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Background: Sub/supercritical fluid chromatography is regarded as a greener separation technique due to the use of carbon dioxide as the main component of the mobile phase compared to conventional liquid chromatography techniques. Organic co-solvents are usually added to carbon dioxide to increase elution strength of the mobile phase. Therefore, it is of great importance to test applicability of green co-solvents in separation methods and to include them among commonly used mobile phase components., Results: A comprehensive study of the suitability of green solvent dimethyl carbonate as a co-solvent for enantioseparation in sub/supercritical fluid chromatography was conducted with a set of novel psychoactive substances from various groups. The experiments were performed on polysaccharide-based columns. For successful enantioseparation of these compounds, the presence of basic or mixed mobile phase additives was essential. The obtained results clearly show that dimethyl carbonate is a suitable co-solvent for enantioseparation on polysaccharide-based columns in sub/supercritical fluid chromatography and in some cases surpasses commonly used co-solvents as methanol and propan-2-ol., Significance: The use of more sustainable co-solvents, such as dimethyl carbonate, instead of conventional ones to carbon dioxide presents a greener approach to analytical applications and reduces the overall environmental impact of analytical processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Different enantiomer forms of amino acids play different roles in multifarious fields, and improper use will cause irreversible effects. Therefore, the identification of chiral amino acids is a vital issue in the field of pharmaceutical analysis. Herein, a chiral sensing system of β-cyclodextrin coated silver nanoparticle (β-CD@AgNPs) with peroxidase-like activity was designed for the fast and efficient colorimetric identification of tryptophan (Trp) enantiomers based on the difference in binding capacity between D/L-Trp and β-CD. The results showed the satisfactory linearity for detecting D/L-Trp over the concentration range from 0.2 to 4 mM with a LOD of 0.16 and 0.18 mM, respectively. Moreover, the absorbance increased linearly with the rise of D-Trp concentration percentage in the Trp enantiomer mixture. The proposed method avoided the use of natural enzymes and improved the stability due to the protective effect of cyclodextrin, which provided a new idea for selective colorimetric recognition and detection of D/L-Trp based on cyclodextrin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bacterial infections are becoming a significant threat to global human health due to the growing prevalence of biofilm-related infections and the rise in antibiotic resistance. D/l-cysteine functionalized chiral gold nanoparticles (D/P-Au NPs or L/P-Au NPs) have demonstrated a potent antibacterial effect against E. coli, while the mechanism remains to be elucidated through additional research. Threonine deaminase (TD) is a crucial enzyme involved in branched-chain amino acid (BCAA) biosynthesis in E. coli and is involved in cysteine's antimicrobial effects. This study investigated the interaction between chiral Au NPs (D/P-Au NPs or L/P-Au NPs) and TD as well as its effect on enzyme activity. It demonstrates that chiral Au NPs interact with TD through hydrophobic forces, forming a ground state complex that induces changes in the secondary structure of TD and reduces enzyme activity in a concentration-dependent manner. We found that the exogenous supplementation of isoleucine and valine (2 mg/mL) significantly reduced the antibacterial activity of chiral Au NPs, especially for L/P-Au NPs. The proteomics results indicate that the expression of ilvA and ilvB was down-regulated after L/P-Au NPs treatment, which would interfere with the synthesis of BCAAs. These results demonstrate that chiral Au NPs cause cell death of E. coli partly due to inhibition of TD enzyme activity and the synthesis of branched-chain amino acids., Competing Interests: Declaration of competing interest No conflict of interest exits in the manuscript titled “Targeting Threonine Deaminase with Chiral Au NPs: A Novel Strategy for E. coli Inhibition”., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The increased detection of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) in aquatic ecosystems, has raised concern worldwide about its possible negative impacts on wildlife. MDMA is produced as racemate but its enantioselective effects on non-target organisms are poorly understood. Therefore, this study aimed to provide a comprehensive study of the toxicity of MDMA and its enantiomers in the early life stages of zebrafish (Danio rerio). Zebrafish embryos (≈3 h post fertilization) were exposed to different concentrations (0.02, 0.2, 2, 20, and 200 μg/L) of (R,S)-MDMA and both pure enantiomers. Both enantiomers induced effects on embryonic development, DNA integrity, and behaviour and enantioselective effects were noted. (S)-MDMA exhibits higher toxic effects on embryonic development level with increased mortality and severity of teratogenic effects, and behavioural abnormalities in acoustic startle-habituation response. (R)-MDMA affected general activity and avoidance behaviour, showing greater inhibitory effects on behavioural activity. Additionally, (R,S)-MDMA induced higher genotoxic effects than the two isolated enantiomers. These results are of concern at populational levels since effects on mortality, development, and behaviour were observed even at environmentally relevant concentrations, which can cause a reduction of larval viability and in the number of individuals in each generation, and an increase in the risk of predation of the organisms. Yet, the bioaccumulation studies showed that MDMA is not accumulated in zebrafish. Therefore, this work demonstrated for the first time the occurrence of MDMA enantiotoxicity in the early life stages of zebrafish, which should be considered in further environmental risk assessments involving fish species or other non-target aquatic organisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Penthiopyrad, a chiral pesticide, has been widely used in agricultural production. However, systematic evaluation of stereoselective bioactivity and biotoxicity of penthiopyrad in soil environment is insufficient. In this study, the stereoselective bioactivity of penthiopyrad against three soil-borne disease pathogens and its stereoselective biotoxicity to soil non-target organisms were investigated. The present results showed that the bioactivities of S-penthiopyrad were 546, 76 and 1.1-fold higher than those of R-penthiopyrad due to their different interaction modes with SDH in different target pathogens. S-penthiopyrad was more persistent in the soil environment and had stronger bioaccumulation than R-penthiopyrad. The accumulation of penthiopyrad in earthworms induced the response of detoxification system, resulting in the significant increases in the activity of detoxifying enzymes, such as GST, CarE, and CYP450. Additionally, both S-penthiopyrad and R-penthiopyrad induced cell apoptosis, intestinal damage and differentially expressed genes in earthworms, especially S-penthiopyrad. Furthermore, S-penthiopyrad has stronger binding capacity with COL6A and ACE proteins, while R-penthiopyrad has stronger binding capacity with CYP450 family proteins, which may be the main reason for the differences in biotoxicity between PEN enantiomers. Considering the differences in bioactivity and biotoxicity of penthiopyrad enantiomers, as well as the modes of action of pesticides on target and non-target organisms, S-penthiopyrad has greater potential for future development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fenpropidin (FPD), a widely utilized chiral fungicide, has been detected in aquatic environments. This study systematically evaluated the bioaccumulation, depuration, biotransformation, and sensitive biomarkers of FPD enantiomers in zebrafish to assess their environmental risks. Compared with S-FPD, R-FPD demonstrated a higher rate of enrichment and an increased level of bioaccumulation. The half-lives of R-FPD and S-FPD were 0.49 ± 0.01 and 0.91 ± 0.02 days at 0.05 mg/L and 1.65 ± 0.01 and 1.85 ± 0.03 days at 0.5 