SCIENCE CHINA Chemistry • REVIEWS • · SPECIAL ISSUE · Recent Research Progress of Biomedical Polymers
April 2014 Vol.57 No.4: 540–551 doi: 10.1007/s11426-013-5059-6
Chiral polymer-based biointerface materials LI MinMin, QING GuangYan, ZHANG MingXi & SUN TaoLei* State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China Received October 22, 2013; accepted November 18, 2013; published online February 27, 2014
Chirality is a unique phenomenon in nature. Chiral interactions play an important role in biological and physiological processes, which provides much inspiration for scientists to develop chiral materials. As a breakthrough from traditional materials, biointerface materials based on chiral polymers have attracted increasing interest over the past few years. Such materials elegantly combine the advantages of chiral surfaces and traditional polymers, and provide a novel solution not only for the investigation of chiral interaction mechanisms but also for the design of biomaterials with diverse applications, such as in tissue engineering and biocompatible materials, bioregulation, chiral separation and chiral sensors. Herein, we summarize recent advances in the study of chiral effects and applications of chiral polymer-based biointerface materials, and also present some challenges and perspectives. chirality, polymer, chiral interaction, biointerface materials, chiral effects, applications
1 Introduction Since the term “chirality” was first introduced by Lord Kelvin in 1894 [1], it has long been a hot topic attracting the interest of researchers in the fields of chemistry, biology and material science. In general, chirality is used to describe the geometric characteristic of an object that is not superimposable on its mirror image, and pervades much of modern science from elementary particles to living systems. The hallmark of living systems is their chirality [2]. On one hand, a significant biochemical signature is high chiral preference for biomolecules—from chiral small molecules such as L-amino acids and D-sugars, to biomacromolecules with special steric conformations and optical activity, like proteins and DNA [3]. On the other hand, chiral interactions play important roles in some biological and physiological processes, such as molecular recognition and intercellular signal transduction [4]. Therefore, the chiral signature of living systems provides the inspiration to introduce chirality *Corresponding author (email:
[email protected]) © Science China Press and Springer-Verlag Berlin Heidelberg 2014
in the design of artificial materials, which will lead to innovative changes in the development of biomaterials [5]. As an important class of biomaterials, polymers have been widely applied in biomedicine due to their biocompatibility, easy programmable design and the tailorability of their compositions and functions [6]. However, the design for biomedical polymers based on traditional chemical compositions, structures and properties do not meet the requirements for practical applications in vivo. Hence, chiral effects in biosystems should be considered as an important factor to prepare biomedical polymers with better compatibility and various biofunctions. Furthermore, interfacial interactions between biomaterials and biological systems play prominent roles in the expression of material performance, and thus the biointerface is vitally important for biomedical applications in vivo or in vitro [7]. Given these considerations, chiral polymer-based biointerface materials have emerged as a new research field providing an ideal solution to counterbalance the shortcomings of traditional biomedical polymers [8], since they not only possess the traditional advantages of biomedical polymers, but also exhibit some special behavior due to the introduction of chem.scichina.com
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chirality, such as stereoselective interactions and stereospecific recognition. In the study of chiral polymer-based biointerface materials, the fundamental chiral effects have been understood in part and applications have been developed as a result of the efforts of different groups [9–12]. However, research into the fundamental mechanisms and relevant applications for chiral polymers is still in the initial stages and thus there are many challenges in this emerging field. From fundamental chiral effects to relevant applications, this review briefly summarizes recent advances in the area of chiral polymer-based biointerface materials, and some ideas about the existing challenges and development perspectives are also presented.
2 Fabrication of chiral polymer-based interface materials Currently, there are two main methods for the fabrication of chiral polymer-based biointerface materials. One is the direct growth of chiral polymers on the surface of a substrate, which mainly involves surface-initiated polymerization. The other is anchoring or coating the pre-synthetic chiral polymer on a substrate by means of chemical grafting or physical adsorption. Given the range of different chiral polymers and different application requirements, the appropriate choice of fabrication method is vitally important for the exploration of chiral effects and applications of chiral polymer-based biointerface materials. 2.1 Synthesis of chiral polymers Learning from naturally occurring polymers, such as proteins and nucleic acids, research on the synthesis and application of chiral polymer has attracted increasing interest. Generally speaking, chiral polymers usually exhibit two types of chirality: main-chain chirality and side-chain chirality. Like the main-chain chiral polypeptides, polysaccharides and helical DNA, the occurrence of main-chain chirality in synthetic polymers mainly arises from the presence of chiral carbon atoms or a helical configuration in the mainchain, which is constructed from chiral monomers or prochiral monomers by means of one of several synthesis methods, such as free radical polymerization [13–15], condensation polymerization [16, 17], cyclopolymerization [18] and asymmetric polymerization [19, 20]. Chiral helical polymers have received intense attention owing to their helicity arising from hydrogen bonds or van der Waals forces. Scientists have developed chiral helical polymers for various applications, including the separation of enantiomers [21], asymmetric catalysis [22], chiral liquid crystals (LCs) [23], and nonlinear optical materials [24]. In the case of side-chain chirality, the chirality of the polymer originates from chiral side groups linked to the
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main chain formed by addition polymerization of vinyl monomers [25, 26]. Such an approach provides an efficient route to prepare various functional chiral polymers with varying chiral functional groups. For example, Sun et al. [27] recently synthesized a series of chiral polymeric films based on side-chain chirality via surface-initiated polymerization of acryloyl monomers for the investigation of stereoselective adhesion behavior of cells. 2.2
Surface-grafting approaches
Surface-grafting of a polymer film on a substrate can be accomplished by either “grafting to” or “grafting from” methods (Figure 1(a)), which provide versatile tools for surface modification and functionalization. The “grafting to” technique is based on the reaction between end-functionalized polymer chains and functional groups immobilized on the substrate to form a polymer brush film [28]. For example, Kressler et al. [29] recently prepared self-assembled films using the “grafting to” method from chiral poly (glycerol methacrylate)s, and they further studied the anti-biofouling properties of these films. The “grafting from” approach mainly involves surface-initiated polymerization, and surface-initiated atom transfer radical polymerization (SI-ATRP) has been successfully employed to prepare various polymer brush films under mild conditions [30, 31]. For example, Jiang et al. [32] reported a novel chiral stationary phase synthesized via the combination of SI- ATRP and click chemistry on the surface of porous silica gel. They found that the grafted film was uniform and dense, and did not suffer from the common problem of poor stability. Therefore, using the surface-grafting method for the fabrication of chiral polymer films allows the controllable orientation of chiral motifs and a high density of functional groups to be obtained, and provides a versatile method to fabricate chiral polymer-based biointerface materials. 2.3 Coating methods In material science, coating methods, such as drop-casting, dip-coating and spin-coating, are commonly used to fabricate thin films [33] (Figure 1(b)). By means of these methods,
Figure 1 Schematic of the fabrication of chiral polymer-based biointerface materials using several different methods. (a) Surface-grafting approaches; (b) coating method; (c) electrophoretic deposition.
