Search Results (151)

Lactic acid is a widely used component in cosmetics such as hair care products. High concentration of lactic acid or inappropriate enantiomeric form can have a negative impact on the skin. This study focuses on the development of methods of analysis for the separation, enantioseparation and determination of lactic acid in cosmetics and the confirmation of its enantiomeric form. Achiral reversed-phase high-performance liquid chromatography (RP-HPLC) on a C18 stationary phase and hydrophilic interaction liquid chromatography (HILIC) on an amino-propyl stationary phase, combined with diode array detection (DAD; 210 nm), were applied for analysis. Chiral HPLC-DAD on a teicoplanin-based stationary phase was an effective method for verification of the enantiomeric form, confirming L-lactic acid in tested samples. The complex samples were treated by solid-phase extraction using an anion-exchange adsorbent. Recovery studies showed good results, 76.1–91.8% (RSD ≤ 5.0%). The methods provide linearity of response in the concentration ranges tested (R² > 0.996). This study demonstrated several approaches to the HPLC-DAD determination of lactic acid and proposed an effective sample preparation procedure. Developed methods were rapid, simple and applicable in the routine analysis of cosmetics for monitoring the safety of products. Full article

N-Methyl-D-aspartate (NMDA) receptors are ligand- and voltage-gated ion channels essential for synaptic plasticity, learning, and memory. The GluN2B subunit, highly expressed in the forebrain and spinal cord, is implicated in multiple neurological and psychiatric disorders, making it an attractive target for positron emission tomography (PET) imaging. However, the development of selective GluN2B PET radioligands remains challenging. Here, we describe the design, synthesis, and evaluation of eighteen 3-alkylaryl derivatives of 7-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol, including enantiomerically resolved compounds, as candidate PET radioligands. Structure–activity relationship studies show that binding affinity is largely insensitive to electronic and steric variation at the terminal aryl group but strongly dependent on alkyl linker length, with a four-carbon chain providing optimal affinity. Binding affinity does not correlate with calculated lipophilicity, suggesting hydrophobicity is not the primary determinant of receptor interaction. Absolute configuration was established using vibrational circular dichroism and infrared spectroscopy, and docking studies provided insight into enantiomer-specific binding modes. Two ligands, L3 and L6, and their enantiomers exhibited high GluN2B affinity, favorable physicochemical properties, and suitability for carbon-11 labeling. Separate PET imaging studies confirmed strong and specific brain binding of the radiolabeled compounds. These findings establish this scaffold as a promising platform for GluN2B PET ligand development. Full article

Chiral polymeric nanoparticles derived from protected L/D-Phe-OMe- and unprotected L/D-Phe-based monomers were developed as functional chiral coatings for PVDF membranes to induce enantioselective recognition. The present study introduced a sonochemichal-assisted approach to the deposition of Phe-based polymeric nanoparticles onto PVDF membranes, generating chiral membrane surfaces that can facilitate enantioselective transport and crystallization. The enantioselective performance of the modified membranes was evaluated through membrane transport experiments using DL-leucine and a crystallization investigation with DL-tyrosine. Enantioselective transport experiments showed pronounced chiral resolution, achieving an enantiomeric excess (ee) of 79/76% for D/L-Leu. Furthermore, enantioselective crystallization was demonstrated using DL-tyrosine in the presence of L/D-Phe-OMe-coated membranes. Optical activity measurements, supported by SEM and DSC analysis, confirm membrane-induced enantiomeric enrichment yielding an ee of 60/68% for L/D-Tyr. These results highlight the potential of chiral polymer-coated PVDF membranes as versatile platforms for enantioselective separation. Full article

