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[Display omitted] An original phenobarbital anticonvulsant Halonal, 5-ethyl-1-(2-fluorobenzoyl)-5-phenylpyrimidine-2,4,6(1 H ,3 H ,5 H)-trione, stimulated the cellular immune and the humoral response in long-term alcoholized male (CBAxC57Bl/6) F1 mice to the level of healthy animals. Voltammetry was found to be suitable for determination of Halonal R / S -enantiomeric ratio, which was exemplified on the authentic sample with the R / S -composition of 40:60. Molecular docking (Schrödinger program, Glide) showed that Halonal behaved as a benzonal derivative interacting with GABA A R via the BARB binding site, with S -Halonal having higher similarity score than its R -enantiomer because of a different orientation of the 2-fluorobenzoyl substituent. [ABSTRACT FROM AUTHOR]

In recent years, incidents of pesticide pollution and abuse of feed additives have occurred frequently, which pose a great threat to human health. Raman spectroscopy has become an important method in the field of food safety due to its rapidity, simplicity and sensitivity. It is important to obtain complex structure to promote surface-enhanced Raman scattering (SERS) effect. In this study, gold helical nanoparticles with rich surface structure were synthesized using cysteine as induce agent. Notably, the complex helical structure and tip led to an excellent electromagnetic enhancement property. The helical structure showed ultra-sensitive detection of hazardous molecular, such as thiram and ractopamine. Interestingly, the D/L-Au structure had significant chiral optical activity and could be used as an unlabeled SERS platform for enantiomer identification. This study provided an effective strategy for the detection of pesticides and feed additives, which could be applied in other aspects of food safety in the future. [Display omitted] • A convenient strategy for preparing Raman substrates was provided. • The gold helix was an excellent Raman substrate. • It could analyze harmful chemical residues in food. • It could recognize amino acid enantiomers and expanded the application range of SERS. [ABSTRACT FROM AUTHOR]

• Chiral materials applied in biosensor applications are reviewed and classified. • The recognition and separation techniques are summarized and discussed. • Various applications of chiral structures are reviewed and discussed. • Different chiral-based biosensor design and synthesis strategies are summarized. • Electrochemically-active chiral molecule biosensors are reviewed. Chirality is a phenomenon commonly observed in biomolecules, which supports various applications such as biosensing, bioimaging, and disease treatments. Chiral molecules and ions are building blocks of advanced materials and technologies enabling intermolecular communication between species competing in receiving, sending, or recognizing chemical scenarios. Therefore, chiral molecules nowadays are at the core of attention in developing sensing materials and devices. A sub-class of stereoisomers known as enantiomers or optical antipodes takes the privilege of chiral structures, supporting distinct optical and electrochemical responses required in sensing and identification applications. Therefore, it is critical to establish a reliable and fast method for chiral identification and separation. Big technological advances have been made in the field of bio-inspired and controlled self-assembly sensing, but there is still a great demand for improving the sensitivity and accuracy of chiral-based biosensors. This review seeks to collect, summarize, classify and discuss the latest advances in chiral-based optical biosensors. Starting from the identification of chiral molecules, photoluminescence, and electrochemical sensors, applications of chiral structures in biosensing molecules are reviewed. Then, biosensors working on the basis of chirality are classified, followed by summarizing the outcomes of research works on design, synthesis, and mechanisms of performances of chiral-based optical biosensors. Electrochemically active molecules are subsequently reviewed, emphasizing molecularly imprinted polymers (MIP), doped electrodeposited conducting polymers, enzymatic chiral sensors, and metal–organic framework (MOF) based chiral molecules applied in biosensing applications. [ABSTRACT FROM AUTHOR]

• Validated assay for arachidonic acid (AA)-underived chiral epoxy-metabolites. • A reliable and reproducible chiral analysis for epoxy-metabolites of AA. • Enantioselective analysis of epoxy-metabolites formed by human liver microsomes. • The assay showed acceptable linearity, precision, and accuracy. 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 r2 > 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. [ABSTRACT FROM AUTHOR]

• This review focuses on terpenoids extracted from essential oils. • Terpenoids have enantiomers with distinct physiological activities. • Predominant extraction methods are HD, SFME, HS-SPME and supercritical fluid. • 2D GC is found to have stronger chiral chromatography resolution ability. • Specific distribution and enantiomer excess results could be used as quality markers. Terpenoids possess significant physiological activities and are rich in essential oils. Some terpenoids have chiral centers and could form enantiomers with distinct physiological activities. Therefore, the extraction and separation of terpenoids enantiomers are very important and have attracted extensive attention in recent years. Meanwhile, the specific distribution and enantiomer excess results (the excess of one enantiomer over the other in a mixture of enantiomers) could be used as quality markers for illegitimate adulteration, origin identification, and exploring component variations and functional interrelations across different plant tissues. In this study, an overview of the progress in the extraction of terpenoids from essential oils and the separation of their enantiomers over the past two decades has been made. Extraction methods were retrieved by the resultant network visualization findings. The results showed that the predominant methods are hydrodistillation, solvent-free microwave extraction, headspace solid-phase microextraction and supercritical fluid extraction methods. GC–MS combined with chiral chromatography columns is commonly used for the separation of enantiomers, while 2D GC is found to have stronger resolution ability. Finally, some prospects for future research directions in the extraction and separation identification of essential oils are proposed. [ABSTRACT FROM AUTHOR]

