Gas-stimuli-responsive molecularly imprinted polymer particles with switchable affinity for target protein

Article abstract of DOI:10.1039/c7cc09889h

Gas-responsive molecularly imprinted polymer (MIP) particles, which have nanocavities in their shell layer for protein recognition, were developed for the first time. The MIP particles showed higher affinity for the target protein inside a CO₂-

Full text of DOI:10.1039/c7cc09889h

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: Y. Kitayama and
M. Isomura, Chem. Commun., 2018, DOI: 10.1039/C7CC09889H.
This is an Accepted Manuscript, which has been through the
Volume 52 Number
1 4 January 2016 Pages 1–216
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Accepted Manuscripts are published online shortly after
Chemical Communications
www.rsc.org/chemcomm
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 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
=
3
rsc.li/chemcomm

Please do not adjust margins
ChemComm
Page 1 of 5
View Article Online
DOI: 10.1039/C7CC09889H
Journal Name
COMMUNICATION
Gas‐Stimuli‐Responsive Molecularly Imprinted Polymer Particles
with Switchable Affinity for Target Protein
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Y. Kitayamaa M. Isomuraa
www.rsc.org/
Gas‐responsive molecularly imprinted polymer (MIP) particles, solvent was used as external stimuli for switching the recognition
which have nanocavities in their shell layer for protein properties.17‐23 Furthermore, the stimuli responsive properties
recognition, were developed for the first time. The MIP particles enabled MIPs to be used in various advanced applications, such as
showed higher affinity for the target protein inside a CO2–treated treatment of antibiotic‐resistant bacteria, control of cell adhesives
aqueous medium as compared to that under N2–treated and programmable downregulation of enzyme activity.24‐26
conditions, while retaining selectivity to the target protein.
Herein, gas‐stimuli responsive MIP particles having switchable
Development of molecular recognition materials has been recognition capability and respond to carbon dioxide (CO2) and
attracting much attention because of their significant contribution nitrogen (N2) as gas stimuli have been developed (Scheme 1). We
to various research and industrial fields, such as environmental used
a gas‐responsive initiator, 2,2’‐azobis[2‐(2‐imidazolin‐2‐
analysis, protein purification, clinical diagnosis, sensors, drug yl)propane] (VA‐061), which has imidazoline groups as a functional
monitoring, and therapy.1‐5 Genetically translated proteins such as initiator (FI) that can target proteins for the preparation of gas‐
antibodies and enzymes, which are known to show molecular stimuli responsive MIP particles. In the molecular imprinting
recognition properties, are widely used in the above mentioned process, FI can interact to template molecules and decomposed to
applications. However, these protein‐based molecular recognition initiator radicals for starting the polymerization, and the initiator‐
materials are fragile and unamenable for further functionalization. derived functional groups must be introduced into the polymer
Artificial molecular recognition materials have great potential as chain end. After the polymerization of comonomer and crosslinking
alternatives to protein‐based materials because of their high agent, the template removal resulted in the imprinted cavities
stability and facile production process.
bearing imidazoline groups as interaction sites derived from FI.
Therefore, the initiator‐derived functional groups may be used as
interaction sites in the molecularly imprinted nanocavities. In this
study, the imidazoline groups inside nanocavities are reacted with
CO2 dissolved in water, forming their bicarbonate salt. The reverse
reaction proceeds by introducing N2 gas.27‐30 Therefore, the
functional groups can be controlled from charged state to
uncharged state via introducing CO2 and N2, respectively. If the
molecular imprinting process was demonstrated in the CO2‐treated
condition, the imprinted cavities were constructed with protonated
imidazoline groups as interaction sites. Therefore, the affinity
toward target molecules would be greater in CO2‐treated condition
compared to N2‐treated condition in which unprotonated
imidazoline groups are present in cavities as interaction sites.
These gases are abundant, inexpensive, and non‐toxic. In particular,
the gas‐responsive materials are advantageous over pH‐responsive
materials based on a conventional acid or base, because salt
accumulation in the latter case weakens the response. More
importantly, CO2 is biocompatible because it is naturally generated
in human cells as one of the important metabolites. Consequently,
gas‐responsive molecular recognition materials have great potential
for use in bio‐related applications. In this study, for the first time,
Molecularly imprinted polymers (MIPs) are known to be promising
artificial materials as substituents of natural antibodies.6‐16 MIPs are
synthesized by molecular imprinting; radical polymerization is
carried out in the presence of template molecules that interact with
functional molecules, co‐monomers, and crosslinking agents to
yield
a polymer matrix around the template molecules.