mg/L. Nontarget metabolism analysis identified nine metabolites, primarily formed through hydroxylation, oxidation, dehydration, glutathione conjugation, and glucuronidation pathways. Some metabolites exhibited high toxicity, underscoring the necessity for continuous monitoring of their toxicological effects and environmental fate in risk assessments. The toxicity of S-FPD in zebrafish was 1.21 times greater than that of R-FPD. Furthermore, this study identified sensitive markers for the enantiomers at both protein and transcriptional levels using an integrated biomarker response approach. S-FPD exhibited increased sensitivity to apoptosis and metabolic gene expression, while R-FPD showed greater sensitivity to antioxidant kinase activity. These findings facilitate timely monitoring of environmental pollution caused by FPD enantiomers. This study provides critical insights for assessing potential risks associated with pesticide exposure to human health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Chiral herbicides applied to agricultural soils are typically mildly to moderately contaminated with heavy metals (HMs), necessitating a thorough investigation into their effects on soil HMs availability. This study evaluated the effect of the chiral herbicide napropamide (NAP) on HMs bioavailability in different soil types, including weakly alkaline clay in Northeast China, neutral sandy loam in Zhejiang, and weakly acidic clay loam in Sichuan, China. The results demonstrate significant differences in the availability of HMs (Cd, Pb, Zn, and Ni) in the soil following enantiomer treatments, with variation ranges of 4.57-45.67 %, 5.03-96.21 %, 2.92-52.30 %, and 10.57-29.79 %, respectively. Overall, R-NAP enhanced the bioavailability of HMs more effectively than S-NAP, specifically by significantly activating available iron 3.33-191.97 % and markedly affecting soil pH and cation exchange capacity. Additionally, R-NAP influenced biotic processes by enriching dominant microbial communities, such as Chitinophaga, Niabella, and Promicromonospora, and by constructing more stable microbial networks. Notably, bioavailable Fe plays a dual regulatory role, affecting both the abiotic and biotic processes affected by soil NAP. In summary, although R-NAP is commonly used in agriculture, it poses a greater risk of HMs contamination in crops, highlighting the need for careful application and management. This study provides a fundamental theoretical basis for the judicious use of chiral herbicides in agricultural soils with mild-to-moderate HMs contamination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The novel chiral fungicide benzovindiflupyr exerts adverse effects on aquatic organisms; however, its toxic mechanism and stereoselectivity remain largely unknown. The current study aimed to investigate the enantioselective ecotoxicity mechanism of benzovindiflupyr in Xenopus laevis tadpoles using a 28-day exposure experiment. Results of the acute toxicity assessment indicated that (1S,4R)- and (1R,4S)-benzovindiflupyr exhibited high toxicity, with (1S,4R)- demonstrating approximately 75 times greater toxicity than (1R,4S)-. Compared to the latter, (1S,4R)-benzovindiflupyr significantly affected the growth, movement behavior, and oxidative stress of X. laevis tadpoles. The integration of metabolomics and transcriptomics data revealed that (1S,4R)-benzovindiflupyr disrupted the glycine, serine, and threonine metabolic pathways by modulating the activities of key enzymes. This dysregulation resulted in aberrant carbohydrate utilization, antioxidant pathways, and structural protein synthesis and degradation. Molecular docking confirmed that (1S,4R)-benzovindiflupyr exhibited superior docking activity with key enzymes, potentially contributing to its stereoselective toxicity. This study offers novel molecular perspectives on the enantioselective ecotoxicity mechanism of benzovindiflupyr toward aquatic organisms and highlights potential target proteins implicated in metabolic disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chirality plays an important role in medicine, biology, and chemistry. Molecules of different chirality could display dramatically different medical effects, pharmacological activities, and physiological impacts. Ibuprofen is an important anti-inflammatory drug in clinics. The anti-inflammatory effect is almost solely attributed to the (S)-(+)-Ibuprofen, while its enantiomer (R)-(-)-Ibuprofen plays a negative effect on increasing the metabolic burden. In this work, a terahertz (THz) polarization-sensitive metasurface sensor is proposed for qualitative and quantitative identification of the chiral Ibuprofen. The chirality parameters of Ibuprofen are extracted from the circular-polarized transmission coefficients. The parameters are further used to simulate the coupling mechanism between the Ibuprofen and the sensor to explain the principle of recognition. The sensitivities of (R)-(-)-Ibuprofen and (S)-(+)-Ibuprofen are found to be 1.5 THz/(mg/L) and 1.8 THz/(mg/L) for the TM polarization, respectively, and 1.7 THz/(mg/L) and 2.1 THz/(mg/L) for the TE polarization, respectively. The difference enables the chirality identification according to the different frequency shift at the same concentration. The exceptional specificity and sensitivity provide a new avenue for chiral molecular recognition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The increased production and use of chiral pesticides will enhance their exposure in the environment. Chiral pesticides typically exhibit varied biological effects among these enantiomers. Therefore, it is very essential to develop and validate chiral analytical methods to investigate their potential ecological risks from a stereoselective perspective. Current separation of pesticides enantiomers relies extensively on chiral stationary phases (CSPs), while the development of β-Cyclodextrin derivatives CSPs become the research focus due to their great modifiability and excellent chiral recognition capabilities., Results: A novel chiral stationary phase, 3,5-dichlorophenylaminomethyl-6-phenylenediamine-β-cyclodextrin chemically bonded silica gel (MPDCDA), was successfully prepared. Based on that, a stereoselective HPLC-MS/MS method was developed and validated for the determination of tebuconazole enantiomers in Rana nigromaculata tadpoles. After extraction by QuEChERS, the tebuconazole enantiomers were completely separated with the resolutions of 1.63 using the mobile phase of methanol-water (70/30, v/v). Good linearity (r > 0.9990) for both enantiomers over a concentration range of 0.20-500.0 ng/mL was obtained with the accuracy ranged from 6.7 % to 9.3 % and the intra-day and inter-day precisions below 6.2 % at three quality control levels. The proposed method was successfully applied in evaluating the enantioselective bioaccumulation and elimination profiles of tebuconazole in tadpoles. At the tested conditions, there was no significantly enantioselective difference in the bioaccumulation process for S- tebuconazole and R-tebuconazole. However, the elimination process of tebuconazole enantiomers was enantioselective with R-tebuconazole preferentially degraded., Significance: This work provided an accurate risk assessment of chiral pesticides to non-target aquatic organisms from a stereoselective perspective. These findings would deepen our understanding of the potential ecological risks of chiral pesticides on aquatic organisms and provide scientific support for the protection of aquatic organisms and their ecological environments, as well as sustainable development., Competing Interests: Declaration of competing interest The authors declares that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Starting from 3-methoxyestra-1,3,5(10),16-tetraene-17-carbaldehydes of natural (13β) and epimeric (13α) series, a series of isomeric 3-hydroxy-17-hydroxymethylestra-1,3,5(10)-trienes, including those containing 16α,17α-annulated cyclopropane and cyclohexane ring D', were prepared using the Corey-Chaykovsky and Diels-Alder reactions followed by reduction-demethylation with diisobutylaluminum hydride and hydrogenation. Target compounds showed antiproliferative effects on MCF-7 breast cancer cells to varying degrees superior to that on MCF-10A cells, in low micromolar concentrations. The ERα-mediated luciferase reporter