High Chiral Recognition 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 electrochemical chiral sensor based on glutamic acid functionalized graphene-gold nanocomposites for chiral recognition of tryptophan enantiomers

• Glu functionalized RGO-Au nanocomposites were synthesized as an electrochemical chiral sensor. • The electrochemical chiral sensor has high chiral recognition capability for Trp enantiomers. • Mechanism and binding thermodynamics were explained by UV–vis and DFT in detail. A novel chiral sensing platform via the glutamic acid (Glu) functionalized graphene-gold nanoparticles (RGO-Au/ l -Glu and RGO-Au/ d -Glu) synthesized via the one-step hydrothermal method is described for the enantioselective recognition of L- and d -tryptophan (Trp). The SEM, TEM, EDS, AFM, FTIR, and XRD characterization techniques showed that RGO-Au/ l -Glu and RGO-Au/ d -Glu chiral composite were successfully synthesized. By combining the chiral features of Glu and the excellent electrochemical behaviors of RGO-Au, two electrochemical chiral sensing interfaces constructed by RGO-Au/ l -Glu and RGO-Au/ d -Glu modified glassy carbon electrode (GCE) were constructed for electrochemical chiral recognition of Trp enantiomers. The results demonstrated that the RGO-Au/ l -Glu/GCE showed the highest chiral recognition efficiency, the enantioselectivity coefficient (I L /I D ) was 2.56. UV–vis absorption spectroscopy and density functional theory (DFT) calculations proved that RGO-Au/ l -Glu had a strong binding ability with l -Trp. In addition, the chiral sensing interface had a linear response in the 1 mM to 5 mM Trp concentration range and a 0.28 mM detection limit (at S/N = 3) for l -Trp, and 0.86 mM to d -Trp, also had good stability and reproducibility, which can be used as an efficient chiral sensing interface for the recognition of Trp enantiomers.

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.

L-Cysteine modified metal-organic framework as a chiral stationary phase for enantioseparation by capillary electrochromatography.

A new kind of chiral zirconium based metal–organic framework, l-Cys-PCN-222, was synthesized using l-cysteine (l-Cys) as a chiral modifier by a solvent-assisted ligand incorporation approach and utilized as the chiral stationary phase in the capillary electrochromatography system. l-Cys-PCN-222 was characterized by X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, Fourier-transform infrared spectra, nitrogen adsorption/desorption, circular dichroism spectrum, zeta-potential and so on. The results revealed that l-Cys-PCN-222 had the advantages of good crystallinity, high specific surface area (1818 m2 g−1), thermal stability and chiral recognition performance. Meanwhile, the l-Cys-PCN-222-bonded open-tubular column was prepared using l-Cys-PCN-222 particles as the solid phase by ‘thiol–ene’ click chemistry reaction and characterized by scanning electron microscopy, which proved the successful bonding of l-Cys-PCN-222 to the column inner wall. Finally, the stability, reproducibility and chiral separation performance of the l-Cys-PCN-222-bonded OT column were measured. Relative standard deviations (RSD) of the column efficiencies for run-to-run, day-to-day, column-to-column and runs were 1.39–6.62%, and did not obviously change after 200 runs. The enantiomeric separation of 17 kinds of chiral compounds including acidic, neutral and basic amino acids, imidazolinone and aryloxyphenoxypropionic pesticides, and fluoroquinolones were achieved in the l-Cys-PCN-222-bonded OT column. These results demonstrated that the chiral separation system of the chiral metal–organic frameworks (CMOFs) coupled with capillary electrochromatography has good application prospects.

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.

Regioselectively substituted cellulose mixed esters synthesized by two-steps route to understand chiral recognition mechanism and fabricate high-performance chiral stationary phases

