Chiral Recognition Ability Research Articles

Chiral Discrimination of Penicillamine Enantiomers: The Role of Aggregation-Caused Quenching in Achieving High Selectivity.

The recognition and separation of chiral isomers are of great importance in both industrial and biological applications. In this study, a chiral recognition system based on electrochemiluminescence was established for the detection of penicillamine (PA) enantiomers. The system utilized a homochiral [Zn2(BDC)(d-lac)] (Zn-BL) platform for the uniform distribution of Ru(bpy)32+ nanoparticles, effectively mitigating aggregation-caused quenching. The chiral recognition ability of Zn-BL was tested to distinguish between PA enantiomers, and the results indicated a substantial increase in the chiral electrochemiluminescence (ECL) signal when l-PA was present, in contrast to d-PA. The mechanism underlying ECL chiral discrimination was investigated using water contact angle measurements, DFT calculations, and electrochemical characterization. The system exhibited high selectivity, stability, and reproducibility for PA enantiomer detection. Furthermore, the proposed method can accurately identify one enantiomer of PA in a mixture. This study provides a reliable and sensitive approach for achieving the highly selective detection of chiral molecules.

Correlation between conformational feature in solution and chiral separation ability of linear and nonlinear amylose tris(alkylcarbamate)s

Five immobilized-type chiral columns were prepared from linear, cyclic, and hyperbranched amylose tris(n-octadecylcarbamate) (ATODC) and amylose tris(n-butylcarbamate) (ATBC). A small amount of the linker site, 3-(triethoxysilyl)propylcarbamate, significantly reduced the chain dimensions of ATBC for which high chain stiffness is attained by intramolecular hydrogen bonding between butylcarbamate groups located on the neighboring glycosidic residue. This phenomenon was not found for ATODC, which is mainly stiffened by bulky side groups. While both columns have appreciable chiral recognition ability, number of separated racemates decreased with decreasing side group bulkiness. The bulkiness of the side groups thus plays a definite role in the chiral separation ability. Furthermore, chain linearity on the silica surface is an important factor for the chiral separation because no substantial chiral separation was found for the chiral columns consisting of cyclic ATODC and cyclic ATBC. The chiral column made of hyperbranched ATODC has an intermediate chiral separation ability between linear and cyclic ATODC, supporting this suggestion.

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.

Exploitation of the enantioselectivity space of coated amylose tris(3,5-dimethylphenylcarbamate) in mixtures of 2-propanol and acetonitrile

Chiral stationary phases (CSPs) with coated amylose tris(3,5-dimethylphenylcarbamate) (ADMPC) selector have long been recognized for their excellent chiral recognition ability in liquid chromatography. The conformational versatility behind this feature is the source of their known hysteretic behavior, which has been previously observed in polar organic (PO) mode eluents containing 2-propanol (IPA). Mixtures of IPA and acetonitrile (MeCN), a typical PO mode eluent system, have not been examined in this aspect yet, even though hysteresis is promising for finding unique unexplored enantioselectivities.Not only was the hysteresis detectable on ADMPC using mixtures of IPA and MeCN, but it was the typical behavior in a diverse set of test compounds. The difference in the retention time of the same analyte under conditions which only differed in the eluent history on the column can go up to 20-fold. The assumed hindered conformational changes of the selector were reflected in retention drift at certain eluent compositions. On the two sides of the transitions, distinct, useful states of the selector were detected. A series of IPA – MeCN compositions with defined pretreatment was selected and recommended as an extension of the preliminary, first choice method screening set that used only alcohols. The incorporation of a solvent possessing substantially different characteristics enhances the potential in practical applications, while keeping the technical simplicity. Stability and robustness of the additional states of the CSP were characterized. The examined columns of different brands shared the observed behavior. Kinetic stability of a column state is adequate for successful application.The evaluated states of ADMPC provide multiple enantiorecognition potential by using mixtures of IPA and MeCN also considering the pretreatment of the column. Unprecedented double and triple elution order reversals along the composition range supported the versatility of the available states. Our findings further enhance the usefulness of ADMPC-containing CSPs. We provide instructions for the application of the widespread chiral selector in common eluent mixtures to avoid pitfalls regarding reproducibility and robustness.

Peptide-derived coordination frameworks for biomimetic and selective separation.

