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Journal of Chromatography A, 1533 (2018) 136–142
Contents lists available at ScienceDirect
Journal of Chromatography A
jo ur nal ho me pag e: www.elsev ier .com/ locate /chroma
ual polyhedral oligomeric silsesquioxanes polymerization
approacho mutually-mediated separation mechanisms of hybrid
monolithictationary and mobile phases towards small molecules
iao Sua, Limin Yanga,∗, Qiuquan Wanga,b,∗
Department of Chemistry & the Key Laboratory of
Spectrochemical Analysis and Instrumentation, College of Chemistry
and Chemical Engineering, Xiamenniversity, Xiamen, 361005,
ChinaState Key Laboratory of Marine Environmental Science, Xiamen
University, Xiamen, 361102, China
r t i c l e i n f o
rticle history:eceived 3 October 2017eceived in revised form7
November 2017ccepted 12 December 2017vailable online 14 December
2017
eywords:ybrid monolithic stationary phaseolyhedral oligomeric
silsesquioxaneeparation mechanismmall moleculeano-LC
a b s t r a c t
Hybrid monolithic stationary phase based HPLC is a typical
example of practices in separation science. Inthis study, we
developed a dual polyhedral oligomeric silsesquioxanes (POSS)
polymerization approachto the preparation of a hybrid monolithic
stationary phase of tri-porous structure and various
surfacechemistry. N-phenylaminopropyl-POSS (PA-POSS) and
glycidyl-POSS (EP-POSS) were exemplified todemonstrate effective
mutually-mediated separation mechanisms of the hybrid monolithic
stationaryphase and mobile phase towards diverse small molecules.
PA-POSS and EP-POSS can be the monomerand/or crosslinker each
other. They were polymerized via the epoxy-ring opening reaction to
formthe poly[(PA-POSS)-(EP-POSS)] (polyPOSS) monolithic stationary
phase of 110.6/164.6 Å3 micropore (asa cube/ball), 10 nm mesopore
and 0.95 �m macropore with the native siloxane cage and
remainingphenyl/epoxy as well as chemically generated
positive-chargeable tertiary phenylamine and hydrophilichydroxyl
groups. Such pore-structure and surface chemistry allow us to
perform the effective separa-tion of targeted small molecules, such
as alkylbenzenes and alkylbenzene ketones, nucleic acid basesand
amino acids, as well as phenols and phenolic acids, under
reversed-phase, HILIC and mixed mode
(polarity, size-exclusion and hydrogen-bonding) by just changing
the molar ratio of POSS-precursors,and the composition and pH of a
mobile phase as well. We believe that the approach developed
hereincan be extended to fabricate other kinds of hybrid monolithic
stationary phases that are suitable for theseparation of
biomacromolecules and chiral molecules when choosing the existed
POSS and/or designingnew POSS with the substituted pendant groups
of different physicochemical properties.
© 2017 Elsevier B.V. All rights reserved.
. Introduction
Today, monoliths are becoming ever more popular as
chro-atographic stationary phases [1]. Their high permeability
and
hus fast separation of targeted analytes, without paying for
theigh back-pressure arising from a small bead-packed
stationary
hase, render them practical usefulness even in a conventionalPLC
system. In general, the organic polymer-based monoliths
hat consist of interconnected microglobules [2] and the
inor-
∗ Corresponding authors: Department of Chemistry & the Key
Laboratory ofpectrochemical Analysis and Instrumentation, College
of Chemistry and Chemicalngineering, Xiamen University, Xiamen,
361005, China.
E-mail addresses: [email protected] (L. Yang),
[email protected]. Wang).
ttps://doi.org/10.1016/j.chroma.2017.12.033021-9673/© 2017
Elsevier B.V. All rights reserved.
