Light-assisted preparation of a cyclodextrin-based chiral stationary phase and its separation performance in liquid chromatography

Article abstract of DOI:10.1039/c7nj02911j

A cyclodextrin-based chiral stationary phase (CD-CSP) is one of the most widely applied CSPs due to its powerful enantioseparation ability. In this study, a facile method was developed to prepare a CD-CSP via carboxyl methyl β-cyclodextrin (CD-COOH) and diazo-resin (DR). Monodisperse silica particles were synthesized using a modified St?ber method. Then DR and CD-COOH were coated on the silica particles via ionic bonding successively and UV light was finally used to couple silica, DR and CD-COOH and the ionic bonds turned into covalent bonds. The resultant CD-DR silica particles were characterized using Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA) and scanning electron microscopy (SEM). The enantioselectivity of the CD@SiO₂ particles was explored in reversed phase high-performance liquid chromatography (RP-HPLC). Baseline separation of chiral drugs was achieved and the effects of separation parameters (elution mode, buffer and analyte mass) were investigated in detail. By using water soluble non-toxic DR to replace a highly toxic and moisture sensitive silane agent to modify silica microspheres, this light-assisted strategy can provide a green and effective technique to manufacture packing materials for enantioseparation applications.

Full text of DOI:10.1039/c7nj02911j

View Article Online
View Journal
NJC
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: Q. Tang, B. Yu, L.
Gao, H. Cong and S. Zhang, New J. Chem., 2017, DOI: 10.1039/C7NJ02911J.
Volume 40 Number
1
January 2016 Pages 1–846
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
NJC
New Journal of Chemistry
www.rsc.org/njc
A journal for new directions in chemistry
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
rsc.li/njc

Page 1 of 8
Pl eNa es we dJ oo u nr no at l ao df jCu hs et mm i as tr rgy ins
View Article Online
DOI: 10.1039/C7NJ02911J
Journal Name
ARTICLE
Light-assisted preparation of cyclodextrin-based chiral stationary
phase and its separation performance in liquid chromatography
oReceived 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
a
ab
a
*ab
a
Qi Tang, Bing Yu , Lilong Gao, Hailin Cong and Shuai Zhang
www.rsc.org/
Cyclodextrin-based chiral stationary phase (CD-CSP) is one of the most widely applied CSPs due to its powerful
enantioseparation ability. In this study, a facile method was developed to prepare CD-CSP via carboxyl methyl β-
cyclodextrin (CD-COOH) and diazo-resin (DR). Monodisperse silica particles were synthesized by a modified Stöber method.
Then DR and CD-COOH was coated on the silica particles via ionic bonding successively and UV light was finally used to
couple silica, DR and CD-COOH and the ionic bonds turned into covalent bonds. The resultant CD-DR silica particles were
characterized by Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA) and scanning electron
2
microscopy (SEM). The enantioselectivity of the CD@SiO particles was explored in reversed phase high-performance
liquid chromatography (RP-HPLC). Baseline separation of chiral drugs was achieved and the effects of separation
parameters (elution mode, buffer and analyte mass) were investigated in details. By using water soluble non-toxic DR to
replace highly toxic and moisture sensitive silane agent to modify silica microspheres, this light-assisted stategy can
provide
a
green and effective technique to manufacture packing materials for enantioseparation applications.
HPLC. After a few decades’ development, the enantiomeric
separation has become an essential, mature technique in
pharmaceutical, bioanalytical, and synthetic organic
Introduction
With an increasing demand for the exploration of
different properties like toxicities and metabolic pathways of
enantiomers, many efforts have been made on the analysis
and purification of chiral drugs, and it has become a
prerequisite process prior to the clinical use of drugs.
Enantioseparation of chiral compounds has been attracting
great interests due to that enantiomers of racemic drugs tend
to show markedly different pharmacological activities.
Enantioseparation of chiral compounds will continue to be a
key research area in pharmaceutical industry, food additives
and life science.
