High Chiral Recognition Ability Research Articles

Chiral Supramolecular Organogel Constructed Using Riboflavin and Melamine: Its Application in Photo-Catalyzed Colorimetric Chiral Sensing and Enantioselective Adsorption.

The synthesis of a chiral supramolecular organogel via the hierarchical helical self-assembly of optically active riboflavin and melamine derivatives is described herein. Owing to the photocatalysis of riboflavin and the supramolecular chirality induced in the helically stacked riboflavin/melamine complex, the gel is observed to act as a light-stimulated chiral sensor of optically active alcohols by detecting the change in color from yellow to green. The gel also served as an efficient chiral adsorbent, enabling optical resolution of a racemic compound with high chiral recognition ability.

One‐Handed Helical Polyacetylenes Bearing Axially‐Chiral 2‐Arylpyridyl‐N‐Oxide Units for Efficient Chromatographic Enantioseparation of Chiral Aromatic and Aliphatic Alcohols

AbstractA series of poly(biarylylacetylene)s (PBAs) bearing axially‐chiral (S)‐and (R)‐pyridyl‐N‐oxide residues with a methoxy, propoxy, or acetyloxy substituent at the 3‐position of the biaryl units was synthesized. All the PBAs formed a preferred‐handed helix, while the helical sense preference was varied depending on the substituents despite the same twist‐sense of the biaryl units. Among them, the propoxy‐bound helical PBA showed an exceptionally high chiral recognition ability as a chiral stationary phase (CSP) for high‐performance liquid chromatography (HPLC) and efficiently resolved not only various chiral aromatic alcohols, but also a variety of chiral aliphatic alcohols; the latter still remains difficult to resolve by commercially‐available CSPs in HPLC. Such practically‐useful both handed helical PBA‐based CSPs can be produced from the racemic PBA composed of fully racemic monomer units through deracemization of the biaryl units with a chiral alcohol.

One-Handed Helical Polyacetylenes Bearing Axially-Chiral 2-Arylpyridyl-N-Oxide Units for Efficient Chromatographic Enantioseparation of Chiral Aromatic and Aliphatic Alcohols.

A series of poly(biarylylacetylene)s (PBAs) bearing axially-chiral (S)-and (R)-pyridyl-N-oxide residues with a methoxy, propoxy, or acetyloxy substituent at the 3-position of the biaryl units was synthesized. All the PBAs formed a preferred-handed helix, while the helical sense preference was varied depending on the substituents despite the same twist-sense of the biaryl units. Among them, the propoxy-bound helical PBA showed an exceptionally high chiral recognition ability as a chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC) and efficiently resolved not only various chiral aromatic alcohols, but also a variety of chiral aliphatic alcohols; the latter still remains difficult to resolve by commercially-available CSPs in HPLC. Such practically-useful both handed helical PBA-based CSPs can be produced from the racemic PBA composed of fully racemic monomer units through deracemization of the biaryl units with a chiral alcohol.

An Evaluation of Immobilized Poly-(S)-N-(1-phenylethyl)acrylamide Chiral Stationary Phases

In this study, brush type and polymer type stationary phases were prepared based on (S)-N-(1-phenylethyl) acrylamide, and the polymeric stationary phase demonstrated superior chiral recognition ability. The two polymeric stationary phases were synthesized by two strategies, one was the “grafting from” method, which obtained polymer CSP by initiating monomer polymerization on the surface of 3-methacrylatepropyl silica gel, and the other was “grafting to”, which fixed the copolymer of (S)-N-(1-phenylethyl) acrylamide and trimethoxysilylpropyl methacrylate on silica gel. A comparison of these two bonding modes revealed that the stationary phase produced by “grafting to” had higher chiral recognition ability. Further improvement can be achieved by the end-capping of silanol groups with trimethylchlorosilane to reduce non-enantioselective retention caused by residual silanol groups and improve the peak shape of enantiomers. Chiral separation in subcritical fluid chromatography was also studied. Similar enantioselectivity results with higher resolution were observed due to the improvement of peak shape.

Characteristic and complementary chiral recognition ability of four recently developed immobilized chiral stationary phases based on amylose and cellulose phenyl carbamates and benzoates.