Peptide-derived metal-organic frameworks (PMOFs) have emerged as a class of biomimetic materials with attractive performances in analytical and bioanalytical chemistry. The incorporation of biomolecule peptides gives the frameworks conformational flexibility, guest adaptability, built-in chirality, and molecular recognition ability, which greatly accelerate the applications of PMOFs in enantiomeric separation, affinity separation, and the enrichment of bioactive species from complicated samples. This review focuses on the recent advances in the engineering and applications of PMOFs in selective separation. The unique biomimetic size-, enantio-, and affinity-selective performances for separation are discussed along with the chemical structures and functions of MOFs and peptides. Updates of the applications of PMOFs in adaptive separation of small molecules, chiral separation of drug molecules, and affinity isolation of bioactive species are summarized. Finally, the promising future and remaining challenges of PMOFs for selective separation of complex biosamples are discussed.

Chiral MOFs encapsulated by polymers with poly-metallic coordination as chiral biosensors.

Chiral materials have drawn the widespread attention for theirits chiral recognition ability. The design and synthesis of chiral material are of importance owing to the unpredictability in controlling chirality during the synthesis process. To circumvent problems, a chiral MOF (D-His-ZIF-8) was synthesized by ligand exchange of 2-methylimidazole (Hmim) on ZIF-8 by D-histidine (D-His), which can be treated as chiral host to distinguish amino acid enantiomers. The obtained D-His-ZIF-8 can provide chiral nanochannels for amino acid guests. Meanwhile, polynary transition-metal ion (Co2+ and Fe3+) coordinating with polydopamine (PDA) wrapped on the surface of D-His-ZIF-8 can increase theactive sites. The electrochemical chiral recognition behavior showed that D-His-ZIF-8@CoFe-PDA exhibited good recognition of the tryptophan enantiomer (L/D-Trp) (working potential of -0.2 V vs. Hg/HgCl2). The LOD and LOQ of L-Trp were 0.066 mM and 0.22 mM, respectively, while the LOD and LOQ of D-Trp were 0.15 mM and 0.50 mM, respectively. Finally, the usefulness of D-His-ZIF-8@CoFe-PDA/GCE was evaluated with a recovery of 94.4-103%. The analysisof real samples shows that D-His-ZIF-8@CoFe-PDA/GCE is a feasible sensing platform for the detection of L-Trp and D-Trp.

Enhanced Direct Crystallization Resolution of Racemates Mediated in Chiral Ionic Liquid Cosolvent Mixtures: Experimental, Statistical, and QM Simulation Studies

Four chiral ionic liquids (CILs) of 1-hexyl-3-methylimidazolium-l-2-aminobutyrate ([Hmim][l-2-AbA]), 1-hexyl-3-methylimidazolium-d-2-aminobutyrate ([Hmim][d-2-AbA]), di-1-hexyl-3-methylimidazolium-l-malate ([Hmim]2[l-MA]), and di-1-hexyl-3-methylimidazolium-d-malate ([Hmim]2[d-MA]) were first prepared by a neutralization method and adequately characterized. In light of a gravimetric method, the molar fraction solubilities of dl- and d- together with l-threonine (Thr) were then acquired in the binary cosolvent mixtures (CM) of CILs and water, with different mass fractions (ω) of CILs under 101.3 kPa from 283.15 to 333.15 K. In CIL cosolvent mixtures (CCM), a cosolvency phenomenon was observed with the biggest solubilization and discrepant solubilities of Thr enantiomers, with ω of 0.3. Meanwhile, the asymmetry phenomenon was also found from the ternary phase diagram of Thr enantiomers and CCM, in which the enantiomeric excess values at the eutectic point (eeeut) were sensitive to temperature. Subsequently, the nucleation experiments and appearance probability statistics confirmed that CCM with ω of 0.3 (CCM-0.3) can act as excellent nucleation inhibitors which preferred to suppress the nucleation of enantiomeric crystals with the opposite chirality to them, leading to the preferential nucleation of enantiomeric crystals with the same chirality. Furthermore, by coupling seeds and CCM-0.3, the yield and yield ratio of l-Thr products through a direct antisolvent crystallization resolution were improved greatly compared with that in water, where the largest yield ratio was up to 27.47%. At the same time, isosurface diagrams and binding energy calculations by quantum mechanics (QM) revealed that the higher chiral recognition ability of [Hmim]2[l-MA] than [Hmim][l-2-AbA] stemmed from the stronger weak interactions. Particularly, the enhanced direct crystallization resolution can be feasibly recycled owing to the stability and recyclability of the CILs.

