Chiral Recognition Ability Research Articles

Electrochemical Chiral Recognition of Tryptophan Isomers Based on Nonionic Surfactant-Assisted Molecular Imprinting Sol-Gel Silica.

A new molecularly imprinted SiO2 (MISiO2) film on the surface of indium tin oxide (ITO) electrode was prepared by the sol-gel method and was then applied successfully in the electrochemical chiral recognition of tryptophan (Trp) isomers. Owing to the high chemical stability, excellent rigidity, and low cost, the resultant sol-gel SiO2 is a good matrix material for molecular imprinting. Nonionic surfactant cicosaethylene glycol hexadecyl ether (Brij58) arranged directionally on the surface of the hydrophobic ITO electrode possesses a large amount of oxygen-containing functional groups and may induce the accumulation of template molecules (L-Trp) on the surface of ITO, resulting in L-MISiO2/ITO after the removal of L-Trp templates by calcination. The characterizations of the L-MISiO2/ITO reveal that the L-Trp templates could be successfully removed from the matrix, producing complementary cavities within the L-MISiO2/ITO. The resultant L-MISiO2/ITO exhibits greatly higher affinity toward L-Trp than D-Trp due to the three-point interaction mechanism, and therefore it exhibits good chiral recognition ability for the Trp isomers. In addition, the as-prepared L-MISiO2/ITO or D-MISiO2/ITO (D-Trp as the templates) can predict the ratio of L- and D-isomers in racemic mixture. Last, the MISiO2 films exhibited quick binding kinetics and good recognition reproducibility.

Voltammetric enantiomeric differentiation of tryptophan by using multiwalled carbon nanotubes functionalized with ferrocene and β-cyclodextrin

Two types of ferrocene-functionalized multiwalled carbon nanotubes (MWCNTs) are described. The first was obtained by adsorption of ferrocene (Fc) on MWCNTs via π-π stacking and is referred to as Fc/MWCNTs. The second was prepared via a conjugation reaction between ferrocenecarboxylic acid and aminated MWCNTs to result on covalently modified MWCNTs referred to as MWCNT-Fc. MWCNT/Fc has a better conductivity than MWCNT-Fc. But electrochemical recognition results clearly showed the MWCNTs-Fc/β-CD/GCE can exhibit better chiral recognition ability to tryptophan enantiomers than β-CD/Fc/MWCNTs/GCE. By combining the merits of β-cyclodextrin (β-CD) and MWCNTs-Fc, an electrochemical sensor for l-tryptophan was obtained. Its characterizations by SEM, TEM, TGA, Raman spectroscopy and XPS showed that the Fc/MWCNTs and MWCNTs-Fc have successfully been synthesized. Enantioselective recognition was accomplished by differential pulse voltammetry. Tryptophan enantiomers can be differentiated with an enantioselectivity coefficient (ID-Trp/IL-Trp) of 5.78. Moreover, the chiral recognition mechanism of β-CD recognition tryptophan enantiomers was proposed.

Pyrene-based bisboronic sensors for multichannel enantioselective recognition of tartaric acid

New chiral bisboronic receptors based on pyrene-excimer were synthesized and applied for the determination of absolute configuration and enantiomeric composition of tartaric acid. The distinction was visualized by portable UV lamp in certain concentration range. There were three ways for the sensors to enantioselectively recognize tartaric acid, including the fluorescence spectrum, UV–vis spectrum, and CD spectrum. The enantiomeric excess of tartaric acid was measured quantitatively by using fluorescence analytical technique. Compared with the previous chiral boronic acid sensors, sensor 1 showed weaker background fluorescence and excellent chiral recognition ability of D/l-tartaric acid throughout the whole pH range.

Separation of enantiomers of native amino acids with polysaccharide-based chiral columns in supercritical fluid chromatography

In this short communication preliminary results are reported on the separation of enantiomers of underivatized amino acids on polysaccharide-based chiral columns in sub/super-critical fluid chromatography (SFC).Racemic mixtures of 14 amino acids were used to evaluate the chiral recognition ability of 8 different polysaccharide-based chiral columns with coated or covalently immobilized chiral selectors. Among the studied columns, the one based on cellulose (3,5-dichlorophenylcarbamate) exhibited the most universal chiral recognition ability providing baseline resolution for the enantiomers of 10 studied amino acids. In addition, the effect of mobile phase composition (in particular, of the amount of additive used), as well as the potential contribution of evaporative light scattering detector (ELSD) to extra column band-broadening was evaluated.

