Chiral Recognition Ability Research Articles

Proportionally controlled dual-chiral covalent organic frameworks via thiol-ene click reaction for efficient enantioseparation

Developing a universally applicable and commercially hopeful chiral material is a significant challenge for the separation and analysis field. In this study, innovative dual-chiral CCOFs ([SH-β-CD-NALC]x-COFs) modified with 6-deoxy-6-mercapto-β-cyclodextrin (SH-β-CD) and N-acetyl-l-cysteine (NALC) are presented. These CCOFs were synthesized using a single, one-step bottom-up approach at room temperature, specifically designed for enantiomer recognition and separation. We investigated the effect of varying ratios of multiple chiral selectors in CCOFs on chiral recognition abilities through adsorption experiments for the first time. The precisely engineered [SH-β-CD-NALC]1/6-COF, with excellent stability, crystallinity, abundant chiral sites, and a greater specific surface area, was well suited as a chiral stationary phase (CSP) in various racemates separation. The results showed satisfactory resolution, column efficiency, stability, and reproducibility. In addition, mechanism studies have revealed that the dual-chiral COF can offer triple selectivity and achieve the effect where 1 + 1 is greater than 2. This work emphasized the advantages of dual-chiral COF in achieving racemic drug separation, providing a new approach for the development of high-performance chiral separation platforms in the future.

Synergistic enantioseparation system based on anovel nanomaterial synthesized by chiral metal-organic framework and chiral molecularly imprinted polymer in capillary electrochromatography.

Acapillary electrochromatography (CEC) synergistic enantioseparation system based on a novel nanomaterial synthesized by chiral molecularly imprinted polymers (CMIPs) and chiral metal organic frameworks (CMOFs) was developed. Compared with CMIPs and CMOFs alone, the enantioseparation performance of ofloxacin (OFL)of the CEC with the novel nanomaterial as stationary phases was greatly improved. CMOFs with chiral recognition ability have synergize with CMIPs to greatly improve the chiral selectivity of the novel stationary phases in CEC.As a proof-of-concept demonstration, a coated capillary column was prepared by a sol-gel method using S-OFL (template), iron-based cyclodextrin MOF (Fe-CD-MOF, a CMOF), 3-aminopropyltriethoxysilane (functional monomer), and tetraethyl orthosilicate (cross-linking agent). Then, the newly constructed CEC system has excellent enantioseparation performance of OFL with a resolution of 3.92. Finally, computerized molecular docking revealed that the difference in the binding ability of Fe-CD-MOF to ofloxacin enantiomers was an important mechanism for CEC chiral separation. This innovative development of synergistic chiral stationary phases based on CMOFs and CMIPs creates a highly efficient potential direction for enantiomer separation.

Chiral helical polyaniline modified electrodes toward efficient enantioselective recognition of tyrosine

Enantiomeric analysis is a crucial aspect of the investigation of the properties of chiral substances, and it plays a pivotal role in the development and application of chiral substances. Therefore, the objective of this study was to develop a highly sensitive and user-friendly tyrosine (Tyr) enantiomer detector based on chiral helical polyaniline (PANI). In this study, the helical PANI was generated in an alcohol-water system and doped with Camphorsulfonic acid (CSA) to enhance its electrochemical properties. The chiral helical PANI was then obtained by eluting the CSA under alkaline conditions. The electrochemical sensors developed using this material enable selective recognition of Tyr enantiomers. The mechanism of enantioselective recognition was also explored from a molecular perspective with the help of modeling software. The chiral recognition ability and properties of the sensor were investigated using DPV, EIS, and CV. The surface characteristics of doped and de-doped chiral sensor were analyzed using FE-SEM, HR-TEM, AFM, CD, XPS, and FT-IR. Finally, an electrochemical analysis method for Tyr enantiomers was established using DPV, offering high sensitivity, superior anti-interference ability, quick analysis speed, and good long-term stability. The constructed chiral electrochemical sensor can be used for the detection of human serum and urine samples, which provides a new idea for the selective recognition of Tyr enantiomers in clinical sample.

Preparation of Chiral Stationary Phase Based on 1,1'-bi-2-Naphthol for Chiral Enantiomer Separation.