All four isomers of 2-chloro-1-(6-fluorochroman-2-yl)ethan-1-ol, as building blocks for the two enantiomers of beta-blocker nebivolol, have been synthesized in high yield. Due to the similar physicochemical properties of these four diastereomeric halohydrins, to date, the only successful method for separation of the isomers has been preparative HPLC. To avoid this, the four halohydrins were transformed into epoxides with subsequent separation of the enantiomeric pairs by column chromatography. The enantiomeric pairs of epoxides were subsequently converted back to their corresponding halohydrins before performing kinetic resolution of the racemates catalyzed by Lipase B from Candida antarctica. (R)-2-Chloro-1-((R)-6-fluorochroman-2-yl)ethanol was isolated in 71% yield, and >99% enantiomeric excess (ee). (R)-2-Chloro-1-((S)-6-fluorochroman-2-yl)ethanol was isolated in 77% yield and >99% ee. Hydrolysis of 2-chloro-1-(6-fluorochroman-2-yl)ethyl butanoate with the same lipase yielded halohydrins (S)-2-chloro-1-((S)-6-fluorochroman-2-yl)ethanol and (S)-2-chloro-1-((R)-6-fluorochroman-2-yl)ethanol. Amination of (R)-6-fluoro-2-((S)-oxiran-2-yl)chromane with ammonia afforded (S)-2-amino-1-((R)-6-fluorochroman-2-yl)ethanol in 79% yield and >99% ee. (S)-2-Amino-1-((R)-6-fluorochroman-2-yl)ethanol was then reacted with (R)-2-chloro-1-((S)-6-fluorochroman-2-yl)ethanol to produce the desired product (R,S,S,S)-nebivolol ((−)-nebivolol) in 81% yield and >99% ee. Full article

The all-d-enantiomeric-peptide RD2 was developed for the treatment of Alzheimer’s disease. This study aimed to develop a specific and highly sensitive liquid chromatography-mass-spectrometric (UHPLC-ESI-QTOF) method for quantifying RD2 in the mouse brain and to validate it according to the ICH M10 guideline to investigate the pharmacokinetic profile of RD2 in its target organ. Sample preparation, chromatographic separation and quantification were very challenging due to RD2’s highly hydrophilic properties, the complex matrix and the required lower limit of quantification (LLOQ). Chromatographic separation was performed on an Acquity UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm particle size) within 5 min at 50 °C with a flow rate of 0.5 mL·min⁻¹. Mobile phases consisted of water and acetonitrile with 0.2% formic acid and 0.015% heptafluorobutyric acid. Ions were generated by electrospray ionization in the positive mode, and RD2 was quantified by QTOF-MS. The developed extraction method revealed complete recovery. The linearity of the calibration curve was in the range of 2 ng·mL⁻¹ to 500 ng·mL⁻¹ (R² > 0.99) with a LLOQ of 5 ng·mL⁻¹. The intraday and interday accuracy and precision ranged from 0.4% to 12.2% and from 1.0% to 12.0%. RD2 remained stable in the freshly homogenized brain even after several freeze–thaw cycles, but stability decreased over time during long-term storage at −80 °C. Using this validated method, RD2-spiked brain homogenate samples and samples of a pharmacokinetic study with RD2 in mice were analyzed. Full article

Chirality remains the most neglected axis of pesticide residue science. Many active ingredients are sold as racemates although their enantiomers differ in potency, persistence, transport, and toxicology; as a result, total concentration is a poor surrogate for risk. This review synthesizes green and enantioselective strategies spanning the full analytical–remediation continuum. We survey solvent-minimized sample preparation approaches (SPME/TF-SPME, FPSE, µSPE, DLLME with DES/NADES), MS-compatible chiral separations (immobilized polysaccharide CSPs in LC and SFC, cyclodextrin-based selectors in GC, CE/CEC), and HRMS-enabled confirmation and suspect screening. Complex matrices (e.g., fermented beverages such as wine and high-sugar products) are critically discussed, together with practical matrix-tolerant workflows and the complementary role of chiral GC for hydrophobic residues. We then examine emerging enantioselective materials—MIPs, MOFs/COFs, and cyclodextrin-based sorbents—for extraction and preconcentration and evaluate stereoselective removal via adsorption, biodegradation, and chiral photocatalysis. Finally, we propose toxicity-weighted enantiomeric fraction (EF) metrics for decision-making, outline EF-aware green treatment strategies, and identify metrological and regulatory priorities (CRMs, ring trial protocols, FAIR data). Our thesis is simple: to reduce hazards efficiently and sustainably, laboratories and practitioners must measure—and manage—pesticide residues in the chiral dimension. Full article

