Chirality最新文献

Pinocembrin, as a natural dihydroflavone compound, is currently in the clinical phase II research stage as a candidate new drug due to its significant therapeutic effect on stroke. However, there is no report on the systematic study of the pharmacokinetic and pharmacological activity differences of the enantiomers of pinocembrin. This study comprehensively investigated the stereoselective properties of pinocembrin enantiomers through integrated pharmacokinetic, network pharmacological and neuroprotective evaluations on HT22 cells. The results demonstrated distinct stereoselective characteristics in rat plasma between the enantiomers of pinocembrin following intravenous administration, with the plasma concentration of (+)-pinocembrin consistently being higher than that of (−)-pinocembrin. Pharmacokinetic studies of individual enantiomers administered intravenously demonstrated no evidence of stereochemical inversion between the two enantiomers of pinocembrin in either plasma or brain tissue of rats. Network pharmacology analysis revealed multiple potential therapeutic targets related to ischemic stroke pathophysiology, particularly involving apoptosis regulation and inflammatory responses. Both (+)-pinocembrin and (−)-pinocembrin exhibited protective effects against OGD/R-induced injury in HT22 cells at concentrations of 6.25–50 μM and 12.5–50 μM, respectively; however, no statistically significant difference was observed between the two enantiomers. Western blot analysis further revealed that (+)-pinocembrin significantly upregulated the Bax/Bcl-2 ratio and the p-Akt/Akt ratio, suggesting that its neuroprotective effects are mediated through modulation of apoptosis and activation of the Akt signaling pathway. These findings provide a foundation for understanding the stereoselective pharmacological properties of pinocembrin and suggest potential therapeutic applications leveraging the unique characteristics of each enantiomer for neuroprotective interventions.

Chiral recognition is a foundation in pharmaceutical and health sciences, particularly for the selective detection of enantiomers in chiral drugs. Over the past 5 years, significant progress has been made in developing chiral fluorescent sensors with improved sensitivity, selectivity, and biocompatibility. This review highlights the structural design, functionalization strategies, and sensing mechanisms of representative systems, including carbon-based quantum dots (CQDs, chiral carbon dots [CCDs], and graphene quantum dots [GQDs]), metal–organic frameworks (MOFs), and composite nanomaterials. Notable advances include graphene quantum dots functionalized with D-cysteine for morphine enantiomer discrimination, CdSe/ZnS QDs modified with L-pyroglutamic acid derivatives for stereoselective amino acid detection, Zn-MOC@CQDs composites enabling enantioselective lactic acid sensing, and Eu-BTB@D-carnitine MOFs for enhanced fluorescence-based recognition. More recent developments, such as BINOL-derived probes and carbazole-based sensors, demonstrate high enantioselectivity and ultralow detection limits in amino acid sensing. Compared with earlier reviews, this article emphasizes the integration of hybrid nanostructures and multifunctional composites as next-generation sensing platforms, bridging fluorescence, electrochemiluminescence, and coordination chemistry approaches. The progress discussed herein underscores how the rational design of chiral nanomaterials is shaping precise enantiomer discrimination technologies, with potential for real-world applications in drug analysis, biosensing, and food quality monitoring.

In this work, a new strategy was proposed for the preparation of a chiral stationary phase based on β-cyclodextrin and calix[4]arene polymer. The chiral stationary phase was characterized by scanning electron microscopy, energy dispersive x-ray spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The introduction of calix[4]arene polymer increased chirality recognition by increasing recognition sites and interactions, including hydrogen bonding, π–π interaction and synergistic inclusion effect. Compared with the home-made β-cyclodextrin–based chiral column, the prepared β-cyclodextrin–calix[4]arene polymer-based chiral column showed superior enantioseparation performance toward 1-phenylethanol, prothioconazole, promethazine, propranolol, and bisoprolol. These chiral compounds can be separated within 10 min under reversed-phase mode with resolutions ranging from 1.62 to 1.80. These findings will provide an important reference for developing novel supramolecule-based chiral stationary phases.

In this work, a CDs-TpBD/UiO-66 hybrid material was firstly synthesized via Schiff base reaction using isocyanate-β-cyclodextrin (CDs) as a chiral modifier, TpBD COF and UiO-66-NH₂ MOF as the frameworks, and was characterized by Fourier-transform infrared spectra, scanning/transmission electron microscopy, X-ray diffraction spectra, X-ray photoelectron spectroscopy, nitrogen adsorption–desorption, and thermogravimetric analysis. The results showed that the hybrid material exhibited a close-packed structure of TpBD and UiO-66-NH₂ crystal, well-defined micropores, and good stability. It was used as the stationary phase in open-tubular (OT) capillary electrochromatography, and 7 amino acids (basic: D/L-arginine, D/L-histidine, D/L-lysine; neutral: D/L-methionine, D/L-valine; acidic: D/L-aspartate, D/L-glutamic acid) and D/L-carnitine (D/L-Car) were baseline separated under the optimal chromatographic conditions within 6 min by capillary electrochromatography. The resolution (Rs) ranged from 1.50 to 5.41, and the selectivity factor (α) ranged from 1.08 to 2.52, respectively. Enantioseparation was attributed to the synergistic effect of CDs, TpBD, and UiO-66-NH₂ in the stationary phase as well as the difference of adsorption and selectivity between the enantiomers and the stationary phase through the adsorption experiments. The detection method of D/L-Car was established by CDs-TpBD/UiO-66 OT column. Good linearity (R² ≥ 0.999) was obtained in the concentration ranges of 8.5–200 μg/mL for D-Car and 7.0–200 μg/mL for L-Car with detection limits of 2.5 and 2.1 μg/mL, respectively. The developed method was simple, rapid, high efficiency as well as broad application, and could be applied for the simultaneous separation and detection of D/L-Car in actual samples.