14-17
laboratories.
However, there are no CSP that can separate
all classes of chiral molecules up to now. Thus, many
researchers who are engaged in stationary phase development
have extensively focussed on synthesizing chiral selectors,
which have high selectivity for various classes of
1
14, 18-20
enantiomers.
A lot of chiral stationary phases (CSPs), which are based
on ligand-exchange, protein, glycoprotein, cyclodextrin,
polysaccharide, macrocyclic glycopeptide and crown ether, are
1
-5
6
21, 22
available for separations of enantiomers in HPLC.
7
-9
Cyclodextrins (CDs) are one of the most commonly used chiral
selectors for enantioseparation due to their ability to form
host-guest inclusion with a large variety of chiral compounds,
Most commercial available synthetic chiral drugs are
obtained as a mixture of two enantiomers through synthesis
1
0
methods. It is well established that direct enantioseparation
by high performance liquid chromatography (HPLC) with CSP
can serve as a robust technique for separation at both
analytical and preparative scale, which feature high efficiency,
which are naturally-occurring cyclic oligosaccharides which
22-24
consisting of several (6, 7, 8) glucose units.
Due to
consisting small number of glucose units, α-CD contained a
small cavity that can only package part of small molecules,
which limited its application. For γ-CD, the cavity is the biggest,
but the high manufacturing cost restricts its application. By
contrast, the cavity size of β-CD is appropriate, and the
inclusion can be many kinds of chiral molecules. β-CD has been
widely used for its low cost and industrialized production but
the poor water solubility of β-CD limited the application to
some extent. Chemical modification can improve the water
solubility of β-CD and broaden its application scope and then
achieve better separation effect. The enantioseparation
11-13
quick analysis and precise resolutions.
Chiral selectors bonded or coated on silica particles are
considered state of art materials for separating enantiomers in
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Pl eNa es we dJ oo u nr no at l ao df jCu hs et mm i as tr rgy ins
Page 2 of 8
ARTICLE
abilities of CDs could be enhanced by derivatizing its hydroxyl
Journal Name
View Article Online
DOI: 10.1039/C7NJ02911J
25
groups.
As we all know, the most commonly used columns for
chromatographic separation are packed with particle-based
26
stationary phase . The modified silica particles have almost been
the most widely used stationary phase for chromatographic
separation among various types of particles used for packings duo
to some advantageous characteristics such as a relatively high
specific surface area, narrow particle size distribution, and good
27
mechanical stability. However, the modification process of silica
particles is usually complicated which contains multiple time-
consuming steps. Moreover, the highly toxic and moisture sensitive
silane coupling agents are traditionally used in the modification
process, which often cause environmental and quality problems
during the manufacture and application. Thus, a much easier and
greener way for modifying silica particles is essential.
According to the previously proposed preparation mechanism
using the layer-by-layer self-assembly technique combined with
13, 28
photochemistry reactions,
the modification of silica particles
using photosensitive diazoresin is expected to be superior to
traditional modified methods using moisture sensitive silane
coupling agents. DR is a non-toxic photoactive component which
29
often used in cell culture supports. The unique photo-crosslinking
reaction of DR is expected to apply for instead of silane coupling
agents. Ionic bonding between DR, silica and CD-COOH can be
Scheme 1 Light-assisted preparation of cyclodextrin-based CSP.
converted into covalent bonding after treatment with UV light Experimental
through a unique photochemistry reaction of DR.
Chemicals and apparatuses
To improve the efficiency of the preparation procedure,
we develop a CSP bonded to silica particles with DR instead of
30, 31
silicon alkylation reagents.
