] N. Mistry. Cosmetics 2017, 4, 57. doi:10.3390/cosmetics4040057
Figure 1. Summary of the produced lipid
nanoparticles
P59
Towards highly performing lithium-metal battery with glyme solution
and olivine cathode
Shuangying Wei1, Shoichi Inoue
2, Daniele Di Lecce
1, Zhenguang Li
2, Yoichi Tominaga
2,*, Jusef
Hassoun1,3,*
1 University of Ferrara, Department of Chemical and Pharmaceutical Sciences, Via Fossato di Mortara
17, 44121, Ferrara, Italy 2 Tokyo University of Agriculture and Technology, Graduate School of Bio-Applications and Systems
Engineering (BASE) 2-24-16, Naka-cho, Koganei-shi, Tokyo 184-8588, Japan
3 National Interuniversity Consortium of Materials Science and Technology (INSTM) University of
Ferrara Research Unit, University of Ferrara, Via Fossato di Mortara, 17, 44121, Ferrara, Italy.
e-mail: [email protected]
The lithium-metal electrode has a theoretical specific capacity as high as 3860 mAh g
−1 (vs. 372 mAh g
−1
for graphite), the lowest electrochemical potential (3.040 V vs. SHE compared to 2.84 V vs. SHE for
graphite) and a density of 0.59 g cm−3
(vs. 2.25 g cm−3
for graphite). Glyme-based electrolytes have
demonstrated suitable Li+ transport and adequate electrochemical stability window for battery application,
higher flash point, as well as tunable chemical and physical properties by changing the chain length [1]
. It
is widely demonstrated that LiNO3-containing electrolytes may form a uniform and stable anode
passivation layer, which can mitigate the parasitic reactions in the cell and limit the lithium dendrite
growth.
We investigate accordingly six LiNO3-containg solutions as a safe electrolyte for an efficient lithium
metal battery using an olivine based LiFePO4 (1C = 170 mA g−1
) cathode. Thus, the solutions exhibited
room-temperature ionic conductivity within 10−3
and 10−2
S cm−1
and lithium transference number higher
than 0.6 (Figure 1). Cyclic voltammetry suggested an electroreduction process of LiNO3 between 1.7 and
1.4 V vs. Li+/Li which led to a lithium/electrolyte interphase with low resistance (ranging from 20 to 30
Ω) after 1 month of cell aging and lithium plating/stripping for prolonged cycling. An oxidative stability
over 4.3 V vs. Li+/Li ensured promising electrochemical performances in Li/LiFePO4 cells with reversible
capacity of the order of 150 mAh g−1
at a C/3 rate (Figure 2).
Hence, the above results suggest the possible applicability of glyme-based, LiNO3-containing solutions in
high-energy lithium-metal batteries.
Figure. 1 Temperature dependence of the ionic conductivity. Figure 2 Voltage profiles of lithium cell.
References
[1] D. Lecce, L. Carbone, V. Gancitano, J. Hassoun "Rechargeable lithium battery using non-flammable
electrolyte based on tetraethylene glycol dimethyl ether and olivine cathodes ", Journal of Power Sources
334 (2016) 146-153.
[2] F. Qiu, X. Li, H. Deng, D. Wang, X. Mu, P. He, H. Zhou "A Concentrated Ternary-Salts Electrolyte
for High Reversible Li Metal Battery with Slight Excess Li ", Advance Energy Mater. 9 (2019) 1803372.