gene assay demonstrated that obtained steroids without an additional carbocycle or with a cyclopropane 16α,17α-annulated carbocycle are effective ERα activators. In this test, steroids of the natural configuration showed high activity at both 10 nM and 100 nM concentrations, whereas 13α-steroids showed a strong dose-dependent effect, surpassing their natural counterparts at a concentration of 100 nM. The 13β-steroid bearing additional 16α,17α-cyclohexane ring had low activity in the test. A simple docking approach using AutoDock Vina was used as a test for a preliminary assessment of the estrogenicity of the compounds. The scope of its applicability and limitations were shown using examples of synthesized molecules., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Enzymatic resolution of ethyl tetrahydrofuroate to produce (S)-2-ethyl tetrahydrofuroate and (R)-2-tetrahydrofuroic acid is a green biomanufacturing strategy. However, enzymatic activity and selectivity are still limiting factors of their industrial applications and development. In previous study, we incidentally found that a Bacillus licheniformis alkaline protease (BLAP), not a lipase, could specifically resolve ethyl tetrahydrofuroate to produce (S)-2-ethyl tetrahydrofuroate and (R)-2-tetrahydrofuroic acid. In this study, the point-saturation-mutation libraries based on the seven amino acid sites (L105, I113, P114, L115, V309, Y310, and M326) were constructed and screened using the molecular docking technology. It was found that activity of the mutant BLAP Y310E reached 182.78 U/mL with high stereoselectivity, 3.14 times higher than that of the wild-type BLAP. Further simulated mutation analysis showed that the Y310E mutation increased the distance from the substrate ligand to the binding pocket from 2.3 Å to 4.5 Å, reducing steric hindrance to the active center. Under the optimal conditions and after 3.5 h of reaction catalyzed by BLAP Y310E , 200 mM ethyl tetrahydrofuroate was converted to (S)-2-ethyl tetrahydrofuroate and (R)-2-tetrahydrofuroic acid with the ee values of 99.9 % and 68.63 %, respectively. The enantiomeric ratio of BLAP Y310E was 105.5, which was 30.23 times higher than that of BLAP. This study advances the comprehension of protease activity and selectivity mechanisms in resolving ester substances and lays a robust foundation for the industrial production of the optically pure (S)-2-ethyl tetrahydrofuroate and (R)-2-tetrahydrofuroic acid via biological enzymatic methods., Competing Interests: Competing interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Bile acids (BAs) are steroidal molecules that play important roles in nutrient absorption, distribution, and excretion. They also act on specific receptors implicated in various metabolic and inflammatory diseases demonstrating their importance as potential drug candidates. Accordingly, there has been a concerted effort to develop new BA derivatives to probe structure-activity relationships with the goal of discovering BA analogues with enhanced pharmacological properties. Among the many steroidal derivatisations reported, the formation of endocyclic azasteroids appeals due to their potential to deliver altered biological responses with minimal change to the steroidal superstructure. Here, we report the synthesis of 3-aza-obeticholic acid (6) via a regioconvergent route. Ammoniolysis of lactones, formed from an m-CPBA-mediated Baeyer-Villiger reaction on a 3-keto-OCA derivative, furnished protected intermediate amido-alcohols which were separately elaborated to amino-alcohols via Hofmann degradation with BAIB. Upon individual N-Boc-protection, these underwent annulation to the 3-aza-A-ring when subjected to either mesylation or a Dess-Martin oxidation/hydrogenation sequence. Global deprotection of the 3-aza-intermediate delivered 3-aza-OCA in ten steps and an overall yield of up to 19%., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The widespread application of chiral fungicides as seed-coating agents in agriculture has led to serious residue accumulation in soil, increasingly drawing attention to soil pollution remediation strategies for chiral pesticides. This study explored the role of earthworms and soil microorganisms in selectively accelerating the degradation of penflufen in soil. The results showed that soil microorganisms significantly accelerated penflufen enantiomer degradation, particularly the R-enantiomer. Nocardioides, Variovorax, Arthrobacter, and Pseudomonas were identified as key degrading microorganisms associated with the preferential degradation of the R-enantiomer. The addition of earthworms further significantly enhanced the preferential degradation of the R-enantiomer. Importantly, earthworms markedly promoted the growth and reproduction of the four aforementioned degrading microorganisms in soil treated with enantiomers. Notably, the relative abundance of these degrading microorganisms was significantly higher in R-enantiomer-treated soil with earthworms than in soil treated with the S-enantiomer. Additionally, earthworms significantly increased the relative abundance of degradation genes p450, bphA1, and benA in the soil, especially in the R-enantiomer treated soil. Nocardioides, Variovorax, Arthrobacter, and Pseudomonas were identified as potential hosts for the degradation gene benA. More importantly, twelve strains of penflufen-degrading bacteria were isolated from the treated soil, of which eight belonged to the aforementioned four microorganisms and exhibited a remarkable ability to preferentially degrade the R-enantiomer. This finding highlights the potential of adding earthworms to soil, in conjunction with key degrading microorganisms, which preferentially accelerates penflufen R-enantiomer degradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We performed quantum chemical calculations based on the density functional theory (DFT) for the all-E- and several Z-isomers of three commercially important carotenoids (lycopene, β-carotene, and astaxanthin) and theoretically obtained the UV-Vis spectrum, response factor (determined from absorption intensities of the all-E- and the Z-isomers), and Q-ratio for each carotenoid isomer. The calculated spectra reproduced the experimental spectral shapes (e.g., the appearance of the Z-peaks and the blue shift of the main peaks for the Z-isomers) very well. The calculated response factors and Q-ratios also showed good agreement with reported values. Notably, response factors, which are difficult to determine experimentally, were well reproduced. These results suggest that quantum chemical calculations can be an effective tool for refining quantitative analysis and obtaining spectral data for carotenoids for which standards are difficult to obtain., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Masaki Honda reports financial support was provided by Japan Science and Technology Agency., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In the past three decades, liquid chromatography (LC) has been recognized as a significant environmental, health, and safety burden due to its heavy reliance on toxic organic solvents. Various chromatographic modes are in vogue today for complex analyses, such as sub/supercritical fluid chromatography (SFC) and enhanced fluidity liquid chromatography (EFLC). These modes are often advertised as "universally green" compared to the traditional allliquid reversed (RPLC) and normal phases (NPLC). Quantitative greenness evaluations must be done to validate or invalidate this assumption and allow separation scientists to make educated choices when deciding on what mode to use., Results: In this work, we modify the Analytical Method Greenness Score (AMGS) to include the cycle time of the instrument, and with the help of the first-order optimality condition (by setting the AMGS gradient = 0), we show that SFC and EFLC are not always the greenest option as they are often thought to be. Most of the greenness metrics have ignored the cycle time of instruments, yet this key component changes the entire AMGS response to flow rate. The complex case of separating tobacco alkaloid enantiomers (nicotine, nornicotine, anabasine, and anatabine) was selected as an illustrative example for comparing and contrasting separation modes using the modified greenness metric. These enantiomers have been selected due to their