Synephrine is a chiral compound that exists as two enantiomers, the (R)- and (S)-forms. The present study investigated the effects of pH and heating conditions on the isomerization of synephrine. Each enantiomer was quantified after FMOC derivatization using chiral liquid chromatography with UV detection (chiral-LC/UV). When (R)-synephrine was incubated under acidic or neutral conditions at elevated temperatures, isomerization was promoted in a temperature-dependent manner under both conditions. The isomerization rate under the acidic condition was approximately 10- to 40-fold higher than that under the neutral condition, and the time-dependent progression followed pseudo-first-order kinetics under both conditions. Analysis of physicochemical parameters, including the activation entropy (ΔS[‡]), suggested that the reaction mechanisms differ between the acidic and neutral conditions. To elucidate the detailed isomerization mechanisms, quantum chemical calculations based on density functional theory (DFT) were performed. Under acidic conditions, DFT geometry optimization demonstrated that the amino group is preferentially protonated (NH2 [+]), consistent with its higher thermodynamic basicity, followed by departure of the β-hydroxyl group to generate a benzylic carbocation intermediate. LUMO localization at the β-carbon of the benzylic carbocation and its planar sp[2] geometry support nucleophilic water attack from either face, leading to racemization. Under neutral conditions, a retro-Mannich-type fragmentation mechanism was proposed, in which the C-C bond between the α- and β-carbons undergoes heterolytic cleavage-driven primarily by electron donation from the β-hydroxyl oxygen lone pair and assisted by vinylogous conjugation from the phenolic oxygen via the aromatic ring-to generate an aldehyde and an imine as intermediates. Subsequent recombination of these fragments was proposed to yield a racemic mixture. These findings confirmed that synephrine undergoes isomerization upon heating under both acidic and neutral conditions.

A series of novel arylalkynylpyridyl-triazacyclononane sensitized macrocyclic europium(III) complexes (EuL) was prepared, and their circularly polarized luminescence characterized in terms of the spectral profile and dissymmetry factor (glum). The series was engineered based on previously reported isostructural complexes by a controlled introduction of structural modifications at different positions with respect to the coordination environment of the emitting europium(III) center. It was established that only those structural features of the macrocyclic ligand that were proximal to the europium(III) center affected CPL properties. These findings could help shape the development of a new class of purpose-built EuL complexes compatible with CPL-unaffecting complex-stage functionalization to introduce advantageous structural features for applications in life and material sciences.

Trifluoroacetylation and varying sulfur oxidation states can modulate the stereodynamic features in N-aryl peptoids. This study elucidates the restricted rotation about both the chiral Caryl-N axis and the N-C(O) amide bond, highlighting the inherently flexible nature of tertiary amide scaffolds. Tertiary amide bond isomerization, axial chirality, and multiple stereochemical forms were investigated utilizing [19]F NMR, dynamic HPLC, crystallographic studies, and computational analysis. Notably, the introduction of a sulfoxide moiety as an auxiliary stereogenic element facilitates the formation of multiple and distinct stereochemical forms, as evident from [19]F NMR studies and computational modeling. These structural modifications can provide a robust platform to understand stereodynamic features in N-aryl peptoids.

A new enantioselective molecularly imprinted polymer (MIP) was developed for recognizing S-ketorolac (S-KR), a model chiral acidic drug. The synthetic process started with a resorcinol-formaldehyde resin (RSF), which was cyanoethylated under phase-transfer catalytic conditions to obtain RSF-CN. Then, the nitrile groups turned into cationic/basic hydrazidine sites after reacting with hydrazine hydrate, resulting in RSF-HD. Next, S-KR was interacted with RSF-HD in a DMF/water solution at pH 7, before adding glutaraldehyde for post-crosslinker. After that, the S-KR template was removed to get the final S-KR-imprinted polymer (S-KR-P). Tests, such as elemental analysis and solid-state [13]C NMR, verified each step. Adsorption tests showed a strong pH dependence, working best between pH 6 and 7. For isotherm studies, the maximum capacity for S-KR on S-KR-P was 525 mg/g, whereas R-KR had 252 mg/g. The non-imprinted polymers (NIPs) worked similarly for both, around 180 mg/g. The Langmuir model fits better than the Freundlich model, pointing to adsorption on defined binding sites. With a selectivity coefficient of about 12, it shows effective stereoselective recognition, making S-KR-P a great option for separating chiral ketorolac.