ganic silica-based monoliths of mesoporous
skeleton-mediatedbicontinuous porous structure [3] feature the
rapid separationof large biopolymers [4–6] and small molecules [7],
respectively.When a silanized organic and/or an organically
modified siliceousmonomer or crosslinker is used, the resulting
organic-inorganichybrid monolith combines their respective
advantages, to a greatextent, such as wider pH stability, enhanced
structure and surfacechemistry, demonstrating a superior ability
for the faster separa-tion of both small and large molecules
[8–11]. Among the variousorganosilicon compounds, polyhedral
oligomeric silsesquioxane(POSS) is a three-dimensional cubic
nanomaterial with thermallyand chemically robust siloxane cage and
eight pendant organic
arms [12,13]. It is conceivable that the inherent nanoscale
silox-ane cage (sub-nanometer Si···Si cage diagonal and
nanometerdiagonal distance of the pendant arms) can offer native
microp-
https://doi.org/10.1016/j.chroma.2017.12.033http://www.sciencedirect.com/science/journal/00219673http://www.elsevier.com/locate/chromahttp://crossmark.crossref.org/dialog/?doi=10.1016/j.chroma.2017.12.033&domain=pdfmailto:[email protected]:[email protected]://doi.org/10.1016/j.chroma.2017.12.033
-
J. Su et al. / J. Chromatogr. A 1533 (2018) 136–142 137
F prepa(
oplaapApsdhothm,w
ig. 1. Schematic diagram of pore distribution (a), selected POSS
structure (b) andd).
res, and the reactive pendant organic groups undertake
furtherolymerization to form mesoporous skeletons in resulting
mono-
iths. Macropores can be also formed when suitable porogensre
employed. Such POSS-based monoliths are expected to have
tri-porous structure with multifunctional characteristics if
theendant arms have different physicochemical properties (Fig.
1a).ctually, POSS-based hybrid monolithic capillary column was
pre-ared via the free radical polymerization between the
methacrylubstituted-POSS (POSS-MA) and
N-(2-(methacryloyloxy)ethyl)-imethyloctadecylammonium bromide. Such
a monolithic columnad fair mechanical and pH stability and column
efficiency for notnly small molecules but also model proteins as
well as the BSAryptic digested mixture [14]. In a similar way,
various POSS-based
ybrid monoliths appeared using POSS-MA crosslinker, and
theonomers including hydrophilic neutral [15], hydrophobic
alkyl-
perfluoroalkyl- and phenyl-substituted compounds [16–19] asell
as alkyl- or perfluorinated phenyl-substituted ionic liquids
ration of the polyPOSS hybrid monolith (c) as well as the small
molecules studied
[20–22]. Other chemical reaction-induced polymerization, such
asamine-epoxy, thiol-epoxy and thiol-ene reactions [23–28],
werealso employed for initiating a progressive phase separation
pro-cess in order to improve structure homogeneity of the
synthesizedmonoliths with highly ordered 3D skeletal structure. All
thesemonolithic columns [29], however, were prepared using one
POSScrosslinker and a small organic monomer. We hypothesize
thatdifferently chemical modified POSS may be the monomer
and/orcrosslinker each other [30], and thus more regular porous
struc-ture and plentiful surface chemistry can be expected. Herein,
weselected two fully substituted POSS,
N-phenylaminopropyl-POSS(PA-POSS) and glycidyl-POSS (EP-POSS) (Fig.
1b), to demonstratea dual POSS-polymerized hybrid monolithic
approach for the first
time towards the separation of small molecules via the
mutually-mediated separation mechanisms by adjusting the molar
ratio ofPOSS-precursors and the composition and pH of the mobile
phaseused.
-
1 ogr. A
2
2
PUbtiaMhbahMguislC
2
caetpdGlspfit
iawUdmBN(tt
2
cv((paw1bot
38 J. Su et al. / J. Chromat
. Experimental
.1. Chemicals
N-Phenylaminopropyl-POSS (PA-POSS) and glycidyl-POSS (EP-OSS)
were purchased from hybrid plastics (Hattiesburg, MS,SA). The
distances of adjacent Si-Si, planar diagonal Si-Si andody diagonal
Si-Si are respectively 3.1 Å, 4.4 Å and 5.4 Å in bothhe POSSs. The
length of Si-R is 10.4 Å in PA-POSS and 9.0 Ån EP-POSS (Fig. 1b,
calculated from ChemBio3D Ultra 12.0).
(3-minopropyl)trimethoxysilane (APTMS), polyethylene glycol (PEG,w
= 20,000 Da), L-histidine, L-phenylalanine, L-tryptophane, 2,6-
ydroxy benzoic acid, 3,4-hydroxy benzoic acid, 3,5-hydroxyenzoic
acid, sorbic acid, p-hydroxy benzoic acid, benzoic acidnd
alkylbenzene ketones were obtained from Aladdin (Shang-ai, China).