Two enantiomeric novel chiral stationary phases (CSPs) R-3-Amide-BINOL CSP (CSP-1) and S-3-Amide-BINOL CSP (CSP-2) were prepared using (R/S)-1,1'-bi-2-naphthol (BINOL) derivatives as chiral selectors. The structure of CSPs was characterized by nuclear magnetic resonance, scanning electron microscope and elemental analysis. Four chiral solutes were selected under normal phase HPLC conditions to evaluate the chiral separation ability of the two novel CSPs. The effects of mobile phase and acidic additives on enantiomeric separation were investigated. The combination of molecular docking simulation and experimental data has elucidated the crucial role of hydrogen bonds and π-π interactions formed between the analyte and CSP in chiral recognition, and different configurations of CSP can cause enantiomeric elution sequence reversal, indicating that the configuration of chiral selectors in CSP has a significant impact on chiral recognition ability.

Fluorescence and Circular Dichroism Dual-Mode Probe for Chiral Recognition of Tyrosine and Its Applications in Bioimaging.

Chiral amino acids (AAs) are essential in metabolism and understanding physiological processes, and they could be used as biomarkers for the diagnosis of different diseases. In this study, chiral Cdots@Van were prepared by postmodifying an achiral Cdots core with vancomycin for recognizing and determining the enantiomeric excess (ee) of tyrosine (Tyr) enantiomers. The fluorescence response of Cdots@Van is based on an "on-off" strategy, with different quenching percentages for d- and l-tyrosine. Interestingly, the circular dichroism (CD) spectrum of Cdots@Van responded to only one form of Tyr enantiomer, specifically d-Tyr, and remained nearly unchanged upon the addition of l-Tyr. Quantum mechanical (QM) calculations were in excellent agreement with the experimental results, confirming the stronger binding affinity of Cdots@Van for d-Tyr compared to l-Tyr. We further investigated the chiral recognition ability of the interconnected vancomycin particles, which was synthesized using the EDC/NHS coupling reaction between vancomycin molecules without a Cdots core. Surprisingly, unlike free vancomycin molecules, interconnected vancomycin displayed an enantiomeric recognition ability by CD spectroscopy, similar to what was observed for Cdots@Van. Crucially, this chiral probe has been successfully utilized for cell imaging applications.

The series of L-lysine-derived gelators-modified multifunctional chromatography stationary phase for separation of chiral and achiral compounds

In this study, using chiral L-lysine as the molecular skeleton, three kinds of L-lysine-derived gelators (GBLB, GBLF and GFLF) were synthesized and then bonded to the surface of silica matrix (5 μm) by amide condensation to prepare a series of multifunctional chromatography stationary phases (GBLB-SiO2, GBLF-SiO2, and GFLF-SiO2) were prepared. The L-lysine-derived gelators not only possess chiral recognition ability, but also can spontaneously form oriented and ordered network structures in liquid medium through the interaction of non-covalent bonding forces such as hydrogen bonding, π-π stacking, and van der Waals forces. The comprehensive effect of multiple weak interaction sites enhances the molecular recognition ability and further improves the separation diversity of different types of compounds on stationary phases. The separation and evaluation of chiral compounds showed that benzoin, 1-phenyl-ethanol, 1-phenyl-propanol and 6-hydroxyflavanone could be separated in normal phase mode (NPLC). The separation of different types of non-chiral compounds, such as sulfonamides, nucleosides, nucleobases, polycyclic aromatic hydrocarbons (PAHs), anilines, and aromatic acids, were achieved in hydrophilic interaction/reversed-phase/ion-exchange mode (HILIC/RPLC/IEC), and the separation of polarized compounds could be performed under the condition of ultrapure water as the mobile phase, which has the typical retention characteristics of per aqueous liquid chromatography (PALC). The effects of organic solvent content, temperature, pH value, and buffer salt concentration on the retention and separation performance of the column were investigated. Comparison of the three prepared columns showed that the separation performance (such as aromatic selectivity) could be improved by increasing the types of functional groups on the surface of the stationary phase and the number of aromatic groups. In a word, the prepared stationary phase have multiple retention properties, can simultaneously separate chiral compounds and various types of achiral compounds. This work provides an idea for developing multifunctional liquid chromatography stationary phase materials, and further expands the application of gelators in separation science.

