Chirality最新文献

Chiral recognition of amino acids is crucial in pharmaceutical and clinical fields due to the enantiomer-dependent bioactivity of chiral compounds. Here, we report an electrochemiluminescent (ECL) sensor utilizing a chiral covalent organic framework (CC-MP CCTF) for the selective discrimination of phenylalanine (Phe) enantiomers. Critical experimental parameters, including buffer pH (optimized to 7.38), tripropylamine (TPrA) concentration (9.99 mM), and CC-MP CCTF dilution ratio (1.6×), were optimized to maximize sensitivity. The sensor achieved a linear detection range (0.2–1.0 mM) for both D- and L-Phe with a limit of detection (LOD) of 0.1 mM. Remarkably, it exhibited exceptional enantioselectivity, showing a 1.96-fold higher ECL response to D-Phe than L-Phe, which originates from the chiral confinement effect of the CC-MP CCTF. This study proposes a cost-effective and rapid strategy for chiral amino acid recognition, demonstrating potential applications in bioanalysis and quality control processes.

Luminogens exhibiting aggregation-induced circularly polarized luminescence (AICPL) properties have garnered significant attention in recent years due to their promising applications in optoelectronics and biomedical research. Typically, aggregation-induced emission (AIE) is evaluated by measuring luminescence spectra using a spectrofluorometer while varying the volume ratio of a poor to a good solvent, whereas circularly polarized luminescence (CPL) is assessed separately using a CPL spectrometer. However, these conventional methods rely on manual operation, which may lead to operational errors, particularly when processing a large number of samples. Furthermore, cases often occur where AIE is observed while CPL is not, suggesting that simultaneous measurement of both phenomena will enhance the efficiency of AICPL characterization. In this study, we demonstrate the applicability of an automated high-throughput CPL system capable of simultaneously obtaining CPL and luminescence spectra of multiple samples for the purpose of AICPL evaluation. We assess the measurement reproducibility of the system, compare the AICPL properties of enantiomers, and investigate the influence of various substituents on chiral platinum(II) complexes. The results obtained collectively demonstrate that this method offers an efficient and reliable approach to the comprehensive evaluation of AICPL properties.

In solution, 2-ureido-4[1H]-pyrimidinones show a strong propensity to dimerize via a well-defined quadruple donor-donor-acceptor-acceptor hydrogen bonding array. For derivatives that have been modified with chiral functional groups, intermolecular associations of this kind are accompanied by conformational and structural perturbations that, acting together, serve to significantly alter measured optical rotation values. Thus, changes in solvent composition, solution pH, along with other environmental “inputs” that either disrupt or encourage hydrogen bonding interactions, can be effectively harnessed to reversibly modulate the chiroptical output signals generated by these simple derivatives. In this regard, the chiral ureidopyrimidinone analogues described herein can be viewed as a new class of molecules that exhibit stimuli-responsive or adaptive chiroptical behavior.

A new series of chiral hydrazide-hydrazone derivatives were synthesized and evaluated their acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase and urease inhibition and antioxidant activities. The chemical structures of newly synthesized chiral aryl hydrazide-hydrazone derivatives were clarified using UV–Vis, IR, ¹H and ¹³C NMR, and mass spectroscopies. According to NMR data, due to the partial double bond character of the amide C-N bond, two conformational isomers (E and Z) exist in solution. Based on this information, the conformational properties of the synthesized compounds were investigated using temperature-dependent NMR spectroscopy and DFT. The results of DFT studies revealed that E_(C=N)-E_(C(O)-N) conformer is the most stable structure for the synthesized hydrazones. In addition, the enzyme inhibition potentials of the synthesized compounds were evaluated. Among all chiral hydrazide-hydrazones, compound 3b (containing nitro group in the hydrazone part) had the best inhibition profile against AChE, whereas compound 3d was found to be the most active compound against BChE. In addition, compound 3d, which carries a methoxy group in both the benzamide and the hydrazone moiety, attracted attention due to its good activity against all examined enzymes. Furthermore, molecular docking calculations were performed to get insights into the interaction patterns between the synthesized compounds and the selected target protein.

In this work, a novel pair of chiral ionic liquids (CILs) based on cis- and trans-myrtanol was designed, synthesized, and applied in the enantioselective liquid–liquid extraction (LLE) of DL-3-phenyllactic acid (DL-3-PLA). DL-3-PLA, a naturally occurring broad-spectrum antimicrobial compound, exhibits distinct biological activities in its enantiomeric forms, making its separation of significant interest for pharmaceutical and food applications. The CILs were synthesized starting from (1S)-(−)-β-pinene via oxidative hydroboration, followed by subsequent functional group modifications, and were fully characterized using ¹H NMR, FTIR, DSC, and TGA. Optimization of the LLE parameters (0.10-M CILs in n-octanol, 0.10-M DL-3-PLA in water, pH 6.8, 298.15 K) yielded a single-stage enantiomeric excess (ee) of 15.68%. Using five consecutive extractions with the trans-CILs isomer, a cumulative ee of 95.18% was achieved. Quantum mechanical calculations, including electrostatic potential analysis, IGMH isosurface mapping, and binding energy evaluations, revealed that both the cis- and trans-CILs isomers exhibited strong chiral recognition toward D-3-PLA, with the trans-CILs isomer showing superior recognition performance compared to the cis-CILs isomer. These results underscore the potential of the designed CILs as effective chiral selectors for the DL-3-PLA separation and provide a promising strategy for practical applications in enantioselective separations.