Subsequently, template removal from the crosslinked polymers
furnishes MIPs bearing three‐dimensional nanocavities that can
recognize the target molecules whose sizes and shapes are
complementary to those of the nanocavities. In a typical MIP
synthesis, a wide range of vinyl monomers and initiators can be
used as building blocks, and functional molecular recognition
materials can be fabricated by using functional building blocks.7, 11
Recently, a method for synthesizing stimuli‐responsive MIPs was
developed, wherein temperature, light, pH, biomolecule, ion and a
a. Graduate School of Engineering, Kobe University, 1‐1, Rokkodai‐cho, Nada‐ku,
Kobe 657‐8501, Japan
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 1
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 5
View Article Online
DOI: 10.1039/C7CC09889H
COMMUNICATION
Journal Name
gas stimuli were applied for the switchable molecular recognition (Figure S4). After the seeded polymerization was complete, the
properties of MIPs, where a protein with a fragile tertiary structure obtained particles were washed by centrifugation with an aqueous
was used as the target molecule.
solution of
a
surfactant and tris(2‐carboxyethyl)phosphine
hydrochloride to remove the remaining monomer species and
template HSA. The dz value of the core‐shell HSA‐imprinted
particles (HEMA‐VA061_MIP) was ~158 nm (zeta potential: +25
mV), indicating that a molecularly imprinted polymeric shell layer of
around 20 nm was successfully created. (Figure S5) Non‐imprinted
polymer (HEMA_VA061‐NIP) particles, which served as reference
particles, were also synthesized by the same procedure but in the
absence of the template HSA.
Scheme 1. Gas‐responsive property of VA‐061
To examine the binding activity, HSA was incubated with HEMA‐
VA061_MIP particles dispersed in the aqueous solution treated with
CO2, and the amount of bound HSA was estimated by microBCA
assay of the supernatant obtained after the centrifugal separation
of the particles. The amount of HSA bound to the HEMA‐
VA061_MIP particles increased as the concentration of HSA
increased. From the binding isotherm, the binding constant (Ka) was
estimated to be 2.06 × 107 M‐1 (Figure 1 and Figure S6). In addition,
the affinity of the HEMA‐VA061_MIP particles toward HSA was
clearly higher than that of the HEMA‐VA061_NIP particles (Ka = 1.50
× 106 M‐1) in the CO2‐treated water. The bound amount of HSA
increased linearly in the case of HEMA‐VA061_NIP, which indicated
Scheme 2. Gas‐responsive core‐shell MIP particles having
molecularly imprinted polymer shell layer.
a
Herein, human serum albumin (HSA) was selected as the model that HSA was non‐specifically bound to these particles. To estimate
target protein. To investigate the gas responsiveness of VA‐061, the the effect of molecular imprinting, we adopted an imprinting factor
chemical shifts were measured by 1H‐NMR using D2O as the solvent (IF), which is defined as the ratio of the Ka values of MIP particles to
after treating it with CO2 and N2. The proton peaks derived from the that of NIP particles. The calculated value was approximately 13.7.
ethylene moiety in the imidazoline groups ( = 3.55, before CO2 Consequently, the molecular imprinting process was determined to
treatment) were shifted toward lower magnetic fields after CO2 be successful in the case of the HEMA‐VA061_MIP particles.
bubbling ( = 3.97). However, subsequent N2 treatment, the
chemical shift was measured at higher magnetic fields ( = 3.77)
(Figure S1). In the case of 2,2’‐azobis[2‐(2‐imidazolin‐2‐yl)propane]
hydrochloride (VA‐044), the chemical shift of the proton peaks,
which is due to the ethylene group in the imidazoline, remained
unaffected after the CO2 and N2 introduction ( = 3.85 (Figure S2)).
This indicated that deprotonation via gas introduction did not occur
in the hydrochloride salt state but occurred in the bicarbonate salt
state formed upon CO2 introduction. These results revealed that the
protonation and deprotonation states for VA‐061 can be switched
via CO2 and N2 gas treatment.