In this paper, we synthesized
water soluble carboxyl methyl β-CD (CD-COOH) and
monodisperse silica particles by a modified Stöber method. A
light-assisted modification method of silica particles is
developed by ionic bonding between positive charged
photosensitive DR with hydroxyl groups of silica particles and
carboxyl group of CD-COOH. With the treatment of UV light, Scheme 2 Chemical structures of the chiral compounds used in this study. (a)
promethazine, (b) benzoin, (c) chlortrimeton.
the ionic bonding between DR and silica particles, DR and CD-
COOH were turned into covalent bonding through a unique
The structures of the chiral compounds are shown in
photochemistry reaction of DR (Scheme 1). Thus, CD could be
Scheme 1. DR was synthesized by polycondensation of 5
attached on the surface of silica particles steadily and novel
diphenylamine-4-diazonium salt and paraformaldehyde in
CSP was obtained. The separation properties of the resultant
concentrated H SO according to a method described in our
2
4
2-35
CSP of three chiral drugs (chlortrimeton, promethazine and
benzoin, Scheme 2) were investigated in details.
3
previous report.
Ammonia (28%) was purchased from
Sanhe Chemical Reagent Company (Yantai, China). KCl (99.5%),
NaOH (98%), AgNO , sodium chloroacetate (98%) ethanol
3
(99.5%), hydrochloric acid, acetic acid, triethylamine and
isopropanol (99.7%) were obtained from Hengxing Chemical
Reagent Company (Tianjin, China). Tetraethyl orthosilicate
(TEOS, 98%), β-cyclodextrin, chlortrimeton, promethazine and
benzoin (99%) were obtained from Aladdin Reagent Company
(
(
Shanghai, China). Methanol (MeOH, 99.9%) and acetonitrile
ACN, 99.9%) were obtained from Tianjin Kemiou Chemical
Reagent Co. All chemicals were used as received without
further purification. Water was distilled before use.
Instrumentation
2
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 8
Pl eNa es we dJ oo u nr no at l ao df jCu hs et mm i as tr rgy ins
Journal Name
ARTICLE
The morphology and structure of the silica particles was water. The process was conducted in the dark cVoienwdAitrtiioclenOannlinde
investigated by scanning electron microscopy (SEM, JEOL JSM- low temperature. The obtained coated DsOilIi:c1a0.1p0a3r9t/iCc7leNsJ0w29e1r1eJ
309LV). The photo-crosslinking of the CD-COOH and SiO by dried under vacuum at room temperature for 12 h. The coated
6
2
DR was carried out using a 365 nm UV curing system (EXFO silica particles were then exposed to 365 nm UV light with an
2
Omnicure S1000) with
a
lamp power of 100 W. intensity of 350 mW/cm for 15 min in order to form the
Thermogravimetric analysis (TGA) data were recorded using a covalently linked CD coatings.
Mettler Toledo TGA/DSC1/1600LF simultaneous thermal
analyzer at a heating rate of 10 °C/min. Fourier transform
infrared spectroscopy (FT-IR) was obtained using Nicolet 6700
produced by Thermo Fisher Scientific. Chromatographic study
was carried out using a SEV P500 HPLC equipped with a UV
detector.
Chromatographic conditions
The CSP were packed into stainless columns (15 × 4.6
mm, I.D.) using a typical slurry-packing technique with
isopropyl alcohol as the solvent by the chromatographic
column packing machine (GLK 2000, GALAK). The packing
pressure was maintained for at least 30 min. The column was
connected to the HPLC system with methanol passing through
at a flow rate of 0.1 mL/min for about 3 h to equilibrate the
column until a constant UV baseline was obtained. Samples for
chromatography were dissolved in MeOH or ACN at a
concentration of 10 mg/mL if not mentioned. The injection
volume was 1 μL if not mentioned. Each solution was injected
in triplicate and the average values are reported.