Alkylbenzenes were purchased from Sigma (St. Louis,O, USA).
Cytosine, uracil and thymine were obtained from San-
on (Shanghai, China). HPLC grade acetonitrile (ACN) and
methanolsed were obtained from Merck (Darmstadt, Germany). Water
used
n all the experiments was doubly distilled and purified by a
Milli-Qystem (Millipore, Milford, MA, USA). Other reagents of at
least ana-ytical grade used were bought from Sinopharm Chemical
Reagento., Ltd (Shanghai, China).
.2. Instruments
Fused-silica capillary (75 �m i.d. and 375 �m o.d.) was
pur-hased from Yongnian Refine Chromatography Ltd. (Hebei, China)nd
used to prepare the monolithic capillary columns. The
nano-LCxperiments were carried out on a Prominence Nano LC sys-em
(Shimadzu, Japan) equipped by two Shimadzu LC-20AD Nanoumps, a
Shimadzu CBM-20A system controller, a MU701 UV-VISetector with a 6
nL capillary fiber optic flow cell (Shimadzu-L, Japan) and a micro
valve injector with a 4 nL inner sample
oop (VICI, USA). The Shimadzu LC-solution chromatography
work-tation was used for data acquisition. All the experiments
wereerformed at room temperature (24 ◦C). All the mobile phases
wereltered through a 0.22 �m membrane and degassed under sonica-ion
before use.
The morphology of the polyPOSS capillary columns was stud-ed
using a Zeiss Sigma FE-SEM instrument (Zeiss, Germany). Theverage
mesopore size and Brunauer-Emmett-Teller surface areaere determined
on a Micromeritics Tristar 3020 (Norcross, GA,SA) through nitrogen
adsorption/desorption. The macropore sizeistribution of the
monolith synthesized was measured on a Pore-aster 60 mercury
intrusion apparatus (Quantachrome, Boynton
each, FL, USA). All the IR measurements were carried out on
aicolet IR360 Spectrometer (Thermo Electron, USA). A Vario EL
III
Elementar, Germany) was used for elemental analysis. A SDT
Q600hermo gravimetric analyzer (TA, USA) was used to
characterizehermal stability of the monoliths.
.3. Pretreatment of the capillary columns
Before preparation of the polyPOSS hybrid monolithic
capillaryolumns, inner surface of the capillary was firstly cleaned
and acti-ated for effective attachment of the POSS skeleton using
acetone30 min), H2O (30 min), 1 M NaOH (12 h), H2O (30 min), 1 M
HCl12 h), H2O (30 min) and acetone (1 h) in sequence with a
syringeump, and then dried under a nitrogen stream at room
temper-ture overnight. Subsequently, a 50% APTMS/THF (V/V)
solutionas pumped through the capillary at a flow rate of 3 �L/min
for
h. After both ends of the capillary were sealed with silicone
rub-er septa, the capillary was submerged in an 80 ◦C water
bathvernight. Finally, the capillary was rinsed by acetone to flush
outhe unreacted residuals and dried by a nitrogen stream again.
The
1533 (2018) 136–142
internal surface of such pretreated capillary was modified
withamine groups for anchoring later formed polyPOSS hybrid
mono-lith.
2.4. Preparation of polyPOSS hybrid monolithic capillary
columns
Homogeneous prepolymerization solution consisting of PA-POSS,
EP-POSS and porogens was manually injected into thepretreated
capillary using a syringe, and then both ends of the
filledcapillary were sealed with silicone rubber septa. The filled
capillarywas incubated at 130 ◦C for 18 h in a muffle furnace and
then nat-urally cooled down to room temperature. The obtained
monolithiccolumn was flushed with MeOH using an HPLC pump in order
toremove the unreacted residuals. In parallel, the corresponding
bulkpolyPOSS hybrid monoliths were prepared in glass vial under
thesame conditions for characterizing the prepared polyPOSS
hybridmonoliths. The bulk hybrid monoliths were cut into smaller
pieces,extracted with methanol overnight in a Soxhlet apparatus,
and thendried in a vacuum at 80 ◦C overnight before further
measurements.