Room temperature synthesis of a chiral covalent organic framework core-shell composite for high-performance liquid chromatography enantioseparation.

In this article, chiral covalent organic framework core-shell composite CCOF-TpPa-Py@SiO2 was facilely synthesized by induction at room temperature. The CCOF-TpPa-Py@SiO2 core-shell composite was used as a chiral stationary phase for the separation of the racemates by high-performance liquid chromatography, which exhibits good separation performance for chiral compounds including ketones, alcohols, esters, epoxides, carboxylic acids, amides, and amines. The effects of analyte injection mass on the enantioseparation were studied. The reproducibility and stability of the CCOF-TpPa-Py@SiO2 chiral column were explored. The intra-day (n=5), inter-day (n=5), and inter-column (n=3) relative standard deviations for the migration times and resolution of benzoin were 0.32%-0.54%, 0.45%-0.61%, and 1.21%-1.53%, respectively. In addition, the chiral separation ability of the CCOF-TpPa-Py@SiO2 chiral column (column A) was compared with that of the MDI-β-CD-Modified COF@SiO2 (column B) as well as a commercial chiral column (Chiralpak AD-H). The chiral recognition ability of column A is complementary to that of column B and AD-H column. The resolution mechanism of CCOF-TpPa-Py@SiO2 stationary phase towards chiral analyte was explored. Hence, the synthesis of CCOF-TpPa-Py@SiO2 core-shell composite by induction at room temperature as chiral stationary phases for chromatographic separation has important research potential and application prospects.

Crystallization resolution of racemic compounds via chiral surfactant

As one of the basic attributes of nature and the universe, chirality is valuable in biology, medicine, and materials science. However, enantiomer resolution remains a long-standing challenge. Herein, a novel surfactant for resolution of racemic compound with high performance has been outlined. Firstly, we synthesized a chiral surfactant and its chiral recognition ability to L-Alanine molecules was confirmed. Subsequently, the solid–liquid equilibrium curves were used to design the resolution route. The synthesized surfactant was further utilized to intensify the crystallization process of the racemic compound, resulting in a remarkable increase of L-Alanine products’ ee values from 0% to 99%. Finally, quantum chemical calculations and molecular dynamics simulations were employed to uncover the stereoselectivity recognition mechanism of surfactant to L-Alanine molecules. Overall, we propose a new idea for direct crystallization resolution of racemic Alanine by chiral surfactants that differs from the “rule of reversal”, which is highly attractive for chiral resolution.

Synthesis of a symmetrically meta-substituted poly(diphenylacetylene) bearing chiral amide groups and its application as a chiral stationary phase for high-performance liquid chromatography

Abstract A symmetrically meta-substituted poly(diphenylacetylene) bearing chiral amide groups was synthesized by reacting (R)-1-phenylethylamine with a carboxy-group-containing precursor polymer, which was obtained by polymerizing the corresponding ester-containing diphenylacetylene using a modified Mo(V)-based catalytic system followed by hydrolysis. The polymer formed a one-handed helical conformation when thermally annealed in a solvent. The chiral recognition ability of the polymer before and after thermal annealing was investigated when used as a chiral stationary phase for high-performance liquid chromatography.

Electrochemical chiral sensor for recognition of amino acid enantiomers with cyclodextrin-based microporous organic networks