Gas‐responsive core‐shell type MIP particles were prepared using
VA‐061 as an FI by
a two‐step emulsifier‐free emulsion
polymerization; consequently, molecularly imprinted nanocavities
were created only in the shell layer for high protein accessibility.31‐
Figure 1. HSA binding isotherms of HEMA‐VA061_MIP in CO2‐
treated aqueous phase (a), HEMA‐VA061_NIP in CO2‐treated
aqueous phase (b), and HEMA‐VA061_MIP in N2‐treated aqueous
phase (c). The particles were prepared at 40 °C.
33
The seed particles were synthesized by the emulsifier‐free
emulsion polymerization of styrene (S) and divinylbenzene (DVB)
with VA‐061 in CO2‐treated water. The z‐average particle size (dz) of
P(S‐DVB) particles was ~117 nm (zeta potential: +48 mV) (Figure
S3). Subsequently, core‐shell MIP particles, which contain molecular
recognition nanocavities in the shell layer, were prepared by the
emulsifier‐free seeded polymerization of 2‐hydroxyethyl
The selectivity of the HEMA‐VA061_MIP particles to HSA was
examined using reference proteins such as immunoglobulin G (IgG:
150 kDa, pI=6.0 – 8.0), cytochrome c (Cyt: 11 kDa, pI=10.2), and
lysozyme (Lys: 14 kDa, pI=11.1). The evaluated selectivity factor (SF)
values for the HEMA‐VA061_MIP particles in CO2‐treated water
were 0.25, ‐0.11, and 0.04 in the case of IgG, Cyt, and Lys,
respectively. (Figure 2) On the other hand, the HEMA‐VA061_NIP
particles did not show selective binding to HSA (0.67, 0.86, and 1.37
for IgG, Cyt, and Lys, respectively). These results indicated that the
methacrylate
(HEMA)
as
a
comonomer
and
N,N’‐
methylenebisacrylamide (MBAA) as a crosslinker using VA‐061 as an
FI. HSA (66 kDa, pI=4.7) was used as a template in the presence of
P(S‐DVB) seed particles dispersed in CO2‐treated water at 40 °C,
where the template HSA was not denatured in CO2‐treated water
2 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 3 of 5
View Article Online
DOI: 10.1039/C7CC09889H
Journal Name
COMMUNICATION
HSA recognizing nanocavities were successfully formed in the HEMA‐VA061_MIP particles reversibly changed but the colloidal
HEMA‐VA061_MIP particles via molecular imprinting.
stability was maintained.
To evaluate the gas‐responsive recognition properties of the HEMA‐
VA061_MIP particles prepared at 40°C, a responsive factor (RF),
defined as the ratio of the Ka values of the MIP particles in the CO2‐
treated aqueous phase to that under N2‐treated conditions, was
adopted. The affinity constant of these particles for HSA (Ka = 8.78 ×
105 M‐1), which was estimated from the binding isotherm of the
HEMA‐VA061_MIP particles dispersed in N2‐treated water, was ~23
times smaller than that of the MIP particles in CO2‐treated water
(RF: 23). (Figure 1) Thus, switching of the gas‐based affinity was
successfully demonstrated in the HEMA‐VA061_MIP particles. The
switching property should be caused by the gas‐responsive
property of interaction sites derived from FI between charged and
uncharged states, and the reversibility could be repeated more than
3 times (Figure S12).
Figure 2. Results of the selectivity test of HEMA‐VA061_MIP in CO2‐
treated aqueous phase (a), HEMA‐VA061_NIP in CO2‐treated
aqueous phase (b), and HEMA‐VA061_MIP in N2‐treated aqueous
phase (c). The protein concentration was 150 nM. The particles
were prepared at 40 °C.
Furthermore, the SF values for HEMA‐VA061_MIP particles
prepared at 40 °C slightly worse in N2‐treated water, i.e., 0.44, 0.14,
and 0.11 for IgG, Cyt, and Lys, respectively compared to CO2‐treated
condition, but selective binding ability to HSA was maintained.
(Figure 2) The results are reasonable because nanocavities showing
affinity to HSA were formed via the molecular imprinting process,
and the nanocavity structure was preserved during N2 treatment.