P60
IONIC SUBSTITUTIONS IN THE CRYSTAL STRUCTURE OF
DICALCIUM PHOSPHATE DIHYDRATE
Francesca Silingardia, Katia Rubini
a, Massimo Gazzano
b, Adriana Bigi
a, Elisa Boanini
a
a Dipartimento di chimica Giacomo Ciamician, Università di Bologna, Via Selmi 2, Bologna;
b ISOF-CNR, Bologna; [email protected]
ABSTRACT
Dicalcium phosphate dihydrate (Ca2HPO4·2H2O, DCPD), also known as the mineral brushite, is a
white solid with a monoclinic lattice (space group Ia). The crystals have a thin plates morphology
with 010 as the main plane. The crystalline structure consists of parallel CaHPO4 chains between
which lattice water molecules are intercalated. It is the first product of the crystallization of calcium
phosphate at low pH value (6.5) and low temperature (40°C).[1]
DCPD is highly soluble and it
hydrolyses in Octacalcium phosphate (Ca8H2(PO4)6·5H2O) and/or in Hydroxyapatite
(Ca5(PO4)3(OH)), depending on experimental conditions. When it is heat treated (125°C) it converts
into its anhydrous form, known as Monetite (CaHPO4).[2]
Ionic substitutions can influence DCPD
structural stability, crystal growth and also morphology and dimensions of crystals.[1]
This work
focuses on ions (II) such as Strontium, Manganese, Magnesium, Cobalt and Zinc, that have been
selected due to their biological role.[3]
The aim of this study is to verify the ability of these ions to
replace the calcium ion in DCPD structure, the obtainable replacement interval and the following
structural modifications. For this purpose, DCPD crystals were prepared by direct synthesis in
aqueous solution containing increasing concentrations of
substituent ion. The products obtained were characterized
by chemical (EDAX), diffractometric (X-rays diffraction),
spectroscopic (IR) analysis and scanning electron
microscopy (SEM).
The selected ions succeed in replacing calcium, although in
different amounts. It is possible to synthesize DCPD in the
presence of Sr up to a 60%at in solution, meanwhile for the
other ions the percentage is lower. Ionic substitution affects
DCPD crystallization both inhibiting precipitation and
promoting the formation of other phases. It also affects cell
parameters leading to variations in dimensions: using Sr
that has a bigger ion radius (Ca-0.099nm, Sr-0.118 nm) the
cell volume increases, whereas substituting ions with a smaller radius (Zn 0.075 nm, Mn 0.080nm,
Mg 0.072nm and Co 0.073nm) provoke a cell volume decrease. Furthermore, morphology of
crystals is deeply affected by the presence of foreign ions, which also induce aggregation. (Figure
1)
REFERENCES
[1] H.E. Lundager Madsen, “Influence of foreign metal ions on crystal growth and morphology of brushite (CaHPO4,
2H2O) and its transformation to octacalcium phosphate and apatite”. Journal of Crystal Growth 310 (2008) 2602–2612
[2] J.C. Elliott, “Structure and chemistry of the apatites and other calcium orthophosphates”. Elsevier (1994)
[3] E. Boanini, M. Gazzano, A. Bigi, “Ionic substitutions in calcium phosphates synthesized at low temperature”. Acta
Biomaterialia 6 (2010) 1882-1894
Figure 1: SEM image of DCPD
P61
DESIGN OF AN IMPLANTABLE POLYMERIC DUAL DRUG
DELIVERY SYSTEM FOR THE TREATMENT OF SARCOMAS
Francesca Tacchi(a)
, Giulia Rossi(b)
, Maria Letizia Focarete(c)
, Lisa Elviri(d)
a) Università di Bologna, Dipartimento di Chimica G. Ciamician, Via Selmi 2,
[email protected], b) Univesrità di Bologna, Dipartimento di Chimica G. Ciamician, Via
Selmi 2, [email protected], c) Università di Bologna, Dipartimento di Chimica G. Ciamician,
Via Selmi 2, [email protected], c) Università di Parma, Dipartimento di Scienze degli
Alimenti e del Farmaco, Parco Area delle Scienze 27/A, [email protected]
ABSTRACT
Cancer is the second leading cause of death worldwide, accounting for over 9.6 million deaths in
2018 according to the World Health Organization. [1] Because of this, different cancer treatments
have been developed over the years, among which chemotherapy is one of the most common.
However, chemotherapy presents many disadvantages, such as low specificity in targeting cancer
cells, poor intracellular uptake and fast excretion of the antitumor drug. [2] A promising alternative
to standard chemotherapy is the development of systems for the controlled release of antitumor
drugs. Among these drug delivery systems, implantable anticancer platforms are of particular
interest.