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a series of chiral polymers readily form polymer films on spherical [34] or flat substrates [35, 36] for diverse applications. For example, Pochan et al. [37] investigated the phase behavior of poly(-benzyl-L-glutamate)-block copolymer films which were prepared by drop-casting from various polymer solvents. Fujiki et al. [38] prepared a chiral helical polysilane film by drop-casting using helical polysilanes as the solution and investigated the chiroptical switching and chiroptical memory of the resulting film. Compared with the chemical grafting method, the coating method is a simple and convenient approach to fabricate chiral polymer films on pre-existing substrates, such as glass slides, gold, mica and silicon wafers. 2.4
Electrochemical methods
Electrochemical methods are attracting increasing attention as a novel and effective strategy to prepare chiral polymer films for biomedical applications [39, 40]. Compared with other methods, electrochemical methods provide the possibility to prepare chiral polymer films on irregularly shaped or large-scale substrates, which brings us closer to practical applications. Recent studies of electrophoretic deposition (EPD) of biopolymers have shown that EPD is ideally suited for the fabrication of chiral polymer films [41]. In 2011, Zhitomirsky et al. [42] prepared poly-L-lysine (PLL) and poly-L-ornithine (PLO) films by means of EPD on conductive substrates (Figure 1(c)). Therefore, the preparation of chiral PLL and PLO films via EPD paves a new way for the fabrication of chiral films and polymer/inorganic phases (for example hydroxyapatite) composite films for biomedical applications, such as biomedical implants and biosensors.
3 Chiral effects in chiral polymer-based biointerface materials With the development of biomaterials, the chiral preference of biosystems prompts us to study the interaction between intrinsic chiral biosystems and artificial chiral materials. Such research not only helps us to understand chiral interaction mechanisms but also promotes applications of the chiral effects in practical systems. Therefore, the chiral effects of chiral-polymer based biointerface materials are summarized from the following three aspects: the cell level, the protein level and the small molecule level. 3.1 Stereoselective adhesion of cells Cell-surface interactions have long been an important research topic and play a vital role in biomaterial applications. Thus, the chemical and physical properties of material surfaces significantly influence applications of synthetic materials in vivo or in vitro [43, 44], such as implant materials,
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tissue engineering, biodetection and drug delivery. With the excellent controllability of surface properties, some smart interface materials based on poly(N-isopropylacrylamide) (PNIPAAm) have been developed and applied for modulating the interfacial behaviors of cells [45–47]. However, what will happen when a chiral living system encounters a chiral material surface remains to be answered. In addressing this question, some research groups have made great efforts and reported some initial findings [48–50]. Related investigations of the stereoselective interactions between cells and chiral surfaces have also attracted more and more interest. For example, Addadi et al. [51] reported a pioneering study which showed that epithelial cells exhibited different adhesion behavior on the chiral surface of calcium tartrate tetrahydrate crystals. Recently, Kehr et al. [52] successfully showed that cells recognized enantiomorphous self-assembled monolayers (SAMs) of zeolite L nanocrystals selectively functionalized with D- and L-penicillamine, which offers a novel strategy for separating one type of cell in the presence of the other. However, compared with the relatively weak chiral characteristics and fragile nature of monolayer films, chiral polymer films have significant advantages for practical applications. In 2010, our research group developed a novel chiral polymer brush film based on chiral poly-valine (denoted as L-PV and D-PV) formed via surface initiated atom transfer radical polymerization (SI-ATRP) from N-acryloylL(D)-valine and showed that COS-7 cells preferred to adhere and grow on the L-PV film rather than the D-PV film at different incubation stages [9]. In addition, COS-7 cells showed significant cross-linking on the L-PV film, while exhibiting a relatively rough round morphology on the D-PV film. Later, we expanded this research to three pairs of chiral polymer films based on aliphatic amino acids with different side groups [27]. Similarly, COS-7 cells were used to investigate the cell behavior on the chiral polymer brush surfaces. We found that the number of cells on the L-films was higher than that on the D-films, which clearly indicates that COS-7 cells prefer the L-surface to the D-surface (Figure 2(a)). In brief, these effects demonstrated that chiral polymer interface materials can trigger differential cell behavior on the chiral surfaces. Biodegradable polymers have attracted increasing interest in the past three decades, one important example being polylactide materials which have been widely used in tissue engineering and drug delivery systems [53, 54]. However, there have been few investigations of the chiral effects of polylactides on cell proliferation and differentiation. In 2009, Gu et al. [10] studied chiral effects on the behavior of osteoblastic cells on the surface of chiral poly-lactides. They prepared poly(L-lactide) (PLLA), poly(D-lactide) (PDLA), poly(DL-lactide) (PDLLA) and the stereocomplex of PLLA and PDLLA films. Scanning electron microscopy images of osteoblastic ROS17/2.8 cells on the films indicated that ROS17/2.8 cells prefer to attach to L-films
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Figure 2 (a) Fluorescent images of COS-7 cells on chiral polymer brush films after 24 h incubation [27]; (b) SEM images of ROS 17/2.8 cells on chiral polylactide films after 24 h [10].
