Helix formation in synthetic polymers by hydrogen bonding with native saccharides in protic media

Water-soluble poly(m-ethynylpyridine)s were designed to realize saccharide recognition in protic media. UV/Vis, 1H NMR, and fluorescence measurements revealed that the polymer forms a helical higher order structure by solvophobic interactions between the ethynylpyridine units in the protic medium. The resulting pore in the helix behaves like a binding pocket in proteins, by taking advantage of inwardly directed hydrogen-bonding functional groups of the polymers. Molecular recognition of native saccharides by the polymers was investigated by circular dichroism (CD). The chirality of the saccharide was transferred to the helical sense of the polymers, accompanied by the appearance of induced CDs (ICDs) in the absorptive region of the polymers. In MeOH/water (10/1), mannose and allose showed intense ICDs, and the apparent association constant between the polymer and D-mannose was 14 M(-1).     

基于环糊精本征识别能力的手性色谱介质点击制备及应用

目前环糊精（CD）手性固定相（CSP）的研究大多集中于对CD或桥联臂进行功能衍生引入更多作用位点以提升手性拆分能力,鲜有能够反映天然CD本征识别能力的CSP的研究报道,该文通过"巯基-烯"点击化学反应合成了结构明确可控的单（6-巯基-6-去氧）-β -环糊精手性固定相（CSP1）,其最大限度地保留了天然CD的本征结构,且桥联臂无识别作用位点,固体核磁共振（¹³ C SSNMR）和红外光谱（FTIR）的表征结果证明了CSP1的成功制备,元素分析结果表明,与双键功能化硅胶相比,CSP1的C、H、N的百分含量均得到了提高,计算得出CSP1的表面CD固载量为0.82 μmol/m²。采用高效液相色谱反相模式对50多种手性对映体包括异（口恶）唑啉、手性交酯、手性酮、黄烷酮以及丹磺酰氨基酸等进行了手性拆分,充分考察了天然CD的本征手性识别能力,结果表明CD的本征识别能力比较有利于异（口恶）唑啉类样品中含有两个疏水苯环基团Ph-Ph类样品的分离,对于其他几类样品仅利于部分样品的分离。同时与前期制备的功能三唑桥联CD-CSP及咪唑嗡桥联CD-CSP在同一色谱条件下进行了结果比对,结果证明样品的分离过程除了与手性介质的结构有关外,还与样品分子的结构有很大关系,对桥联臂进行功能改性可提升对部分对映体的选择性,但同时会小幅损失CD的本征手性识别能力。对于环糊精本征识别能力易于分离的样品,在设计手性介质时,其桥联臂不需要任何官能团,这为CD固定相结构的设计提供了有益参考。     

新型糖基聚合物的合成及其作为高效液相色谱手性固定相的应用(英文)

Two novel polymers containing glucose units as the main-chain that only differ in terms of their regioregularity were synthesized to evaluate their chiral recognition abilities as chiral stationary phases(CSPs)for high performance liquid chromatography(HPLC).The regioregular polymer(poly-5)shows clear resolution ability for the racemate of cobalt(Ⅲ)acetylacetonate(Co(acac)3),whereas the corresponding regioirregular polymer(poly-3)does not show any chiral recognition for Co(acac)3.The regioregular polymer main-chain seems to play an important role not only in providing an efficient interaction with the racemate but also in expressing the chiral recognition ability as a CSP for HPLC.     

Chiral Recognition and Resolution Based on Helical Polymers

Helical polymers have attracted a great deal of attention and been extensively investigated due to their various applications.One of the most important applications of helical polymers is chiral recognition and resolution of enantiomers for the reason that a pair of enantiomers is commonly with different physiological and toxicological behaviors in biological systems.Helical polymers usually present unexpected high chiral recognition ability to a variety of racemic compounds.What's more,the chiral recognition and resolution abilities of the system are dependent on the highly ordered helical structures of the helical polymers.This mini review mainly focuses on the recent progress in chiral recognition and resolution based on helical polymers.The synthetic methodology for helical polymers is firstly discussed briefly.Then recent advances of chiral recognition and resolution systems based on helical polymers,especially polyacetylenes and polyisocyanides,are described.We hope this mini review will inspire more interest in developing helical polymers and encourage further advances in chiral-related disciplines.     