BackgroundChirality is a ubiquitous phenomenon in nature, but enantiomers exhibit different pharmacological activities and toxicological effects. Therefore, Chiral recognition plays a pivotal role in various fields such as life sciences, chemical synthesis, drug development, and materials science. The synthesis of novel chiral composites with well-defined loading capabilities and ordered structures holds significant potential for electrochemical chiral recognition applications. However, the design of selective and stable electrochemical chiral recognition materials remains a challenging task. ResultIn this work, we construct a simple and rapid electrochemical sensing platform for tryptophan (Trp) enantiomer recognition using cyclodextrin-modified microporous organic network as chiral recognition agent. CD-MON with chiral microenvironment was prepared by Sonogashira-Hagihara coupling reaction of the chiral molecule heptyl-6-iodo-6-deoxyβ-cyclodextrin and 1, 4-Diethynylbenzene. The adhesion of BSA makes CD-MON firmly fixed on the electrode surface, and as a chiral protein, it can improve the chiral recognition ability through synergistic effect. Chiral amino acids are in full contact with the chiral microenvironment during pore conduction of MON, and L-Trp is more stably bound to CD-MON/BSA due to steric hindrance, host-guest recognition and hydrogen bonding. Therefore, the electrochemical sensor can effectively identify tryptophan enantiomers (IL-Trp/ID-Trp = 2.02), and it exhibits a detection limit of 2.6 μM for L-Trp. UV–Vis spectroscopy confirmed the adsorption capacity of CD-MON towards tryptophan enantiomers in agreement with electrochemistry results. SignificanceThe prepared chiral sensor has excellent stability, reproducibility (RSD = 3.7%) and selectivity, realizes the quantitative detection of single isomer in tryptophan racemic and quantitative analysis in real samples with 94.0%–101.0% recovery. This work represents the first application of MON in chiral electrochemistry which expands the application scope of chiral sensors and holds great significance in separation science and electrochemical sensing.

A covalent organic framework nanosheet-nanochannel composite with signal amplification strategy for electrochemical enantioselective recognition

Recognition and separation of chiral isomers are of great importance in both industrial and biological applications. However, owing to identical molecular formulas and chemical properties of enantiomers, signal transduction and amplification are still two major challenges in chiral sensing. In this study, we developed an enantioselective device by integrating chiral covalent organic framework nanosheets (CONs) with nanochannels for sensitive identification and quantification of enantiomers. Using 3,4-dihydroxyphenylalanine (DOPA) as the model analyte, the as-prepared chiral nanofluidic device exhibits a remarkable chiral recognition ability to l-DOPA than d-DOPA. More importantly, due to the chelation of DOPA with Fe3+ ions, it can efficiently block the ion transport through channel and shield the channel surface charge, which will amplify the difference in the electrochemical response of l-DOPA and d-DOPA. Therefore, a sensitive chiral recognition can be achieved using the present nanofluidic device coupled using electrochemical amplification strategy. Notably, using this method, an ultra-low concentration of l-DOPA (as low as 0.21 pM) can be facilely and successfully detected with a linear range of 1 pM–10 μM. This study provides a reliable and sensitive approach for achieving highly selective detection of chiral molecules.

Chiral resolution of ketoprofen by modified polymethyl methacrylate microspheres

AbstractDue to unique structural characteristics and chiral environment, β‐cyclodextrin (β‐CD) has a strong chiral separation ability. 4‐Chlorophenyl isocyanate (4CPI) also plays an important role in separating chiral drugs. In this paper, a chiral stationary phase: 4‐CPI‐β‐CD stationary phase (4CPI‐β‐CD@PMMA) was designed and prepared. Polymethyl methacrylate (PMMA) microspheres with uniform particle size and good monodispersity were prepared by modified seed polymerization and seed expansion methods. Using diazo resin as a coupling agent, PMMA microspheres were connected with 4CPI‐β‐CD to prepare a stationary phase with chiral recognition ability. PMMA microspheres and 4CPI‐β‐CD were also characterized. Compared with the traditional silica gel column, PMMA microspheres have higher preparation efficiency, better monodispersity, and better mechanical properties as chromatographic fillers. Finally, the chiral separation of ketoprofen was carried out by reversed‐phase high‐performance liquid chromatography, and the separation conditions were optimized. This paper is a good idea for the preparation of the chiral stationary phase.

New Levan-Based Chiral Stationary Phases: Synthesis and Comparative HPLC Enantioseparation of (±)-trans-β-Lactam Ureas in the Polar Organic Mode.