To date, various immobilized chiral stationary phases (CSPs) have been developed. The immobilized CSPs have opened up possibilities not only maintaining the high chiral recognition abilities as well as corresponding coated ones but also affording high durability to various mobile phase. This report directed to investigate enantioseparation of recently launched four immobilized CSPs with cellulose and amylose backbones under normal phase liquid chromatography conditions. Their chiral recognition abilities were compared with previously developed six immobilized CSPs. Particularly, we focused on the complementarity for chiral recognitions. Among them, amylose tris(3‐chloro‐5‐methylphenylcarbamate) CSP, namely, CHIRALPAK IG, showed notable chiral recognition abilities to various racemates. As expected, the investigated immobilized CSPs represented remarkable durability to wide range of mobile phases, whereas the corresponding coated CSPs could not be run due to the irreversible degradation. Taking advantage of unrestricted solvent compatibility, chiral separation selectivities were improved for some racemates.

Preparation of cellulose derivative bearing bulky 4-(2-benzothienyl)phenylcarbamate substituents as chiral stationary phase for enantioseparation.

A novel cellulose derivative bearing bulky 4-(2-benzothienyl)phenylcarbamate substituents (Cel-1) was readily synthesized by carbamoylation followed by Suzuki-Miyaura coupling reaction. The corresponding coated-type chiral stationary phase (CSP) was prepared on basis of the derivative, and its chiral recognition ability was then evaluated by high-performance liquid chromatography (HPLC). The chiral recognition ability of the cellulose derivative was greatly influenced by introduction of the bulky benzothienyl pendants on the aromatic moieties of phenylcarbamates, compared with its analog with smaller groups. Many racemates, including the metal tris(acetylacetonate) complexes, chiral drug, and the analyte with axial chirality, were sufficiently separated with good enantioselectivities on Cel-1. Some of them were even higher than those on the commercially powerful Chiralcel OD, which is also a coated-type CSP derived from cellulose phenylcarbamate derivative containing smaller 3,5-dimethyl pendants. The 1 H NMR and circular dichroism (CD) spectra of Cel-1 indicated that the obtained derivative possessed a regular higher order structure, and a strong cotton effect was observed within the absorption range of π-conjugated pendant at 350-500 nm. Impressively, the cellulose derivative bearing the bulky 4-(2-benzothienyl)phenylcarbamates exhibited good enantioselective fluorescence quenching behavior to the enantiomer pair of 1-phenylethylamine, probably suggesting its potential for the application as a chiral fluorescent sensor with high efficiency. The combination of the arrangement of bulky π-conjugated benzothienyl pendants on the phenylcarbamate moieties surrounding the helical backbone and the regular higher order structure of the polymer itself probably played a key role for this high chiral fluorescent recognition ability of Cel-1. The interaction sites of bulky 4-(2-benzothienyl)phenylcarbamate pendants in its excited state can exhibit higher enantioselective discrimination via fluorescent response to the chiral compound Q1, whereas the chiral recognition ability of Cel-1 to the same compound in the ground state had no clear improvement.

Hindered Tetraphenylethylene Helicates: Chiral Fluorophores with Deep‐Blue Emission, Multiple‐Color CPL, and Chiral Recognition Ability

AbstractNew hindered tetraphenylethylene (TPE) helicates with substitution at 2,6‐position of phenyl rings were designed and synthesized. Due to the increased hindrance, the TPE helicates emit strong deep‐blue to violet fluorescence both in the solid state and in solution, and could be resolved into enantiomers that emit strong and multicolor circularly polarized luminescence (CPL), and exhibit a high enantioselective recognition of chiral tartaric acid and its derivatives. Surprisingly, the derived helicate tetramines possess amino groups with an unpredented planar structure and sp2‐hybridized nitrogen, arousing the change between AIE effect and ACQ phenomenon through photoinduced electron transfer (PET). With advantages of short synthetic route, many modification positions, deep‐blue to violet emission, wide CPL tuning, and high chiral recognition ability, the hindered TPE helicates show broad prospects as chiral materials.

Hindered Tetraphenylethylene Helicates: Chiral Fluorophores with Deep-Blue Emission, Multiple-Color CPL, and Chiral Recognition Ability.

New hindered tetraphenylethylene (TPE) helicates with substitution at 2,6-position of phenyl rings were designed and synthesized. Due to the increased hindrance, the TPE helicates emit strong deep-blue to violet fluorescence both in the solid state and in solution, and could be resolved into enantiomers that emit strong and multicolor circularly polarized luminescence (CPL), and exhibit a high enantioselective recognition of chiral tartaric acid and its derivatives. Surprisingly, the derived helicate tetramines possess amino groups with an unpredented planar structure and sp2 -hybridized nitrogen, arousing the change between AIE effect and ACQ phenomenon through photoinduced electron transfer (PET). With advantages of short synthetic route, many modification positions, deep-blue to violet emission, wide CPL tuning, and high chiral recognition ability, the hindered TPE helicates show broad prospects as chiral materials.