(PLLA and PDLLA films) relative to the D-film (PDLA), and exhibited spindly morphologies and spherical shapes respectively (Figure 2(b)). Moreover, all the levels of total protein amount, DNA content and alkaline phosphatase (ALP) activity of ROS17/2.8 cells on the D-film (PDLA) were much lower than the corresponding values for the L-films (PLLA and PDLLA films). Thus, the biological responses of ROS17/2.8 cells clearly depend on the stereoconfiguration of the polylactides. These studies provide much inspiration for us to develop chiral polymer surfaces for controlling the interaction between cells and material surfaces. On one hand, the use of chiral biointerface materials for cell adhesion rather than traditional materials allows us take full advantage of natural chiral sources, such as amino acids and lactides, to develop biomaterials with better biocompatibility and diverse functionality. On the other hand, the introduction of chirality into cell-material interactions may significantly help in understanding chiral effects and the origin of chirality in nature. 3.2
Enantioselective adsorption of proteins
Interactions between material surfaces and proteins have also been recognized as important roles in biomedical applications, such as implanted materials, biosensors and protein delivery. Generally, it is known that the first response of implanted materials in vivo is the adsorption of proteins [55]. Thus, the adsorption of proteins on a material surface determines the biocompatibility of the material to some ex-
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tent [56]. In 2011, our group investigated protein adsorption on chiral surfaces based on chiral polymer brush films and chiral monolayer surfaces [11]. The quartz crystal microbalance (QCM) technique, which analyzes adsorption of molecules in situ by measuring the change in frequency (f) of a quartz crystal resonator, was used to evaluated protein adsorption on chiral surfaces. Two proteins—bovine serum albumin (BSA) and gelatin—both exhibited much stronger adsorption on an L-PV surface than on the corresponding D-PV surface (Figure 3(c)). Since the polymer film is negatively charged, and BSA and gelatin are negatively and positively charged respectively, the quantity of gelatin adsorbed was much larger than BSA on both L-film and D-film as a result of the electrostatic attraction. This also in turn clearly shows that stereoselective hydrophobic interactions between proteins and chiral surfaces play a dominant role in the selective adsorption of proteins, and the result of a recent study of the chiral recognition of L-gramicidine on a chiral methionine-modified gold surface is also in agreement with such a conclusion [57]. The above results were confirmed by the fact that when the polymer probe was titrated consecutively into the BSA fluorescein isothiocyanate conjugate (BSA-FITC) mother liquor in a fluorescence titration experiment, significant reductions in fluorescence intensity were observed for both the L-polymer and the D-polymer. However, the faster decrease in the fluorescence intensity of the L-PV polymer clearly showed that the affinity of L-PV for BSA is much stronger than that for D-PV. It is generally accepted that polymer brushes combined with comb-teeth functionalities have obvious advantages, including high coverage and no overlapping of polymer chains, as well as a high density of functional groups dispersed on the surface [58, 59]. To address this point, chiral monolayers of L(D)-valine monomers (denoted as L-MV and D-MV) were also prepared via the self-assembly process as a comparison with above results [11]. However, the difference in BSA adsorption between L-MV and D-MV is not significant, as shown in Figure 3(d). This result suggests that the weaker chiral characteristics of the SAMs significantly reduced the recognition of, and interaction efficiency with, proteins due to their ultrathin thickness and much lower chiral terminal group density. This in turn illustrates the advantages of chiral polymer brush films for chiral recognition and discrimination. This work indicates that chiral polymer surfaces may provide an excellent platform for the study of the stereoselective adsorption of proteins and may lead to the development of important applications, such as protein separation, biochips, and chiral biodevices. Subsequently, in order to explore the role of proteins in cell adhesion on chiral surface, Chen et al. [60] investigated protein adsorption on a chiral surface based on a L(D)cysteine modified gold surface. Figure 4(a) clearly indicates that fibrinogen (Fg) and fibronectin (Fn), which have rela-
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Figure 3 (a, b) CD spectra for poly-L(D)-valine (L(D)-PV) and the corresponding monomers N-acryloyl-L(D)-valine (L(D)-MV). The perfect mirror-image relationship between the CD spectra for the L(D)-PV polymers (a) and the much higher optical rotation activity compared with the monomers (b) indicate that the chirality was preserved and amplified after the polymerization process; (c, d) time-dependent curves of frequency change (∆f) in QCM experiments. BSA adsorption on chiral polymer brush film surfaces (c) and chiral monolayer surfaces (d) [11].
Figure 4 (a) SPR data for the adsorption of Fg, Fn, LYZ and HSA (50 μg/mL protein in PBS, pH 7.4, flow rate: 50 μL/min) on chiral surfaces [60]; (b) plasminogen adsorption on polymer films with different L-lysine densities [61].
tively large molecular weights, bind tightly on the chiral surface. However, the binding of the smaller lysozyme (LYZ) was comparatively weak. Meanwhile, the differences in surface plasmon resonance (SPR) measurements further revealed that the proteins were preferentially adsorbed onto the L-surface rather than the D-surface. Stereoselective non-covalent interactions, such as electrostatic interactions, hydrogen bonding and hydrophobic interactions significantly affected the adsorption of proteins. In recent work, Chen et al. [61] demonstrated that a chiral copolymer film with a high density of chiral sites obviously enhanced the interaction with proteins. Figure 4(b) shows the amount of plasminogen adsorbed on polymer film surfaces with different L-lysine densities. Among these, a deprotected copolymer film of L-lysine/2-hydroxyethyl- methacrylate (P(HEMA/Lys)-2) with a lysine density of 63.9 nmol/cm2 showed much higher adsorption than P(HEMA/Lys)-2 with
a lysine density of 11.6 nmol/cm2, which indicates that protein adsorption can be regulated by changing the lysine density of the polymer. The result confirms that the density of polymers on the surface, which directly determines the content of chiral interaction sites, significantly affects their functionality in various applications. The different extent of protein adsorption on chiral surfaces demonstrated in these studies provides guidelines for the rational design and fabrication of novel biomaterials and biorelated devices based on chiral effects. However, due to the diversity and complexity of proteins, the clear mechanisms of the adsorption of proteins on chiral surfaces remain unclear, and research is still in its infancy. Thus, further studies of the enantioselective adsorption of proteins on chiral polymer surfaces are required in order to develop novel biomedical polymer materials to meet diverse application requirements.
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3.3 Chirality-induced transformation of macroscopic properties In studies of chiral effects, chiroptical methods (i.e. circular dichroism and optical rotatory dispersion) are often employed to characterize or detect chiral signals at the nano- or micro-level. However, inspired by macroscopic chiral phenomena in nature (for example the specific rotation directions of shells), how to transform a chiral effect into macroscopic properties is significant for chirality-related applications. In this respect, chiral polymers provide an ideal solution to bridge the gap between chiral effects and bioapplications via a chiral signal-induced transformation of macroscopic properties giving characteristics that are easier to detect or even visible [62–64]. Surface wettability is one of the most important properties of materials, and thus controlling the wettability of a material surface is of great importance in fundamental science and industrial technology [65, 66]. In 2011, our group reported for the first time chirality-triggered wettability switching on smart copolymer films [67]. Based on a cooperative hydrogen bonding mechanism of responsive polymers, we developed a chiral copolymer film containing L-dipeptide (β-Asp-Phe) chiral recognition units. Such chiral copolymer films exhibited an obvious difference in water contact angle change (CA) when it treated with saccharide enantiomers. For example, for D- and L-lyxose solutions with a concentration of 0.05 mol/L, the CA values were about 52° ± 2° and 39° ± 2°, respectively (Figure 5(a)).