notorious difficulty in separation over the past 30 years. Using this family of molecules, four unique retention patterns were observed covering a wide variety of retention phenomena seen in small molecule enantioseparations., Significance: The modified AMGS metric will assist practicing analytical chemists in assessing the environmental impact of their separation methods from a single run in a given chromatographic mode. The proposed methodology identifies the minimum AMGS score corresponding to the greenest separation for routine chemical analysis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daniel W. Armstrong has a potential research conflict of interest due to a financial interest with the company AZYP, LLC. A management plan has been created to preserve objectively in research in accordance with UTA policy., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Chiral-selective molecular interactions are considered crucial in numerous physiological processes. Chiral-selective analytical methods of biomolecules with sufficient sensitivity are of great interest in numerous applications. Several surface-enhanced Raman scattering (SERS)-based methods have recently been reported for chiral sensing of biomolecules. However, the lack of molecular-level understanding of SERS spectral changes of reporter and analyte molecules may mislead the development of chiral detection methods., Results: We report the chiral sensing of glucose (Glu) by SERS of L- and D-phenylalanine (Phe) with colloidal gold nanoparticles (AuNPs) synthesized by borohydride ions. The Phe SERS showed drastic spectral changes only when Glu of the same chirality as Phe was added, which also showed strong dependence on Glu concentration. The increase of δ(COO - ) and decrease of ν s (COO - ) modes in Phe SERS, exclusively observed with the chiral-selective bimolecular interactions of chirally matching Glu, are understood as modified surface adsorption geometry of the carboxylate group. Quantitative spectral analysis for the Glu concentration of a specific chirality showed the detection limit down to 2 × 10 -9 - 2 × 10 -7  M levels depending on the existence of the opposite enantiomer of Glu., Significance: In this study, we demonstrated that the Phe SERS on AuNPs can be utilized in the chiral sensing of Glu molecules with quantitative concentration analysis. The bimolecular interactions of surface-adsorbed Phe and chirally matching Glu are suggested for the chiral recognition of Phe SERS. These results imply that a molecule-level understanding is indispensable for developing SERS-based chiral sensing methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The need for stationary phases with unique selectivity in reversed-phase liquid chromatography has been of utmost importance to chromatographers for advancing the analysis of complex samples. Macrocyclic glycopeptide based stationary phases have been widely used for chiral separations with different chromatographic modes such as normal phase, reversed phase, and supercritical fluid chromatography. Given the multimodal retention mechanisms namely π-π complex interaction, hydrogen bonding, dipole-dipole interaction, and strong Coulombic interactions by which analytes are separated using the macrocyclic glycopeptides, these stationary phases are expected to provide novel selectivity when used under the reversed phase for achiral separations., Results: Herein, for the first time we have conducted a systematic study using the improved hydrophobic subtraction model (HSM) which incoporates dipole-dipole interactions to demonstrate the novel selectivity offered by four different macrocyclic glycopeptide based stationary phases, namely NicoShell, TeicoShell, TagShell, and VancoShell. A comparison of the HSM parameters for these columns has been made with 551 commercially available reversed phase stationary phases and the differences in the values point to the importance of adding these columns to the already existing arsenal. These stationary phases offer separations over a wide range of pH and show variability in selectivity depending on the pH of the mobile phase which make them versatile for method development in the reversed phase mode. Additionally, we have provided an actual example of a separation from an Amgen discovery project using the VancoShell column aided by computer-assisted modelling., Significance: This is the first report characterizing macrocyclic glycopeptides for achiral RPLC applications. The selectivity of these stationary phases were found to be unique when compared to other commercially available stationary phases thereby acting as their own class of columns. The unusual selectivity of the columns enabled separation of complex pharmaceutical samples., Competing Interests: Declaration of competing interest DWA is president of AZYP, LLC. All other authors declare no competing financial or personal interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Wastewater effluent is the main contributor of psychiatric pharmaceuticals (PPs) pollution in surface waters. However, little is known about its spatial evolution dynamics in effluent-dominated rivers. Herein, 10 representative PPs, including 6 chiral pharmaceuticals and 4 achiral pharmaceuticals, were explored in the Beiyun River, a typical wastewater effluent-dominated river, to explore their occurrence, in-stream attenuation and enantioselective fractionation behaviors at a watershed scale. Among the target substances, 8 and 9 drugs were detected in surface water and sediment samples with the ΣPPs concentrations ranging from 78.4 to 260.1 ng/L and 4.8 to 43.4 ng/g dw in surface water and sediments, respectively. Along the mainstream of the Beiyun River, only several PPs detected in surface water, e.g., citalopram, O-demethylvenlafaxine, and fluoxetine, exhibited in-stream attenuation behaviors when reaching rural area, while all PPs detected in sediments displayed in-stream attenuation behavior. Four chiral PPs detected in surface water exhibited an enantioselective attenuation phenomenon, while in sediments, only citalopram displayed an enantioselective fractionation behavior. The differences in the in-stream attenuation and enantioselective environmental behavior of individual PPs caused complex contaminant evolution along the stream reach. This work provides enantiomeric profiles of chiral pollutants for evaluating their in-stream attenuation processes, which would facilitate better understanding of the changing contaminant exposure conditions in complex natural environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cyclodextrin-based stationary phases are important chiral selectors in liquid chromatography. These chiral selectors are most commonly used in the reversed-phase mode because native cyclodextrin assumes a torus conformation with a hydrophobic cavity, facilitating inclusion complexation in aqueous environments. However, the value of native and aliphatic-derivatized cyclodextrins in other modes, such as the normal phase liquid chromatography (NPLC) or super/subcritical fluid chromatography (SFC), remains unexplored. In this work, we report chiral separations of pharmaceutically relevant compounds with the 1,4-dihydropyridine (DHP) scaffold on a 2-hydroxypropyl-β-cyclodextrin (CD-RSP) stationary phase in NPLC and SFC modes. Although CD-RSP is conventionally considered only effective in the reversed-phase mode, we show that these compounds tend to separate better in other modes. This is particularly apparent for analytes with hydrogen-bonding moieties. We propose that the separation mechanism primarily depends on external adsorption rather than inclusion complexation. The negligible impact of a complexation-competitive additive on retention in non-aqueous modes further supports this claim. Additionally, van Deemter analysis demonstrated the efficiency and environmental benefit of using this stationary phase in the SFC mode, further highlighting the promise of aliphatic derivatized cyclodextrin stationary phases for greener separations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Daniel W. Armstrong has a potential research conflict of interest due to a financial interest with the company AZYP, LLC. A management plan has been created to preserve objectively in research in accordance with UTA policy, (Copyright © 2024. Published by Elsevier B.V.)