Synthesis and characterization of polybinaphthalene incorporating chiral (R) or (S)-1,1′-binaphthalene and oxadiazole units by Heck reaction

Chiral conjugated polymers P-1 and P-2 were synthesized by the polymerization of (R)-3,3′-diiodo-2,2′-bisbutoxy-1,1′-binaphthalene ((R)-M-1) and (S)-3,3′-diiodo-2,2′-bisbutoxy-1,1′-binaphthalene ((S)-M-1) with 2,5-bis(4-vinylphenyl)-1,3,4-oxadiazole (M-2) under Pd-catalyzed Heck coupling reaction, respectively. Both monomers and polymers were analysed by NMR, MS, FT-IR, UV, DSC-TG, fluorescent spectroscopy, GPC and CD spectra. The chiral conjugated polymers exhibit strong Cotton effect in their circular dichroism (CD) spectra indicating a high rigidity of polymer backbone. CD spectra of polymers P-1 and P-2 are almost identical and have opposite signs for their position. These polymers have strong blue fluorescence.     

Saccharide-dependent induction of chiral helicity in achiral synthetic hydrogen-bonding oligomers

Conformational transitions of biopolymers are well-known to be affected by noncovalent interactions with small molecules. We found that synthetic polymers, poly- and oligo(meta-ethynylpyridine)s, are guided to helical structures by uncharged hydrogen-bonding interactions with saccharides enclosed in the inner sphere of the polymers. Circular dichroism (CD) studies revealed that chirality of saccharide was transferred to the helical sense of the polymers. Among the n-octyl pyranosides of naturally important hexoses, beta-glucoside induced CDs most effectively. Size-regulated 18-mer and longer oligomers also showed the induced CDs similar to those for the polymers. Furthermore, native monosaccharides were extracted into less polar organic solvent with the help of the polymers, inducing similar CD signals.     

SYNTHESIS OF CHIRAL CONJUGATED POLYBINAPHTHYLS BY SONOGASHIRA REACTION

Chiral polymers P-1 and P-2 were synthesized by the polymerization of （R）-3,3＇-diiodo-2,2＇-bisbutoxy-1,1＇- binaphthyl （M- 1 ） with 2,5-di（4-ethynylphenyl）- 1,3,4-oxadiazole （M-3） and （R）-3,3＇-diethylnyl-2,2＇-bisbutoxy- 1,1 ＇-binaphthyl （M-2） with 1,2-di（4-bromophenyl）acetylene （M-4） under Sonogashira reaction, respectively. Both monomers and polymers were analyzed by NMR, MS, FT-IR, UV-Vis spectroscopy, DSC-TGA, fluorescence spectroscopy, GPC and CD spectroscopy. CD spectra of P-1 and P-2 are similar due to the same chiral center units and main chain structure. The long wavelengths CD effect of P-1 and P-2 can be regarded as the more extended conjugated structure and a highly rigid backbone in the polymer chain. Polymers have strong blue fluorescence due to the efficient energy migration from the extended n-electronic structure of the polymers to the chiral binaphthyl core and are expected to provide understanding of the relationship between molecular structure and fluorescent property of the chiral polymers.     

Chiral ionic liquids: synthesis, properties, and enantiomeric recognition

We have synthesized a series of structurally novel chiral ionic liquids which have a either chiral cation, chiral anion, or both. Cations are an imidazolium group, while anions are based on a borate ion with spiral structure and chiral substituents. Both (or all) stereoisomeric forms of each compound in the series can be readily synthesized in optically pure form by a simple one-step process from commercially available reagents. In addition to the ease of preparation, most of the chiral ILs in this series are liquid at room temperature with a solid to liquid transformation temperature as low as -70 degrees C and have relatively high thermal stability (up to at least 300 degrees C). Circular dichroism and X-ray crystallographic results confirm that the reaction to form the chiral spiral borate anion is stereospecific, namely, only one of two possible spiral stereoisomers was formed. Results of NMR studies including 1H{15N} heteronuclear single quantum coherence (HSQC) show that these chiral ILs exhibit intramolecular as well as intermolecular enantiomeric recognition. Intramolecularly, the chiral anion of an IL was found to exhibit chiral recognition toward the cation. Specifically, for a chiral IL composing with a chiral anion and a racemic cation, enantiomeric recognition of the chiral anion toward both enantiomers of the cation lead to pronounced differences in the NMR bands of the cation enantiomers. The chiral recognition was found to be dependent on solvent dielectric constant, concentration, and structure of the ILs. Stronger enantiomeric recognition was found in solvent with relatively lower dielectric constants (CDCl3 compared to CD3CN) and at higher concentration of ILs. Also, stronger chiral recognition was found for anions with a relatively larger substituent group (e.g., chiral anion with a phenylmethyl group exhibits stronger chiral recognition compared to that with a phenyl group, and an anion with an isobutyl group has the weakest chiral recognition). Chiral anions were also found to exhibit intermolecular chiral recognition. Enantiomeric discrimination was found for a chiral IL composed of a chiral anion and achiral cation toward another chiral molecule such as a quinine derivative.     