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Moreover, a chiral copolymer film was also prepared on a structured silicon substrate, and it exhibited a superhydrophobic property with a CA of about 157° ± 2°. Similarly, when the film was treated with lyxose enantiomers with a concentration of 0.05 mol/L, the maximum CA difference observed for L- and D-lyxose was about 93° (Figure 5(b)). The proposed mechanism is that monosaccharide molecules stereoselectively combine with the chiral dipeptide units through hydrogen bonding interactions, which destroys the original intramolecular hydrogen bonding system. Recently, Shundo et al. [12] demonstrated dynamic enantioselective wetting of a chiral polymer film for chiral discrimination. They synthesized a chiral polymer containing the flexible main chains of methacrylate, alkyl linkers, biphenyl moieties and alkyl terminal chains with a chiral center (Figure 5(c)), and then prepared chiral polymer films (S-P and R-P films). (S)- and (R)-1,2-propanediols (S-L and R-L) were used as probe liquids to measure the CA of films. The results for S-P and R-P films are shown in Figure 5(e). The initial CA on the S-P film for the S-L and R-L droplet were both 63°, yet the CA for R-L droplet decreased with increasing time and reached 41°. For the R-P film, the opposite result was found in that the stable CA after 30 s was smaller for S-L than for R-L. These results clearly suggest that the polymer films possess enantioselective wetting properties. Since the enantiomeric liquids contact the chiral film surface and induce the chiral surface to reorganize, such enantioselective wettability provides a visualizable method for enantiomer discrimination.
Figure 5 (a) Relationship between water CAs of a film on a flat silicon wafer and the concentrations of D- and L-lyxose solutions [67]; (b) relationship between CAs of the film on a structured silicon substrate and the concentrations of D- and L-lyxose solutions; (c) a chiral polymer containing a flexible main chain of methacrylate, alkyl linkers, biphenyl moieties and alkyl terminal chains with a chiral center [12]; (d) time-dependence of the contact angle of a mixture of S-L and R-L with various R-L fractions on the S-P film; (e) photograph showing the S-L and R-L droplets on the S-P and R-P films after 30 s.
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In summary, chirality-induced wettability switching provides a way to transform a weak chiral signal at the nano- or micro level into macroscopic properties. However, surface wettability is only one of the significant macroscopic properties of materials, and how to realize a variety of other transformations from microscopic chirality to macroscopic properties via chiral polymer films is still a challenge, but progress in this area will greatly promote the application of chiral materials.
4 Applications of chiral polymer-based biointerface materials In the investigation of chiral effects, biorelated applications based on chiral materials have been explored in a wide range of fields. Chiral polymer-based biointerface materials, which contain a high density of chiral recognition sites, open up new opportunities for the fabrication of practical advanced functional materials, such as biocompatible materials, anti-biofouling materials, chiral separation materials and chiral biosensors. Herein, some emerging applications will be briefly introduced from three aspects: chiral antibiofouling, chiral separation and chiral sensors. 4.1
Chiral anti-biofouling
Biofouling is a series of undesired adhesion events that take place on various surfaces, owing to protein adsorption, cell adhesion and biofilm formation [68]. Anti-biofouling has emerged as a great challenge in the past few years [69, 70], since it has a wide range of significant applications, such as in biomedical implants, shipping, biosensors and carriers for drug delivery. In general, coating a surface with a bioinert component is one of the most universal and effective approaches for anti-biofouling [71]. However, the influence of surface stereochemistry on anti-biofouling has rarely been investigated. Here, the effects of surface chirality on anti-biofouling of materials are discussed in detail. In 2011, Luk and co-workers [72] investigated the antibiofouling properties of chiral polyol-terminated alkanethiol monolayer films. Swiss albino 3T3 fibroblasts were cultured on L-/D-gulitol-terminated surfaces and racemic mixture surface, and optical microscopy was used to monitor the process. Surprisingly, the D-surface was found to be more resistant to cell adhesion than the corresponding L-surface. Subsequently, they also examined the ability of such chiral polyol-terminated films to resist the formation of biofilms by E. coli [73]. In the early stages, fluorescence signals were weaker on the chiral polyol-terminated surface than on the achiral circular region. When the culture medium was continuously flowed through the channels, fluorescence signals gradually emerged in the outer area of the circular region after a relatively long period of time (~22 days) (Figure 6). These results suggest that the racemic film
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was more resistant to biofilm formation than monolayers consisting of either of the single enantiomers. However, the finding that the anti-biofouling ability of racemic surfaces is significantly better than both D- and L-surfaces is unexpected. We speculate that different D-D, L-L, and D-L interactions at a molecular level result in different anti-biofouling abilities of D-/L-surfaces and the racemic surface. Recently, Kressler et al. [29] reported that chiral poly (glycerol methacrylate) (PGMA) self-assembled films effectively inhibited biofouling. Figure 7 shows the SPR sensorgrams for BSA adsorption onto a bare gold surface, PGMA (rac)27, PGMA(rac)27-92%, PGMA (S)28 and PGMA (R)24 surface. A remarkable feature of BSA adsorption is that both enantiopure surfaces and racemic surfaces significantly inhibited BSA adsorption compared with the bare gold surface. The PGMA (S)28 and PGMA (R)24 surfaces exhibited much lower protein adsorption than the racemic PGMA surfaces. The difference in protein adsorption between enantiopure surfaces and the racemic surface was mainly attributed to polymer-polymer intermolecular hydrogen bonding and the interaction of the polymer with water molecules. The numbers of cells adhering on PGMA (rac)27, PGMA (S)28 and PGMA (R)24 surfaces were reduced to approximately 33%, 11% and 7%, respectively, of the amount on the bare gold surface. The results suggest that PGMA films with the same chemical composition but different chirality resist cell adhesion and protein adsorption to different extents. In addition, the chiral PGMA film provides an effective candidate for the design of new bio-
Figure 6 Fluorescence signals of biofilms formed by E. coli on patterned chiral surfaces. The patterned chemistry consists of circular regions of pentanedecanethiolates surrounded by chiral self-assembled films (from left, D-gulitol, L-gulitol and their racemic mixture). Scale bar is 152 μm [73].
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Figure 7 SPR sensorgrams of BSA adsorption (1 mg/mL in PBS buffer solution) on various surfaces measured at 25 °C. The top line is bare gold surface (gray), followed by PGMA(rac)27 (orange), PGMA(rac)2792% (green), PGMA(S)28 (red) and PGMA(R)24 (blue) SAMs from top to bottom [29].