In this paper, the preparation of three new polysaccharide-type chiral stationary phases (CSPs) based on levan carbamates (3,5-dimethylphenyl, 4-methylphenyl, and 1-naphthyl) is described. The enantioseparation of (±)-trans-β-lactam ureas 1a-h was investigated by high-performance liquid chromatography (HPLC) on six different chiral columns (Chiralpak AD-3, Chiralcel OD-3, Chirallica PST-7, Chirallica PST-8, Chirallica PST-9, and Chirallica PST-10) in the polar organic mode, using pure methanol (MeOH), ethanol (EtOH), and acetonitrile (ACN). Apart from the Chirallica PST-9 column (based on levan tris(1-naphthylcarbamate), the columns exhibited a satisfactory chiral recognition ability for the tested trans-β-lactam ureas 1a-h.

Short bridging and partial derivatization synergistically modified β-cyclodextrin bonded chiral stationary phases for improved enantioseparation

β-Cyclodextrin (β-CD) and its derivatives have been widely employed in the field of chiral separation, but they are still faced the limitation of low enantioselectivity and complex processes. Derivatization with functional molecules or preparation as bridging dimers are the two main modifications for β-CD to obtain chiral recognition compounds. Herein, a partially derived bridged β-CD (CPI-EBCD) bonded chiral stationary phases was prepared to improve enantioseparation. The chiral recognition moiety was synthesized by a bridged β-cyclodextrin dimer using a short-chain bridging agent (ethylenediamine) and then modifying the bridged cyclodextrin with a 4-chlorophenylisocyanate (CPI) containing a benzene ring and polar group. Compared with natural β-CD, dual-chambered CPI-EBCDs have better encapsulation synergies and more recognition sites with the guest molecule, while the short flexible bridging groups make the double cavities closer and more easily recognizable as linear molecules. The introduction of derived groups CPI provided more recognition sites and more types of interactions, including π-π interaction force, hydrogen bonding effect, and dipole-dipole interaction, thus improving the enantiomer-specific chirality recognition effect. The chiral stationary phase CPI-EBCDP was obtained by connecting CPI-EDCB with mesoporous silica microspheres by simple photochemical reaction using a green non-toxic diazo resin as coupling agent, simplifying preparation process. In the reversed phase mode of liquid chromatography, CPI-EBCDP has excellent chiral recognition ability, and 12 chiral compounds are successfully isolated by optimizing mobile phase conditions, with good reproducibility and stability. The successful preparation of this new chiral stationary phase provides an important reference for the subsequent development of cyclodextrin-like chiral stationary phases.

Mercapto-β-cyclodextrin covalent organic frameworks for enantioselective liquid-liquid extraction

β-Cyclodextrin (β-CD) exhibits exceptional chiral recognition ability, and covalent organic frameworks (COFs) have been reported as highly promising chiral carriers. Therefore, incorporating cyclodextrin into COFs may result in chiral covalent organic frameworks (CCOFs) suitable for chiral applications. In this work, a solvothermal method was employed to synthesize a classical porous covalent organic framework (COF-V), while β-CD underwent a two-step modification process, resulting in the synthesis of mercapto-β-cyclodextrin (β-CD-SH). Subsequently, a β-CD-based covalent organic framework (COF-S-CD) was synthesized through a Thiol-Ene “click” reaction. The synthesized COF-S-CD was successfully applied in enantioselective liquid-liquid extraction for five racemic arylcarboxylic acids, including 2-phenylpropionic acid, 2-(4-methylphenyl) propionic acid, 2-(3-chlorophenyl) propionic acid, 2-(4-nitrophenyl) propionic acid and α-cyclohexylmandelic acid. Under optimized conditions, enantioseparation factors for the five racemates reached 1.78, 2.20, 1.84, 1.76 and 1.96, respectively, which indicated a significant enhancement in chiral recognition ability upon the incorporation of cyclodextrin into the COF material. This new application suggested that the synthesis of covalent organic framework materials incorporating β-CD, with the ability to uniformly disperse in the aqueous phase, holds promising potential for highly effective enantioselective liquid-liquid extraction.

Construction and Application of a Pepsin-Functionalized Covalent Organic Framework with Prominent Chiral Recognition Ability.