It is challenging to design and fabricate new and high-performance cellulose-based chiral stationary phases (CSPs), due to the indistinct chiral recognition mechanism and the inherent difficulty to control the structure of cellulose derivatives. Herein, taking advantage of the high regioselective benzoylation of cellulose in 1-allyl-3-methylimidazolium chloride, a series of regioselectively substituted cellulose mixed esters, cellulose 6-benzoate-2,3-phenylcarbamate, are directly obtained by a facile two-steps route without protecting and deprotecting process. The resultant cellulose mixed esters exhibit high chiral recognition capability. In particular, when the benzoate group has an electron-donating substituent on phenyl ring, such as 4-tert-butyl group, the corresponding regioselectively substituted cellulose mixed esters have much better enantioseparation capability than cellulose tri(3,5-dimethylphenylcarbamate), which is commercially available as Chiralcel OD column, one of the most powerful CSPs. More importantly, via adjusting the chemical structure of cellulose derivatives and adding a post-treatment process to optimize their chiral recognition properties, the chiral recognition mechanism is clearly revealed. The synergy of the hydrophobic helical conformation, weak hydrogen-bond donating ability and appropriate distribution of substituents of cellulose derivatives is essential to fabricate high-performance CSPs.

Effective Guest Inclusion by a 6‐O‐Modified β‐Cyclodextrin Dimer in Organic Solvents

A 6-O-tert-butyldimethylsilylated β-cyclodextrin (TBDMS-β-CD) dimer, in which two TBDMS-β-CD rings are connected in a head-to-head fashion by a m-xylylene linker, effectively forms inclusion complexes with pyrene and naphthalene in nonpolar organic solvents such as cyclohexane and benzene. This TBDMS-β-CD dimer shows a higher inclusion ability toward these guests than a TBDMS-β-CD dimer bearing a p-xylylene linker due to the greater cooperation of the two TBDMS-β-CD rings for the guest inclusion. Unlike the corresponding monomer, the TBDMS-β-CD dimer bearing a m-xylylene linker is also a good host even in polar organic solvents such as tetrahydrofuran. High chiral recognition of aromatic amines and alcohol is realized by utilizing inclusion within the cavity of the TBDMS-β-CD dimer in cyclohexane. In particular, an extremely high binding selectivity for (S)-1-(1-naphthyl)ethylamine and (S)-1-(1-naphthyl)ethanol over the corresponding (R)-isomers is achieved. Moreover, by utilizing the high chiral recognition with the TBDMS-β-CD dimer in cyclohexane, a non-enzymatic kinetic resolution of racemic 1-(1-naphthyl)ethylamine via enantioselective N-benzoylation is attained with an enantiomer excess of up to 87 % and an s-factor of 15.

Separation of enantiomers of selected chiral sulfoxides with cellulose tris(4-chloro-3-methylphenylcarbamate)-based chiral columns in high-performance liquid chromatography with very high separation factor

The present study reports successful separations of enantiomers of selected chiral sulfoxides with very high separation factor in high-performance liquid chromatography by using chiral columns prepared with the chiral selector cellulose tris(4-chloro-3-methylphenylcarbamate). High separation factors were observed in polar organic, as well as in hydrocarbon-alcohol-type mobile phases. The key structural components of the solute for obtaining high chiral recognition are discussed as well as thermodynamic quantities of analyte adsorption on the chiral stationary phase were determined. Experiment aimed at the enantioselective extraction of racemates from solution are also described.

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.

Preparation and chiral recognition of heterosubstituted amylose derivatives-based chiral stationary phases

Two novel amylose derivatives, namely amylose 2-benzoate-3-(4-methylphenylcarbamate)-6-(3,5-dichlorophenylcarbamate) and amylose 2-benzoate-3-(3,5-dichlorophenylcarbamate)-6-(4-methylphenylcarbamate), were prepared utilizing a serial regioselective process. After coated onto aminopropyl silica gel, they were utilized as chiral stationary phases (CSPs) for high performance liquid chromatography. Investigations indicated that the CSPs exhibited characteristic chiral recognition and their chiral recognition abilities were much higher than those of amylose tris(3,5-dichlorophenylcarbamate) (ADCPC), a homosubstituted derivative. The nature and position of the substituents at 3-, and 6-positions of a glucose unit had great influence on the chiral resolution abilities of the amylose derivatives. Some chiral compounds which were not effectively resolved on the commercial column Chiralpak AD were effectively separated on the new CSPs. Moreover, with all the eight tested racemates resolved, amylose 2-benzoate-3-(4-methylphenylcarbamate)-6-(3,5-dichlorophenylcarbamate) exhibited relatively high chiral recognition and might be a potential useful CSP.

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.