materials that can significantly improve the anti-biofouling properties of the surface of materials. Although the antibiofouling properties of chiral surfaces can only be maintained for a period of time, such chiral polymer surfaces provide a powerful anti-biofouling approach by utilizing surface chirality to resist the different stages of biofilm formation. 4.2
Chiral separation
A pair of drug enantiomers often exhibit different biological activity and toxicological behavior in clinical applications. In fact, very often only one enantiomer exhibits a specific biological activity, whereas the other may be ineffective or even toxic. Therefore, the development of chiral drugs with a high enantiomeric excess has attracted great attention in the pharmaceutical industry. Due to their chiral interactions with target molecules, chiral polymers have been widely used to separate many classes of racemates, including drugs and their precursors [74]. The main form of chiral separation based on chiral polymers is chiral stationary phases (CSP) materials for chromatography formed by grafting or coating chiral polymers on the surface of small spherical silica gel particles or capillary inner walls. There have been great developments in commercial applications of these materials over the past 30 years [75, 76]. In pioneering work by Okamoto et al. [77] in 1981, chiral packing materials (CPMs) based on chiral helical poly (triphenylmethyl methacrylate) (PTrMA) were developed for the first time (Figure 8(a)). First, silanized macroporous spherical silica gel particles were coated with (+)-PTrMA by using THF as the solvent. Then, an atropisomeric chiral compound 2,2′-dihydroxy-1,l′-binaphthyl was used to evaluate the separation efficiency, and the result showed that enantiomers were completely separated by this column. It was suggested that the driving force for chiral recognition in this chiral polymer stationary phase is mainly nonpolar
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interaction between the packing and racemic compounds. Subsequently, various kinds of chiral helical polymers were prepared and their applications as CSP for chromatographic separation were developed [78, 79]. Recently, in order to study the influence of different helical configurations on chiral recognition ability, Yashima et al. [80] prepared two helical polyisocyanide-based CSPs, which were composed of the same L-alanine repeat units, but with opposite helicity (right- and left-handed helices), as illustrated schematically in Figure 8(b). The results for the resolution of a variety of racemic compounds showed different or specific chiral recognition ability for right- and left-handed helical CSPs. The enantioselectivity and elution order of the enantiomers were mainly determined by the helical structure of the chiral polymers, while the chirality of the pendant L-alanine residues only provided positive or negative synergistic effects. These results are of significant benefit in terms of increasing our understanding of the chiral discrimination mechanism of chiral polymer-based CSPs and for designing significantly better CSPs. Over the past few decades, chiral separation based on chiral helical polymers as CSPs has made a great contribution to commercial applications in the field of chiral drug separation. Nevertheless, commonly used CSPs mainly based on stereoselective interactions suffer from the drawbacks of low resolution efficiency, low loading capacity and a limited range of applications. The development of novel CSPs with excellent recognition ability, such as chiral responsive copolymers, is expected to remedy such defects. 4.3
Chiral sensors
By converting the chiral signal from a chiral selector interacting with chiral guests to other easily detected information, like electrochemical signal and mass, chiral sensor systems
Figure 8 (a) Structure of the chiral helical polymer PTrMA and HPLC resolution of 2,2′-dihydroxy-1,l′-binaphthyl on (+)-PTrMA coated silica gel [77]; (b) schematic illustration of the immobilization of left- and right-helical poly(phenyl isocyanide) on silica gel and chiral separation ability for racemic analyte as CSPs for HPLC [80].
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can realize immediate qualitative or quantitative determination of enantiomers [81, 82]. With the development of chiral engineering, there is an urgent need to develop chiral sensor systems with simple, fast, real-time and on-line use. To date, chiral sensor systems based on QCM transducers and electrochemical methods have been widely investigated [83–87]. The main methods for fabricating chiral sensor surfaces are direct coating or chemical grafting of chiral polymers or chiral small molecules onto the substrate surface. Early in 1997, Hierlemann et al. [88] achieved enantiomer discrimination by utilizing thickness shear-mode resonators (TSMR) and reflectometric interference spectroscopy (RIF) techniques in a chiral polymer gas sensor system. A commercial chromatographic column material octyl-chirasilval, which contains chiral peptide residues and non-chiral lipophilic side chains, was used to prepare a chiral sensor. TSMR results showed a stronger affinity between (S)-sensor and (S)-analyte compared to (R)-sensor and (S)-analyte. However, for the (R)-analyte, stronger adsorption on the (R)-sensor was observed. Additional experiments were performed with both sensors exposed to a mixture of methyl lactate enantiomers, which showed systematic and consistent signal increases or decreases with changing enantiomeric composition of the analyte. Both sensors allowed effective discrimination between (R)- and (S)-enantiomers, and allowed fast, real-time and in situ determination of the enantiomeric excess with 10% resolution. In recent years, Fu et al. [89, 90] have reported a series of studies of electrochemical chiral sensor systems based on chiral SAMs. In 2012, they developed an electrochemical chiral sensor to investigate the stereoselective interaction between human serum albumin (HSA) and N-isobutyrylcysteine (NIBC) enantiomer modified gold surfaces [91]. They employed cyclic voltammetry (CV) to study the characteristics of NIBC-modified surfaces before and after interaction with HSA. For L-NIBC and D-NIBC surfaces, the electrochemical responses were almost identical. However, the peak currents decreased when L-NIBC and D-NIBC surfaces were treated with 0.1 mmol/L HSA for about 60 min, and the peak current of the D-NIBC surface was larger than
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that for the corresponding L surface (Figure 9). The results indicate that surface chirality significantly affects the adsorption of HSA. Thus, the investigation of chiral interactions by means of electrochemical methods not only promotes our understanding of the chiral interaction mechanism from an electrochemical point of view, but also provides assistance in the design of chiral sensors with highsensitivity.
5 Conclusion and perspective Inspired by the high chirality preference of biological systems, chiral polymer-based biointerface materials have been intensively studied over the past few years. Many studies of chiral effects have given much inspiration to develop novel biomaterials with new effects and new functions. As a great breakthrough compared with traditional materials, chiral polymer-based biointerface materials have received interest for various applications in vitro and in vivo, such as tissue engineering, anti-biofouling, chiral separation and chiral sensors. To date, some significant progress has been achieved in our understanding of chiral polymer-based biointerface materials and their potential application. Nevertheless, fundamental research and applications are still at the initial stage and many challenges remain to be solved, such as the nature of the underlying interaction mechanism, ways of achieving higher specificity and sensitivity of chiral recognition, and the development of chiral bio-devices. Therefore, future efforts should be mainly devoted to the following several aspects. Firstly, since a clear molecularlevel understanding of chiral interactions is lagging behind various reported chiral effects, researchers should investigate the underlying mechanism of chiral interactions in detail, especially the intermolecular interactions among chiral moieties themselves or with other functional groups on surfaces by modern analytical techniques. For example, Bürgi et al. [92] studied chiral interactions giving chiral discrimination at SAMs of chiral thiols on a gold surface utilizing attenuated total reflection infrared (ATR-IR) spectroscopy
Figure 9 Cyclic voltammograms (A) and electrochemical impedance spectroscopy (B) of different electrodes in 5 mmol/L [Fe(CN)6]4/3 solution (pH 6.7). (a) L-NIBC-Au; (b) D-NIBC-Au; (c) D-NIBC-Au; (d) L-NIBC-Au interacted with 0.1 mol/L HSA for 1 h [91].