3. Results and discussion
3.1. Characterization of the polyPOSS hybrid monoliths
One-pot method via amine-epoxy ring-opening polymerizationwas
applied to prepare the polyPOSS hybrid monolithic capillarycolumns
as we previously did [31,32]. The fabrication process andcondition
can be found in Experimental section, and is schemati-cally
illustrated in Fig. 1c. FT-IR study indicated that the
stretchingvibration peaks at 907 and 847 cm−1 (C O in the epoxy
group) ofEP-POSS and 3410 cm−1 (N H in the aromatic secondary
aminegroup) became unnoticeable, while a broad stretching peak
at3407 cm−1 (O H) appeared in the synthesized polyPOSS
hybridmonolith when the molar ratio of PA-POSS to EP-POSS was
1/1,in addition to the peaks remained at 1600 and 1505 cm−1 (C Cin
the benzene ring), and 1117 cm−1 (the Si O Si in the POSScage),
suggesting the effective ring opening nucleophilic substitu-tion
reaction between the phenylamine in PA-POSS and the epoxyin
EP-POSS. Furthermore, the results obtained from elemental anal-ysis
indicated that C/N ratio increased from 10.88 to 15.56
whenstoichiometric ratio of PA-POSS to EP-POSS decreased from
1.75/1to 1/1.7 in polymerization system (Table S1), again
confirming thesuccessful polymerization.
As we know, components of solvent mixtures (porogens) cangreatly
affect the macroporous structure and related permeabil-ity of
prepared stationary phase. Therefore, proper porogens werecarefully
selected considering the factors of polarity, solvation
andespecially solubility (the solubility parameter, ı) [30,33]. The
ıvalues of DMF (ı = 20.87 J1/2 cm−3/2) and PEG (19.25 J1/2
cm−3/2)calculated by means of group contribution [34] are close
to22.12 J1/2 cm−3/2 (PA-POSS) and 19.93 J1/2 cm−3/2 (EP-POSS),
butH2O (47.87 J1/2 cm−3/2) [35] differs significantly. Therefore,
aternary mixture of H2O, DMF and PEG for preparing the
polyPOSShybrid monolithic capillary columns was used as the
porogensto adjust the macropore and mesopore structures, in
additionto the mass percentage (%) of the porogens in the
prepoly-merization solution and the molar ratio of PA-POSS to
EP-POSS(Table S2). Actually, the preparation of a monolith is a
process ofpolymerization-induced phase separation, and the final
morphol-ogy is a competition result between the kinetics of
polymerizationand phase separation [36]. When keeping DMF constant
(80%) for
obtaining a homogeneous solution of PA- and EP-POSS, the
bal-ance between the poor solvent H2O and good solvent PEG showeda
remarkable influence on the morphology of the resulting mono-lithic
columns (Fig. 2A–C). When the mass percentages of both H2O
-
J. Su et al. / J. Chromatogr. A 1533 (2018) 136–142 139
Fig. 2. SEM images of the polyPOSS hybrid monoliths prepared
under the conditions of a mass percentage of 80% DMF, 10% H2O and
10% PEG; 75% porogens in thep ). 80%7 . 80%,1
addtfpitss1tsI1coatttooplma4fp3(c
repolymerization solution; and the molar ratio of PA-POSS to
EP-POSS = 1.75/1 (A0%; 1.75/1 (D). 80%, 8% and 12%; 80%; 1.75/1
(E). 80%, 8% and 12%; 85%; 1.75/1 (F)/1.5 (I). 80%, 8% and 12%;
75%; 1/1.7 (J).