Triethylammonium acetate buffer (TEAA) was prepared by
dissolving 0.3% (v/v) triethylamin in ultrapure water and
adjusting to the pH 4.0 with acetate acid. All the buffers and
samples were filtered through 0.22 μm membranes before use
Preparation of CD-COOH
CD-COOH was synthesized according to the reported
36
method. In brief, a certain amount of NaOH and β-CD was
added into 20 mL of water under stirring at 0 °C. After the
substances were dissolved, the mixture solution was stirred 1
h at 90 °C and a certain amount of sodium chloroacetate was
added in it and stirred for 3 h. Next, the reaction solution was
cooled to room temperature and its pH value 4-6 was adjusted
by HCl. Superfluous organic solvent (methanol and ethanol,
v:v=1:3) was added into the obtained solution to get white
precipitates of carboxyl methyl-β-cyclodextrin (CD-COOH). The
supernatant was removed and the precipitates were
redissolved in water. The purification process was repeated
again until there were no precipitates produced. The
and detection was performed at 250 nm
.
supernatant was treated with AgNO to test whether surplus
chloride ions remains or not. Finally, CD-COOH was dried at RT
in vacuum drying oven before use.
3
Results and discussion
Light-assisted preparation of CD-CSP
I
n this work, monodisperse silica particles were
Preparation of the silica particles
synthesized by a modified Stöber method, in which TEOS was
continuously added into the reaction mixture containing KCl
electrolyte, water, ethanol and ammonia at room
temperature. CD-COOH was ironically bonded on the surface
The synthesis of silica particles was conducted by a
3
7
modified Stöber method. In a 250 mL semibatch chemical
reactor where an ethanolic solution of TEOS (solution I) was
continuously supplied with a syringe pump to the reaction
mixture (solution II) of water, KCl electrolyte, ethanol, TEOS
and ammonia. The amounts of ethanol and TEOS in solution I
were 26.12 g and 4.12 g. The amounts of water, KCl, ethanol,
TEOS and ammonia in solution II were 9.45 g, 0.0238 g, 75.39
g, 1.648 g and 4.039 mL, respectively. The supply rate of
solution I was 0.1 mL/min and the stirring speed was 260 rpm.
After further reaction for another 1 h, the obtained particles
were purified by centrifugation and washed with ethanol for
by the charged photosensitive DR. SEM images of bare SiO2
and CD@SiO are shown in Fig. 1. The surface of bare silica is
smooth as shown in Fig. 1(a). After CD was bonded on the SiO2
2
surface by DR, the surface becomes less smooth and a clear
coating can be observed (Fig. 1(b)).
no less than three times. Finally, the SiO particles were dried
2
under vacuum at ambient temperature.
Light-assisted preparation of the CD-CSP
The preparation of CD-COOH CSP was shown in Scheme 1.
The DR coated silica particles were carried out as follows: the
2 2
Fig. 1 SEM images of (a) bare SiO and (b) CD @SiO .
SiO particles were firstly treated in 0.1 M HCl for 30 min and
2
washed to neutral with water. These particles were added into
the aqueous solution of DR (10mg/mL) with magnetic stirring
for 30 min, and washed with deionized water. These particles
were added into the aqueous solution of CD-COOH (10 mg/mL)
with magnetic stirring for 30 min, and washed with deionized
As shown in Fig. 2, the successful conjugation of CD onto
the surface of silica particles was confirmed by FT-IR spectra.
The spectrum of CD modified silica particles by DR was shown
in Fig. 2. Compared with the FT-IR spectrum of bare silica
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Pl eNa es we dJ oo u nr no at l ao df jCu hs et mm i as tr rgy ins
Page 4 of 8
ARTICLE
Journal Name
-
1
particles, the peaks at 2926, 1607 and 1037 cm were ascribed Enantioseparation Performance of CD-CSP in PO and RP mode
View Article Online
DOI: 10.1039/C7NJ02911J
39-43
the characteristic peaks of CD-COOH. The results indicate that
the CD-COOH modification was successfully carried out on the
surface of SiO2.