Surface-up click access to allylimidazolium bridged cyclodextrin dimer phase for efficient enantioseparation.

In this work, a novel allylimidazolium-bridged bis(β-cyclodextrin) chiral stationary phase was fabricated via a surface-up thiol-ene click chemistry reaction between 7-SH-β-cyclodextrin and 1-allylimidazole-β-cyclodextrin bonded on a silica surface. The structure of the allylimidazolium-bridged bis(β-cyclodextrin) chiral stationary phase was characterized by Fourier transform infrared spectra, 13 C nuclear magnetic resonance, thermogravimetric analysis, and elemental analysis. Its chiral chromatographic performances were systematically evaluated by separating 35 racemic analytes including isoxazolines, dansyl-amino acids, and flavanones under reversed-phase high-performance liquid chromatography. Compared with the corresponding bottom and top layer of the β-cyclodextrin stationary phase, the allylimidazolium-bridged bis(β-cyclodextrin) chiral stationary phase afforded significantly accentuated chiral recognition ability due to its abundant hydrogen bond sites, electrostatic interactions, and synergistic inclusion. Furthermore, the allylimidazolium-bridged bis(β-cyclodextrin) chiral stationary phase showed better enantioseparation ability compared to other reported bridged cyclodextrin stationary phases. In particular, Ar-Phs and dansyl-amino acid could be completely separated by allylimidazolium-bridged bis(β-mono-6A -deoxy-6-allylimidazolium-β-cyclodextrin chiral stationary phase) chiral stationary phase with high resolutions of 1.14-7.20 and 3.16-5.82, respectively. Molecular docking reveals that good enantioseparation ability arises from the different interaction modes and the synergistic effect of allylimidazolium-bridged bis(β-cyclodextrin) chiral stationary phase.

Molecular Conformation and Intermolecular Interactions of Linear and Cyclic Amylose Derivatives in Solution

AbstractFour kinds of rigid and semiflexible ring polymers are synthesized from flexible cyclic amylose. Their conformational properties in dilute solution are determined from dimensional and hydrodynamic properties in terms of the wormlike ring model. The helix rise per residue h of some ring polymers is larger or smaller than that for the corresponding linear chains, indicating that the local helical structure of the ring polymer is not the same as that for the linear chain. Intermolecular interactions detected by the second virial coefficient and chiral recognition ability of some ring polymers are different from the linear chain, suggesting the local structural change causes the intermolecular interactions. The study also finds that rigid ring polymers can form liquid crystal phase at high concentration. X‐ray diffraction results suggest that the ring chains form pseudo rodlike conformation in the liquid crystal phase, showing that intermolecular excluded volume effects significantly influence the conformation of the polymer chains.

Synthesis of an Immobilized Three-state Switchable Chiral Stationary Phase for HPLC Using a Metal Cation-responsive Optically Active Poly(phenylacetylene) Derivative and Its Chiral Recognition Ability

A metal cation-responsive optically active poly(phenylacetylene)-based copolymer containing a small number of hydroxy groups in the pendant was synthesized and immobilized onto silica gel by crosslinking between the hydroxy groups of the copolymer chains using a dicarboxylic acid as the crosslinker. The obtained immobilized copolymer acted as a three-state switchable chiral stationary phase for high-performance liquid chromatography like the corresponding homopolymer coated on silica gel.

Chiral Covalent-Organic Framework MDI-β-CD-Modified COF@SiO2 Core-Shell Composite for HPLC Enantioseparation.

The chiral covalent-organic framework (CCOF) is a new kind of chiral porous material, which has been broadly applied in many fields owing to its high porosity, regular pores, and structural adjustability. However, conventional CCOF particles have the characteristics of irregular morphology and inhomogeneous particle size distribution, which lead to difficulties in fabricating chromatographic columns and high column backpressure when the pure CCOFs particles are directly used as the HPLC stationary phases. Herein, we used an in situ growth strategy to prepare core-shell composite by immobilizing MDI-β-CD-modified COF on the surface of SiO2-NH2. The synthesized MDI-β-CD-modified COF@SiO2 was utilized as a novel chiral stationary phase (CSP) to explore its enantiomeric-separation performance in HPLC. The separation of racemates and positional isomers on MDI-β-CD-modified COF@SiO2-packed column (column A) utilizing n-hexane/isopropanol as the mobile phase was investigated. The results demonstrated that column A displayed remarkable separation ability for racemic compounds and positional isomers with good reproducibility and stability. By comparing the MDI-β-CD-modified COF@SiO2-packed column (column A) with commercial Chiralpak AD-H column and the previously reported β-CD-COF@SiO2-packed column (column B), the chiral recognition ability of column A can be complementary to that of Chiralpak AD-H column and column B. The relative standard deviations (RSDs) of the retention time and peak area for the separation of 1,2-bis(4-fluorophenyl)-2-hydroxyethanone were 0.28% and 0.79%, respectively. Hence, the synthesis of CCOFs@SiO2 core-shell composites as the CSPs for chromatographic separation has significant research potential and application prospects.