苯丙氨酸桥联手性锌双卟啉受体对胺的分子识别

金属卟啉的分子识别研究是当今卟啉仿生化学的重要课题.手性金属卟啉作为光学活性分子的对映选择识别受体和手性核磁共振试剂^[1]尤为引人注目.     

用于毛细管电泳手性分离的一种新的手性选择剂－ Β环糊精聚合物

用新合成的Β 环糊精聚合物(EP-Β-CD),并以天然环糊精(Β-CD) 和羧甲基环糊精(CM-Β-CD)手性拆分剂作对比,选取扑尔敏、山梗菜碱、维拉帕米为测试物􀁯优化分离条件􀁯研究了EP-Β-CD的拆分能力􀁯并与其它两种拆分剂进行了比较。     

Synthesis and characterization of <Emphasis Type="Italic">D</Emphasis>-/<Emphasis Type="Italic">L</Emphasis>-methionine grafted PEDOTs for selective recognition of 3,4-dihydroxyphenylalanine enantiomers

Two pairs of amino-acid functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) derivatives, namely, poly(N-(tert-butoxycarbonyl)-L-methionyl (3,4-ethylenedioxythiophene-2’-yl)methylamide) (L-PEDOT-Boc-Met) and poly(N-(tert-butoxycarbonyl)-D-methionyl (3,4-ethylenedioxythiophene-2’-yl)methylamide) (D-PEDOT-Boc-Met); poly(L-methionyl (3,4-ethylenedioxythiophene-2’-yl)methylamide) (L-PEDOT-Met) and poly(D-methionyl (3,4-ethylenedioxythiophene-2’-yl)methylamide) (D-PEDOT-Met) were synthesized via chemical oxidative polymerization of corresponding monomers. The structural characterization, spectroscopic properties and thermal stability of these monomers and polymers were systematically explored by FTIR spectra, Raman spectra, XRD spectra, UV-Vis spectra and thermogravimetric analysis. As chiral electrode materials, these polymers were employed to successfully recognize 3,4-dihydroxyphenylalanine (DOPA) enantiomers by cyclic voltammetry (CV) in sulphuric acid solution. The measurement results reveal that the tendency was hetero-chiral interaction between L-PEDOT-Met/PVA/GCE and D-DOPA, D-PEDOT-Met/PVA/GCE and L-DOPA, respectively. Also, the mechanism of chiral discrimination was discussed. All the results implied that the combination of electrochemical molecular recognition technology and chiral PEDOT materials can be a promising approach for chiral recognition and may open new opportunities for facile, biocompatible, sensitive and robust chiral assays in biochemical applications.     

Chiral separation with dipeptide-terminated polymeric surfactants: the effect of an extra heteroatom on the polar head group

Chiral recognition of two binaphthyl derivatives and three benzodiazepines were studied by use of polymeric surfactants in electrokinetic chromatography. Four specific dipeptide terminated (multichiral) micelle polymers were synthesized for this study. These include poly (sodium-N-undecanoyl-L-alanyl-leucinate)-(poly L-SUAL), poly (sodium-N-undecanoyl-L-valyl-leucinate) (poly L-SUVL), poly (sodium-N-undecanoyl-Lseryl-leucinate) (poly L-SUSL), and poly(sodium-N-undecanoyl-L-threonyl-leucinate) (poly L-SUTL). In addition to the chiral separation study, the physicochemical properties (critical micelle concentration and specific rotation) of each polymer were investigated. The molecular weights of the various dipeptide-terminated micelle polymers were determined using analytical ultracentrifugation. These dipeptide-terminated micelle polymers were designed to study the effect of the extra heteroatom at the polar head group of the micelle polymer (i.e., poly L-SUSL compared to poly L-SUAL and poly L-SUTL compared to poly L-SUVL) on the enantiomeric separation of the binaphthyl derivatives and benzodiazepines. The synergistic effect of three chiral centers (poly L-SUTL) provided improved resolution over that of two chiral centered dipeptide-terminated micelle polymer in the case of (+/-)-temazepam, (+/-)-oxazepam, (+/-)-binaphthol, and (+/-)-binaphthol phosphate. The chiral recognition mechanisms in these cases were additionally controlled by the presence of the extra heteroatom located on the polar head group of the micelle polymers.     