nd PEG were 10%, a center-hollow monolith (column A) formedue to
that the poor solvent H2O limited the actually
homogeneousistribution of the POSS monomer/crosslinker in the
apparentlyransparent prepolymerization solution. As the decrease of
H2Orom 10 to 6% while the increase of PEG 10–14%, continuedorous
monoliths were obtained with the average macropore size
ncreased from 0.95 �m to 3.5 �m (columns B and C). Althoughhe
large macropores could provide good permeability, they causelow
mobile phase mass transfer. In general, optimal macroporeize should
be within 0.5–1 �m [37]. In the case of 8% H2O and2% PEG (column
B), the average macropore size was 0.95 �m, andhe measured BET
mesopore size was 10 nm, which was corre-ponding to the size formed
by ca. 4 PA-POSS/EP-POSS (Fig. 1a).t should be noted that the
native sub-nanometer siloxane cage,10.6 Å3 as estimated by
ChemBio3D Ultra 12.0 considering as aube and/or 164.6 Å3 as a ball,
which were related to the microp-re of the resulting monolith,
could not be reflected effectively by
conventional BET measurement, but still existed and contributedo
the tri-porous structure of the polyPOSS hybrid monolithic
sta-ionary phase. Moreover, mass percentage (%) of the porogens
inhe prepolymerization solution, which controls the concentrationf
the POSS precursors and thus the polymerization rate and
theccurrence of phase separation as well, was investigated. The
fasterolymerization rate and relative retarded phase separation
under
ess percentage (70%) of the porogens led to detachment of
theonolith from the capillary wall because of interface stress
[38],
lthough the fine skeleton (ca. 300 nm) and smaller macropore
(ca.00 nm) formed (column D). As the porogens percentage
increasedrom 70 to 85%, the polymerization rate decreased and
relative early
hase separation occurred, resulting in the skeleton size from
ca.00 to 850 nm and growing macropore from ca. 400 nm to 8 �mFig.
2D, B, E and F). Generally, 75% porogens was optimal in thease of
column B (470 nm). On the other hand, in spite of the
, 8% and 12%; 75%; 1.75/1 (B). 80%, 6% and 14%; 75%; 1.75/1 (C).
80%, 8% and 12%; 8% and 12%; 75%; 1.5/1 (G). 80%, 8% and 12%; 75%;
1/1 (H). 80%, 8% and 12%; 75%;
insignificant difference in terms of the morphology and
porousstructure under optimal preparation conditions (Fig. 2B, G,
H, I andJ) owing to the same reactivity of the eight fully
substituted pen-dant arms on PA-POSS and/or EP-POSS, the free
phenylamine orepoxy groups remained in the monoliths when the molar
ratio ofPA-POSS to EP-POSS was changed from 1.75/1 to 1/1.70. It
shouldbe pointed out that unreacted phenylamine and/or epoxy
groupsmight remain in the polyPOSS monolith even in the case of
PA-POSS/EP-POSS = 1/1, because of possible steric hindrance, one of
thepossible reasons. They may act different surface chemistry
underthe sophisticated mobile phase of different composition and
espe-cially the pH. We thus selected column B (1.75/1, guaranteeing
offree phenylamine remained) and J (1/1.70, free epoxy) as
examplesin the following chromatographic behavior study.
Furthermore, themechanical stability of column B and J was
investigated using purewater, methanol and acetonitrile (Fig. S1).
Good relationships (thecorrelation coefficient R2 > 0.99)
between the flow rate from 5 to30 �L/min (corresponding to 4.7 to
28.3 mm/s linear velocity) andthe backpressure from 0.3 to 23.4 MPa
using a conventional HPLCpump were observed, indicating good
mechanical stability of themonoliths. These monoliths also
presented good thermostabilitybecause significant weight loss began
until 350 ◦C when heatedunder N2 atmosphere (Fig. S2), implying
that they might be usedas the stationary phase in gas
chromatography. Additionally, in thecase of column B, its
reproducibility was evaluated in term of RSD(%, n = 3) for the
retention factors (k) of toluene as a model analyte(thiourea as the
void time marker) on nano-LC. The RSDs of run-to-run, day-to-day
and batch-to-batch were 0.33%, 3.98% and 6.85%,respectively.
Meanwhile, neither significant decrease of column
efficiency nor obvious column deterioration was observed
evenafter hundreds of continuous injections, demonstrating the
highstability of the synthesized polyPOSS hybrid monolithic
capillarycolumn.
-
140 J. Su et al. / J. Chromatogr. A 1533 (2018) 136–142
Fig. 3. Typical reversed-phase chromatographic separation of
alkylbenzenes and alkylbenzene ketones on the polyPOSS hybrid
monolithic capillary column B. Columnsize: 75 �m i.d. ×22.5 cm in
length; mobile phase: 60% ACN and 40% H O; flow rate: 200 nL/min;
UV detection at 214 nm. Analytes: (1) thiourea, (2) toluene, (3)
ethylben-z ) proh
3m
3a
caltdmpecsgBtazAat24t(attflhcanv(epptcaatia
2
ene, (4) propylbenzene, (5) butylbenzene, (6) pentylbenzene, (7)
acetophenone, (8eptanophenone.