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combined with modulation excitation spectroscopy (MES). Another great example from Ohta’s group [93] showed that the octameric o-phenylene (OP8NO2) undergoes a rapid chiral helix inversion in solution, and the chiral helical structure could be locked into one conformation during crystallization, so this might give a new approach to probe the intermolecular interaction between chiral selectors and chiral analytes by “freezing” the chiral structure in a one-handed phase. Secondly, since the recent demonstration of chirality-induced wettability switching on chiral polymer surfaces [12, 67], the transformation of the signal of chiral interactions to a change in macroscopic properties of materials through chiral polymers brings us clear guidance for the development of chiral functional devices. However, apart from surface wettability, other ways of translating from microscopic chirality to macroscopic properties are still required for a range of practical applications. Thirdly, although different behaviors of biological entities on chiral surfaces have been reported, how to regulate and control the interfacial behavior and functionality through the design of chiral polymers still presents a challenge, but is becoming a significant topic. Finally, studies of chiral polymer-based biointerface materials should be continued in an effort to develop practical bioapplications which combine the advantages of chiral polymer interfaces and functional materials. In future work, we firmly believe that more effort will be focused on the study of chiral polymer-based biointerface materials, and this will greatly contribute to the development and applications of chiral materials.
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23 We appreciate the financial support of the National Natural Science Foundation of China (21104061, 21275114, 91127027, 51173142), the National Basic Research Program of China (2013CB933002) and the Fundamental Research Funds for the Central Universities (2013-YB-026).
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Barron LD. Chemistry: chirality, magnetism and light. Nature, 2000, 405: 895–896 Barron LD. Chirality and life. Space Sci Rev, 2008, 135: 187–201 Hein JE, Blackmond DG. On the origin of single chirality of amino acids and sugars in biogenesis. Acc Chem Res, 2012, 45: 2045–2054 Bentley R. Role of sulfur chirality in the chemical processes of biology. Chem Soc Rev, 2005, 34: 609–624 Sun TL, Qing GY, Su BL, Jiang L. Functional biointerface materials inspired from nature. Chem Soc Rev, 2011, 40: 2909–2921 Tonzani S. Polymers for biomedical applications. J Appl Polym Sci, 2013, 129: 527 Somorjai GA, Frei H, Park JY. Advancing the frontiers in nanocatalysis, biointerfaces, and renewable energy conversion by innovations of surface techniques. J Am Chem Soc, 2009, 131: 16589–16605 Zhang MX, Qing GY, Sun TL. Chiral biointerface materials. Chem Soc Rev, 2012, 41: 1972–1984 Wang X, Gan H, Sun TL, Su BL, Fuchs H, Vestweber D, Butz S. Stereochemistry triggered differential cell behaviours on chiral polymer surfaces. Soft Matter, 2010, 6: 3851–3855 Yi QY, Wen XT, Li L, He B, Nie Y, Wu Y, Zhang ZR, Gu ZW. The chiral effects on the responses of osteoblastic cells to the polymeric substrates. Eur Polym J, 2009, 45: 1970–1978 Wang X, Gan H, Sun TL. Chiral design for polymeric biointerface: the influence of surface chirality on protein adsorption. Adv Funct
26
27
28
29
30
31
549
Mater, 2011, 21: 3276–3281 Shundo A, Hori K, Ikeda T, Kimizuka N, Tanaka K. Design of a dynamic polymer interface for chiral discrimination. J Am Chem Soc, 2013, 135: 10282–10285 Miyake GM, DiRocco DA, Liu Q, Oberg KM, Bayram E, Finke RG, Rovis T, Chen EY-X. Stereospecific polymerization of chiral oxazolidinone-functionalized alkenes. Macromolecules, 2010, 43: 7504–7514 Zhi JG, Guan Y, Cui JX, Liu AH, Zhu ZG, Wan XH, Zhou QF. Synthesis and characterization of optically active helical vinyl polymers via free radical polymerization. J Polym Sci A: Polym Chem, 2009, 47: 2408–2421 Hoshikawa N, Yamamoto C, Hotta Y, Okamoto Y. Helix-senseselective radical polymerization of N-(triphenylmethyl) methacrylamides and properties of the polymers. Polym J, 2006, 38: 1258–1266 Choe UJ, Sun VZ, Tan JKY, Kamei, DT. Self-assembled polypeptide and polypeptide hybrid vesicles: from synthesis to application. Top Curr Chem, 2012, 310: 117–134 Cai CH, Wang LQ, Lin JP. Self-assembly of polypeptide-based copolymers into diverse aggregates. Chem Commun, 2011, 47: 11189– 11203 Coates GW, Waymouth RM. Enantioselective cyclopolymerization of 1,5-hexadiene catalyzed by chiral zirconocenes: a novel strategy for the synthesis of optically active polymers with chirality in the main chain. J Am Chem Soc, 1993, 115: 91–98 Itsuno S. Chiral polymer synthesis by means of repeated asymmetric reaction. Prog Polym Sci, 2005, 30: 540–558 Haraquchi N, Kiyono H, Takemura Y, Itsuno S. Design of mainchain polymers of chiral imidazolidinone for asymmetric organocatalysis application. Chem Commun, 2012, 48: 4011–4013 Okamoto Y, Suzuki K, Ohta K, Hatada K, Yuki H. Optically active poly(triphenylmethyl methacrylate) with one-handed helical conformation. J Am Chem Soc, 1979, 101: 4763–4765 Yamamoto T, Suginome M, Helical poly(quinoxaline-2,3-diyl)s bearing metal-binding sites as polymer-based chiral ligands for asymmetric catalysis. Angew Chem Int Ed, 2009, 48: 539–542 Furumi S. Self-assembled organic and polymer photonic crystals for laser applications. Polym J. 2013, 45: 579–593 Shiraki T, Dawn A, Tsuchiya Y, Shinkai S. Thermo- and solvent-responsive polymer complex created from supramolecular complexation between a helix-forming polysaccharide and a cationic polythiophene. J Am Chem Soc, 2010, 132: 13928–13935 Cao HQ, Cui JX, Liu AH, Wan XH. Synthesis and helix-senseselective polymerization of chiral vinyl biphenyl monomers. Acta Polym Sin, 2010: 222–230 Bag DS, Dutta D, Shami TC, Bhasker Bro KU. Synthesis and characterization of L-leucine containing chiral vinyl monomer and its polymer, poly(2-(methacryloyloxyamino)-4-methyl pentanoic acid). J Ploym Sci Part A Polym Chem, 2009, 47: 2228–2242 Wang X, Gan H, Zhang MX, Sun TL. Modulating cell behaviours on chiral polymer brush films with different hydrophobic side groups. Langmuir, 2012, 28: 2791–2798 Zhang MX, Qing GY, Xiong CL, Cui R, Pang DW, Sun TL. Dual-responsive gold nanoparticles for colorimetric recognition and testing of carbohydrates with a dispersion-dominated chromogenic process. Adv Mater, 2013, 25: 749–754 Li Z, Köwitsch A, Zhou G, Groth T, Fuhrmann B, Niepel M, Amado E, Kressler J. Enantiopure chiral poly(glycerol methacrylate) self-assembled monolayers knock down protein adsorption and cell adhesion. Adv Healthcare Mater, 2013, 2: 1377–1387 Gualandi C, Vo CD, Focarete ML, Scandola M, Pollicino A, Di Silvestro G, Tirelli N. Advantages of surface-initiated ATRP (SI-ATRP) for the functionalization of electrospun materials. Macromol Rapid Commun, 2013, 34: 51–56 Wei QB, Wang XL, Zhou F. A versatile macro-initiator with dual functional anchoring groups for surface-initiated atom transfer radical polymerization on various substrates. Polym Chem, 2012, 3: 2129– 2137
550 32
33
34 35
36
37
38
39 40
41
42
43 44 45
46
47 48
49
50
51 52
53 54 55
56
Li MM, et al.