Hybridization of helical poly(phenylacetylene)s bearing L-proline tripeptide pendants into porous silica microspheres as a solvent-tolerable chiral stationary phase for liquid chromatography.

A novel one-handed helical copoly(phenylacetylene) (CPA) bearing L-proline tripeptide pendants and a few triethoxysilyl residues was synthesized and hybridized into SiO2 porous microspheres (PMSs) during microsphere growth through the hydrolytic polycondensation of ethoxysilyl groups. Nuclear magnetic resonance and Fourier transform infrared spectroscopy results verified the successful preparation of CPA and its hybrid product using SiO2 PMSs. The chiral recognition ability of the resulting CPA with a hybridized-type chiral stationary phase (HCSP) for high-performance liquid chromatography (HPLC) was investigated, revealing its high recognition ability for selected racemates. Moreover, the HCSP showed good solvent tolerability, thus broadening the selection of suitable eluents. The separation effect of the HCSP for the racemate N,N-diphenylcyclohexane-1,2-dicarboxamide (7) improved significantly after introducing CHCl3 in the eluent, resulting in separation factors equivalent or superior to common commercially available polysaccharide-based chiral stationary phases. The proposed preparation strategy provides a new and valuable method for obtaining poly(phenylacetylene)-based HCSPs suitable for a wide range of applications and eluent conditions.

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.

Protein synergistic action-based development and application of a molecularly imprinted chiral sensor for highly stereoselective recognition of S-fluoxetine

In order to improve the recognition performance of MIPs sensors in chiral drug enantiomers, a novel a highly selective molecular recognition method based on protein-assisted immobilization of chiral molecular conformation was developed. S-fluoxetine (S-FLX) as the target chiral molecule, human serum albumin (HSA), which has a high affinity and strong interactions with S-FLX, was screened from 11 proteins to serve as an auxiliary recognition unit for the fixation of chiral conformation. By incorporating HSA into the preparation of molecularly imprinted polymers (MIPs), the natural chirality and high stereoselectivity of the protein were leveraged for the induction and fixation of the stereo conformation of S-FLX, refinement of internal structures of the imprinted cavities. The sensor exhibited excellent chiral recognition ability and high detection sensitivity. The changes of probe signal intensity of the MIPs/HSA sensor were positively correlated with the logarithmic concentration of S-FLX in the range of 1.0 × 10−16–1.0 × 10−11 mol L−1, where a detection limit of 6.43 × 10−17 mol L−1 was achieved (DL = 3δb/K). The selectivity of MIPs/HSA sensor in recognizing S-FLX was increased by 18.5 times and the sensitivity was increased by 2.6 times after the incorporation of HSA. The developed sensor was successfully used for the analysis of S-FLX in fluoxetine hydrochloride capsules.

Chiral quaternary ammonium ionic liquids derived from natural dehydroabietylamine and their potential application in chiral molecular recognition

A series of chiral ionic liquids (CILs) based on a quaternary ammonium core substituted with (+)-dehydroabietylamine (DAA) moiety have been synthesized, which are used for the chiral discrimination of non-ionic racemic carboxylic acid and derivatives. The enantioselective recognition ability of the obtained DAA-CILs was investigated using (rac)-mandelic acid and its derivatives as substrates. The results showed that the choice of the anion was crucial for the chiral discrimination of these DAA-CILs. In general, bistrifluoromethanesulfonimide anion (NTf2-) resulted in the improvement and a broad spectrum of enantioselectivity of the CILs. The alkyl chain attached to the DAA group and quaternary ammonium cation was also responsible for the chiral discrimination, and the C3 or C4 carbon chain was favorable for the chiral molecule recognition ability of the CILs. A molecular simulation of the diastereomeric interactions between the selected [DAAPrTMA]NTf2 CIL and racemic α-methoxy mandelic acid (α-MPAA) achieved a well understanding of the chiral recognition mechanism. Additionally, the optical purity of α-MPAA could be detected via NMR analysis easily and quickly. This work leads us to develop new CILs with good molecular recognition ability, DAA-based quaternary ammonium salts.