Clindamycin phosphate (CP) exhibits good enantioselectivity for many basic drugs, but its separation effect for most amino alcohol drugs is not satisfactory. In this work, a deep eutectic solvent (DES) chiral selector based on CP was prepared for the first time and utilized as a single chiral selector in nonaqueous capillary electrophoresis (NACE) to separate twelve amino alcohol drugs. Compared with unmodified CP, the separations of model drugs in the DES chiral selector system were significantly improved. Most amino alcohol drugs could be completely separated, and the peak shapes were good. In addition, we used infrared spectroscopy and nuclear magnetic resonance method to study the specific separation mechanism and explored the reasons why DES chiral selector has better enantioselectivity. This work is the first to directly modify antibiotic chiral selector into DES, indicating a direction for us to develop novel chiral recognition materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Simultaneous separation of compounds with multiple chiral centers and highly similar structures presents significant challenges. This study developed a novel supercritical fluid chromatography (SFC) method with reduced organic solvent consumption and robust separation capabilities to address these challenges. The method was applied to simultaneously achieve enantioselective, diastereoselective, and achiral separation of palonosetron hydrochloride and its six impurities. The effects of the polysaccharide-based chiral stationary phase (CSP), modifier, additive, and column temperature on retention and separation were comprehensively evaluated. It was found that a combination of a polysaccharide-based CSP and a single modifier or a mixture of protonic modifiers could not achieve complete separation due to high structural similarity. However, an ADH column and a ternary solvent mixture containing acetonitrile (methanol: acetonitrile: diethylamine, 60:40:0.2, v/v/v) provided satisfying separation, particularly for the enantiomer and diastereomers of palonosetron. Using the optimized method, the enantioselective, diastereoselective, and achiral separation of palonosetron hydrochloride and its six impurities can be accomplished in 18 min under gradient elution. Thermodynamic results indicated that the separation process was entropy driven. A molecular docking study revealed that the separation was mainly achieved through the differences in hydrogen bond and π - π interactions between the analytes and CSP. This study lays the foundation for SFC analysis of palonosetron hydrochloride and provides a reference for the simultaneous SFC separation of the enantiomers, diastereoisomers and structurally similar compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As a novel class of chiral stationary phase (CPS) material, chiral covalent organic frameworks (CCOFs) have already shown great promise in open-tubular capillary electrochromatography (OT-CEC) for chiral separation. The synthesis methods of CCOFs used in OT-CEC mainly include bottom-up, post modification and chiral induction. The CCOFs synthesized by bottom-up and post modification strategies already have lots of applications in capillary electrochromatography, however, the chiral-induced synthesized via an asymmetric catalytic strategy has not yet been reported for using as the chiral stationary phase (CPS) in OT-CEC or even in chromatographic separation. Herein, the chiral-induced COF (Λ)-TpPa-1 was synthesized by asymmetric catalytic synthesis and coated on the inner surface of a capillary by an in-situ growth strategy as the CPS for chiral drug separation. The baseline separation of six enantiomers was achieved within 14 min, with a high-resolution (R s ) range from 1.85 to 6.75. Moreover, the resolution and migration time of the capillary keep stable within 160 runs, showing its superior stability and repeatability. This research provides a new idea for the development and application of novel CPS materials in the field of capillary electrochromatography separation, also shows the new application of chiral induced COFs. Furthermore, the chiral-induced CCOFs can be easily applied to other chromatographic separation fields, exhibiting its extensive application value in chiral analysis separation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A stereoselective synthesis of fused tricyclic framework of epi-parvistemonine A from D-glucono-δ-lactone is described. The synthetic strategic is based on the stereoselective construction of the 7-membered cyclic skeleton via a cross-metathesis reaction followed by a Michael type cyclization promoted by Tf 2 O., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The influence of chiral materials on organisms is crucial. However, there is little research on the impact of chiral carbon dots (CDs), a kind of typical chiral materials, on biology. Herein, chiral CDs (L-/D-CDs) were synthesized using the thermal polymerization method from citric acid and chiral cysteine. The effect of chiral CDs on silkworms was explored through feeding silkworms with chiral CDs. The breaking strength of silk fibers (667.9 MPa) in D-CDs group exhibit a 71.4 % increase compared with control-silk (389.5 MPa), while the breaking strength of silk fibers in L-CDs group increases by 51.6 %. In addition, Fourier transform infrared spectra display CDs can prevent the transformation from random coil/α-helix structures to β-sheet structures. Furthermore, D-CDs group exhibit the highest percentage of four primary amino acids (glycine, alanine, serine, and tyrosine) relative to the total amino acids in silkworm hemolymph. This percentage is elevated by 70.5 % compared to the control group, thereby furnishing an ample supply of raw materials for the synthesis of silk proteins. In contrast, L-CDs group exhibit increase by 39.3 %. Our work provides new ideas and approaches for studying the effects of chiral materials on living organisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Novel hydrogel biocatalysts with immobilized lipase, stabilized by ionic liquids (ILs) of different hydrophobicity, were synthesized and evaluated. Variations of the time of immobilization and ratio of substrates during hydrogel synthesis were considered to obtain the most stable biocatalyst with the highest activity. Physicochemical characterization proved the success of the hydrogel synthesis and enzyme deposition on the surface of the support. Nevertheless, the key objective was to produce a biocatalyst for further application in ibuprofen methyl ester resolution, with the aim of obtaining an enantiomerically pure product. The hydrogel biocatalysts obtained in the presence of 5 wt% ILs after 8 h of immobilization achieved the highest activity recovery of 62 %. After 10 reaction cycles, enzymatic activity was still above 60 %, and the negative effect of pH and temperature on the activity of immobilized lipase was much lower than in the case of the free enzyme. After application of the catalyst in the resolution of ibuprofen methyl ester, the enantiomeric excess and conversion rate of the process were obtained for the dynamic kinetic resolution in isooctane. A conversion rate of 95 % was achieved due to the stabilization of the biocatalyst with IL and its resulting high catalytic activity. The study thus provides the pharmaceutical industry with a new potential approach with a strong scientific foundation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Regio- and stereo-selective synthetic routes to 2-deoxy-2-fluoro-d-mannose building blocks are often experimentally challenging when using Selectfluor with the corresponding glycal. We targeted a late-stage method to introduce fluorine in a stereospecific manner using inversion via a triflate. Accordingly, synthesis of a conventionally protected 2-deoxy-2-fluoro-d-mannose β-thioglycoside donor, directly applicable to oligosaccharide synthesis, was attempted using C2-triflate inversion of the corresponding d-glucoside with TBAF. Unexpectedly, an anomeric pyridinium salt was isolated when attempting to form the C2-triflate using Tf 2 O in pyridine. Indicatively, this proceeds via a 1 → 2 S-migration delivering a 1,2-trans product with α-d-manno configuration and the anomeric pyridinium in a pseudo-equatorial position. The structure of this unexpected intermediate was confirmed in the solid-state using X-ray crystallography. Omission of the pyridine solvent led to dimer formation. Switching the aglycone to an O-para-methoxyphenyl enabled smooth C2 inversion to the desired 2-deoxy-2-fluoro d-mannose system, suitably equipped for further anomeric manipulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Stereoselective synthesis of 2,3-diazido-2,3-dideoxy-β-d-mannosides has been accomplished via Cs 2 CO 3 -mediated anomeric O-alkylation of 2,3-diazido-2,3-dideoxy-β-d-mannoses with primary electrophiles. Selective oxidation of the C6 primary alcohol of the 2,3-diazido-2,3-dideoxy-β-d-mannoside successfully produced corresponding 2,3-diazido-2,3-dideoxy-β-d-mannuronic acid., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Herein, we describe the efficient, diastereoselective syntheses of the iminosugars 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) 1b, lentiginosine 3a, and the seven stereoisomers of each of these iminosugars starting from 