38-41
Nature of CSPs
and separation conditions
have
significant effect on elution of enantiomers. β-CD is widely
used for seperation of enantiomers for its chiral molecular
recognition. In the ring paste molecules, the sugar unit is used
as a chair configuration, and the shape of a hollow cone
structure, water solubility and non-water-soluble compounds
can be entered into the cavity to form a clathrate.Object
molecules can paste essence in whole or in part in ring cavity,
mainly through the object and chiral cavity horse matchs with
in chiral recognition and separation, and benzene ring
compounds can and cyclodextrin cavity to carry on the good
horse matchs, so cyclodextrin more types of chiral stationary
phase for separation of chiral compounds with benzene ring.
Herein, PO (polar organic) and RP (reverse phase) elution
modes of enantiomers were investigated on the as-prepared
CD-CSP.In RP-HPLC, the organic solvent can greatly influence
the enantioseparation. In this study, MeOH and ACN were
used as the mobile phase for enantioseparations of the above
mentioned chiral compounds on the as-prepared CSP.
In PO elution mode, the enantioseparations of
promethazine and benzoins were evaluated using MeOH as
mobile phase. As shown in Fig. 4, promethazine (Rs=2.675) and
benzoin (Rs=1.131) enantiomers were separated with MeOH
as the eluting phase. The results suggest that the prepared CD-
CSP has a resolving ability under PO elution mode.
Furthermore, the separation of some other racemates (ESI,†
Fig. S1) were reported in the supplementary materials.
2 2
Fig. 2 The FTIR spectra of (a) bare SiO , (b) CD-COOH and (c) CD@SiO .
As shown in Fig. 3, TGA tests are performed on the bare
and CD-COOH modified SiO particles. The samples lost weight
2
with the increase of the temperature due to the removal of
physically adsorbed water and degradation of TEOS residuals
in the samples. However, the CD-COOH modified SiO particles
2
have more weight loss than the bare particles from 100 to 600
°C, which induced by the decomposition of CD and DR on the
surface of silica particles. According to the difference in weight
loss of the bare and modified SiO particles, the CD content of
2
modified SiO particles is calculated to be 10.6 wt%.
2
Fig. 4 Enantiomeric separation of (a) promethazine and (b) benzoin on CD@SiO
2
column (15 cm × 4.6 mm i.d.); mobile phase, MeOH; flow rate, 0.2 mL/min; UV detector,
250 nm; temperature, 25 °C.
2 2
Fig. 3 TGA curves of (a) bare SiO and (b) CD@SiO .
In RP elution mode, the inclusion complexation between
CD and the analytes is considered as the main driving force for
4
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 8
Pl eNa es we dJ oo u nr no at l ao df jCu hs et mm i as tr rgy ins
Journal Name
ARTICLE
4
4
enantioseparations. Evaluation of chiral recognition ability of enantiomers differences because of the difference of the force
View Article Online
DOI: 10.1039/C7NJ02911J
CSP in RP-elution mode was shown in Fig. 5. Promethazine strength with stationary phase.
(Rs=2.498) and benzoin (Rs=1.59) enantiomers were separated
with VACN:V =7:3 as the eluting phase as shown in Fig. 5. The
2
H O
results suggest that the prepared CSP has a resolving ability
under RP elution mode.
2
Fig. 6 Enantiomeric separation of chlortrimeton on CD@SiO column (15 cm × 4.6 mm
i.d.); flow rate, 0.2 mL/min; UV detector, 250 nm; temperature, 25 °C; mobile phase
conditions: (a) ACN 100%, (b) TEAA-ACN 1:9 (v/v), (c) TEAA-ACN 2:8 (v/v), (d) TEAA-ACN
3:7 (v/v).
Fig. 5 Enantiomeric separation of (a) promethazine and (b) benzoin on CD@SiO
2
2
column (15 cm × 4.6 mm i.d.); mobile phase, ACN-H O 7:3 (v/v); flow rate, 0.2 mL/min;
UV detector, 250 nm; temperature, 25 °C.