Spectroscopy, NMR and DFT studies on molecular recognition of crown ether bridged chiral heterotrinuclear salen Zn(II) complex

A barium-containing crown ether bridged chiral heterotrinuclear salen Zn(II) complex BaZn2L(ClO4)2, where L is a folded dinuclear chiral (R,R)-salen ligand, has been synthesized and characterized by elemental analysis, 1H NMR, UV-vis, IR, circular dichroism (CD) spectra, and mass spectra. As a folded dinuclear chiral host, its recognition with achiral guests (imidazole derivatives), rigid bidentate guest (1,4-diazobicyclo[2,2,2]octane, DABCO) and chiral guests (amino acid methyl esters) was investigated by means of UV-vis spectrophotometric titration, CD spectra. The association constants of D-amino acid methyl esters are found to be higher than those of their L-enantiomer. The sandwich-type binding of BaZn2L(ClO4)2-DABCO supramolecular assembly was specially studied via 1H NMR titration and 1H ROESY. To understand the recognition on molecular level, density functional theory (DFT) calculations on B3LYP/LanL2DZ were performed on the minimal energy conformations of host, guests, and host-guest complexes. The minimal energy conformations were obtained by molecular mechanics (MM) optimization and molecular dynamics (MD) simulation. The results of single point energy, HOMO energy, and charges transfer were analyzed. The results of theoretical calculations are in good agreement with the experimental data.     

Retentivity and enantioselectivity of uniformly-sized molecularly imprinted polymers for (S)-nilvadipine in aqueous and non-aqueous mobile phases.

Uniformly-sized molecularly imprinted polymers (MIPs) for (S)-nilvadipine have been prepared by a multi-step swelling and polymerization method using methacrylic acid or 4-vinylpyridine (4-VPY) as a functional monomer, ethylene glycol dimethacrylate (EDMA) as a cross-linker, and toluene, chloroform, cyclohexanol or phenylacetonitrile as a porogen. The chiral recognition abilities of the MIPs for nilvadipine were evaluated using aqueous and non-aqueous mobile phases. Among the MIPs, the (S)-nilvadipine-imprinted 4-VPY-co-EDMA polymers prepared using toluene as a porogen showed the highest recognition ability for nilvadipine in both aqueous and non-aqueous mobile phases. In addition to molecular shape recognition, hydrogen-bonding interactions of the NH proton of nilvadipine with a pyridyl group of the (S)-nilvadipine-imprinted 4-VPY-co-EDMA polymers could play an important role in the retention and chiral recognition of nilvadipine in aqueous and non-aqueous mobile phases. Furthermore, the MIP for (S)-nilvadipine gave the highest molecular recognition ability when a porogenic solvent during polymerization was used as the mobile phase modifier.     

Designed combination of chiral selectors for adjustment of enantioseparation selectivity in capillary electrophoresis.

In this study an attempt has been made to explain the reasons for changing the enantioseparation selectivity in some dual cyclodextrin (CD) systems compared to the use of single chiral selectors in capillary electrophoresis (CE). An explanation for selectivity changes is proposed based on the effect of the chiral selector on the mobility of the analyte. In order to support the proposed mechanism, several dual systems were designed on the basis of the known recognition pattern of enantiomers for individual CDs. In most cases the separation selectivity could be adjusted in a designed way. There was no experimental evidence for simultaneous binding of a given chiral analyte with both chiral selectors or of chiral recognition of an analyte complex with one CD by another CD.     

Chiral acid selectivity displayed by PEDOT electropolymerised in the presence of chiral molecules

Chiral conducting polymers prepared by electropolymerising PEDOT in the presence of chiral anions such as hyaluronic acid and anionic collagen or in a chiral nematic phase (hydroxypropyl cellulose, HPC) show excellent chiral acid recognition. This paper demonstrates the enantioselective recognition and transfer of protonated mandelic acid and protons using chiral PEDOTs. Discrimination between (R)-(-)- and (S)-(+)-mandelic acid was observed using cyclic voltammetry and square-wave voltammetry.     

Chiral Polymers and Optical Resolution: Investigation of the Mechanism of Ligand Exchange for Resolution of DL-Amino Acids

Abstract

Using novel class chiral ligand polymers which have different chemical environment in chiral cavity, we investigated their functional properties of chiral recognition for DL-amino acids and discussed ligand exchange chromatography of DL-amino acids on different chromatographic conditions in detail.     