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 with yields ranging from 38 % to 68 % for the DAB and isomers 1a-1h and from 44 % to 89 % for the lentiginosine and isomers 3a-3h. We also report the syntheses of the eight stereoisomers of the 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 from commercially available sugars. Key to the iminosugar syntheses is a single multistep reaction that converts the 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 to a vinyl pyrrolidine through a one-pot zinc mediated reductive elimination, followed by a reductive amination and finally an intramolecular nucleophilic substitution. Strategic selection of the amine utilized in the reductive amination and the functionalization of the intermediate carbon-carbon double bond provides access to a vast array of iminosugars., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Louis J. Liotta reports financial support was provided by National Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Alginates are brown algal polysaccharides consisting of β-D-mannuronic (M) and α-l-guluronic acid (G) residues linked with 1→4 glycosidic bonds. To functionalize these natural resources for biomedical use, alginates can be chemically modified, including by sulfation. Here regioselective sulfation of alginates at M-2 in DMSO with Py∙SO 3 is described, by either sulfating alginates directly or through using alginates with added protecting groups (PG-s), including TBDMS-ether, Piv-, Bz-esters and intramolecular 3,6-lactone. Highest regioselectivity was found by sulfating TBDMS- and Piv-protected alginates, with over 65 % of M-residues being 2-O-sulfated. However significant reduction in molecular weight was found when alginates were sulfated in DMSO. Results from this work will allow a degree of control over substitution patterns in sulfated alginates. This will allow to more accurately determine structure-property relationships in biomedical research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Biothiols are important for numerous cellular processes, such as resisting oxidative stress and protecting cell health. Their abnormal levels and molecular configurations have been associated with various diseases. So, establishing an effective and reliable method for the specific detection and enantiomeric discrimination of diverse biothiols is highly meaningful., Results: We have developed a new NMR and CD probe using 1,4-dinitroimidazole, specifically targeting the thiol group. This probe allows for the specific detection and enantiomeric recognition of biothiols in complex mixtures. We achieved this by identifying the distinguishable 1 H NMR signals of 2nd in imidazole-ring of the resulting 4NI-biothiols in the downfield region at 7-8 ppm and newly discovered induced CD signals within 290-430 nm. Using this probe, the limits of detection of Cys, GSH, and Hcy, the recovery rates, and the concentration of GSH extracted from HEK293T cells were determined by measuring the unique downfield 1 H NMR signals. Moreover, Cys, GSH, and Hcy can be discriminated simultaneously in complicated samples at a pH range of 2-3.5. Furthermore, this probe can also be utilized to sense chiral thiol-drugs., Significance: This method offers a cost-effective and accurate sensing solution for the specific detection of biothiols in complex mixtures, with stereochemical recognition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

(-)-β-Elemene is a primary bioactive compound derived from Curcuma wenyujin and has been widely utilized as an anti-tumor agent for various types of cancer. Due to the inefficiency of plant extraction methods for β-elemene, significant efforts have been directed toward the heterogeneous biosynthesis of β-elemene using microbial cell factories. However, there has been less emphasis on the stereochemical configuration of germacrene A and its rearranged product, β-elemene. In this study, we constructed a yeast cell factory to produce (-)-β-elemene by optimizing the mevalonate pathway and screening for germacrene A synthases (GASs) from both plant and microbial sources. Notably, we discovered that the rearranged products of GASs exhibited different conformations, and only (+)-germacrene A produced by plant-derived GASs could rearrange to form (-)-β-elemene. Building on this discovery, we further investigated the catalytic mechanisms of GASs and developed an efficient catalytic gene module for generating (+)-germacrene A. Ultimately, the engineered yeast produced 1152 mg/L of (-)-β-elemene, marking the highest titer reported in yeast to date. Overall, this work highlights the differences in the stereoconformations of catalytic products between plant- and microbial-derived germacrene A synthases and establishes a foundation for the green and efficient production of β-elemene with a specific stereochemical configuration., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chiral phenyllactic acid (PLA) is a new type of antiseptic agent and a valuable precursor for active ingredients in pharmaceuticals and agrochemicals. In this study, we designed a multi-enzyme cascade that combined stereocomplementary d- and l-lactate dehydrogenases with threonine aldolase, phenylserine dehydratase, and formate dehydrogenase for the one-pot conversion of achiral glycine and benzaldehyde to synthesize d-PLA and l-PLA. To overcome the imbalance of multi-enzymes in a single cell, two enzyme modules, overexpressing four enzymes, were assembled in Escherichia coli cells to construct whole-cell catalysis systems (WCCSs). Furthermore, by optimizing reaction conditions and components, recombinant E. coli (WCCS 26) was able to produce 100 mM d-PLA with >99 % ee using a fed-batch strategy, while E. coli (WCCS 60) produced 47.2 mM l-PLA with >99 % ee. This study presents a sustainable and efficient method for synthesizing chiral PLAs from food-grade achiral starting materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Artificial metalloenzymes, in which a metal complex and protein matrix are combined, have been synthesized to catalyze stereoselective reactions using the chiral environment provided by the protein cavity. Artificial metalloenzymes can be engineered by the chemical modification and mutagenesis of the protein matrix. We developed artificial non-heme metalloenzymes using a cupin superfamily protein (TM1459) with a 4-His tetrad-metal-binding motif. The Cu-bound H52A/C106D mutant with 3-His triad showed a S-enantioselective Michael addition of nitromethane to α,β-unsaturated ketone, 2-aza-chalcone 1. In this study, we demonstrated a chemical modification near the copper-binding site of this mutant to reverse its enantioselectivity. For chemical modification, the amino acid on the Si-face of the binding state of 1 to the copper center was replaced with Cys, followed by reaction with 4,4'-dithiopyridine (4-PDS) to form S-(pyridin-4-ylthio)cysteine (Cys-4py). Cu-bound I49C-4py/H52A/C106D showed reversal of the enantioselectivity from S-form to R-form (ee = 71%, (R)). The effect of steric hindrance of the amino acids at position 49 on enantioselectivity was investigated using I49X/H52A/C106D mutants (X = A, C, I, F, and W). Additionally, chemical modification with 2,2'-dithiopyridine (2-PDS) produced I49-2py/H52A/C106D, which showed lower R-enantioselectivity than I49-4py/H52A/C106D. Among the mutants, the 4py-modification on the Si-face was the most effective in reversing the enantioselectivity. By tuning the Re-face side, the H54A mutation introduced into the I49C-4py/H52A/C106D increased the R-enantioselectivity (ee = 88%, (R)). X-ray crystallography revealed a coordinated structure with ligation of thiopyridine in Cu-bound I49C-4py/H52A/H54A/C106D., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Epoxyeicosatrienoic acids (EETs) are increasingly recognized as key metabolites in the arachidonic acid (AA) metabolic pathway. EETs are epoxy derivatives of AA with two chiral centers formed by cytochrome P450 (CYP) enzymes. EETs have reported biological activities as racemates; however, knowledge on specific optical isomers of EET is lacking. A main reason is the absence of practical assay to quantify EETs isomers associated with specific pathological conditions and enzymes. The reported underivatized chiral LC-MS/MS assays utilize different mobile phases and flow rates or required long run times to achieve separation of EET stereoisomers. Others incorporated a derivatization step before the separation of EETs in their assays. Therefore, the objective of this study was to develop and validate a stereoselective assay for the simultaneous quantitation of underivatized EET enantiomers using Liquid Chromatography Mass Spectrometry (LC-MS/MS) with an optimum baseline separation using binary mobile phase and gradient elution. Herein, we report the development and validation of an LC-MS/MS assay, and its application to quantify the formation of EET enantiomers mediated by human liver microsomes. Assay linearity extends over 10-600 ng/mL with r 2  > 0.99 for all EETs enantiomers. The inter-run accuracy was within ± 15 %, and precision was ≤ 15 %, and < 20 % for the LLOQ. The matrix effect for the current assay was within ≤ ±20 %, and the mean recovery for quantitative methods was 70-125 %. The assay proved to be reliable and practical for chiral analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Metamifop (MET) is a widely used pesticides in paddy field and it has good weed control effect. As a chiral pesticide that may be hazardous to human health through food chain transmission, there could be selective differences in the metabolism and toxicity of its enantiomers, so the study of chiral MET may offer an assessment of MET toxicity and stereoselectivity at the enantiomeric level. A total of 39, 43 and 31 differential metabolites were screened from the data sets of Rac-, R-(-)- and S-(+)-MET, respectively. Metabolic pathway analysis revealed that MET and its enantiomers primarily affected sphingolipid metabolism, glycerophospholipid metabolism, linoleic acid metabolism, α-linolenic acid metabolism and arachidonic acid metabolism. Rac- and S-(+)-MET affected the synthesis of glycosylphosphatidylinositol (GPI)-anchored biomolecules. R-(-)- and S-(+)-MET affected glutathione metabolism. R-(-)-MET affected vitamin B6 metabolism, selenium compound metabolism, and steroid biosynthesis. Pyrimidine metabolism was only affected by Rac-MET. The experimental results indicated that MET and its enantiomers may affect the nervous and immune systems in rats. Further inter-group difference analysis also demonstrated stereoselectivity of MET and its enantiomers on rat serum metabolism. These findings may provide more detailed information on the toxicity of Rac-, S-(+)- and R-(-)-MET in rat, as well as some context for assessing the environmental risk of the three agents to organisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chiral analysis with simple devices is of great importance for analytical chemistry. Based on the photothermal (PT) effect, a simple chiral sensor with a portable laser device as the light source and a thermometer as the detection tool was developed for the chiral recognition of tryptophan (Trp) isomers and the sensitive sensing of one isomer (L-Trp). Gold nanorods (GNRs), which have outstanding photo-thermal conversion ability due to their localized surface plasma resonance (LSPR) effect, are used as PT reagents, and biomacromolecules bovine serum albumin (BSA) are used as natural chiral sources, and thus, GNRs@BSA was obtained through Au-S bonds. The resultant GNRs@BSA displays higher affinity toward L-Trp than D-Trp owing to the inherent chirality of BSA. Under the irradiation of near-infrared (NIR) light, the temperature of GNRs@BSA//L-Trp is greatly lower than that of GNRs@BSA//D-Trp due to its greatly decreased thermal conductivity, and thus chiral discrimination of Trp isomers can be achieved. In addition, the developed PT effect-based chiral sensor can be used for sensitive detection of L-Trp, and the linear range and limit of detection (LOD) are 1 μM-10 mM and 0.43 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chirality plays a crucial function in the regulation of normal physiological processes and is widespread in organisms. Chirality can be imparted to nanomaterials, whether they are natural or manmade, through the process of asymmetric assembly and/or grafting of molecular chiral groups or linkers. Chiral inorganic nanomaterials possess unique physical and chemical features that set them apart from regular nanomaterials. They also have the ability to interact with cells and tissues in a specific manner, making them useful in various biomedical applications, particularly in the treatment of tumors. Despite the growing amount of research on chiral inorganic nanomaterials in the tumor microenvironment (TME) and their promising potential applications, there is a lack of literature that comprehensively summarizes the intricate interactions between chiral inorganic nanomaterials and TME. In this review, we introduce the fundamental concept, classification, synthesis methods, and physicochemical features of chiral inorganic nanomaterials. Next, we briefly outline the components of TME, such as T cells, macrophages, dendritic cells, and weak acids, and then discuss the anti-tumor effects of several chiral inorganic nanoparticles targeting these components and their potential for possible application during cancer therapy. Finally, the present challenges faced by chiral inorganic nanomaterials in cancer treatment and their future areas of investigation are disclosed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Reported herein is the synthesis of benzyl β-d-glucopyranoside and its derivatives that provide straightforward access to 3,4-branched glycans. Modes to diversify the synthetic intermediates via introduction of various temporary protecting groups have been demonstrated., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Stereocontrolled 1,2-trans-α-arabinofuranosylation using polysilylated mono- and disaccharide glycosyl donors was investigated. A complete α-stereoselectivity of 1,2-trans-arabinofuranosylation was found for Ara-β-(1 → 2)-Ara disaccharide glycosyl donors containing five triisopropylsilyl (TIPS) groups with arylthiol (1) (as shown in our previous publications) or N-phenyltrifluoroacetimidoyl (2) (this work) leaving groups. Conversely, in case of monosaccharide thioglycosides polysilylated with acyclic silyl groups (TIPS, TBDPS), stereoselectivity of glycosylation was lower (α:β = 7-8:1), although the desired α-isomer still dominated. Disaccharide glycosyl donor 2 was successfully used in the synthesis of linear α-(1 → 5)-, β-(1 → 2)-linked hexaarabinofuranoside useful for further preparation of conjugates thereof as antigens valuable for the diagnosis of mycobacterioses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Isoiminosugars are highly biological active substances. Herein, we report a concise synthetic approach for this class of compounds. The key step relies on a stereospecific 1,2-hydride shift in O-2 tosylated glycopyranosides leading to C-2 branched glycofuranosides. This approach enables a 4-step synthesis of powerful β-galactosidase inhibitor 4-epi-isofagomine starting from a simple d-glucopyranoside., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Biocatalysis has emerged as a strong tool for the synthesis of active pharmaceutical ingredients (APIs). In the early twentieth century, whole cell biocatalysis was used to develop the first industrial biocatalytic processes, and the precise work of enzymes was unknown. Biocatalysis has evolved over the years into an essential tool for modern, cost-effective, and sustainable pharmaceutical manufacturing. Meanwhile, advances in directed evolution enable the rapid production of process-stable enzymes with broad substrate scope and high selectivity. Large-scale synthetic pathways incorporating biocatalytic critical steps towards >130 APIs of authorized pharmaceuticals and drug prospects are compared in terms of steps, reaction conditions, and scale with the corresponding chemical procedures. This review is designed on the functional group developed during the reaction forming alcohol functional groups. Some important biocatalyst sources, techniques, and challenges are described. A few APIs and their utilization in pharmaceutical drugs are explained here in this review. Biocatalysis has provided shorter, more efficient, and more sustainable alternative pathways toward existing small molecule APIs. Furthermore, non-pharmaceutical applications of biocatalysts are also mentioned and discussed. Finally, this review includes the future outlook and challenges of biocatalysis. In conclusion, Further research and development of promising enzymes are required before they can be used in industry., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the present work, we describe the synthesis of new 1,3,4-thiadiazole derivatives from natural (R)-carvone in three steps including, dichloro-cyclopropanation, a condensation with thiosemicarbazide and then a 1,3-dipolar cycloaddition reaction with various nitrilimines. the targeted compounds were structurally identified by 1 H & 13 C NMR and HRMS analyses. The cytotoxic assay demonstrated that some synthesized novel compounds were potent on certain cancer cell lines. Molecular modeling studies were undertaken to rationalize the wet lab study results. Furthermore, molecular docking was performed to unveil the binding potential of the most active derivatives, 3a and 6c, to caspase-3 and COX-2. The stabilities of the protein-compound complexes obtained from the docking were evaluated using MD simulation. Furthermore, FMO and related parameters of the active compounds and their stereoisomers were examined through DFT studies. The docking study showed compound 6c had a higher binding potential than caspase-3. However, the binding strength of 6c was found to be less than that of the standard drug, doxorubicin, as it formed lower conventional hydrogen bonds. On the other hand, compound 3a had a higher binding potential to COX-2. However, the binding potential 3a was much lower than that of the standard COX-2 inhibitor, celecoxib. The MD simulation demonstrated that the caspase-3-6c complex was less stable than the caspase-3-doxorubicin complex. In contrast, the COX-2-3a complex was stable, and 3a was anticipated to remain inside the protein's binding pocket. The DFT study showed that 3a had higher chemical stability than 6c. The electron exchange capacity, chemical stability, and molecular orbital distributions of the stereoisomers of the active compounds were also found to be alike., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