In this presentation a novel bioresorbable drug delivery system, implantable after the surgical
resection of sarcomas, will be presented. The device has a layered structure formed by an internal
hydrogel layer and different external electrospun mats, and it has the dual aim of destroying any
residual tumoral cells and promoting tissue regeneration. In order to obtain this effect, the device is
designed to release Epirubicine, an antitumoral agent, from the internal hydrogel layer over a three
days period and Diclofenac Potassium (DK), an antinflammatory drug, from the electrospun mats
over a period of seven days. Different materials have been used to obtain differentiated release
profiles. In particular, for the external electrospun layers, we considered both a blend of poly(L-
lactic acid) (PLLA) and Pluronic F127 (90:10 w/w), and a random copolymer of poly(lactic acid)
and poly(ε-caprolactone) in molar ratio 70:30 (P(LACL) 70:30), whereas for the hydrogel layer, we
considered ionically crosslinked sodium alginate and photocrosslinked gelatin methacryloyl
(GelMa).
P(LACL) 70:30 and ionically crosslinked alginate were found to be unsuitable materials, as in the
case of P(LACL) the addition of DK to the fibers causes the formation of a film-like morphology,
which can hinder cellular attachment and proliferation, while ionically crosslinked alginate was not
stable when immersed in PBS at 37°C for the intended time of use of three days. GelMa and
PLLA:Pluronic 90:10 were considered suitable materials, as Gelma was stable in PBS for over a
week and the polymeric blend maintained a suitable fibers morphology even after the addition of
DK.
DK release tests showed that, when a proper sequence of the different layers was used, the desired
sustained drug release was achieved over the intended seven days period.
REFERENCES [1] P. Boyle, B. Levin, World Cancer Report, 2008, IARC press, p. 510
[2] S. Senapati, A. K. Mahanta, S. Kumar, P. Maiti, Controlled drug delivery vehicles for cancer treatment and their
performance, 2018, Signal Transduct Target Ther, Vol. 3, 1, online
P62
ADVANCES IN THE SET-UP OF A FLUORESCENCE-ANISOTROPY ASSAY FOR THE SEARCH OF NOVEL INHIBITORS OF THE TEAD-4 COMPLEXES
Filippo Romito(a), Lorenzo Tagliazucchi(a), Cecilia Pozzi (b), Stefano Mangani(b),, Ludovica Lopresti(b), Glauco Ponterini(a) Maria Paola Costi(a)
(a) Department of Life Science, University of Modena and Reggio Emilia (b) Department of Pharmaceutical Science, University of Siena, It
Background. TEAD-4 is a protein of the transcriptional enhancer factor family known as TEA (TEAD-4 = TEA domain family member 4). This is found at the end of the Hippo pathway; when activated, it shows antiproliferative and proapoptotic properties. Such a pathway is made of consecutive cytoplasmatic kinases, whose main feature is the phosphorylation, from Lats1/2, of a regulative protein known as YAP. This happens every time the Hippo pathway is activated. Should this be inactive, YAP would be able to migrate inside the nucleus, bind TEAD-4 and activate it, allowing transcription of genes regulative of cellular proliferation. This pathway is fundamental in regulating the growth of mammalian organs; a small change in this process (such as changes to the main proteins responsible for the kinasic core) leads to a failure in phosphorylation of YAP, thus allowing solid tumor formation to happen. The main objective of this study is to interfere with the interaction between YAP and TEAD to halt cancer progression[1]. YAP interacts with TEAD with three main mechanisms: a strand-strand interaction (antiparallel β-sheet), a triple α-helix with a highly conserved LXXLX motif and a twisted-coil region that comprises an Ω loop, which occupies a highly hydrophobic region[2].Therefore, TEAD-4 inhibitors represent a promising therapeutic strategy to address unmet medical needs in antiblastic medicine, above all colorectal adenocarcinoma, breast cancer and falloppian tube carcinoma. Very few inhibitors have been published and are available for drug discovery development. Objectives of the present project is the discovery and development of new TEAD binders affecting YAP-TEAD interactions showing anticancer activity. Within the project a novel HIT series was identified. The communication topic is related to TEAD recombinant