Chiral covalent organic frameworks (CCOFs) integrate high crystallinity, permanent porosity, and programmable chiral microenvironments, making them attractive platforms for chiroptical materials and circularly polarized light-responsive devices. This review summarizes recent progress in CCOFs, covering the introduction of chirality through post-synthetic modification, de novo synthesis, chiral induction, and catalytic asymmetric synthesis, as well as the amplification of chirality from molecular units to pore architectures, helical morphologies, thin films, and devices. We further discuss representative CCOF systems for circularly polarized luminescence and circularly polarized light detection, focusing on the relationships among framework structure, host-guest confinement, chirality-induced spin selectivity-mediated transport, and dissymmetry factors. Helical morphology amplifies chirality across scales through ordered chromophore organization and anisotropic charge and spin transport. Together, these advances establish a multiscale design framework for translating molecular chirality into measurable optical and device responses. Finally, we identify key challenges in balancing luminescence efficiency with chiroptical asymmetry, stabilizing helical architectures, fabricating oriented films, and establishing quantitative structure-property relationships.

Emerging contaminants are an increasing global concern, with antibiotics representing a notable case due to their continuous release and possible contribution to antimicrobial resistance. Fluoroquinolones (FQs) combine high stability, low biodegradability, and biological activity at trace levels, which result in persistence, ecotoxicity, and bioaccumulation in aquatic systems. Nadifloxacin (NAD) is a chiral FQ prescribed as a racemate for dermatological infections, but (S)-NAD is more potent than the racemate and 64 to 256 times more active than (R)-NAD against both Staphylococcus aureus and Propionibacterium acnes, as well as other gram-positive and gram-negative pathogens. Though the stereochemistry plays a decisive role in both pharmacological activity and environmental fate, the enantioselective ecotoxicological evaluation of NAD is of high importance. Thus, this work described the enantioseparation of NAD by chiral liquid chromatography (cLC) on a Lux amylose-1 column (4.6 mm I.D. × 250 mm L, particle size 5 μm) under normal-phase conditions. Optimized analytical conditions provided good chromatographic parameters (Rs = 5.92, α = 2.77, retention 6-10 min) and were successfully scaled up to semipreparative enantioseparation on a CHIRALPAK AD-H DAICEL column (10 mm I.D. × 250 mm L, particle size 5 μm), allowing the separation of both enantiomers in > 98% enantiomeric purity. The absolute configuration and the elution order of the enantiomers were determined by the agreement between the experimental and calculated data of electronic circular dichroism. The acute ecotoxicity of the NAD racemate and its enantiomers was evaluated using Daphnia magna as an aquatic model organism.

Extending morphological complexity and thus achieving emergent functions remain a central challenge in materials science. Here, we report a chirality-engineering strategy to tune morphological complexity and optical activity (OA) in Ag-thiolate coordination polymers (ATCPs). By introducing either the opposite enantiomer D-cys or the achiral 3-mercaptopropionic acid (MPA) into L-cys-induced ATCP synthesis, we found two coinduction systems exhibiting distinct molecular mixing behaviors quantified via the entropy of mixing (EoM) of thiol precursors. The resulting morphologies, including triangular nanosheets, flower-like architectures, nanoscrolls, and nanotube-like assemblies, were quantitatively analyzed using a graph-theoretical complexity index (CI). In the L-/D-cys system, increasing EoM led to chirality cancelation, a decreased CI and an attenuated g-factor, demonstrating that maximum EoM does not necessarily generate higher complexity or stronger OA. In contrast, in the L-cys/MPA system, packing mismatch transformed maximum EoM into an enhanced CI alongside OA inversion and enhancement (a maximal 8.3-fold enhancement). These results reveal that the molecular role of the second thiol component, rather than EoM alone, determines whether molecular mixing suppresses or amplifies complexity and OAs. This work provides ligand-modification strategy for programming complex functional coordination-polymer assemblies.