.2. Chromatographic performance of the polyPOSS hybridonolithic
capillary columns on nano-LC
.2.1. Chromatographic separation of alkylbenzenes andlkylbenzene
ketones using neutral mobile phases
As we know, the siloxane cage and chemically
generatedrosslinking part (Fig. 1c), which include the tertiary
phenylaminend hydroxyl groups in the synthesized polyPOSS hybrid
mono-ithic stationary phase, contribute to the surface chemistry
andhe corresponding interactions with an analyte, controlling
theistribution of the analyte between the stationary phase andobile
phase. The cubic siloxane cage is very hydrophobic, its
olarity (logP) reaches 7.66 as calculated by molinspiration
prop-rty calculator on the website http://www.molinspiration.com;
therosslinking part is also hydrophobic as a whole (logP = 3.14).
Ithould be noted that there are unreacted PA
(phenylaminopropyl)roups (logP = 2.67) existing in the stationary
phase of column
due to the excess PA-POSS used. Such a surface chemistry ofhe
monolithic stationary phase was thus expected to perform
reversed-phase chromatographic separation towards alkylben-enes
using a relative polar and neutral mobile phase composed ofCN and
H2O. The obtained results indicated that the alkylbenzenesnd
thiourea were well separated in the sequence according toheir
polarity (thiourea, logP = −0.46; toluene, 2.39; ethylbenzene,.85;
propylbenzene, 3.24; butylbenzene, 3.80; pentylbenzene,.31) (Fig.
3a), and their retention factors decreased along withhe increase of
ACN content in the mobile phase from 55 to 70%Fig. 3b),
demonstrating a typical reversed-phase separation mech-nism based
mainly on the hydrophobic and �-� interactions withhe siloxane
cages and the aminophenyls. The plate heights ofhiourea and toluene
were 7.4 and 6.4 �m under 60% ACN at theow rate of 200 nL/min.
Moreover, the alkylbenzene ketones, whichave the carbonyl besides
the same phenyl and alkyl substitutesompared to their corresponding
alkylbenzene counterparts, werelso baseline separated according to
their polarity of acetophe-one (logP = 1.84), propiophenone (2.34),
butyrophenone (2.90),alerophenone (3.40), caprophenone (3.91) and
heptanophenone4.41) (Fig. 3c). It should be pointed out that the
chemically gen-rated hydroxyl and the remaining hydrogen in the
secondaryhenylamine groups on the polyPOSS hybrid monolithic
stationaryhase may theoretically offer additional hydrogen bonding
interac-ions. Such hydrogen bonding interactions with the oxygen in
thearbonyl of the molecules should result in higher retention of
thelkylbenzene ketones, but the results observed indicated that
the
lkylbenzene ketones have shorter retention time (less
retention)han their alkylbenzene counterparts. Clearly, the
hydrogen bond-ng between the carbonyl oxygen and the hydrogen in
hydroxylnd phenylamine was much more compromised by H2O and ACN
piophenone, (9) butyrophenone, (10) valerophenone, (11)
caprophenone, and (12)
in the mobile phase; on the other hand, the inductive effect of
thecarbonyl in the alkylbenzene ketone molecules contributed a
cer-tain extent to the weaker hydrophobic and �-� interactions
withthe stationary phase, resulting in less retention.
3.2.2. Chromatographic separation of polar small molecules
usingacidic mobile phases
Compared with column B, free EP containing epoxy group(logP =
1.01) exists on the monolithic stationary phase of column J,in
addition to the siloxane cages and chemically generated
tertiaryphenylamine and hydroxyl groups. The redundant epoxy
groupscan be hydrolyzed under acidic medium to form adjacent
hydroxyls(logP = −0.59) [39]; moreover, the tertiary phenylamine
(pKa = 5.8)can be protonated under an acidic condition. These mean
that thesurface chemistry of column J will be changed by merely
adjust-ing pH of the mobile phase to be used. Separation of
cytosine(logP = −1.61), uracil (−1.09) and thymine (−0.6) was first
per-formed using water (−0.29) as the mobile phase (Fig. 4a).