Chiral mesoporous silica nanostructures (MSNs) have emerged as a cutting-edge material in nanotechnology. These nanostructures not only retain the tunable physicochemical properties of traditional MSNs—such as adjustable pore size, high surface area, and excellent biocompatibility—but also exhibit unique functionalities and biological behaviors due to their helical architectures at both molecular and macroscopic levels. This inherent chirality grants chiral MSNs exceptional potential in diverse applications, including chiral catalysis, enantiomeric separation, chiral recognition, and advanced drug delivery systems. Over the past five years, substantial progress has been made in understanding their synthesis mechanisms and practical applications. This review provides a comprehensive analysis of recent advancements in chiral silica nanostructures, with a focus on the synthesis strategies and applications of chiral MSNs. Emphasis is placed on their roles in chiral recognition, drug delivery, chiral separation, nanomedicine, and asymmetric catalysis. By highlighting these developments, this review serves as a roadmap for the rational design and translational applications of chiral silica nanostructures, offering valuable guidance for unlocking their full potential. Full article

Lepechinia mutica, an endemic species of the Ecuadorian Andes, was studied to identify the seasonal variation in volatile organic compounds emitted from leaves and flowers in winter and summer using solid-phase microextraction–gas chromatography–mass spectrometry (SPME-GC-MS). A total of 101 and 100 volatile compounds were identified in flowers and leaves, respectively. The main compounds in flowers were β-phellandrene (7.81–17.74%), dictamnol (3.57–31.89%) and 9-epi-(E)-caryophyllene (3.93–14.37%), while in the leaves, they were dictamnol (9.85–34.64%), (Z)-β-ocimene (1.24–29.24%) and δ-3-carene (1.14–11.51%). This is the first report of enantiomeric separation in L. mutica using a capillary column with 2,3-diethyldecyl-6-tert-butyl-dimethylsilyl-β-cyclodextrin, revealing three enantiomerically pure compounds as (S)-(-)-β-pinene, (1S,3R)-(+)-δ-3-carene and (S)-(+)-linalool, while (+) (-) α-pinene, (+) (-) δ-cadinene and (+) (-) α-muurolene were found as racemic mixtures. Principal component analysis confirmed distinct chemical profiles between plant parts and seasons. This result has important implications for the future highlighting its potential as a source of seasonally variables components with applications in fragrance and phytotherapy. Full article

Chiral liquid chromatography (cLC) using chiral stationary phases (CSPs) has become a crucial technique for separating enantiomers. Understanding enantiomeric discrimination is essential for improving chromatographic conditions and elucidating chiral molecular recognition; the computational methods are extremely helpful for this. To assess the relevance of the association of these two approaches and to analyze the current trends, in this review, a systematic analysis of the scientific literature was performed, covering recently published works (from 2015 to January 2025) on enantioseparation by cLC using CSPs and computational studies. CSPs based on polysaccharides and Pirkle-type were the most described (accounting for 52% and 14% of the studies, respectively). Regarding the computational methods, molecular docking and molecular dynamics (MD) were the most reported (accounting for 50% and 25% of the studies, respectively). In the articles surveyed, a significant growth in research concerning both cLC enantioseparation and computational studies is evident, emphasizing the benefit of the synergy between these two approaches. Full article