We describe the synthesis of the full set of the so far unknown methyl altrobiosides and the initial analysis of the conformational dynamic which occurs in some of the synthesized compounds. d-Altrose chemistry has largely been neglected as it is a rare sugar and has first to be synthesized from glucose or mannose, respectively. Nevertheless, d-altrose is particularly interesting as the energy barrier between the complementary chair conformations is rather low and therefore dynamic mixtures of conformers might occur. We describe the ready synthesis of the selectively protected altrosyl acceptors for the glycosidation from d-mannose and the altrosyl-trichloroacetimidate as useful glycosyl donor to achieve the (1 → 2), (1 → 3), (1 → 4), and (1 → 6)-α-linked altrobiosides. The diastereomeric α- and β-O-(d-altropyranosyl)-trichloroacetimidates adopt different ring conformations as analyzed by NMR and VCD spectroscopy. Also, the pyranose ring conformations of the obtained altrobiosides apparently differ from a regular 4 C 1 chair according to NMR analysis and are influenced by the regiochemistry of the interglycosidic linkage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tebuconazole (TEB), a prominent chiral triazole fungicide, has been extensively utilized for plant pathogen control globally. Despite experimental evidence of TEB metabolism in mammals, the enantioselectivity in the biotransformation of R- and S-TEB enantiomers by specific CYP450s remains elusive. In this work, integrated in silico simulations were employed to unveil the binding interactions and enantioselective metabolic fate of TEB enantiomers within human CYP1A2, 2B6, 2E1, and 3A4. Molecular dynamics (MD) simulations clearly delineated the binding specificity of R- and S-TEB to the four CYP450s, crucially determining their differences in metabolic activity and enantioselectivity. The primary driving force for robust ligand binding was identified as van der Waals interactions with CYP450s, particularly involving the hydrophobic residues. Mechanistic insights derived from quantum mechanics/molecular mechanics (QM/MM) calculations established C 2 -methyl hydroxylation as the predominant route of R-/S-TEB metabolism, while C 6 -hydroxylation and triazol epoxidation were deemed kinetically infeasible pathways. Specifically, the resulting hydroxy-R-TEB metabolite primarily originates from R-TEB biotransformation by 1A2, 2E1 and 3A4, whereas hydroxy-S-TEB is preferentially produced by 2B6. These findings significantly contribute to our comprehension of the binding specificity and enantioselective metabolic fate of chiral TEB by CYP450s, potentially informing further research on human health risk assessment associated with TEB exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

An attractive strategy for efficiently forming CS bonds is through the use of diazo compounds SH insertion. However, achieving good enantioselective control in this reaction within a biocatalytic system has proven to be challenging. This study aimed to enhance the activity and enantioselectivity of to enable asymmetric SH insertion. The researchers conducted site-saturation mutagenesis (SSM) on 5 amino acid residues located around the iron carbenoid intermediate within a distance of 5 Å, followed by iterative saturation mutagenesis (ISM) of beneficial mutants. Through this process, the beneficial variant VHb SH (P54R/V98W) was identified through screening with 4-(methylmercapto) phenol as the substrate. This variant exhibited up to 4-fold higher catalytic efficiency and 6-fold higher enantioselectivity compared to the wild-type VHb. Computational studies were also conducted to elucidate the detailed mechanism of this asymmetric SH insertion, explaining how active-site residues accelerate this transformation and provide stereocontrol., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Studies have confirmed that the spatial arrangement of chiral molecules has a decisive influence on supramolecular assembly. However, the effect of epimerization caused by the change of a single chiral center on the self-assembly of chiral molecules has not been reported. Herein, we explored a pair of epimers 18 α-glycyrrhetinic acid and 18 β-glycyrrhetinic acid from Glycyrrhiza uralensis Fisch, which had completely different medicinal activities. In this study, we found that these epimers of glycyrrhetinic acid showed distinct self-assembly properties under the condition of the deionized water and a small amount of DMSO solution. Interestingly, the cis-configured 18 β-GA could form a 'head-to-tail' interlaced structure and further self-assembled to form nanoparticles, while trans-configured 18 α-GA was connected in a "head-to-head" manner, and due to the excessive steric hindrance that made it difficult to assemble. This work not only clearly demonstrates the impact of epimerization due to changes in a single chiral center on the self-assembly of chiral molecules as well as biological activity, but also provides new insights into the self-assembly of natural organic molecules in the development of nanomedicines and biofunctional materials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

DNA hybrid catalysts are constructed by embedding active metal species into the chiral scaffolds of DNA, which have been successfully applied to some important aqueous-phase enantioselective transformations. Owing to simple components and inherent chirality, nucleotide hybrid catalysts are emerging in response to soving the unclear locations of catalytic centers and the plausible catalytic mechanisms in DNA-based asymmetric catalysis. However, the tertiary structure of nucleotides lacks tunability, severely impeding further design of nucleotide hybrid catalysts for potential applications. To this end, a design strategy for tunable nucleotide hybrid catalysts is put forward by introducing metal-mediated base pairs. Herein, we found that the formation of uracil‑mercury(II)-uracil (U-Hg 2+ -U) base pairs could enhance the enantioselectivity in uracil-containing nucleotide-based asymmetric reactions. Compared with uracil triphosphate (UTP) complexing with Cu 2+ ions (UTP∙Cu 2+ ), the presence of Hg 2+ ions gave rise to an increased enantiomeric excess (ee) of 38 % in Diels-Alder reactions and 22 % ee in Michael reactions. The Hg 2+ -tuning behaviors of UTP hybrid catalyst have been demonstrated to largely depend on nucleotides, Hg 2+ concentrations, metal cofactors, additives and reaction types. Based on ultraviolet-visible, circular dichroism and nuclear magnetic resonance spectroscopic techniques, the chiral enhancement of Hg 2+ -containing UTP hybrid catalyst is proved to largely depend on the formation of U-Hg 2+ -U base pairs and the plausible cross-linked structure of UTP-Hg 2+ -UTP/Cu 2+ assembly. This work provides a tunable strategy based on the concept of metal-mediated base pairs, allowing further design of potent oligonucleotide-based catalysts for other enantioselective reactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lysine (Lys) is an essential nutrient that plays a crucial role in the growth and development of living organisms. Chiral analysis of Lys holds significant importance for ensuring the safety of food, pharmaceuticals, and health products. In this work, an achiral Zr-based metal organic frameworks (MOFs), UiO-66-NH 2 , was proposed as a fluorescent probe to achieve rapid response to l-lysine (L-Lys) in solution. Additionally, Zr 4+ in the skeleton of UiO-66-NH 2 framework exhibited different binding capacities towards Lys enantiomers, leading to distinct fluorescence responses for L-Lys and d-lysine (D-Lys). Leveraging these properties, the UiO-66-NH 2 probe enabled accurate determination of L-Lys concentrations in solution, as well as the enantiomeric excess (ee) values of Lys solutions. Notably, in the detection of Lys enantiomers, the achiral UiO-66-NH 2 acted as both a chiral selector and a fluorescent indicator, greatly improving the efficiency and stability of the detection system. The probable mechanism was further elucidated by pH titration experiments and density functional theory calculations. Additionally, the general applicability of this mechanism was validated by similar amino MOFs. The application of the UiO-66-NH 2 fluorescent probe in analysis of infant formula milk powders and liquid milk samples confirmed the reliability of the method. Moreover, the construction of fluorescence test paper by immobilizing UiO-66-NH 2 onto filler papers enabled the rapid identification of Lys enantiomers. Compared to previous fluorescent analyses of chiral amino acids assisted by additional metal ions, this study presented a novel approach and methodology that offers high efficiency, stability, reproducibility and reusability for the identification and detection of Lys enantiomers, highlighting the potential of the UiO-66-NH 2 fluorescent probe in advancing analytical techniques., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, using chiral L-lysine as the molecular skeleton, three kinds of L-lysine-derived gelators (G BLB , G BLF and G FLF ) 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 (G BLB -SiO 2 , G BLF -SiO 2 , and G FLF -SiO 2) 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)