protein extraction and purification and to the target-inhibitor interaction assay set-up. Results. For protein production, competent BL21 E. coli cells, were transformed with the PGEX plasmid and harvested in an adequate growth medium, then treated with isopropyl β d-1-thiogalactopyranoside to induce GST-TEAD4 transcription through lac operon activation. The protein suspension in the cell lysate obtained by sonication was submitted to an FPLC purification using GTS-HiTrap™FF, followed by cleavage by thrombin to separate the recombinant protein from the GST tag. The collected eluate was run on SDS page to evaluate the amount of tag free TEAD. Although a small amount of target protein was recovered, this was characterized and a fluorescence-ansotropy displacement assay was set-up and used on the GST-TEAD4 complex and then on the purified TEAD4, after thrombin linker hydrolysis. Conclusions and future developments. The results obtained show a higher amount of TEAD4 protein obtained, after thrombin cleavage compared with previous purification experiments. The first step to set up the displacement assay was successful as it shows a concentration dependent increase of anisotropy when the protein was added to the fluorescent inhibitor S049 in the sample cell. This
REFERENCES 1 Smith A.S., R. B Sessions et al. Antiproliferative and antimigratory effects of a novel YAP-TEAD interaction inhibitor identified using in silico molecular docking, Journal of Medicinal Chemistry, 2019; 62,3, 1291-1295 2 Elisi G. M., Santucci M, D’Arca D, Lauriola A, Marverti G, Losi L, Scalvini L, Bolognesi M. L, Mor M, Costi M.P, Repourposing of Drugs Targeting YAP-TEAD Functions, Cancers 2018 Sept 14, 10(9)
P63
indication may suggest an effective binding between the two molecules, which however will need
further experiments for confirmation and will be presented in the poster presentation.
RATIONAL DESIGN, SYNTHESIS, AND EVALUATION OF
HYDROXAMATE CHELATORS FOR STABLE
COMPLEXATION OF Zr (IV)
Yuliya Toporivska(a)
, Andrea Baldi(b)
, Remo Guerrini(b)
, Maurizio Remelli(b)
and
Elżbieta Gumienna-Kontecka(a)
(a) University of Wroclaw, Faculty of Chemistry, 14 F. Joliot-Curie,
50-383 Woclaw, Poland (b) University of Ferrara, Dipartimento di Scienze Chimiche e Farmaceutiche, Via Luigi
Borsari 46, 44121 Ferrara, Italy email: [email protected]
Radiometals are radioactive isotopes that can be used for applications in medical
diagnosis, as well as for cancer therapy. If they have suitable emission properties, they can be
used for positron emission tomography (PET). Zirconium-89 (89
Zr), a positron-emitting
radionuclide, possesses excellent physical properties for PET imaging, namely, an ideal 78.41
h half-life and low energy positron (βavg = 395.5 keV) [1,2]. A fundamental critical
component is the chelator, the ligand system that binds the radiometal ion in a tight stable
coordination complex and is also attached to an antibody which can be properly direct the
complex to a desirable molecular target in vivo. Currently, desferrioxamine (DFO) is the
chelator most commonly used to radiolabel biomolecules with 89
Zr; a large number of
antibodies have been labeled with 89
Zr-DFO and used in pre-clinical and clinical studies, in
recent years [3,4]. However, the in vivo stability of the Zr-DFO complex has often proven
insufficient as seen by the accumulation of free, osteophilic 89
Zr in bones 2 to 4 days after
injection of the labeled antibody [4-6]. In order to improve stability of Zr(IV) complexes,
alternative ligands with oxygen-rich donor groups, including hydroxamates, carboxylates,
carbonyls and hydroxyquinolines, have been investigated [1-2]. However, in most cases, there
is lack of information on solution stability constants of complexes with proposed ligands; in
fact, the solution study on the coordination chemistry of such complexes is not trivial, due to
the strong hydrolysis of Zr(IV) (occurring in almost entire pH range) and the lack of spectral
activity of Zr(IV) complexes. On the other hand, the knowledge of the speciation of Zr(IV)
complexes, especially at physiological pH, could provide information concerning the actual
chemical form of the complex in biological media, and this can contribute to a better
understanding of the in vivo speciation and differences in the biological activity.