Effect of the Analyte Mass
Effect of buffer
Very often, buffers are recommended to be added into
mobile phases to enable the separation of basic drugs or to
45
improve the chiral resolutions of some drugs. In this study,
chlortrimeton, which could not be resolved in PO mode, were
successfully separated with the addition of TEAA buffer (0.3%,
pH 4.0) to ACN. The UV spectra of chlotrimeton isomers (ESI,†
Fig. S2) were reported in the supplementary materials. As
shown in Fig. 6 (a), when there is no TEAA buffer was added
into the mobile phase, only one peak of chlortrimeton could
be observed. When 10% TEAA buffer (0.3%, pH 4.0) were
added into ACN (Fig. 6 (b)), there are two peaks can be
observed, which indicated that the chlortrimeton enantiomers
were separated by the addition of TEAA. Further increasing of
the ratio of TEAA buffer could give rise to the increase of Rs
(Fig. 6 (c) and (d)). Both two entatiomers of chlortrimeton can
generate hydrogen bonding easily, and the two entatiomers can
form π-π conjugate bond. Thus, entatiomers and stationary phase
is easy to form molecular inter-atomic forces (such as hydrogen
bonds or static electricity, etc.). In the acidic condition, the
interaction between the two and the ring paste is strengthened and
obtained a good separation. The adhesion strength of the two
2
Fig. 7 Enantiomeric separation of promethazine on CD@SiO column (15 cm × 4.6 mm
i.d.); mobile phase, MeOH; flow rate, 0.2 mL/min; UV detector, 250 nm; temperature,
5 °C; injected mass: 10 μg (1 μL, 10 mg/mL), 25 μg (2.5 μL, 10 mg/mL), 50 μg (5 μL, 10
2
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Pl eNa es we dJ oo u nr no at l ao df jCu hs et mm i as tr rgy ins
Page 6 of 8
ARTICLE
Journal Name
mg/mL), 100 μg (10 μL, 10 mg/mL). Inset: relationship between injiected mass and
Notes and references
View Article Online
DOI: 10.1039/C7NJ02911J
peak area of promethazine.
1
2
3
4
M. E. Bosch, A. J. Sánchez, F. S. Rojas and C. B. Ojeda, J.
Pharm. Biomed. Anal., 2008, 46, 9-17.
M. Castro-Puyana, K. Lomsadze, A. L. Crego, M. L. Marina
and B. Chankvetadze. Electrophoresis, 2007, 28, 388-394.
Z. Wang, M. Jonca, T. Lambros, S. Ferguson and R. Goodnow,
J. Pharm. Biomed. Anal., 2007, 45, 720-729.
To examine the loading capacity of the CSP without
compromising resolution, a loading test was carried out using
different injection masses. It was evident that the retention
time of the enantiomer for promethazine became closer with
increasing injection mass from 10 to 100 μg with flow rate of
F. Gasparrini, D. Misiti and C. Villani, J. Chromatogr. A, 2001,
9
06, 35-50.
5
6
G. Felix, J. Chromatogr. A, 2001, 906, 171-184.
0
.2 mL/min at 25°C (Fig. 7). When the promethazine loading
M. Mujahid, J. Subramanian, V. Nalla, M. Sasikumar, S. S.
Kunte and M. Muthukrishnan, New. J. Chem., 2016, 41, 824-
was increased from 10 to 100 μg of each racemate, the
chromatographic peak area of each single antipode rises
linearly (as shown in the inset of Fig. 7). The result may be due
to stronger hydrogen bonding between carboxyl groups of CD-
COOH and amino groups of promethazine. In addition, the
reproducibicity of the CSPs and the effect of flow rate were
also been investigated (ESI,† Fig. S3 and Fig. S4).
8
29.
P. Etayo and A. Vidalferran, Chem. Soc. Rev., 2013, 42, 728-
54.
7
8
9
7
S. Maddi, S. K. Yamsani, A. Devandla, G. Scriba and M. R.
Yamsani, Med. Chem. Res., 2013, 22, 2403-2410.
S. Mohr, J. A. Weiß, J. Spreitz and M. G. Schmid, J.
Chromatogr. A, 2012, 1269, 352-359.