The remarkable progress in nanomedicine has opened new frontiers in boosting therapeutic efficacy and reducing off-target side effects. However, fabricating chiral nanomaterials remains challenging due to difficulties in sustaining chiral configuration stability. In this study, chiral injectable liquid formulations are fabricated via the co-assembly of phenylalanine-derived enantiomers, flavonoids and chitosan, to tackle the drawbacks of existing chiral nanomaterials for wound healing. The weakly acidic chitosan solution effectively resolved the low-solubility defect of flavonoids extracted from Scutellaria baicalensis, and the chiral transfer strategy among these co-assembled components overcomes the problem of chiral lability. The resulting chiral formulations displayed strong antioxidant and antibacterial capacities and significantly accelerated wound closure in the Staphylococcus aureus-infected chronic wound model. This research provides valuable insights for the design of herb-functionalized formulations and lays a foundation for the development of advanced chiral nanomaterials with broad applications in nanomedicine.

Chiral metal complexes are important in catalysis and medicinal chemistry, where understanding their structural and optical properties is crucial. This study presents a combined experimental and theoretical Raman optical activity (ROA) investigation of the chiral tris(ethylenediamine)cobalt(III) complex, Δ- and Λ-[Co(en)3][3+], in aqueous solution. ROA spectra were recorded using near-resonance excitation at 532 nm. Under these conditions, a significant ECD-Raman contribution from the solution was observed and quantitatively corrected, enabling extraction of the intrinsic ROA spectra. Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were used to simulate ROA, Raman, UV-visible absorption, and electronic circular dichroism (ECD) spectra. Four representative conformers were analyzed, and their stability and spectral properties were evaluated using both the polarizable continuum model (PCM) and the solvation model based on density (SMD). While both models reproduced key experimental trends, SMD provided a more accurate description of vibrational features, especially NH2 scissoring and CH2 rocking modes. This work shows that near-resonant ROA spectra of a cationic transition-metal complex in water can be accurately reproduced using first-principles methods without empirical adjustments, highlighting the importance of conformational averaging and solvation effects.

Enantioselective desymmetrization represents an efficient strategy for accessing enantioenriched products from relatively simple achiral starting materials, and it has been widely recognized as a pivotal approach in asymmetric synthesis. As one of the most versatile organocatalysts identified to date, chiral phosphoric acids (CPAs) have been extensively applied in the aforementioned research field. In this review, we summarized the substantial advances in enantioselective desymmetrization reactions enabled by CPA catalysis. Additionally, representative cases involving CPAs as cooperative catalysts are also discussed in detail.

ATP is the core substance of energy metabolism in all forms of life. The chirality of d-ribose is essential for ATP's function, ensuring efficient molecular recognition, metabolic stability, and co-evolution with RNA in biological processes. However, origin of chirality of d-ribose is still unknown. Here, we demonstrate that wollastonite, an abundant Earth mineral, catalyzes the formose reaction between formaldehyde and glycolaldehyde and achieves high enantioselectivity (63.3%-91.3% ee) toward d-ribose. The lower energy barrier for the transition state of d-glyceraldehyde compared to that of l-glyceraldehyde, which possesses a similar configuration to glyceraldehyde, results in the enantioselective synthesis of ribose. Experimental and computational studies reveal that the surface chirality of wollastonite, which is characterized by its wavy atomic arrangement, selectively reduces the adsorption energy of the d-glyceraldehyde intermediate compared to its l-enantiomer. This preferential adsorption kinetically promotes the d-glyceraldehyde pathway and steers the reaction toward d-ribose. Our work establishes wollastonite as an intrinsically enantioselective mineral catalyst, provides a mechanistic foundation for prebiotic chiral selection toward d-ribose, and highlights surface design principles for asymmetric synthesis.