Here we present a detailed speciation studies of Zr(IV) – DFO system, performed
through a competition method against Fe(III). Additionally, we show the preliminary results
on the synthesis of a novel cyclic hydroxamate chelator for Zr(IV), containing four chelating
units and designed to form Zr(IV) complexes of significantly higher stability than DFO.
The financial supports from the National Science Centre Poland, UMO-2015/19/B/ST5/00413 and from
Ferrara University are gratefully acknowledged.
REFERENCES [1] T. I. Kostelnik and C. Orvig, Chem. Rev., 119, 902−956 (2019).
[2] J. R. Dilworth and S. I. Pascu, Chem. Soc. Rev., 47, 2554-2571 (2018).
[3] M. A. Deri, B. M. Zeglis, L. C. Francesconi and J. S. Lewis, Nucl. Med. Biol., 40, 3-14 (2013)
[4] J. P. Holland and N. Vasdev, Dalton Trans., 43, 9872-9884 (2014).
[5] Y. Toporivska and E. Gumienna-Kontecka, J. Inorg. Biochem., 198, 110753/1-110753/7 (2019).
[6] B. M. Zeglis, J. L. Houghton, M. J. Evans, N. Viola-Villegas and J. S. Lewis, Inorg. Chem., 53, 1880-1899
(2014).
P64
SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL DISPIRO COMPOUNDS AS INHIBITORS OF THE
MITOCHONDRIAL PERMEABILITY TRANSITION PORE
Giulia Turrin(a), Delia Preti(a), Giampaolo Morciano(b), Salvatore Pacifico(a), Tiziano De Ventura(a), Anna Fantinati(a), Valentina Albanese(a), Carlotta Giorgi(b), Paolo Pinton(b) and Claudio Trapella(a). a) Department of Chemical and Pharmaceutical Sciences, Via Fossato di Mortara, 17, University of Ferrara, 44121 Ferrara, Italy b) Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Via Fossato di Mortara, 70, 44121 Ferrara, Italy [email protected] ABSTRACT Recent cardiology studies have reported the role, the function, and the structure of the mitochondrial permeability transition pore (mPTP): the research has shown that its opening plays a key role in the progression of myocardial cell death as well as the reperfusion injury damage (IRI), both involved in ischemia, neurodegenerative illnesses, kidney diseases and others1. Previous very promising results demonstrated how some small spiropiperidinic molecules (in particular PP11) can cause the inhibition of the mPTP opening and so the decreasing of the IRI, due to a very strong interaction with the c-ring2. Based on these considerations, we tried to find some novel compounds able to provide an inhibition of the mPTP opening, with a similar or more powerful effect than the reference compound PP11. We synthesized two series of molecules, having respectively isatin and 5-F-isatine scaffold (known in pharmaceutical chemistry as a good framework in many fields) and a dispiropyrrolidinic structure: this particular type of arrangement confers a very high rigidity to the molecule, so it can interact with the target maintaining its conformation unchanged. The dispiropyrrolidinic moiety was functionalized using various monocyclic and polycyclic ketones (essential for the interaction with aminoacidic residues of the target, in particular with Glu59). We obtained different structures, variously hindered and functionalized; all the compounds were tested using the cobalt2+-calcein assay with HeLa cells and three of these in particular demonstrated to have a very effective inhibition potential of the mPTP opening. From these data, we concluded that the presence of the fluorine (maybe involved in the metabolism protection) and the aromatics elements (for the interaction with the protein) are fundamental for the activity. To investigate more deeply the inhibiting effects and to be certain about the implication in the cardiovascular disease, the three compounds cited above are also been tested on isolated rat hearts, in which the ischemia has been induced: here, the cardioprotection capability of the molecules has been confirmed. REFERENCES [1] Bernardi P., et al., The Mitochondrial Permeability Transition Pore: Channel Formation by F-ATP Synthase, Integration in Signal Transduction, and Role in Pathophysiology. Physiol Rev (2015) 95:1111–1155. [2] Morciano, G., et al., Discovery of Novel 1,3,8-Triazaspiro[ 4.5]decane Derivatives That Target the c Subunit of F1/FO-Adenosine Triphosphate (ATP) Synthase for the Treatment of Reperfusion Damage in Myocardial Infarction, Journal of Medicinal Chemistry, (2018), 61(16):7131-7143