1
1
1
0 B. Kasprzykhordern, Chem. Soc. Rev., 2010, 39, 4466-4503.
1 P. S. Mukherjee, J. Pharm. Biomed. Anal., 2007, 43, 464-470.
2 I. Brondz, D. Ekeberg, D. S. Bell, A. R. Annino, J. A. Hustad, R.
Svendsen, V. Vlachos, P. Oakley, G. J. Langley and T. Mohini,
J. Pharm. Biomed. Anal., 2007, 43, 937-944.
Conclusions
In summary, we developed a green and effective light-
assisted strategy to prepare CD-CSP for enantioseparation of
racemic drugs. This material’s morphology and chemical
composition were characterized using FTIR, TGA and SEM. The
enantioseparation performance of as-prepared CD-CSP was
evaluated with racemates in mixed modes HPLC. The effect of
separation parameters including different mobile phase, buffer
and analyte mass on the enantioselectivity of the as-prepared
CSP were investigated in details. Meanwhile, the possibility of
successful separation for this CSP might be dependent on the
hydrogen bonding and dipole-dipole interaction between
analytes and the CSP.
1
1
1
1
1
3 B. Yu, C. Tian, H. Cong and T. Xu, J. Mate. Sci., 2016, 51,
5240-5251.
4 K. Hrobonova, J. Moravčík, J. Lehotay and D. W. Armstrong,
Anal. Methods., 2015,
7
, 4577-4582.
5 M. Zhang, X. D. Xue, J. H. Zhang, S. M. Xie, Y. Zhang and L. M.
Yuan, Anal. Methods., 2013,
6
, 341-346.
6 Q. Tian, Z. Zhou, C. Lv and J. Yang, Anal. Methods., 2012, 4,
2307-2317.
7 K. Tanaka, N. Hotta, S. Nagase and K. Yoza, New. J. Chem.,
2
016, 40, 4891-4894.
1
1
2
8 S. Takahashi and T. Okada, Analyst, 2014, 139, 1830-1833.
9 X. H. Lai and S. C. Ng, J. Chromatogr. A, 2004, 1031, 135-142.
0 S. I. Kebe, M. B. Boubaker, M. Guerrouache and B.
Carbonnier, New. J. Chem., 2016, 40, 6916-6923.
2
2
2
2
1 H. Yamamoto and E. M. Carreira, Comprehensive Chirality:
Elsevier; 2012. 507-678.
Conflict of interest
2 Y. Xiao, S. C. Ng, T. T. Tan and Y. Wang, J. Chromatogr. A,
2
012, 1269, 52-68.
The authors confirm that this article content has no conflict
of interest.
3 N. R. Ramisetti and S. Kondapalli, New. J. Chem., 2016, 40
408-8417.
，
8
4 M. Guitet, P. Zhang, F. Marcelo, C. Tugny, J. Jiménezbarbero,
O. Buriez, C. Amatore, V. Mourièsmansuy, J. P. Goddard and
L. Fensterbank, Angew. Chem., 2013, 52, 7213-7218.
5 E. Schneiderman and A. M. Stalcup, J. Chromatogr. B. Biomed.
Sci. Appl., 2000, 745, 83-102.
6 K. K. Unger, R. Skudas and M. M. Schulte. J. Chromatogr. A,
2008, 1184, 393-415.
Acknowledgements
2
2
This work is financially supported by the National Natural
Science Foundation of China (21574072, 21675091, 21375069,
5
1703107), the Taishan Young Scholar Program of Shandong 27 J. Nawrocki, C. Dunlap, A. Mccormick and P. W. Carr. J.
Province (tsqn20161027), the Key Research and Development
Project of Shandong Province (2016GGX102028,
016GGX102039, 2017GGX20111), the Project of Shandong
Province Higher Educational Science and Technology Program
J15LC20), the Scientific Research Foundation for the Returned
Overseas Chinese Scholars of State Education Ministry
20111568), the Natural Science Foundation of Shandong Province
ZR2017BB047), the People's Livelihood Science and Technology
Project of Qingdao (166257nsh, 173378nsh), the Innovation
Chromatogr. A, 2004, 1028, 1-30.