Synthesis of cellulose carbamates bearing regioselective substituents at 2,3- and 6-positions for efficient chromatographic enantioseparation

Nine cellulose derivatives bearing two different carbamate substituents at 2,3- and 6-positions of a glucose unit were synthesized by a sequential process based on the regioselective protection at 6-position. Their chiral recognition abilities were then evaluated as the chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) after coating them onto the macroporous silica gel. The introduction of two different phenylcarbamates at 2,3- and 6-positions of glucose unit was comparatively more attractive than that of one phenylcarbamate and one cyclohexylcarbamate to enhance the chiral recognition ability of these cellulose derivatives. Different combination of carbamate substituents of cellulose derivatives seems to offer superior resolution of different racemic compounds. The chiral recognition ability of these derivatives is apparently dependent on the nature, position and number of the substituents on the aromatic moieties. Many derivatives exhibit good enantioselectivity for the racemates in this study, and those based on cellulose 2,3-(3,5-dimethylphenylcarbamate) showed relatively better chiral recognition than others. Some racemates could be even more efficiently resolved on the cellulose derivatives with different carbamate groups at 2,3- and 6-positions than on the cellulose tris(3,5-dimethylphenylcarbamate), which is commercially available as one of the most popular chiral columns, Chiralcel OD. The structures of the obtained cellulose derivatives were also investigated by circular dichroism spectroscopy.

Chiral recognition capabilities of melamine and cyanuric acid supramolecular structures

ABSTRACTCurrently, there are numerous papers that discuss local chiral domains in supramolecular structures of achiral molecules established using the STM method, and by using DFT calculations. However, there are no data regarding the obtainment of macroscopically chiral 2D-supramolecular structures from achiral molecules. In this study, melamine and cyanuric acid supramolecular structures were self-assembled on a graphitized carbon black surface, which had a surface structure that was identical to HOPG, and also on the surface of an inert solid support for chromatography. Chirality induction according to the Kondepudi effect was used. For the supramolecular structures, MD calculations showed the possibility of obtaining a chiral structure. To establish macroscopic chirality, we proposed the use of the difference in enantiomer adsorption on the modified adsorbents. For this, two indirect methods were used: static adsorption with a polarimetric control and gas chromatography. Both methods indicated the chiral recognition ability of the adsorbents used.

The development of biphasic chiral recognition in chiral separation.

In chiral separation, enantioseparation factor is an important parameter which influences the resolution of enantiomers. In this current overview, a biphasic chiral recognition method is introduced to the readers. This method can significantly improve the enantioseparation factor in two-phase solvent through adding lipophilic and hydrophilic chiral selectors which have opposite chiral recognition ability to organic and aqueous phases, respectively. This overview presents the development and applications of biphasic chiral recognition in liquid-liquid extraction and counter current chromatography. It mainly focuses on the topics of mechanism, advantages and limitations, applications, and key factors of biphasic chiral recognition. In addition, the future outlook on development of biphasic chiral recognition also has been discussed in this overview.

Separation of enantiomers of chiral sulfoxides in high-performance liquid chromatography with cellulose-based chiral selectors using methanol and methanol-water mixtures as mobile phases

The interplay between structural details of chiral analytes and selectors in the separation of 14 chiral sulfoxides was systematically studied on 18 different polysaccharide-based chiral columns. Retention and enantioselectivity of a set of chiral sulfoxides were of primary interest. Several of chiral columns studied exhibited quite powerful chiral recognition ability in pure methanol. With addition of water to the mobile phase retention increased in the most cases and the separation factor improved. However, several exceptions were also noted. Of monosubstituted phenylcarbamates of cellulose as chiral selectors, chlorosubstituted ones did not show better enantiomer resolving ability compared to unsubstituted cellulose tris(phenylcarbamate). Out of disubstituted phenylcarbamates of cellulose the ones with methylsubstituents showed higher enantiomer resolving ability compared to chloro-substituted ones and substitution in positions 3 and 5 of the phenyl moiety was clearly advantageous. From disubstituted derivatives those possessing a combination of methyl- and chloro-substituents were advantageous compared to the ones having dimethyl- or dichloro-substituents. Interesting examples of reversal in enantiomer elution order (EEO) were observed on cellulose tris(4-chloro-3-methylphenylcarbamate)- and cellulose tris(3-chloro-4-methylphenylcarbamate)-based chiral stationary phases (CSPs) function of the water content in the mobile phase.