UnderpH 5.31, not only majority of the tertiary phenylamine (logP =
2.04)(ca. 31% are protonated, −1.12) but also the epoxy (0.52)
remainedintact in the stationary phase, the separation sequence of
thenucleic acid bases was again dominantly according to their
polar-ity. Similar results were obtained from the separation of
histidine(His, logP = −3.00), phenylalanine (Phe, −1.23) and
tryptophan (Trp,−1.08) using water (pH 6.81) as the mobile phase
(Fig. 4b). The res-olution factors RHis/Phe and RPhe/Trp were 2.57
and 2.38, and the plateheights 31.2 (His), 24.9 (Phe) and 40.3 �m
(Trp). While their sepa-ration became more efficient with very
sharp peaks and shorterretention time under pH 1.30; RHis/Phe and
RPhe/Trp increased to3.65 and 5.17, and the plate heights reached
4.0 (His), 4.7 (Phe)and 10.2 �m (Trp). These observations suggested
that the chem-ically generated hydrophilic hydroxyls and tertiary
phenylaminethat were totally positive-charged at pH 1.30 works on
the separa-tion of the three amino acids, which were also
positively chargedunder such an acidic condition considering their
pI of 7.64 (His),5.91 (Phe) and 5.88 (Trp). One could speculate
that electrostaticrepulsion and hydrophilic interaction become
significant due to thesurface chemistry change resulted from
pH-switch of the mobilephase, and thus fast mass transfer rates
(C-term = 3.01 ms for His,2.87 Phe and 3.93 Trp) (Fig. 4c). Such a
pH-switchable surface chem-istry from predominantly hydrophobic to
significantly hydrophilicstatus provides an opportunity to separate
other polar compoundsunder HILIC mode.
We thus selected the typical HILIC mechanism probing com-
pounds of formamide (logP = −0.89), thiourea (−0.46),
dimethyl-formamide (DMF) (−0.27) and toluene (2.39) to see whether
themonolithic stationary phase of column J has HILIC
characteristicsor not. As the increase of ACN percentage from 40%
to 80% in the
http://www.molinspiration.comhttp://www.molinspiration.comhttp://www.molinspiration.comhttp://www.molinspiration.com
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J. Su et al. / J. Chromatogr. A 1533 (2018) 136–142 141
Fig. 4. Separation of nucleic acid bases (a); amino acids (b)
and their corresponding H-u plots (c); HILIC probe compounds (d);
phenols (e) and phenolic acids (f) on thep n lenga ACN (
ataaTrlwcmtem
nr0rtscmfdoq(tA(SamD1zie
olyPOSS hybrid monolithic capillary column J. Column size: 75 �m
i.d. ×22.5 cm ind 1.30); (c) water (pH 1.30); (d) ACN (40% and 80%
containing 0.1% TFA); (e) 20%
cidic mobile phase containing 0.1% TFA, we observed conversion
ofhe retention time of toluene and thiourea (Fig. 4d),
demonstrating
typical HILIC behavior. The four compounds were efficiently
sep-rated in the sequence of toluene, DMF, formamide and
thiourea.his sequence was also somewhat contributed by the
electrostaticepulsion effect, because of the positive-charged
tertiary pheny-amine in the stationary phase, meanwhile DMF and
formamide
ere also positively charged. The plate heights under 80%
ACNontaining 0.1% TFA were 11.1 (toluene), 8.41 (DMF), 8.86
(for-amide) and 9.79 �m (thiourea). Such a nano-LC performance
of
he prepared polyPOSS hybrid monolithic capillary column J wasven
comparable to that of CEC using the silica-based
polypeptideonolithic capillary column [32].Compared with the amino
acids and nucleic acid bases, phe-
ols and phenolic acids as well as benzoic acid and sorbic
acidemain intact (do not ionize) under the mobile phase
containing.1% TFA. They are not affected significantly by the
electrostaticepulsion effect arising from the positive-charged
phenylamine onhe stationary phase while the hydrophobic
interactions becameignificant, which may drive them entering into
the siloxaneages (ca. 110.6/164.6 Å3). The siloxane cages
contribute to theicropore structure of the hybrid monolithic
stationary phase as
ore-mentioned, playing an additional size-exclusion effect as
evi-enced by the polarity- and size-dependent separation sequencef
phloroglucin (logP = 0.43; molecular volume = 108.10 Å3),
hydro-uinone (0.98; 100.08 Å3), resorcinol (0.95; 100.08 Å3),