Macromolecular helicity induction and static helicity memory of poly(biphenylylacetylene)s bearing aromatic pendant groups and their use as chiral stationary phases for high-performance liquid chromatography.

Two novel poly(biphenylylacetylene)s (PBPAs) bearing achiral alkylphenyl groups at the 4'-position of the biphenyl pendant through ester linkers with different sequences were synthesized by the rhodium-catalyzed polymerization of the corresponding monomers. The influence of the alkylphenyl pendants and the ester sequences on the macromolecular helicity induction and subsequent static helicity memory was investigated. In addition, the chiral recognition ability as chiral stationary phases for high-performance liquid chromatography of the helicity-memorized PBPAs was also examined. Both polymers formed almost perfect right- and left-handed helical conformations through noncovalent chiral interactions with enantiomeric alcohols, and their induced macromolecular helicities were completely retained ("memorized") after removal of the helix inducer. A PBPA bearing a 4-n-butylphenoxycarbonyl pendant group with a static helicity memory showed a remarkably high chiral recognition ability toward a wide variety of chiral aromatics, including simple point chiral compounds, axially chiral biaryls, a chiral spiro compound, helicenes, and planar chiral cyclophanes, particularly under the reversed-phase conditions.

Influence of surfactants on the properties of cellulose derivative-based hybrid materials as chiral stationary phases

Due to the regular backbone structure and high chiral recognition ability, polysaccharide derivatives have become most attractive polymer-based candidates for preparation of chiral stationary phases (CSPs) for efficient enantioseparation. However, the traditional polysaccharide-based CSPs usually took up 20 wt% organic contents, implying that only a small proportion of the CSPs had favorable contribution to their enantioseparation properties. To break through this limitation, seven hybrid bead-type CSPs bearing organic components of higher than 30 wt% have been prepared from cellulose tris(3,5-dimethylphenylcarbamates) (CDMPC) and tetraethyl orthosilicate by a sol–gel process. The influence of three types of surfactants on morphology, organic content and particle size of the hybrid bead-type CSPs was carefully investigated. Cetyltrimethyl ammonium bromide (CTAB), a cationic surfactant with a longer alkyl chain, seemed to be favorable to obtain the hybrid CSPs with a high yield and regular morphology. Then their enantioseparation performance was evaluated by high-performance liquid chromatography (HPLC). The hybrid CSPs containing more organic components exhibited stronger enantioseparation power than those with lower organic contents and previous analogue CSP. For some chiral compounds, the hybrid bead-type CSPs exhibited higher enantioselectivity than Chiralpak IB, which is also prepared from CDMPC and one of the most attractive commercialized CSPs nowadays. A higher loading capacity shown by the hybrid CSPs is beneficial for efficient enantioseparation of chiral compounds, especially for preparative purpose.

Synthesis and characterization of cellulose derivative-based hybrid beads as chiral stationary phases for efficient chromatographic enantioseparation

Polysaccharide derivatives have become the most attractive polymer candidates for the preparation of chiral stationary phases (CSPs) for efficient chromatographic enantioseparation due to their regular structure and high chiral recognition ability.

Differentiation of enantiomeric anions by NMR spectroscopy with chiral bisurea receptors.

Chiral anionic species are ubiquitous and play important roles in biological systems. Despite the recent advancements in synthetic anion receptors bearing urea functionalities, urea-based chiral solvating agents (CSAs) that can separate the NMR signals of racemic anions remain limited. Herein, three dibenzofuran-based C2-symmetric chiral bisureas were synthesized from the reaction of (R,R)-4,6-bis(1-aminopropyl)dibenzo[b,d]furan with phenyl isocyanate, phenyl thioisocyanate, or tosyl isocyanate. The chiral anion recognition properties of these bisureas were examined by 1H NMR spectroscopy using dl-tetrabutylammonium mandelate (TBAM) as a model substrate. A clear baseline separation of the enantiomeric signals of the benzylic proton of TBAM was achieved upon mixing with 0.5 equivalents of bis(phenylurea). In contrast to previous urea-based chiral anion receptors that differentiate the enantiomers of chiral anions by forming 1 : 1 host-guest complexes, a high chiral recognition ability of chiral bis(phenylurea) was achieved owing to the generation of an equilibrium between free guests, 1 : 1 host-guest complexes, and 1 : 2 host-guest complexes. Chiral bis(phenylurea) was also successfully employed in the separation of the enantiomeric 1H NMR signals of various racemic anions.