Chiral ansa-η⁵-complexes of transition metals have shown remarkable efficacy in organometallic synthesis and catalysis. Additionally, enantiomerically pure ansa-complexes hold promise for the development of novel chiral materials and pharmaceuticals. The discovery and synthesis of a diverse range of group IVB and IIIB metal complexes represents a significant milestone in the advancement of stereoselective catalytic methods for constructing metal-C, C-C, C-H, and C-heteroatom bonds. The synthesis of enantiomerically pure metallocenes can be accomplished through several strategies: utilizing optically active precursors of η⁵-ligands, separation of diastereomers of complexes with enantiomerically pure agents, and synthesis via the stereocontrolled reactions of enantiomerically pure σ-complexes with prochiral anions of η⁵-ligands. This review focuses on the analysis of various nuances of the synthesis of enantiomerically pure ansa-η⁵-complexes of titanium and lanthanum families. Their applicability as effective catalysts in asymmetric carbomagnesiation, carbo- and cycloalumination, oligo- and polymerization, Diels–Alder cycloaddition, reactions of zirconaaziridines, cyclization, hydrosilylation, hydrogenation, hydroamination, and other processes are highlighted as well. Full article

Background/Objective: Avapritinib is an orally bioavailable tyrosine kinase inhibitor and was approved by the FDA in 2020 for gastrointestinal stromal tumor treatments. Although avapritinib is known to be chiral, its stereochemistry was initially established randomly. This study aims to develop a definitive method for determining avapritinib’s absolute configuration and propose a universal methodology for stereochemical characterization of flexible chiral drugs. Methods: The absolute configuration of avapritinib was determined through an integrated approach combining chiral resolution, chiroptical spectroscopy and synthetic validation. Enantiomeric separation was achieved via chiral liquid chromatography, followed by comprehensive chiroptical characterization including electronic circular dichroism (ECD), specific optical rotation and optical rotatory dispersion. Conformational analysis and density functional theory (DFT) calculations correlated experimental spectra with theoretical predictions, facilitating definitive configurational assignment. The stereochemical determination were further verified through ECD derivatization and chemical synthesis. Finally, the enantiomers’ kinase inhibition profiles against c-KIT D816V were quantitatively assessed. Results: Two enantiomers of avapritinib were resolved via chiral HPLC and a Chiralpak IG column. Through combined experimental ECD spectra and time-dependent DFT calculations employing the core extraction method, the levo-isomer was unambiguously determined as S configuration. This stereochemical assignment was confirmed by p-cyanobenzaldehyde derivatization and de novo synthesis. Biological evaluation revealed (S)-(−)-avapritinib exhibited superior c-KIT D816V inhibitory activity compared to its (R)-(+)-counterpart, a finding corroborated by molecular docking studies elucidating their differential target interactions. Conclusions: This study advances avapritinib stereochemical understanding and establishes a definitive protocol for its absolute configuration assignment, serving as a paradigm for flexible chiral drug characterization. Full article

A direct enantio- and chemo-selective high-performance liquid chromatographic method was developed for determining the enantiomeric impurity of the chiral active pharmaceutical ingredient silodosin. The simultaneous separation of enantiomers of silodosin and its main organic related substances listed in the Japanese Pharmacopoeia (JP) monograph for drug substance was achieved on Chiralpak AD-3 (250 mm × 4.6 mm, 3 μm) column under normal-phase isocratic conditions. The optimized conditions employed the mixture n-heptane-ethanol-diethylamine (70:30:0.1) (v/v/v) as a mobile phase and a temperature of 35 °C. The complete separation of the enantiomers of silodosin and its main impurities was obtained within 12 min. The chromatographic method has been validated according to the International Conference on Harmonization (ICH) guidelines and compared with the method reported in the JP monograph. The standard curve for silodosin exhibited linearity (R² > 0.999) within the concentration range of 1.13–2500 µg mL⁻¹. The Chiralpak AD-3 has demonstrated a remarkable level of efficiency, enabling the attainment of limits of quantitation for silodosin of 1.13 µg mL⁻¹ (equivalent to 0.057% of a sample solution of 2 mg mL⁻¹) and ranging from 0.48 µg mL⁻¹ to 1.94 µg mL⁻¹ for other impurities. Full article