NH
N
O
ONH
N
O
O
NH
N
O
OF
GT4 GT8 GT15
Figure 1. Structure of the most powerful compounds
P65
COMPARISON OF ULTRA-LOW LEVELS OF TOTAL
MERCURY IN TAP WATERS AND BOTTLED MINERAL
WATERS IN A REGION OF SOUTHERN ITALY (CALABRIA)
Massimiliano Vardè(a,b)
, Alessandro Servidio(c)
, Franco Cofone(c)
, Giovanni Vespasiano(d,e)
,
Annalisa Rosselli(f)
, Luisa Pasti(b)
, Alberto Cavazzini(b)
, Carmine Apollaro(d)
a Istituto di Scienze Polari – Consiglio Nazionale delle Ricerche (CNR-ISP), Venezia-Mestre;
b Dip. di Scienze Chimiche e Farmaceutiche, Università degli Studi di Ferrara, Ferrara;
c Istituto di Nanotecnologia – Consiglio Nazionale delle Ricerche (CNR-NANOTEC), Rende (CS);
d Dip. di Biologia, Ecologia e Scienze della Terra, Università della Calabria, Rende (CS);
e EalCUBO (Environment, Earth, Engineering), Università della Calabria (Unical), Rende (CS);
f Dip. di Medicina Sperimentale, Università degli Studi della Campania "Luigi Vanvitelli", Napoli;
E-mail: [email protected]
ABSTRACT
In recent years numerous papers on the determination and speciation of mercury (Hg) in
environmental matrix have been published. These studies are particularly relevant to evaluate the
impact of mercury on ecosystems and human health due to its neurotoxicity and teratogenic effect
[1,2]. Detection of mercury at ultra-trace concentrations is a challenging task, that requires clean lab
facilities, accurate sampling procedures and analytical methods
having very low quantification limit for Hg [2]. In this study, the
potential impact of mercury in drinking water in the Calabria
region, has been evaluated. To reach this goal 81 water samples
between drinking (tap water, TW) and bottled natural mineral
waters (BW), scattered throughout the Calabria region, were
considered for assessment and comparison of their total mercury
(HgT) content. A total of 60 TW samples were collected from
public drinking fountains and private houses/public places,
supplied by municipal pipelines, over five provinces of Calabria.
Commercially available still and sparkling bottled waters (n=21),
randomly selected, were purchased from a supermarket and
commercial activities (bars, restaurants and hotels). Sampling of
TW was performed following the strict criteria suggested in
USEPA method 1669 [3]. Both TW and BW were analyzed using
cold-vapor atomic fluorescence spectrometry (CVAFS) following
USEPA Method 1631 [4]. Levels of this toxic element in all
samples, ranging from sub- to few nanogram per litre, were found well below the European and
Italian regulatory limits set at 1 μg L−1
for both typologies [2,5]. Concentrations of HgT in BW
(LOQ-0.91 ng L-1
) resulted largely lower than those found in TW (0.14-5.57 ng L-1
). Indeed, for
81% of BW we detected HgT between LOQ (<0.09 ng L-1
) and 0.30 ng L-1
, whereas only for 20%
of TW we had Hg at or below 0.30 ng L-1
. Considering the whole dataset, we evaluated HgT results
between TW and BW, and between still and sparkling waters. Total mercury levels of these two
typologies of drinkable water may be attributable to the fact that TW and BW undergo or do not
undergo physical/chemical treatment processes and originate from differences sources [2,5].