The interaction sites (imidazoline groups) were more active under
the CO2‐treatment condition, which led to greater affinity and
selectivity to HSA. It is worth noting that the gas‐responsive
molecular recognition property was also confirmed for HEMA‐
VA061_MIP particles prepared at 65 °C with similar gas‐responsive
colloidal property (Figure S13), i.e. the greater affinity toward HSA
was confirmed in CO2‐treated water (Ka= 6.41×106 M‐1) than that for
N2‐treated water (Ka= 1.79×106 M‐1), but the gas‐responsiveness
was clearly lower than that for HEMA‐VA061_MIP‐NPs prepared at
40 °C (Figure S9).
To investigate the effect of polymerization temperature during the
molecular imprinting process on the recognition properties of the
HEMA‐VA061_MIP particles, another batch of MIP particles was
synthesized by the same procedure at 65 °C, and their binding
affinity and selectivity were evaluated. It is known that the
template HSA is not denatured below 70 °C.34 The HEMA‐
VA061_MIP particles thus obtained had particle sizes and colloidal
properties similar to those of the particles prepared at 40 °C.
(Figure S7) From the HSA binding isotherm of the HEMA‐
VA061_MIP particles prepared at 65 °C, the binding affinity, Ka, was
found to be 6.41×106 M‐1 in the CO2‐treated water, which was 4.2
times greater than that of HEMA‐VA061_NIP particles prepared at
65 °C (IF: 4.2, Ka=1.54×106 M‐1). However the binding affinity was
3.2 times smaller than that of the MIP particles prepared at 40 °C
(Ka = 2.06 × 107 M‐1). (Figures S8 and S9) The selective binding
capability of the HEMA‐VA061_MIP particles prepared at 65°C was
confirmed (0.06, 0.43, and 0.66 for IgG, Cyt, and Lys, respectively, in
CO2), but the selectivity was poorer when compared to that of the
HEMA‐VA061_MIP particles prepared at 40 °C. (Figure S10) These
results indicate that the polymerization temperature is an
important factor and that a lower polymerization temperature is
favorable for creating nanocavities with precise recognition ability,
high affinity, and high selectivity.
Since the polymer matrix constitutes nanocavities, the creation of
nanocavities is independent of the comonomer species. However,
the nature of the comonomers should influence the non‐specific
binding on the polymer matrix. To investigate the versatility of our
proposed molecular imprinting process and the effect of the
comonomer on the binding affinity, the selectivity and gas‐
responsive properties of the MIP particles, two additional water‐
soluble comonomers, i.e., N‐isopropylacrylamide (NIPAm) and
di(ethyleneglycol) methyl ether methacrylate (DEGMA), were used
for the MIP particle synthesis. The MIP particles thus obtained had
similar particle sizes (dz values: 149 nm and 138 nm, respectively).
(Figures S14) For all the MIP particles, saturable binding isotherms
were observed under the CO2‐treatment conditions, whereas linear
binding profiles were observed under the N2‐treatment conditions.
(Figure 3) The estimated binding affinity values for the NIPAm‐
VA061_MIP and DEGMA‐VA061_MIP particles in CO2 were
Ka=8.74×106 M‐1 and Ka=1.03×107 M‐1, respectively. The affinity
values for both MIP particles decreased in N2 (Ka=3.14×106 M‐1 and
Ka=1.40×106 M‐1, respectively), where the RF values were 2.8 and
7.4, confirming gas responsiveness for all the comonomers used in
this study. (Figures 3 and S15) The SF values in the case of the MIP
particles using NIPAm in CO2 were 0.34, 0.74, and 0.85 for IgG, Cyt,
The gas‐responsive properties of the HEMA‐VA061_MIP particles
were examined via binding experiments using CO2‐ and N2‐ treated
aqueous solutions. First, to investigate the gas responsive colloidal
properties of the HEMA‐VA061_MIP particles, CO2 treatment was
carried out for 90 min, followed by N2 treatment for 90 min. The dz
value of the MIP particles was similar during these gas treatments
(~156 nm after CO2 treatment and ~160 nm after N2 treatment),
whereas the zeta potential was clearly increased after CO2
treatment (+37 mV) and the value was clearly decreased after the
N2 treatment (+17 mV). The zeta potential value after N2 treatment
was back to that before CO2 treatment (+ 25 mV). (Figure S11) This
indicated that the electrostatic properties of the shell layer of the
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 5
View Article Online
DOI: 10.1039/C7CC09889H
COMMUNICATION
Journal Name
and Lys, respectively. The corresponding values for the MIP particles The authors deeply appreciate Prof. Toshifumi Takeuchi for his
using DEGMA were 0.38, 0.39, and 0.71 in the case of IgG, Cyt, and fruitful discussion. This work was supported by JSPS KAKENHI (Grant
Lys. (Figure 3) These results indicated that all MIP particles prepared number 25870429) and partially supported by Hosokawa Powder
using the three different comonomers showed HSA‐specific binding Technology Foundation, Japan and Kawanishi Memorial Shin Meiwa
capability with gas‐responsive recognition property, and that Education Foundation, Japan.