Chiral Stationary Phases for Liquid Chromatography Based on Chitin- and Chitosan-Derived Marine Polysaccharides

The development of chiral stationary phases (CSPs) for liquid chromatography (LC) revolutionized the enantioseparation and, nowadays, different types of CSPs are commercially available. Polysaccharide-based CSPs are one of the most versatile and widely used for both analytical and preparative applications and they are able to resolve several classes of racemates. Phenylcarbamates of amylose and cellulose derivatives are the most successful; however, polysaccharide-based CSPs comprising marine-derived polysaccharides are also described revealing high chiral recognition abilities and wider range of mobile phases. A literature survey covering the report on chitin and chitosan based CSPs is presented. The chemical structure of the chiral selectors, their development and applications in chiral LC are emphasized.

Temperature-Triggered Switchable Helix-Helix Inversion of Poly(phenylacetylene) Bearing l-Valine Ethyl Ester Pendants and Its Chiral Recognition Ability.

A phenylacetylene containing the l-valine ethyl ester pendant (PAA-Val) was synthesized and polymerized by an organorhodium catalyst (Rh(nbd)BPh4) to produce the corresponding one-handed helical cis-poly(phenylacetylene) (PPAA-Val). PPAA-Val showed a unique temperature-triggered switchable helix-sense in chloroform, while it was not observed in highly polar solvents, such as N,N′-dimethylformamide (DMF). By heating the solution of PPAA-Val in chloroform, the sign of the CD absorption became reversed, but recovered after cooling the solution to room temperature. Even after six cycles of the heating-cooling treatment, the helix sense of the PPAA-Val’s backbone was still switchable without loss of the CD intensity. The PPAA-Val was then coated on silica gel particles to produce novel chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC). These novel PPAA-Val based CSPs showed a high chiral recognition ability for racemic mandelonitrile (α = 2.18) and racemic trans-N,N′-diphenylcyclohexane-1,2-dicarboxamide (α = 2.60). Additionally, the one-handed helical cis-polyene backbone of PPAA-Val was irreversibly destroyed to afford PPAA-Val-H by heating in dimethyl sulfoxide (DMSO) accompanied by the complete disappearance of the Cotton effect. Although PPAA-Val-H had the same l-valine ethyl ester pendants as its cis-isomer PPAA-Val, it showed no chiral recognition. It was concluded that the one-handed helical cis-polyene backbone of PPAA-Val plays an important role in the chiral recognition ability.

Preparation and chromatographic evaluation of β-cyclodextrin derivative CSPs bearing substituted phenylcarbamate groups for HPLC

ABSTRACTFive β-cyclodextrin (β-CD) derivatives bearing substituted phenylcarbamate/3-(triethoxysilyl)propylcarbamate groups at the 2-, 3-, and 6-positions of glucose unit and another five derivatives containing benzoate at the 2-position and substituted phenylcarbamate/3-(triethoxysilyl)propylcarbamate groups at the 3- and 6-positions were synthesized using the regioselective esterification method. The obtained β-CD derivatives were efficiently immobilized onto the silica gel through the intermolecular polycondensation of a small amount of the triethoxysilyl groups, which were used as the chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC). The chiral separation properties of these CSPs were evaluated under the normal-phase HPLC. The effects of solvent polarity and the side chain structures of β-CD derivatives on the chiral recognition ability of the immobilized CSPs were investigated. Among these β-CD derivative CSPs, 2,3,6-tris(3,5-dichlorophenylcarbamate)-β-CD CSP showed a relatively high chiral recognition ability for the studied racemates. The regioselective esterification at the 2-position of glucose unit in the β-CD decreased the chiral recognition ability at the same conditions. For some racemates, the β-CD derivative CSPs showed chiral recognition abilities comparable or better to some chemical bonded β-CD derivative CSPs and 3,5-dichloro- and 3,5-dimethylphenylcarbamates of cellulose and amylose CSPs.

Homogeneous synthesis of partially substituted cellulose phenylcarbamates aiming at chiral recognition

AbstractHomogeneous carbanilation of cellulose with nine kinds of substituted phenyl isocyanates, in which the substituents were varied from electron‐donating to electron‐withdrawing groups, was carried out in 1‐allyl‐3‐methylimidazolium chloride (AmimCl) without any catalyst. The degree of substitution (DS) of cellulose phenylcarbamates in a range from 0 to 3 was readily controlled by altering reaction temperature, reaction time and molar ratio of phenyl isocyanate/anhydroglucose unit. Furthermore, the electronic effect of the substituents on the aromatic ring had a prominent impact on the reactivity of phenyl isocyanates. The phenyl isocyanates with stronger electron‐withdrawing substituents exhibited a higher reactivity. A plot of DS and Hammett substituent constants exhibited linearity with a positive slope. Subsequently, four kinds of partially substituted cellulose phenylcarbamates with DS of 2.0 were synthesized successfully in AmimCl, and then employed as coated‐type chiral stationary phases (CSPs) for high‐performance liquid chromatography. The enantioseparation results demonstrated that these CSPs exhibited high chiral recognition abilities for some racemates. The substituents on the phenyl moieties had a considerable effect on the chiral recognition ability of cellulose phenylcarbamate‐based CSPs. © 2015 Society of Chemical Industry

Precision synthesis, structure and function of helical polymers.