catechol0.99; 100.08 Å3) and phenol (1.46; 92.06 Å3) using 20% ACN
con-aining 0.1% TFA as the mobile phase (Fig. 4e). Further
increasingCN content in the mobile phase led to shorter retention
time
Fig. S3), demonstrating a mixed mode separation mechanism.imilar
results (Figs. 4f and S3) from the separation of phenoliccids
including 2,6-dihydroxybenzoic acid (2,6-DBA; logP = 1.39;olecular
volume = 127.08 Å3), 3,4-dihydroxybenzoic acid (3,4-BA; 0.88;
127.08 Å3), 3,5-dihydroxybenzoic acid (3,5-DBA; 0.82;
27.08 Å3) and p-hydroxybenzoic acid (1.37; 119.06 Å3) and
ben-oic acid (1.85; 111.06 Å3), except sorbic acid (0.97; 111.03
Å3) thats a linear unsaturated acid, generally confirmed the
size-exclusionffect of the siloxane cages again. It should be noted
that, how-
th; UV detection at 214 nm. Mobile phase: (a) water (pH 5.31);
(b) water (pH 6.810.1% TFA) and (f) water (0.1% TFA) at the flow
rate of 200 nL/min.
ever, separation order of the three hydroxy phenols
(hydroquinone,resorcinol and catechol) of similar polarity and size
but differenthydroxyl substitution positions indicated that the
positive-chargedphenylamines and hydroxyls influence their
separation; these mys-tic effects became more remarkable in the
case of 2,6-DBA thatwas first eluted among the three phenolic acids
studied. It issimilar in size with its analogues of 3,4-DBA and
3,5-DBA, andmore hydrophobic, thus should be theoretically eluted
later. Onepossible reason for its first elution might be its
intramolecularhydrogen bonding while intermolecular hydrogen
bonding is dom-inant in the other two phenolic acids. This can be
reflected byobservations of not only their changing separation
order but alsoless retention even co-eluted (Fig. S3) along with
the increase inACN content because the non-protonic solvent ACN
affects muchmore remarkably on the intermolecular hydrogen bonding
thanthe intramolecular one. A mixed mode separation with
multipleinteractions should again apply to this situation,
suggesting thatthe novel stationary phase with tri-porous structure
and multiplesurface chemistry provides flexibility to improve the
resolution ofparticular small molecules using a sophisticated
mobile phase.
4. Conclusions
We developed a dual POSS-polymerized approach to preparepolyPOSS
hybrid monolithic stationary phases. The two nanoscalePOSS with PA
and EP modifications offer more surface chemistry,in addition to
the resulted tri-porous monolithic structure, allow-ing us to
perform a more effective separation of the targeted smallmolecules
on reversed-phase through HILIC to mixed mode mech-anisms via
adjusting the molar ratio of POSS precursors while thecomposition
and pH of a mobile phase. Not limited to the smallmolecules studied
here, this polyPOSS approach can be expectedto fabricate other
kinds of hybrid monolithic stationary phases thatare suitable for
biomacromolecules and chiral molecules separation
when choosing the existed and/or designing new POSS with
thependant groups of different structure and chemical property as
wellas chirality. Moreover, we believe that the thermostability of
themonolithic stationary phases obtained via such an approach
ren-
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[38] G. Guiochon, Monolithic columns in high-performance
liquid
42 J. Su et al. / J. Chromat
ers their potential usefulness as gas chromatographic
stationaryhases in the near future.
cknowledgments
This work was financially supported by the National Natural
Sci-nce Foundation of China (Grants 21535007, 21475108,
21275120),he National Basic Research 973 Program (Grant
2014CB932004)nd National Science and Technology Basic Work
(2015FY111400)s well as the Foundation for Innovative Research
Groups of theational Natural Science Foundation of China (Grant
21521004),rogram for Changjiang Scholars and Innovative Research
Team inniversity (PCSIRT, Grant IRT13036).
ppendix A. Supplementary data
Supplementary material related to this article can be found,
inhe online version, at
doi:https://doi.org/10.1016/j.chroma.2017.2.033
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