以苯甘氨酸基为侧链的光学活性甲基丙烯酰胺聚合物的合成及手性识别能力

合成了N-[(R)-α-叔丁氧基羰基苄基]甲基丙烯酰胺((R)-BCBMAM),通过自由基聚合法获得相应的光学活性聚合物(P(R-BCBMAM)),并以三氟乙酸为水解催化剂除去叔丁基而得到(P(R-CBMAM)).用1H-NMR,IR,CD和GPC对聚合物进行了结构表征,发现聚合溶剂和聚合物分子量对所得聚合物P(R-BCBMAM)的光学活性没有明显影响,P(R-BCBMAM)水解后光学活性有较大的改变.与单体相比,聚合物的比旋光度有较大的区别,且在对应于其侧基的紫外吸收处呈现明显不同于单体的Cotton效应,说明聚合物的主链可能形成了一定的二级结构.以P(R-BCBMAM)和P(R-CBMAM)制备的2种涂敷型高效液相色谱用手性固定相,对部分对映体具有一定的手性拆分能力.利用1H-NMR技术研究了上述2种聚合物与1,1'-联-2-萘酚(BINOL)的相互作用,它们对BINOL都具有良好的手性识别能力.     

Synthesis and property of helical poly(phenylacetylene)s bearing chiral ruthenium complexes and real space imaging of meso- and nanoscopic structures by atomic force microscopy

Novel sets of helical poly(phenylacetylene)s bearing a chiral ruthenium (Ru) complex with opposite chirality (Δ and Λ forms) as a bulky pendant (poly- 1 and poly- 2 ) were synthesized through the polymerization of the corresponding optically pure phenylacetylenes with a rhodium catalyst, and their structures in solution and morphology on solid substrates were investigated with NMR, ultraviolet–visible, and circular dichroism (CD) spectroscopies and with atomic force microscopy (AFM), respectively. The obtained cis–transoidal polymers (poly- 1 and poly- 2 ) showed characteristic Cotton effects in the region of metal-to-ligand charge transfer of the chiral Ru pendants. Poly- 1 and poly- 2 were thought to have a predominantly one-handed helical conformation induced by the chiral pendants. However, the apparent Cotton effects derived from the helically twisted π-conjugated polymer backbone could not be observed, probably because of the strong chiral chromophoric pendants. However, in the AFM images, the helical polymers adsorbed on mica could be easily discerned as isolated strands, and the visualization and discrimination of the right- and left-handed helical structures of the chiral polymers were achieved by high-resolution AFM imaging. On the basis of the AFM observations together with the CD measurements and computational calculation results, possible structures of poly- 1 and poly- 2 were examined. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4621–4640, 2004     

Synthesis, helicity, and chromism of optically active poly(phenylacetylene)s carrying different amino acid moieties and pendant terminal groups

Functional phenylacetylene derivatives containing l-alanine and l-leucine moieties with chiral menthyl and achiral n-octyl terminal groups {HC[triple bond]C-C6H4-p-CONHCH(R)CO2R': R = CH3, R'= (-)-(1R,2S,5R)-menthyl [1(-)]; R = CH2CH(CH2)3, R' = (-)-(1R,2S,5R)-menthyl [2(-)]; R'= CH2CH(CH2)3, R' = (+)-(1S,2R,5S)-menthyl [2(+)]; R'= CH2CH(CH2)3, R' = (CH2)7CH3 (2o)} are synthesized. Polymerizations of the acetylene monomers are effected by organorhodium catalysts, giving corresponding polymers P1(-), P2(-), P2(+), and P2o of high molecular weights (Mw up to 1.2 x 10(6)) in high yields (up to 89%). The polymers are thermally stable (Td >or= 300 degrees C) and soluble in common organic solvents. The polymer structures are characterized by IR, NMR, UV, and CD spectroscopies. Intense CD signals are observed in the visible spectral region, indicating that the polymer chains are taking a helical conformation with an excess of preferred handedness. The backbone conjugation and chain helicity of the polymers can be tuned by changing their molecular structures [(a)chiral pendant groups] and by applying external stimuli (solvent and pH). Addition of trifluoroacetic acid to the polymer solutions decreases their molar ellipticities and enhances their backbone conjugations, inducing a halochromism with a continuous and reversible color change (yellow <==> red).