Synthesis by carbonate aminolysis and chiral recognition ability of cellulose 2,3-bis(3,5-dimethylphenyl carbamate)-6-(α-phenylethyl carbamate) selectors

Novel chiral selectors based on cellulose 2,3-bis(3,5-dimethylphenyl carbamate)-6-(α-phenylethyl carbamate) were regioselectively synthesized by carbonate aminolysis and isocyanate chemistry. By oxycarbonylation with phenyl chloroformate, carbamoylation with 3,5-dimethylphenyl isocyanate, and subsequent aminolysis of the previously introduced reactive carbonate moiety at C6 with enantiopure (R)-or (S)-α-phenylethylamine, chiral selectors have been obtained, which regioselectively carry two different phenyl carbamate substituents. The cellulose derivatives were comprehensively characterized by ATR-FTIR, solid-state NMR, GPC, and elemental analysis. In parallel, 3-aminopropyl-functionalized silica gel as an inert carrier material for the chiral selectors was prepared and the obtained coated-type chiral stationary phases were characterized by both solid-state 29Si NMR, 13C NMR, and elemental analysis. The enantioseparation performance of the chiral selectors was studied and compared to cellulose tris(3,5-dimethylphenyl carbamate) as a reference. With this protocol in hand, certain shortcomings of conventional approaches towards the regioselective synthesis of polysaccharide-based chiral selectors were overcome, such as the limitation to standard isocyanate reagents, being able to apply now the whole wealth of commercially available (chiral) primary and also secondary alkylamines instead.Graphical abstract

Recent progress in the design, synthesis and applications of chiral metal-organic frameworks.

Chiral Metal-Organic Frameworks (CMOFs) are unique crystalline and porous class of materials which is composed of organic linkers and metal ions. CMOFs surpass traditional organic and inorganic porous materials because of their tunable shape, size, functional diversity, and selectivity. Specific applications of CMOFs may be exploited by introducing desired functional groups. CMOFs have chiral recognition abilities, making them unique for chiral compound synthesis and separation. The CMOFs can be synthesized through different approaches. Two main approaches have been discussed, i.e., direct and indirect synthesis. Synthetic strategies play an essential role in getting desired properties in MOFs. CMOFs find potential applications in adsorption, asymmetric catalysis, luminescence, degradation, and enantioselective separation. The MOFs’ porosity, stability, and reusability make them an attractive material for these applications. The plethora of applications of CMOFs have motivated chemists to synthesize novel MOFs and number of MOFs have been ever-escalating. Herein, the synthetic methods of CMOFs and their various applications have been discussed.

Construction of cellulose-based highly sensitive extended-gate field effect chiral sensor.

Chiral recognition is an emerging field of modern chemical analysis, and the development of health-related fields depends on the production of enantiomers. Cellulose is a kind of natural polymer material with certain chiral recognition ability. Limited by the chiral recognition ability of natural cellulose itself, more cellulose derivatives have been gradually developed for chiral recognition and separation. Based on the difference in action between cellulose derivatives and enantiomers, this work synthesized cellulose-tris(4-methylphenylcarbamate) (CMPC) chiral recognition mediators and a CMPC-functionalized extended-gate organic field effect transistor (EG-OFET) was constructed for the first time. Three chiral molecules were selected as model analytes to evaluate the enantiomeric recognition ability of the platform, including threonine (Thr), 2-chloromandelic acid (CA), and 1,2-diphenylethylenediamine (DPEA). The detection limit for 1,2-diphenylethylenediamine (DPEA) is down to 10-13M. Through the amplification effect of the EG-OFET platform, the difference in the interaction between CMPC and three chiral molecules with different structures is converted into a current signal output. At the same time, the enantiomer discrimination mechanism of CMPC was further studied by means of spectroscopy and nuclear magnetic resonance.

Chiral and Achiral Pendant-Bound Poly(biphenylylacetylene)s Bearing Amide and/or Carbamate Groups: One-Handed Helix Formations and Chiral Recognition Abilities

Chiral and Achiral Pendant-Bound Poly(biphenylylacetylene)s Bearing Amide and/or Carbamate Groups: One-Handed Helix Formations and Chiral Recognition Abilities