S-Naproxen (NPX) exhibits an unusual inversion of its ECD spectrum upon solvent change, a phenomenon that this work analyzes both experimentally and theoretically. By evaluating NPX in water, ethanol, and acetonitrile, it was observed that pH variation shifts the chemical equilibrium between protonated and deprotonated forms, making this transition the direct cause of the ECD signal inversion. Molecular dynamics and TD-DFT (CAM-B3LYP/aug-cc-pVDZ) calculations corroborated the experimental data, demonstrating that structural changes alter the predominant electronic transitions from π → π* in NPX to n → π* in the NPX[-] anion, as evidenced by transition density differences and natural transition orbitals (NTOs). These findings demonstrate that explicit solvent treatment and statistical analysis are requisite to accurately reproduce the data, validating that the negative signal in water and the positive signal in acetonitrile is governed by the predominant species dictated by the chemical equilibrium.

Vibrational circular dichroism (VCD) spectroscopy enables direct determination of enantiomeric excess (ee), but its application as a quantitative analytical tool is limited by low signal-to-noise ratios (SNR), which typically require long measurement times. Using limonene as a model system, predictive models were developed by combining targeted, SNR-based region selection with simple multivariate regression applied to both 30- and 5-min acquisition data. The 30-min data yielded excellent model performance with cross-validated R[2] of 0.997 and RMSE of ~2% ee. Notably, the 5-min acquisition retained ~97% of predictive performance enabling a sixfold increase in throughput, albeit with increased prediction error. This work therefore demonstrates that data-driven optimisation of spectral selection can enable reliable ee prediction with short acquisition VCD spectra, outperforming equivalent univariate models and providing a practical route toward high-throughput chiral analysis.

A stereodivergent synthetic strategy enabling access to enantiopure C5-α-substituted linezolid analogues has been developed from D-mannitol as an inexpensive chiral pool precursor. The approach provides controlled access to both syn- and anti-configured derivatives bearing ethyl or phenyl substituents at the α-position of the C5 acetamidomethyl side chain, thereby introducing a second stereogenic center with high diastereocontrol. Key steps include highly selective nucleophilic additions of organometallic reagents to chiral N-benzyl imines derived from protected D-glyceraldehyde and base-promoted condensation of enantiopure N-Boc-aminoepoxides with aryl carbamates to construct the 2-oxazolidinone core. Comparative analysis of both configurational series revealed marked differences in cyclization efficiency, particularly for α-phenyl-substituted intermediates in the anti series, highlighting the steric sensitivity of oxazolidinone formation. In vitro assays against Gram-positive and Mycobacterium spp. species showed complete loss of antibacterial activity for all α-substituted derivatives, irrespective of configuration. These results establish a clear structural limitation at C5 and demonstrate that steric expansion at the α-position overrides stereochemical effects. This study underscores the value of stereodivergent synthesis for rigorously disentangling configurational and substituent contributions in chiral bioactive scaffolds.

Methamphetamine, an amphetamine-type stimulant, is a potent and psychoactive compound distinguished by the presence of a single stereogenic center in its structure. Consequently, it exists as two enantiomers: (S)-(+)-methamphetamine [(S)-(+)-MA (1)] and (R)-(-)-methamphetamine [(R)-(-)-MA (2)]. The chirality of these molecules confers distinct biological and pharmacological properties, with notable differences between the two forms. These enantioselective variations extend beyond their mechanisms of action, encompassing differences in the central nervous system interactions, metabolism, excretion, and other physiological processes. Understanding these disparities is crucial for elucidating the pharmacological and potential therapeutic profiles of each enantiomer. Achieving such insight requires examination of the enantioselective synthetic routes through which the desired chirality can be either inherited or constructed. This review integrates chemical and biological perspectives to provide a comprehensive overview of both methamphetamine enantiomers, thereby bridging the gap between laboratory synthesis and biological behavior in these two chemically fascinating yet dangerous molecules.