XIX GIORNATA DELLA CHIMICA DELL'EMILIA ROMAGNA

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

Abstract delle presentazioni

ORALI

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

[email protected]

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

Abstract delle presentazioni

FLASH

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.

*[email protected]

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

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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.

[email protected]

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:

[email protected]

(d) Lisa Lancellotti, Department of Chemical and Geological Sciences, University of Modena

and Reggio Emilia, via G. Campi 103, 41125 Modena, Italy, Email:

[email protected]

(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

[email protected]

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

Abstract delle presentazioni

POSTER

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

*[email protected]

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

[email protected]

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

([email protected]).

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.

[email protected]

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)

[email protected]

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

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<

SYNTHETICALLY MODIFIED NATURAL BETALAINS

Edoardo Marchini, Stefano Caramori, Arianna Brandolese and Alessandro Massi

University of Ferrara, Via L. Borsari, 46, 44121 Ferrara - Italy

[email protected]

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.

*[email protected]

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.

*[email protected]

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,

[email protected]

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

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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.

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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

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