Enantioseparation of Sulfoxides and Nitriles by Inclusion Crystallization with Chiral Organic Salts Based on l‐Phenylalanine

Enantioselective inclusion of aromatic sulfoxides and nitriles was achieved in a host framework created by organic salts comprising achiral benzoic acids and a chiral primary amine (1a) derived from l‐phenylalanine. Tuning of the combined achiral acid component successfully changed the chiral recognition ability of the organic salts. The guest molecules were hydrogen‐bonded to form three‐component inclusion crystals, and the enantiomers of nitriles and sulfoxides were separated with high selectivity up to 92 and 98 % ee. As far as we know, this is the first example of the enantioseparation of non‐functionalized aromatic nitriles.

Chiral Sensing Platform Based on the Self-Assemblies of Diphenylalanine and Oxalic Acid.

Molecular self-assemblies offer a promising strategy for the synthesis of advanced materials for the construction of novel chiral sensing systems, and latest innovations on such self-assemblies are focused on simple building blocks in biology such as nucleic acids, lipids, and peptides. Herein, the self-assemblies of diphenylalanine (FF) and oxalic acid (OA) were prepared as the chiral sensing device for the recognition of tryptophan (Trp) isomers. Interestingly, the self-assemblies composed of OA and FF with different charging states (neutral, positively charged, and negatively charged) exhibited quite different morphologies, resulting in significantly different chiral recognition ability toward the Trp isomers. Also, in this work, the temperature sensitivity and chiral selectivity of the proposed FF-OA self-assemblies were also studied. From a practical point of view, the FF-OA self-assemblies were finally applied for the determination of precise levels of d-Trp in the racemic mixture of Trp isomers.

Homochiral metal-organic framework for HPLC separation of enantiomers

In recent years, homochiral metal-organic frameworks (MOFs) have been widely used as novel media for separation of chiral compounds. Herein, we report a homochiral MOF [Cu(S-mal)(bpe)]n (S-mal=S-malic acid, bpe=trans-1,2-bis(4-pyridyl)ethylene) packed column for HPLC separation of racemates. A variety of different types of racemic compounds such as alcohols, acids, ketones and phenols can be separated on the homochiral MOF column with high enantioselectivity. Compared with the chiral recognition ability of another homochiral MOF [Cu(S-mal)(bpy)]n column previously reported by our group, the results show that the chiral microenvironment and pore sizes of homochiral MOFs play a vital role in chiral recognition process. The repeatability of homochiral MOF [Cu(S-mal)(bpe)]n column was investigated. The relative standard deviation (RSD) for the retention time of DNB-leucine was less than 1.1% (n=5), indicating the good stability and repeatability of the homochiral MOF [Cu(S-mal)(bpe)]n column for HPLC enantioseparation. These results demonstrated that the homochiral MOF [Cu(S-mal)(bpe)]n is promising for enantioseparation, which can be complementary to the currently reported homochiral MOFs columns in HPLC.

A high-performance chiral selector derived from chitosan (p-methylbenzylurea) for efficient enantiomer separation

N-Methoxycarbonyl chitosan was prepared by selectively modifying the amino group at the 2-position of chitosan with methyl chloroformate, which was further functionalized with p-methylbenzylamine to produce chitosan (p-methylbenzylurea). Then, the hydroxyl groups at the 3- and 6-positions of the glucose skeleton were modified with various phenyl isocyanates, affording a series of chitosan 3,6-bis(arylcarbamate)-2-(p-methylbenzylurea)s, which were characterized and proposed as chiral selectors for enantiomer separation. Nineteen racemates, most of which are drugs or intermediates for drugs, were selected as the model analytes to evaluate the enantioseparation performance. The structure-performance relationship of the chiral selectors was investigated in detail. It was found that the methyl-substituted chiral selectors possessed more preferable enantioseparation performance compared with the chloro-substituted ones, and the chiral selectors containing a methyl substituent at the 4-position of the benzene ring showed the best chiral recognition and separation ability with 17 racemates being recognized and 13 racemates being baseline separated. The prepared chiral separation materials derived from these chiral selectors exhibited favorable solvent tolerance towards ethyl acetate, acetone, chloroform and a low proportion of tetrahydrofuran in normal phase. To sum up, this work provided a useful reference for the design and preparation of high-performance chiral separation materials for efficient enantiomer separation.