molecular imprinting with FI could be applied to the various
Conflicts of interest
comonomers. The smallest extent of non‐specific binding of off‐
target proteins was confirmed in the HEMA‐VA061_MIP particles,
which may be due to the highest hydrophilicity of this comonomer
among the selected comonomers in this study, i.e., the logP values
estimated by Pallas were 0.54 for HEMA, 0.87 for NIPAm, and 1.01
for DEGMA. The worse Ka and SF values for NIPAm‐VA061_MIP
particles may be caused by the non‐specific binding based on the
hydrogen bonding to amide group in NIPAm. Therefore, selection of
the appropriate hydrophilic comonomer is important for precise
molecular recognition due to the decrease in the non‐specific
binding of the off‐target proteins.
There are no conflicts to declare.
Notes and references
1. C. Souriau and P. J. Hudson, Expert Opin. Biol. Ther., 2001, 1, 845.
2. A. Sassolas, B. D. Leca‐Bouvier and L. J. Blum, Chem. Rev., 2008, 108,
109.
3. K. Tawa, F. Kondo, C. Sasakawa, K. Nagae, Y. Nakamura, A. Nozaki and T.
Kaya, Anal. Chem., 2015, 87, 3871.
4. Y. Jiang, M. L. Shi, Y. Liu, S. Wan, C. Cui, L. Q. Zhang and W. H. Tan,
Angew. Chem. Int. Ed., 2017, 56, 11916.
5. T. A. Waldmann, Science, 1991, 252, 1657.
6. K. Haupt, Molecular imprinting, Springer, Berlin, 2012.
7. T. Takeuchi, H. Sunayama, E. Takano and Y. Kitayama, in Molecularly
imprinted polymers in biotechnology, eds. B. Mattiasson and L. Ye, 2015, vol.
150, pp. 95‐106.
8. D. E. Hansen, Biomaterials, 2007, 28, 4178.
9. K. Mosbach, Trends Biochem. Sci., 1994, 19, 9.
10. G. Wulff, Angew. Chem. Int. Ed. Engl., 1995, 34, 1812.
11. R. Horikawa, H. Sunayama, Y. Kitayama, E. Takano and T. Takeuchi,
Angew. Chem. Int. Ed., 2016, 55, 13023.
12. A. Kawamura, T. Kiguchi, T. Nishihata, T. Uragami and T. Miyata, Chem.
Commun., 2014, 50, 11101.
13. K. Takimoto, E. Takano, Y. Kitayama and T. Takeuchi, Langmuir, 2015, 31, 4981.
14. T. Takeuchi, T. Mori, A. Kuwahara, T. Ohta, A. Oshita, H. Sunayama, Y.
Kitayama and T. Ooya, Angew. Chem. Int. Ed., 2014, 53, 12765.
15. Z. J. Zhang, Y. J. Guan, M. Li, A. D. Zhao, J. S. Ren and X. G. Qu, Chem.
Sci., 2015, 6, 2822.
16. Z. J. Zhang, M. Li, J. S. Ren and X. G. Qu, Small, 2015, 11, 1258.
17. Y. Kanekiyo, R. Naganawa and H. Tao, Angew. Chem. Int. Ed., 2003, 42, 3014.
18. Z. Y. Chen, L. Xu, Y. Liang and M. P. Zhao, Adv. Mat., 2010, 22, 1488.
19. W. T. Wu, J. Shen, Y. X. Li, H. B. Zhu, P. Banerjee and S. Q. Zhou,
Biomaterials, 2012, 33, 7115.