Sci China Chem
Wang HS, Peng JT, Wei JP, Jiang A. Synthesis of novel chiral stationary phase based on atom transfer radical polymerization and click chemistry. Acta Chim Sinica, 2012, 70: 1355–1361 Palermo V, Morelli S, Simpson C, Müllen K, Samorì P. Self-organized nanofibers from a giant nanographene: effect of solvent and deposition method. J Mater Chem, 2006, 16: 266–271 Okamoto Y. Chiral polymers for resolution of enantiomers. J Polym Sci Part A: Polym Chem, 2009, 47: 1731–1739 Suárez-Suárez S, Carriedo GA, Tarazona MP, Soto AP. Twisted morphologies and novel chiral macroporous films from the self-assembly of optically active helical polyphosphazene block copolymers. Chem Eur J, 2013, 19: 5644–5653 Saxena A, Guo GQ, Fujiki M, Yang YG, Ohira A, Okoshi K, Naito M. Helical polymer command surface: thermodriven chiroptical transfer and amplification in binary polysilane film system. Macromolecules, 2004, 37: 3081–3083 Minich EA, Nowak AP, Deming TJ, Pochan DJ. Rod-rod and rod-coil self-assembly and phase behavior of polypeptide diblock copolymers. Polymer, 2004, 45: 1951–1957 Ohira A, Okoshi K, Fujiki M, Kunitake M, Naito M, Hagihara T. Versatile helical polymer films: chiroptical inversion switching and memory with re-writable (RW) and write-once read-many (WORM) modes. Adv Mater, 2004, 16: 1645–1650 Li WG, Wang HL. Electrochemical synthesis of optically active polyaniline films. Adv Funct Mater, 2005, 15: 1793–1798 Switzer JA, Kothari HM, Poizot P, Nakanishi S, Bohannan EW. Enantiospecific electrodeposition of a chiral catalyst. Nature, 2003, 425: 490–493 Boccaccini AR, Keim S, Ma R, Li Y, Zhitomirsky I. Electrophoretic deposition of biomaterials. J Royal Soc Interface, 2010, 7: S581–S613 Wang Y, Pang X, Zhitomirsky I. Electrophoretic deposition of chiral polymers and composites. Colloids Surf B Biointerfaces, 2011, 87: 505–509 Thevenot P, Hu WJ, Tang LP. Surface chemistry influences implant biocompatibility. Curr Top Med Chem, 2008, 8: 270–280 Bai CL, Liu MH. Implantation of nanomaterials and nanostructures on surface and their applications. Nano Today, 2012, 7: 258–281 Pasparakis G, Cockayne A, Alexander C. Control of bacterial aggregation by thermoresponsive glycopolymers. J Am Chem Soc, 2007, 129: 11014–11015 Chen L, Liu MJ, Bai H, Chen PP, Xia F, Han D, Jiang L. Antiplatelet and thermally responsive poly(n-isopropylacrylamide) surface with nanoscale topography. J Am Chem Soc, 2009, 131: 10467–10472 Sun TL, Qing GY. Biomimetic smart interface materials for biological applications. Adv Mater, 2011, 23: H57–H77 Sun TL, Han D, Rhemann K, Chi LF, Fuchs H. Stereospecific interaction between immune cells and chiral surfaces. J Am Chem Soc, 2007, 129: 1496–1497 Gan H, Tang KJ, Sun TL, Hirtz M, Li Y, Chi LF, Butz S, Fuchs H. Selective adsorption of DNA on chiral surfaces: supercoiled or relaxed conformation. Angew Chem Int Ed, 2009, 48: 5282–5286 Wang LL, Fu YZ, Zhou J, Chen Q. Stereoselective interaction between DNA and stable chiral surfaces modified with 1,2-diphenylethylenediamine enantiomers. Electroanalysis, 2011, 23: 529–535 Hanein D, Geiger B, Addadi L. Differential adhesion of cells to enantiomorphous crystal surfaces. Science, 1994, 263: 1413–1416 Ei-Gindi J, Benson K, De Cola L, Galla HJ, Kehr NS. Cell adhesion behavior on enantiomerically functionalized zeolite L monolayers. Angew Chem Int Ed, 2012, 51: 3716–3720 Kawai F. Polylactic acid (PLA)-degrading microorganisms and PLA depolymerases. Appl Microbiol Biotechnol, 2006, 72: 244–251 Martina M, Hutmacher DW. Biodegradable polymers applied in tissue engineering research: a review. Polym Int, 2007, 56: 145–157 Chen H, Yuan L, Song W, Wu ZK, Li D. Biocompatible polymer materials: role of protein-surface interactions. Prog Polym Sci, 2008, 33: 1059–1087 Keller K, Amirian A, Akcora P. Elastic properties of a protein-polymer-grafted surface. Langmuir, 2012, 28: 3807–3813
April (2014) Vol.57 No.4
57
58
59 60
61
62
63
64
65 66 67 68
69 70 71
72
73
74
75 76
77
78 79 80
81
Humblot V, Pradier CM. Chiral recognition of l-gramicidine on chiraly methionine-modified Au(111). J Phys Chem Lett, 2013, 4: 1816–1820 Hucknall A, Rangarajan S, Chilkoti A. In pursuit of zero: polymer brushes that resist the adsorption of proteins. Adv Mater, 2009, 21: 2441–2446 Ayres N. Polymer brushes: applications in biomaterials and nanotechnology. Polym Chem, 2010, 1: 769–777 Zhou F, Yuan L, Li D, Huang H, Sun TL, Chen H. Cell adhesion on chiral surface: the role of protein adsorption. Colloids Surf B Biointerfaces, 2012, 90: 97–101 Tang ZC, Li D, Wu ZQ, Liu W, Brash JL, Chen H. Vinyl-monomer with lysine side chains for preparing copolymer surfaces with fibrinolytic activity. Polym Chem, 2013, 4: 1583–1589 Huang J, Egan VM, Guo H, Yoon JY, Briseno AL, Rauda IE, Garrell RL, Knobler CM, Zhou F, Kaner RB. Enantioselective discrimination of D- and L-phenylalanine by chiral polyaniline thin films. Adv