Nano-amylose-2,3-bis(3,5-dimethylphenylcarbamate)-silica hybrid sol immobilized on open tubular capillary column for capillary electrochromatography enantioseparation.

The chiral organic-inorganic hybrid materials can exhibit a high loading, and the chiral selector nanoparticles can create efficient stationary phases for open-tubular capillary electrochromatography (OT-CEC). Hence, a novel protocol for the preparation of an OT column coated with nano-amylose-2,3-bis(3,5-dimethylphenylcarbamate) (nano-ABDMPC)-silica hybrid sol through in situ layer-by-layer self-assembly method was developed for CEC enantioseparation. By controlling the assembly cycle number of nano-ABDMPC-silica hybrid sol, a homogeneous, dense and stable coating was successfully prepared, which was confirmed by SEM and elemental analysis. As the main parameter influencing the chiral separating effect, the nano-ABDMPC bearing 3-(triethoxysilyl)propyl residues concentration was investigated. The experimental results showed that 10.0 mg/mL nano-ABDMPC bearing 3-(triethoxysilyl)propyl residues coated OT capillary column possessed chiral recognition ability toward the six enantiomers (phenylalanine, tyrosine, tryptophan, phenethyl alcohol, 1-phenyl-2-propanol, and Tröger's base) at some of the different conditions tested. Additionally, the coated OT column revealed adequate repeatability concerning run-to-run, day-to-day and column-to-column. These results demonstrated the promising applicability of nano-ABDMPC-silica hybrid sol coated OT column in CEC enantioseparations.

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.

Preparation and Characterization of Poly-<i>N</i>-isopropylacrylamide Cryogels containing Liposomes and Their Adsorption Properties of Tryptophan

Poly-N-isopropylacrylamide (PNIPA) cryogels containing liposomes were prepared by polymerization under freezing conditions at sub-zero temperature. The cryogel had a highly porous structure with 20–30 μm pore size. The wall thickness of the cryogel containing liposomes was larger than that without liposomes. The structural change and aggregation of the liposomes in the cryogel were observed. The immobilization of the phospholipid and the dynamic property of the lipid membrane in the cryogel were confirmed. The cryogel containing liposomes showed chiral recognition ability toward L-Trp. The selective adsorption of L-Trp was achieved with the PNIPA cryogel containing liposome.

Synthesis of core cross-linked star polymers carrying helical poly(phenyl isocyanide) arms via “core-first” strategy and their surface chiral recognition ability

A norbornene functionalized alkyne-Pd(II) complex was designed and synthesized, which copolymerized with a bisnorbornene cross linker via ring-opening metathesis polymerization (ROMP) afforded a cross-linked Pd(II) macroinitiator. Living polymerization of phenyl isocyanides with the Pd(II) macroinitiator lead to the formation of well-defined core cross-linked star polymer carrying helical poly(phenyl isocyanide)s arms. Because of the living nature of Pd(II)-initiated phenyl isocyanide polymerization, a series of star polymers with controlled structure and tunable compositions was readily prepared. Optically active star polymers with excess of one handed helical arms were obtained by using enantiopure phenyl isocyanide monomers. Such star polymer exhibited excellent chiral recognition ability. The contact angle of the star polymer is strongly dependent on the chirality of the D/L-phenylglycinol droplets. The enantioselective surface recognition can be further applied to the chiral resolution of racemic D/L-phenylglycinol. The enantiomeric excess (ee) of the isolated enantiomer is up to 75%. The chiral star polymers can also be used to induce enantioselectively crystallization of racemic Boc-alanine. The ee value of the induced enantiomer can be up to 91%.

Smartphone-based colorimetric chiral recognition of ibuprofen using aptamers-capped gold nanoparticles.

Sensitive and fast detection of ibuprofen enantiomers is very critical for required routine monitoring and risk assessment of trace pollutants in water samples. Here a simple, rapid and highly sensitive android smartphone application for chiral recognition was developed. Aptamer-capped gold nanoparticles (AuNPs) was demonstrated as an efficient detection platform for (S)-(+)-ibuprofen (S-Ibu) and (R)-(-)-ibuprofen (R-Ibu). Detachment of an enantioselective aptamer from the AuNPs surface and binding with an enantiomer of Ibu lead to AuNPs aggregation, which allows a rapid enantiodiscrimination of Ibu by monitoring the absorbance changes of AuNPs solution in the UV-vis spectrum. Under optimal conditions, the limit of detection for S-Ibu and R-Ibu was 1.24 and 3.91pg/mL, respectively. These probes showed good chiral recognition ability in mixed samples (i.e. S-Ibu + R-Ibu) and environmental samples. These advantages can be further developed by quantitative measurement with smartphone, which opens new opportunities for on-site detection of trace chiral pollutants in a simple and practical manner.