(S)-Bepotastine is a highly selective histamine H1-receptor antagonist in the treatment of allergic rhinitis and other allergic diseases. We achieved a facile and convenient synthesis of (S)-bepotastine by resolving an early stage synthetic precursor. We devised a new class of resolving agent, BINOL-3,3′-dicarboxylic acid which could be considered as an axial version of tartaric acid. As the first example, we successfully resolved racemic piperidinyl ether by (S)-BINOL-3,3′-dicarboxylic acid with high optical purity. The final installation is quite straightforward and readily accomplished without any chiral loss.

As one of the most widely used fungicides in global agriculture, chiral triazole fungicides play a crucial role in crop protection due to their broad-spectrum efficacy. However, the environmental problems caused by their widespread use are becoming increasingly prominent. These problems not only cause ecological pollution but also pose potential risks to human health and the safety of ecosystems. In response to these problems, developing optically pure monomer pesticides that are highly efficient yet low in toxicity has become a key strategy. This reduces both the dosage required and the impact on nontarget organisms. In recent years, the research focus on chiral triazole fungicides has expanded from evaluating a single biological activity to assessing stereoselective toxicity, environmental behavior, and metabolic fate in a multidimensional way. Despite growing academic interest in the stereoselective toxicological effects and metabolic differences of nontarget organisms (particularly mammals), most available reviews have focused on biological activity and environmental fate. Furthermore, there is a lack of reviews that systematically evaluate the stereoselective behavior of these pesticides in mammals, which restricts our overall understanding of the safety of this class of pesticides. Based on this, this paper not only lists the stereoselective bioactivities and toxicological differences of chiral triazole fungicides but also, for the first time, focuses on the mammalian system, providing a comprehensive elucidation of their stereoselective behaviors from the perspectives of metabolism in rat liver microsomes, toxicokinetic characteristics, metabolomics, and gut microbiota. The aim of this review is to address the shortcomings of existing reviews and to serve as a reference for the development of optically pure, environmentally friendly, low-toxicity, and efficient monomer pesticides.

Molecular homochirality — the uniformity of chirality in biological molecules — is a fundamental feature of life, yet its origins remain unresolved. The correspondence between the chirality of biological monomers on Earth and that observed in ancient meteorites implies a systematic selection of chirality sign in prebiotic chemistry, rather than a stochastic process. While classical theories attribute symmetry breaking to chiral autocatalysis, such self-amplifying processes are rare and have not been empirically demonstrated in the synthesis of amino acids and carbohydrates. In contrast, chiral cross-catalysis between amino acids and carbohydrates — a mechanism consistent with known chemical behavior — could similarly amplify chiral purity. However, cross-catalysis alone cannot determine the chirality sign due to its inherent symmetry, leaving the origin of the initial bias unexplained. Although weak interactions have been proposed as a potential source of this bias, their effects are theoretically negligible, raising questions about their sufficiency. Our kinetic analysis of cross-catalytic systems reveals that even an infinitesimal preference for left-handed amino acids and right-handed carbohydrates could be sufficient to establish the homochirality observed in life. This mechanism provides a plausible link between prebiotic chemistry and the homochirality of the biosphere, offering a potential resolution to this longstanding enigma.

This study represents a special, time-dependent resolution strategy of an atropisomeric, bifunctional 1-phenylpyrrole derivative, using the nonactive enantiomer of the key amine intermediate Apremilast as an efficient resolving agent. Among the solvents investigated, ethyl acetate was identified as the optimal solvent, allowing rapid crystallization and high enantiomeric purity (> 99% ee). A detailed study of kinetic behavior revealed that early-stage crystallization and timely separation of diastereomeric salt are critical to achieving high enantiopurity and avoiding recrystallization to lead to a racemic product. Time-dependent studies suggest that solvate formation of enantiomers and ethyl acetate plays a crucial role in the resolution mechanism. This resolution process enables the direct separation of racemic 2-(2-carbamoyl-1H-pyrrol-1-yl)-3-(trifluoromethyl) benzoic acid suitable for further applications, such as resolving agents for amine-type compounds. Significantly, this approach recycles an amine-type drug intermediate that is typically discarded during the large-scale production of Apremilast, thus being in line with green chemistry principles by minimizing waste and enabling resource recovery.

A recent publication by Kopec et al., “The effect of enantiomers of thalidomide on colon cells-Raman spectroscopy studies”, reported to “demonstrate that Raman spectroscopy reveals distinct spectral differences between the enantiomers of thalidomide” and provided both experimental and computational evidence. However, the theory of Raman spectroscopy inherently establishes that two enantiomers must exhibit identical Raman frequencies and intensities. While the slightly different experimental Raman spectra for the two enantiomers of thalidomide can be traced back to samples with different chemical and/or optical purities, the significant discrepancies observed in the computed Raman spectra arise from a computational artifact related to methodological shortcomings.