Figure 3 HSA binding isotherms in CO2‐ and N2‐treated water (a, c)
and selectivity test of NIPAm‐VA061_MIP (b) and DEGMA‐
VA061_MIP (d). The particles were prepared at 40 °C. Affinity
constants estimated from binding isotherm of HSA for HEMA‐
VA061_MIP, NIPAm‐VA061_MIP, and DEGMA‐VA061_MIP to HSA in
CO2‐ and N2‐treated water (e).
20. W. Chen, Y. Ma, J. M. Pan, Z. H. Meng, G. Q. Pan and B. Sellergren,
Polymers, 2015, 7, 1689.
In conclusions, novel gas‐stimuli responsive core‐shell MIP particles
having nanocavities in the shell layer that are capable of molecular
recognition were successfully synthesized. A gas‐responsive initiator
was used as a functional molecule that interacted with a specific
target protein. The affinity toward this target protein was
controlled by the introduction of gases having selective binding
properties. Greater affinity was observed in the CO2‐treated
aqueous phase as compared to that under N2‐treatment conditions.
Furthermore, the versatility of the molecular imprinting process,
which used a gas‐responsive FI for gas‐responsive MIP synthesis,
was successfully confirmed by using different types of comonomers.
We believe that the gases act as better stimulants than other
stimuli because gases like CO2 and N2 are abundant, inexpensive,
and non‐toxic. In addition, CO2 is a key metabolite in cells and helps
in maintaining the intracellular pH. Therefore, we hope that the
21. K. Yoshimatsu, B. K. Lesel, Y. Yonamine, J. M. Beierle, Y. Hoshino and K.
J. Shea, Angew. Chem. Int. Ed., 2012, 51, 2405.
22. W. Bai, N. A. Gariano and D. A. Spivak, J. Am. Chem. Soc., 2013, 135, 6977.
23. M. Watanabe, T. Akahoshi, Y. Tabata and D. Nakayama, J. Am. Chem.
Soc., 1998, 120, 5577.
24. G. Q. Pan, Q. P. Guo, Y. Ma, H. L. Yang and B. Li, Angew. Chem. Int. Ed.,
2013, 52, 6907.
25. W. Li, K. Dong, J. S. Ren and X. G. Qu, Angew. Chem. Int. Ed., 2016, 55, 8049.
26. Z. J. Zhang, Z. Z. Wang, F. M. Wang, J. S. Ren and X. G. Qu, Small, 2015,
11, 6172.
27. D. H. Han, X. Tong, O. Boissiere and Y. Zhao, ACS Macro Lett., 2012, 1, 57.
28. X. Su, P. G. Jessop and M. F. Cunningham, Macromolecules, 2012, 45, 666.
29. C. I. Fowler, P. G. Jessop and M. F. Cunningham, Macromolecules, 2012, 45,
2955.
30. Y. X. Liu, P. G. Jessop, M. Cunningham, C. A. Eckert and C. L. Liotta, Science,
2006, 313, 958.
31. A. Uchida, Y. Kitayama, E. Takano, T. Ooya and T. Takeuchi, RSC Adv., 2013,
3, 25306.
32. N. Murase, S. Taniguchi, E. Takano, Y. Kitayama and T. Takeuchi, J. Mat.
Chem. B, 2016, 4, 1770.
aforementioned
gas‐based
stimuli‐responsive
molecular
recognition materials will be used in various biological applications,
such as reversible affinity chromatography, reusable sensors,
functional substrates for cell adhesive control, and analytical tools
for cells to identify metabolic disorders.
33. N. Murase, S. I. Taniguchi, E. Takano, Y. Kitayama and T. Takeuchi,
Macromol. Chem. Phys., 2015, 216, 1396.
34. T. Takeuchi, Y. Kitayama, R. Sasao, T. Yamada, K. Toh, Y. Matsumoto and K.
Kataoka, Angew. Chem. Int. Ed., 2017, 56, 7088.
4 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 5
ChemComm
View Article Online
DOI: 10.1039/C7CC09889H
Table of Contents
Molecularly imprinted polymer particles bearing gas-responsive property was successfully
prepared using functional initiator