REFERENCES [1] Leopold, et al., Methods for the determination and speciation of mercury in natural waters—a review, Anal. Chim.
Acta, 2010, 663, 2, 127-138.
[2] Vardè et al., Ultra-trace determination of total mercury in Italian bottled waters, Chemosphere, 2019, 219, 896-913.
[3] U.S. EPA Method 1669, Sampling Ambient Water for Trace Metals at EPA Water Criteria Levels, July 1996.
[4] U.S. EPA Method 1631, Revision E: Mercury in Water by Oxidation, Purge and Trap, and Cold Vapor Atomic
Fluorescence Spectrometry, August 2002.
[5] Apollaro et al., Comparative geochemical study between the tap waters and the bottled mineral waters in Calabria
(Southern Italy) by compositional data analysis (CoDA) developments, Appl. Geochem., 107, 19-33.
Figure 1. Simplified
hydrogeological map of Calabria.
P66
CARBON MATERIALS FOR THE ELECTROCHEMICAL
DETECTION OF DRUGS OF ABUSE
Fabio Vulcano
a,b, Laura Pigani
a, Chiara Zanardi
a,b, Alessandro Kovtun
b, Andrea Candini
b,
Andrea Liscioc, Emanuele Treossi
b, Vincenzo Palermo
b,d
a) Department of Chemical and Geological Sciences, Università di Modena e Reggio Emilia, Via G.
Campi 103, 41125, Modena, Italy
b) Istitute of Organic Synthesis and Photoreactivity (ISOF), National Research Council of Italy
(CNR), via P. Gobetti 101 – 40129 Bologna, Italy
c) Istitute of Microelectronics and Microsystems (IMM), National Research Council of Italy (CNR),
via del Fosso del Cavaliere 100 - 00133 Rome, Italy
d) Department of Industrial and Materials Science, Chalmers University of Technology, SE-412 96
Gothenburg, Sweden
ABSTRACT
Carbon-based surfaces are used since decades for the electrochemical detection of many organic
species. In particular, the morphology and the surface composition of the electroactive surface play
a crucial role in defining the performance of the resulting electrochemical sensors.
In this work we used different carbon electrodes to detect two important drugs of abuse: morphine,
an opiate used as a sedative and constituting the main metabolite of heroin present on biological
fluids, and 9-tetrahydrocannabinol (THC), which is the main psychoactive component of
marijuana and hashish. They both possess a similar electroactive group, namely a phenol moiety,
which allows their direct electrochemical detection.
We could observe that electrochemical sensors based on electrochemically exfoliated graphene
oxide allows the detection of morphine with particularly high sensitivity and low detection limit.[1]
In order to understand the origin of this peculiar performance, we performed electrochemical tests
with an “ideal” carbon material, namely highly oriented pyrolitic graphite (HOPG). The
electrochemical response of pristine HOPG in presence of morphine was compared with those
obtained at HOPG surfaces containing oxidized moieties, in order to possibly unravel the role of the
chemical composition of the surface in respect to the nanostructured morphology of graphene based
surfaces.
Similar tests were also repeated in the presence of two cannabinoids, namely THC and cannabidiol
(CBD), constituting main psychoactive and not-psychoactive components present in Cannabis
derivatives. Test performed with this ideal carbon-based surface allows us to direct the formulation
of the electrochemical surface to that leading to best selectivity toward the simultaneous
determination of these two cannabinoids when present in the same matrix. In particular, we are
focusing our attention to the use of carbon black and reduced graphene oxide, two nanosized
materials nowadays widely explored in the field of electrochemical sensors.
References
[1] G. Maccaferri et al., Sensor and Actuators B: Chemical, 281 (2019), 739 - 745
P67