Helical structures are chiral, which means that if we can synthesize a polymer having a stable one-handed helicity, the polymer is optically active. In 1979, we succeeded in the synthesis of a one-handed helical polymer from an optically inactive achiral monomer, triphenylmethyl methacrylate (TrMA). This is the first example of the asymmetric synthesis of an optically active one-handed helical polymer. The polymer (PTrMA) exhibited an unexpected high chiral recognition ability and afforded a practically useful chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC) by coating it on silica gel. In addition, we also succeeded in the development of very useful CSPs for HPLC using the phenylcarbamate derivatives of polysaccharides, cellulose and amylose. These CSPs can efficiently resolve a broad range of chiral compounds, and have been used all over the world for separating and analyzing chiral compounds.

Synthesis of chitosan 3,6-diphenylcarbamate-2-urea derivatives and their applications as chiral stationary phases for high-performance liquid chromatography

Fourteen chitosan 3,6-diphenylcarbamate-2-urea derivatives were synthesized using well-deacetylated chitosan and the corresponding phenyl isocyanates. After coating them on silica gel, their chiral recognition abilities were evaluated as the chiral stationary phases (CSPs) for high-performance liquid chromatography. These coated-type CSPs exhibited different chiral recognitions depending on the position, nature, and number of the substituents introduced on the phenyl group, and the introduction of either an electron-withdrawing or an electron-donating substituent improved the chiral recognition of the CSPs. Among the CSPs, the 2-substituted CSPs showed low chiral recognition abilities, while those with 3,5-dimethyl and 3,5-dichloro substituents showed relatively higher chiral recognition abilities, which enabled the baseline separation of some racemates. The CSPs could be used with some eluents containing chloroform, which cannot be used for other polysaccharide-based CSPs. Some racemates were more efficiently resolved with these nonstandard eluents. The correlation between the chiral recognition ability and the chemical shifts of the N-H protons in the 1H NMR spectra of the chitosan derivatives or the N-H frequencies in the IR spectra of the carbamate moieties was discussed.

Synthesis and chiral recognition ability of helical polyacetylenes bearing helicene pendants

Novel polyacetylenes bearing an optically active or racemic [6]helicene unit as the pendant groups directly bonded to the main-chain (poly-1s) were prepared by the polymerisation of the corresponding acetylenes (1-rac, 1-P and 1-M) using a rhodium catalyst. The optically active polyacetylenes (poly-1-P and poly-1-M) formed a preferred-handed helical conformation biased by the optically active helicene pendants, resulting in the induced circular dichroism (ICD) in their π-conjugated polymer backbone regions. The optically active helical polymers, when employed as an enantioselective adsorbent, showed a high chiral recognition ability towards racemates, such as the monomeric [6]helicene and 1,1′-binaphthyl analogues, and enantioselectively adsorbed one of the enantiomers.

Separation Performance of MOFs Zn(ISN)2·2H2O as Stationary Phase for High-Resolution GC

Metal–organic frameworks (MOFs) as a new type of porous materials have attracted tremendous attention for their potential applications in recent years. Here, we used a simple chiral MOF, Zn(ISN)2·2H2O, as chiral stationary phase for high-resolution gas chromatography. A Zn(ISN)2·2H2O-coated fused-silica capillary column (3 m long × 75 μm i.d.) was fabricated by using a dynamic coating method with ethanol suspension of Zn(ISN)2·2H2O (1 mg mL−1). Then, the coating properties, polarity, and column efficiency of the column were studied. The column efficiency of Zn(ISN)2·2H2O-coated column was up to 3,020 plates m−1. The separation performance was investigated by separating a wide range of organic compounds such as Grob test mixtures, alkanes, alcohols, isomers, and racemates. The relative standard deviations for the five replicate separations of alanine were 0.32 and 2.6 % for retention time and peak area, respectively. The experimental results showed that the new stationary phase possesses high column efficiency, good reproducibility, excellent selectivity, and chiral recognition ability.