2
2
8 B. Yu, W. Cui, H. Cong, M. Jiao, P. Liu and S. Yang. Rsc
Advances, 2013, 3, 20010-20015.
2
9 A. Plewa, W. Niemiec, J. Filipowska, A. M. Osyczka, R. Lach
and K. Szczubiałkaaa. European Polymer Journal, 2011, 47
503-1513.
0 B. Yu, T. Xu, H. Cong, Q. Peng and M. Usman, Materials,
,
(
1
3
3
(
(
2
017, 10, 440-452.
1 B. Yu, H. Zhang, H. Cong, C. Gu, L. Gao, B. Yang and M.
Usman, New. J. Chem., 2017, 41, 4637-4643.
Leader Project of Qingdao (168325zhc), the Postdoctoral 32 J. Wang and Y. Zou, J. App. Polym. Sci., 2013, 127, 4850-
Scientific Research Foundation of Qingdao, and the First Class
Discipline Project of Shandong Province.
4857.
3
3
3 B. Yu, X. Shu, H. Cong, X. Chen, H. Liu, H. Yuan and M. Chi, J.
Chromatogr. A, 2016, 1437, 226-233.
4 B. Yu, M. Chi, Y. Han, H. Cong, J. Tang and Q. Peng, Talanta,
2
016, 152, 76-81.
6
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 8
Pl eNa es we dJ oo u nr no at l ao df jCu hs et mm i as tr rgy ins
Journal Name
ARTICLE
3
3
3
3
3
4
4
5 B. Yu, M. Jiao, H. Cong, X. Shu and S. Yang, J. Sep. Sci., 2014,
, 725-730.
View Article Online
DOI: 10.1039/C7NJ02911J
3
7
6 E. Furusaki, Y. Ueno, N. Sakairi, N. Nishi and S. Tokura,
Carbohyd. Polym., 1996, 29, 29-34.
7 W. Stöber, A. Fink and E. Bohn. J. Colloid Interface Sci., 1968,
26, 62-69.
8 K. Tamura, T. Miyabe, H. Iida and E. Yashima, Polym. Chem.,
2
010, 2, 91-98.
9 I. Matarashvili, L. Chankvetadze, S. Fanali, T. Farkas and B.
Chankvetadze, J. Sep. Sci., 2013, 36, 140-147.
0 L. Zhou, B. Mao and Z. Ge, J. Pharm. Biomed. Anal., 2008, 46
,
8
98-906.
1 A. Mskhiladze, M. Karchkhadze, A. Dadianidze, S. Fanali, T.
Farkas and B. Chankvetadze, Chromatographia, 2013, 76
449-1458.
,
1
4
4
4
4
2 Q. Wang, Y. Xiong, B. Lu, J. Fan, S. Zhang, S. Zheng and W.
Zhang, J. Sep. Sci., 2013, 36, 1343-1348.
3 L. Mosiashvili, L. Chankvetadze, T. Farkas and B.
Chankvetadze, J. Chromatogr. A, 2013, 1317, 167-174.
4 Y. Lin, J. Zhou, J. Tang and W. Tang, J. Chromatogr. A, 2015,
1
406, 342-346.
5 A. Espada and A. Riverasagredo, J. Chromatogr. A, 2003, 987
11-220.
,
2
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

New Journal of Chemistry
Page 8 of 8
View Article Online
DOI: 10.1039/C7NJ02911J
Graphic abstract
Light-assisted preparation of cyclodextrin-based chiral stationary
phase and its separation performance in liquid chromatography
a
ab
a
*ab
a
Qi Tang, Bing Yu , Lilong Gao, Hailin Cong and Shuai Zhang
A facile light-assisted preparation of cyclodextrin-based chiral stationary phase was developed for
enantioseparations in HPLC.