Preparation of polysaccharide-based chiral stationary phases on SiO2@Ag core-shell particles by means of coating and intermolecular polycondensation and comparative liquid chromatography enantioseparations.

Material with a core-shell structure based on a porous silica core and Ag nanoparticles (AgNPs) as shell (SiO2@Ag) was prepared with the seed growth method. Cellulose derivatives as chiral selectors were coated on the surfaces of SiO2@Ag particles by means of coating and intermolecular polycondensation as chiral stationary phases (CSPs), respectively. Fifteen racemates were used to evaluate their chiral recognition ability by high-performance liquid chromatography (HPLC). The results implied that the CSPs based on SiO2@Ag particles obtained stronger interaction with the analytes leading to better enantioseparation due to the existence of AgNPs on the surfaces of silica gel, compared with a cellulose derivative-modified silica column. In addition, the new CSPs showed special selectivity for ketone enantiomers, and AgNPs played a synergistic effect with cellulose derivatives on enantioseparation. Graphical abstract Schematic of SiO2@Ag stationary phase.

Performance comparison of chiral separation materials derived from N-cyclohexylcarbonyl and N-hexanoyl chitosans

Chitosan bis(phenylcarbamate)-(N-cyclohexylformamide)s and chitosan bis(phenylcarbamate)-(N-hexanamide)s were synthesized as chiral selectors for enantiomeric separation. Since two types of substituents with different structures were, respectively, introduced onto the 2-position and the 3-/6-positions of the glucose skeleton in the chitosans through a “heterogeneous” modification pathway, the enantioseparation performances of the chiral selectors could be improved. Influence of the type and position of the substituents on chiral recognition and enantioseparation abilities was studied in detail, and the structural dependence on enantioseparation performance was particularly demonstrated. It was found that methyl- and chloro-substituted chitosan bis(phenylcarbamate)-(N-hexanamide)s possessed comparable enantioseparation performances, whereas chloro-substituted chitosan bis(phenylcarbamate)-(N-cyclohexylformamide)s exhibited much more powerful chiral recognition and enantioseparation abilities than the methyl-substituted ones. Among all the prepared chiral selectors, those with the combination of the cyclohexyl group at the 2-position of the glucose skeleton in the chitosan derivatives and the chlorophenyl group at the 3-/6-positions seemed to be more preferable for enantiomeric separation. As a result, the chitosan bis(3,4-dichlorophenylcarbamate)-(N-cyclohexylformamide) possessed the best enantioseparation performance. The solvent tolerability of the prepared chiral selectors was also investigated in the present study. Compared with the classical coated-type chiral separation materials derived from cellulose/amylose derivatives, the N-cyclohexylcarbonyl and N-hexanoyl chitosans based chiral stationary phases were observed to possess more favorable solvent tolerability, thus possibly widening their applications for various practical enantioseparations.

Enantioseparation of Phenylsuccinic Acid Enantiomers by Solvent Sublation with Collaborative Selectors

A new solvent sublation (SS) system for chiral separation is introduced by using phenylsuccinic acid (H2A) as the model enantiomers. The experiments were carried out in a traditional SS apparatus but with collaborative chiral selectors: dibenzoyl-L-tartaric acid (L-DBTA) in the organic phase and hydroxypropyl-β-cyclodextrin (HP-β-CD) in the aqueous phase. The chiral recognition abilities of the two selectors are opposite for the H2A enantiomers. Several important parameters were investigated. The results demonstrate that enantioselective sublation and partitioning behavior are mainly dependent on the pH of the solution, the concentrations of chiral selectors and H2A. Furthermore, the flow rate of air and flotation time also have some effects on the enantioseparation. Under the optimized conditions, the enantioselectivity expressed by the separation factor (β) and enantiomer excess (e.e.%) are 2.47 and 29.50%, and the yields of R-H2A and S-H2A are 0.23 and 0.13 g·L−1, respectively. Compared with the SS system with the single selector HP-β-CD in the aqueous phase (or L-DBTA in the organic phase), the increased values of β and e.e.% in the new SS system with collaborative selectors are 1.31 (or 1.38) and 5.90% (or 13.82%), respectively.