The stable Pepsin@covalent organic framework (Pepsin@COF) were constructed base on matching COF pore diameter to pepsin dimension. It exhibits excellent chiral recognition capabilities (e. e. % up to 62.63 %) and potential for enantioseparation. Furthermore, a positive correlation between the immobilized enzyme activity and chiral recognition was revealed, offering insights for the design of biocatalytic nanosystems in chiral separation.

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.

Regioselective modification at the 2,3- and 6-positions of chitosan with phenylcarbamates for chromatographic enantioseparation

Chitosan derivatives with two different phenylcarbamate pendants at the 6-position and 2,3-positions of the glucosamine unit were synthesized by triphenylmethyl as a protective group. The regioselective chitosan derivatives were prepared corresponding to coated-type chiral packed materials (CPMs), which were evaluated with thirteen chiral compounds by high-performance liquid chromatography (HPLC). The regioselective chitosan derivatives (4aⅠ/4aⅡ, 4bⅠ/4bⅡ) bearing electron-withdrawing 3,5‑chloro or 4‑chloro at the 6-position can recognize 7 or 8 of the 13 enantiomers and achieve baseline separation for enantiomers 5 and 7. They exhibited better chiral recognition abilities than the other derivatives with different substituents at the 6-position and the same 3,5-dimethylphenyl substituent at the 2,3-postion. In comparison to Chit-1 featuring a 3,5-dimethylphenyl substituent at the 2,3- and 6-positions, it was observed that the combination of both an electron-withdrawing and an electron-donating substituent of the regioselective chitosan derivatives (4aⅠ/4aⅡ, 4bⅠ/4bⅡ) showed better or similar enantioseparation abilities for racemic Compounds 7 and 6, respectively. The molecular weight-performance relationship of the regioselective chitosan derivatives was investigated in detail. It was found that with increasing molecular weight, the derivatives 4aⅡ and 4bⅡ all possessed greater enantioseparation power for 4 enantiomers, such as enantiomers 4, 7, 11, and 15, than the corresponding derivatives with low molecular weights. The molecular docking simulation results showed that excellent enantioseparation power significantly depended on the combination and interaction of multiple factors, such as steric hindrance, and polarity of the substituents on the CPMs and enantiomers.

Chiral analysis and semi-preparative separation of metconazole stereoisomers by supercritical fluid chromatography and cytotoxicity assessment in vitro.

Metconazole is one of the widely-used chiral triazole fungicides in controlling wheat leaf rust, powdery mildew, Fusarium head blight with high efficacy, and so forth. In the current work, the effects of chiral stationary phases, alcoholic modifiers, and column temperature on the chiral separation of metconazole were discussed in detail. Amylose tris(3,5-dimethylphenylcarbamate)-coated chiral stationary phase exhibited much stronger chiral recognition ability toward metconazole stereoisomers in the CO2 /ethanol mixture as compared to the others. Then, a two-step semi-preparative separation of metconazole was performed through supercritical fluid chromatography and high-performance liquid chromatography, and the enantiomeric excess values of four stereoisomers were achieved over 98%. Moreover, the enantioselective cytotoxicity of cis-metconazole against HepG2 cells has been investigated, and the order of the cell proliferation toxicity against HepG2 cells was (1R, 5S)-metconazole>(1S, 5R)-metconazole>the mixture. Briefly, this study would provide valuable information in the preparative separation of optically pure metconazole products through chromatographic techniques and their environmental risk assessment.

Adsorption Isotherms of Enantiomer on Hippuric Acid Crystals Obtained under Viedma Ripening Conditions Using a Temperature Gradient

The work is devoted to the study of the capacity for chiral recognition during the adsorption process of hippuric acid crystals obtained by the temperature gradient method under Viedma ripening conditions. This method is distinguished by the fact that the primary violation of chiral equilibrium between the nuclei formed during crystallization is not caused by the mechanical action of the stirrer but by crystallization at low temperatures. Limonenes and α-pinenes were used as test enantiomers. Adsorption isotherms were obtained using inverse gas chromatography, and their analysis made it possible to establish the chiral recognition ability of the surface. It was shown that both the enantioselectivity and adsorption capability of the synthesized hippuric acid crystals were significantly higher than those of crystals obtained under classical Viedma ripening conditions. High surface heterogeneity is probably the reason for this phenomenon.