Mater, 2003, 15: 1158–1161 Ho RM, Li MC, Lin SC, Wang HF, Lee YD, Hasegawa H, Thomas EL. Transfer of chirality from molecule to phase in self-assembled chiral block copolymers. J Am Chem Soc, 2012, 134: 10974–10986 Qing GY, Sun TL. The transformation of chiral signals into macroscopic properties of materials using chirality-responsive polymers. NPG Asia Materials, 2012, e4 Yao X, Song YL, Jiang L. Applications of bio-inspired special wettable surfaces. Adv Mater, 2011, 23: 719–734 Jin X, Yang S, Li Z, Liu KS, Jiang L. Bio-inspired special wetting surfaces via self-assembly. Sci China Chem, 2012, 55: 2327–2333 Qing GY, Sun TL. Chirality triggered wettability switching on smart polymer surface. Adv Mater, 2011, 23: 1615–1620 Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science, 1999, 284: 1318– 1322 Ma CF, Yang HJ, Zhou X, Wu B, Zhang GZ. Polymeric material for anti-biofouling. Colloids Surf B Biointerface, 2012, 100: 31–35 Kirschner CM, Brennan AB. Bio-inspired antifouling strategies. Annu Rev Mater Res, 2012, 42: 211–229 Hong F, Xie LY, He CX, Liu JH, Zhang GZ, Wu C. Effects of hydrolyzable comonomer and cross-linking on anti-biofouling terpolymer coatings. Polymer, 2013, 54: 2966–2972 Bandyopadhyay D, Prashar D, Luk YY. Stereochemical effects of chiral monolayers on enhancing the resistance to mammalian cell adhesion. Chem Commun, 2011, 47: 6165–6167 Bandyopadhyay D, Prashar D, Luk YY. Anti-fouling chemistry of chiral monolayers: enhancing biofilm resistance on racemic surface. Langmuir, 2011, 27: 6124–6131 Khan M, Viswanathan B, Rao DS, Reddy R. Chiral separation of Frovatriptan isomers by HPLC using amylose based chiral stationary phase. J Chromatogr B, 2007, 846: 119–123 Okamoto Y, Ikai T. Chiral HPLC for efficient resolution of enantiomers. Chem Soc Rev, 2008, 37: 2593–2608 Ikai T, Okamoto Y. Structure control of polysaccharide derivatives for efficient separation of enantiomers by chromatography. Chem Rev, 2009, 109: 6077–6101 Okamoto Y, Honda S, Okamoto I, Yuki H, Murata S, Noyori R, Takaya H. Novel packing material for optical resolution: (+)-Poly (triphenylmethyl methacrylate) coated on macroporous silica gel. J Am Chem Soc, 1981, 103: 6971–6973 Nakano T, Okamoto Y. Synthetic helical polymers: conformation and function. Chem Rev, 2001, 101: 4013–4038 Yashima E, Maeda K. Chirality-responsive helical polymers. Macromolecules, 2008, 41: 3–12 Tamura K, Miyabe T, Iida H, Yashima E. Separation of enantiomers on diastereomeric right- and left-handed helical poly(phenyl isocyanide)s bearing L-alanine pendants immobilized on silica gel by HPLC. Polym Chem, 2011, 2: 91–98 Leitereg TJ, Guadagni DG, Harris J, Mon TR, Teranishi R. Evidence
Li MM, et al.
82
83 84
85
86 87
Sci China Chem
for the difference between the odours of the optical isomers (+)- and (−)-carvone. Nature, 1971, 230: 455–456 Torsi L, Farinola GM, Marinelli F, Tanese MC, Omar OH, Valli L, Babudri F, Palmisano F, Zambonin PG, Naso F. A sensitivityenhanced field-effect chiral sensor. Nat Mater, 2008, 7: 412–417 Trojanowicz M, Kaniewska M. Electrochemical chiral sensors and biosensors. Electroanalysis, 2009, 21: 229–238 Guo HS, Kim JM, Chang SM, Kim WS. Chiral recognition of mandelic acid by L-phenylalanine-modified sensor using quartz crystal microbalance. Biosens Bioelectron, 2009, 24: 2931–2934 Luo LM, Zhang WG, Zhang S, Fan H, Su WC, Yin X. Self-assembly and chiral recognition of quartz crystal microbalance chiral sensor. Chirality, 2010, 22: 411–415 Weng W, Han JL, Chen YZ, Huang XJ. Progress in chiral sensors. Prog Chem, 2007, 19: 1820–1825 Bustos E, Gacía JE, Bandala Y, Godínez LA, Juaristi E. Enantioselective recognition of alanine in solution with modified gold electrodes using chiral PAMAM dendrimers G4.0. Talanta, 2009, 78: 1352–1358
April (2014) Vol.57 No.4
88
89
90
91
92 93
551
Bodenhöfer K, Hierlemann A, Seemann J, Gauglitz G, Koppenhoefer B, Göpel W. Chiral discrimination using piezoelectric and optical gas sensors. Nature, 1997, 387: 577–580 Chen Q, Zhou J, Han Q, Wang YH, Fu YZ. A new chiral electrochemical sensor for the enantioselective recognition of penicillamine enantiomers. J Solid State Electrochem, 2012, 16: 2481–2485 Fu YZ, Chen M, Cui X, Wang LL, Chen Q, Zhou J. Recognition behavior of chiral nanocomposites toward biomolecules and its application in electrochemical immunoassay. Sci China Chem, 2010, 53: 1453–1458 Chen Q, Zhou J, Han Q, Wang YH, Fu YZ. The selective adsorption of human serum albumin on N-isobutyryl-cysteine enantiomers modified chiral surfaces. Biochem Eng J, 2012, 69: 155–158 Bieri M, Gautier C, Bürgi T. Probing chiral interfaces by infrared spectroscopic methods. Phys Chem Chem Phys, 2007, 9: 671–685 Ohta E, Sato H, Ando S, Kosaka A, Fukushima T, Hashizume D, Yamasaki M, Hasegawa K, Muraoka A, Ushiyama H, Yamashita K, Aida T. Redox-responsive molecular helices with highly condensed π-clouds. Nat Chem, 2011, 3: 68–73