In this research, estimation of enantioselective pharmacokinetics and biological interconversion of sotorasib were investigated. This is the first report for the novel chiral liquid chromatography–tandem mass spectrometry method for the enantioselective pharmacokinetics determination in biological matrix. Attempts were made to achieve separation in reverse phase mode with mass compatible mobile phase. The baseline chiral separation was achieved with a mobile phase consisting of acetonitrile and aqueous ammonium bicarbonate (15 mM; 95/5 v/v) on Chiralpak IC (250 × 4.6 mm, 5 μm). Positive electrospray ionization was used for monitoring multiple reactions by triple quadrupole. The developed bioanalytical method was validated for each SOT enantiomer, assessing selectivity and specificity, linearity, accuracy, precision, recovery, matrix effect, dilution integrity, and stability. The lower limit of quantification was identified as 1 ng/mL for both SOT enantiomers. The results were found to be in compliance with the bioanalytical method validation guideline. The preclinical study revealed the disparate pharmacokinetic profile between the (R) and (S)-sotorasib, after single oral administration (10 mg/kg) to rats. This is the first investigational evidence of enantioselective behavior of sotorasib in vivo. The results demonstrated that lower maximum concentration, area under curve, and higher clearance and volume of distribution for (R)-sotorasib reveal the poorer bioavailability and higher elimination rate. The study provides insights in controlling the enantiomeric impurity in quality control aspects. This research also provides a reference for clinical practice and supports further research in distomer toxicity, enantioselective drug metabolism, and drug interactions.

The present study reports the chemical investigation on the aerial parts of Cleome droserifolia yielding the related eudesmane sesquiterpene solyraterpenoid A (1) and the novel cledrone A (2) from the acetonitrile fraction of the dichloromethane extract. These compounds were separated by column chromatography, centrifugal thin layer chromatography (CTLC) followed by semipreparative reversed-phase high performance liquid chromatography (RP-HPLC). The chemical structure of these compounds was determined by mono and bidimensional NMR techniques, IR spectroscopy, and HRESIMS, while the absolute configuration was established by computational analysis of ECD spectra. Furthermore, the structure and absolute configuration of both 1 and 2 were unambiguously confirmed via single crystal X-ray diffraction (scXRD). Both compounds showed antibacterial activity against Escherichia coli and Pseudomonas aeruginosa strains, with compound 2 being more active.

Using L-cysteine capped gold nanoparticles (L-Cys-AuNPs) as a colorimetric sensor, an easy, low-cost, and highly efficient strategy for the optical chiral identification of ketoprofen enantiomers was developed. R-ketoprofen tends to rapidly adsorb onto L-Cys-AuNPs, resulting in a color change of the solution from red to purple; however, no significant change was observed upon the addition of S-ketoprofen. The potential of L-cysteine capped with AuNPs (L-Cys-AuNPs) as chiral selectors for the recognition of ketoprofen enantiomers has been investigated using UV–Vis, FESEM, FT-IR, SERS, and zeta potential. The recognition process is easily identified by the naked eye or by using a UV–Vis spectrometer. Sensors L-Cys-AuNPs revealed a good linear response to ketoprofen enantiomers in the concentration range of 8.33–33.33 μM with a relative standard deviation of 3.08%. And detection limit of 2.35 μM. The proposed method was applied to determine the ketoprofen racemic mixture in water samples and commercial tablets. This method represents easy, inexpensive, simple, and very effective methods for the recognition of ketoprofen enantiomers.

Hexahydroquinoline (HHQ) scaffold attracts great interest due to its diverse pharmacological activities. HHQ framework also includes 1,4-dihydropyridine (DHP) ring, the pharmacophore of the most popular group of drugs known as calcium channel blockers, which are frequently used in the treatment of cardiovascular conditions. In this work, we synthesized 15 HHQ-based potential calcium channel modulators (EM1–EM15) as racemic mixtures. The 15 chiral compounds were assayed on five high-efficiency liquid chromatography columns containing different small chiral selectors: derivatized β-cyclodextrin, called CDShell-RSP, WhelkoShell, and three macrocyclic glycopeptide selectors: vancomycin, VancoShell; teicoplanin, TeicoShell; and a modified macrocycle referred as NicoShell. These small chiral selectors were bonded to modern superficially porous 2.7-μm particles and packed in 10-cm columns. Small structural differences in the compounds affect their enantioselectivity. The NicoShell column was the most effective, fully separating the whole set in both the reversed-phase and normal-phase chromatographic modes. For seven compounds, the enantioresolution factor was higher than 7. The VancoShell and WhelkoShell columns could also separate the enantiomers of the entire set of chiral HHQs. The TeicoShell column was somewhat less effective, separating only 13 compounds, while the CDShell-RSP column was not as effective for these particular compounds. In the supercritical fluid chromatographic phase mode, the WhelkoShell column gave outstanding results, fully separating all 15 compounds. For nine compounds, the enantioresolution factors were higher than 5. The three macrocyclic-based chiral columns could fully separate 10 compounds. Preparative separations of these compounds will be possible using the chiral NicoShell column in reversed-phase liquid chromatography or the WhelkoShell column in supercritical fluid chromatography with minimal mobile-phase optimization.