The banana weevil (Cosmopolites sordidus) is a significant pest that reduces banana yields and can result in plant mortality. (2R,5S)-theaspirane, a kairomone from senesced banana leaves, is one of the natural banana volatiles, aiding weevil attraction. A rapid and cost-effective synthesis of (2R,5S)-theaspirane was developed utilizing microwave-assisted conditions and the principles of green chemistry. The process comprised five steps, beginning with the reduction of dihydro-β-ionone, followed by lipase-mediated kinetic resolution to attain high enantiomeric excess. Microwave-assisted heating significantly reduced reaction times. Optimized cyclization with the minimum quantities of selenium dioxide oxidation was employed. The final diastereomers were separated by chromatography, yielding compounds which exceeded 99% enantiomeric purity. Full article

The tetrahydroisoquinoline skeleton is a pharmacologically significant core structure containing chiral centers, making enantiomeric separation crucial due to the potentially distinct biological effects of each enantiomer. In this study, laudanosine (N-methyl-tetrahydropapaverine) and its three derivatives (6′-bromo-laudanosine, norlaudanosine, and N-propyl-norlaudanosine) were synthesized and used as model compounds to investigate chiral recognition mechanisms. Screening over twenty cyclodextrins (CyDs) as chiral selectors in capillary electrophoresis (CE), we found anionic CyDs to be the most effective, with sulfated-γ-CyD (S-γ-CyD) achieving a maximum R_s of 10.5 for laudanosine. Notably, octakis-(6-deoxy-6-(2-carboxyethyl)-thio)-γ-CyD (sugammadex, SGX), heptakis-(2,3-O-diacetyl-6-O-sulfo)-β-CD (HDAS), heptakis-(2,3-O-dimethyl-6-O-sulfo)-β-CD (HDMS), and octakis-(2,3-O-dimethyl-6-O-sulfo)-γ-CD (ODMS) provided excellent enantioseparation for all four analytes. Following HPLC screening on CyD-based and polysaccharide-based chiral stationary phases, semi-preparative HPLC methods using amylose and cellulose-based columns were optimized to isolate enantiomers. The purity of the isolated enantiomers was evaluated by HPLC, and their configurations were confirmed via circular dichroism spectroscopy. The isolated enantiomers allowed us to explore enantiomer migration order reversals in CE and enantiomer elution order reversal in HPLC. Further ¹H and 2D ROESY NMR experiments provided atomic-level insights into enantioselective complex formation, confirming enantiomer differentiation by SGX and elucidating the inclusion complex structure, where the ring C immersion into the CyD cavity is prevalent. Full article

Midazolam is a benzodiazepine that is utilized for the induction of anesthesia and the facilitation of procedural sedation. Despite the absence of stereogenic centers, the non-planar seven-membered ring devoid of reflection symmetry elements confers planar stereogenicity to the molecule. Due to the rapid conformational inversion of the Rp and Sp enantiomers, which occurs via a simple ring flip, high-performance liquid chromatography (HPLC) enantiomeric separation is restricted to sub-room temperature conditions. In this study, the energy barriers for the racemization of midazolam at five distinct temperatures and in acetonitrile/water mixtures were determined by monitoring the decay of the circular dichroism signal at a specific wavelength over time. The kinetic and thermodynamic data obtained were compared with those determined by dynamic enantioselective high-performance liquid chromatography using the Chiralpak IG-3 chiral stationary phase, which contains the amylose tris(3-chloro-5-methylphenylcarbamate) as the selector. The temperature-dependent dynamic HPLC of midazolam was carried out at the same temperatures and with the same aqueous mixtures used in parallel kinetic off-column experiments. To simulate dynamic chromatographic profiles, a lab-made computer program based on a stochastic model was utilized. The results indicated that the moderate influence of the stationary phase resulted in a slight increase in the activation barriers, which was more pronounced as the time spent in the column increased. This phenomenon was found to be mitigated when switching from a 250 mm × 4.6 mm, 3 µm, Chiralpak IG-3 column to a 50 mm × 4.6 mm, 1.6 µm, Chiralpak IG-U UHPLC column. The outcomes obtained under UHPLC conditions were found to be more closely aligned with those obtained through the ECD technique, with a discrepancy of only 0.1 kcal/mol or less, indicating a high degree of concordance between the two methods. Full article