With exercise, muscle and bone produce factors with beneficial effects on brain, fat, and other organs. Exercise in mice increased fibroblast growth factor 23 (FGF23), urine phosphate, and the muscle metabolite L-β-aminoisobutyric acid (L-BAIBA), suggesting that L-BAIBA may play a role in phosphate metabolism. Here, we show that L-BAIBA increases in serum with exercise and elevates Fgf23 in osteocytes. The D enantiomer, described to be elevated with exercise in humans, can also induce Fgf23 but through a delayed, indirect process via sclerostin. The two enantiomers both signal through the same receptor, Mas-related G-protein-coupled receptor type D, but activate distinct signaling pathways; L-BAIBA increases Fgf23 through Gαs/cAMP/PKA/CBP/β-catenin and Gαq/PKC/CREB, whereas D-BAIBA increases Fgf23 indirectly through sclerostin via Gαi/NF-κB. In vivo , both enantiomers increased Fgf23 in bone in parallel with elevated urinary phosphate excretion. Thus, exercise-induced increases in BAIBA and FGF23 work together to maintain phosphate homeostasis. [Display omitted] • Exercise-induced L-BAIBA correlates with intact FGF23 and urine phosphate in mice • Both L- and D-BAIBA induce Fgf23 in osteocytes in vitro and ex vivo • Both BAIBA enantiomers use the same receptor but activate distinct pathways • Both BAIBA enantiomers increase Fgf23 in bone and urine phosphate in mice Kitase, Bonewald et al. demonstrate that the exercise metabolite BAIBA induces Fgf23 expression in osteocytes through the same receptor but through distinct, enantiomer-specific signaling pathways and molecular mechanisms. [ABSTRACT FROM AUTHOR]

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1 – 7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2 H -pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1 – 7. Compounds (−)- 2 and (+)- 2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC 50 values of 7.07 ± 1.02 μM and 11.39 ± 0.24 μM, respectively. [Display omitted] [ABSTRACT FROM AUTHOR]

The present study investigates the use of dextrins (maltodextrin, β-cyclodextrin, and hydroxypropyl-β-cyclodextrin) to improve the efficiency of the agarose-based gel electromembrane extraction technique for extracting chiral basic drugs (citalopram, hydroxyzine, and cetirizine). Additionally, it examines the enantioselectivity of the extraction process for these drugs. To achieve these, dextrins were incorporated into either the sample solution, the membrane, or the acceptor solution, and then the extraction procedure was performed. Enantiomers were separated and analyzed using a capillary electrophoresis device equipped with a UV detector. The results obtained under the optimal extraction conditions (sample solution pH: 4.0, acceptor solution pH: 2.0, gel membrane pH: 3.0, agarose concentration: 3 % w/v, stirring rate: 1000 rpm, gel thickness: 4.4 mm, extraction voltage: 62.3 V, and extraction time: 32.1 min) indicated that incorporating dextrins into either the sample solution, membrane or the acceptor solution enhances extraction efficiency by 17.3–23.1 %. The most significant increase was observed when hydroxypropyl-β-cyclodextrin was added to the acceptor solution. The findings indicated that the inclusion of hydroxypropyl-β-cyclodextrin in the sample solution resulted in an enantioselective extraction, yielding an enantiomeric excess of 6.42–7.14 %. The proposed method showed a linear range of 5.0–2000 ng/mL for enantiomers of model drugs. The limit of detection and limit of quantification for all enantiomers were found to be < 4.5 ng/mL and <15.0 ng/mL, respectively. Intra- and inter-day RSDs (n = 4) were less than 10.8 %, and the relative errors were less than 3.2 % for all the enantiomers. Finally, the developed method was successfully applied to determine concentrations of enantiomers in a urine sample with relative recoveries of 96.8–99.2 %, indicating good reliability of the developed method. [Display omitted] • Dextrin-assisted gel electromembrane extraction was developed. • The effect of dextrins on enantioselective extraction was investigated. • Addition of maltodextrin to the sample solution increased the extraction efficiency. • Including HP-β-CD in the acceptor solution resulted in increased extraction efficiency. • Addition of HP-β-CD to the sample solution led to an enantioselective extraction. [ABSTRACT FROM AUTHOR]

Background: Non-racemic amisulpride (SEP-4199) is an 85:15 ratio of aramisulpride:esamisulpride with a 5-HT7 and D2 receptor binding profile optimized for the treatment of bipolar depression. The aim of this study was to evaluate the efficacy and safety of SEP-4199 for the treatment of bipolar depression.Methods: Patients meeting DSM-5 criteria for bipolar I depression were randomized to 6 weeks of double-blind, placebo-controlled treatment with SEP-4199 200 mg/d or 400 mg/d. The primary endpoint was change in the Montgomery-Asberg Depression Rating Scale (MADRS) at Week 6. The primary efficacy analysis population consisted of patients in Europe and US (n = 289); the secondary efficacy analysis population (ITT; n = 337) included patients in Japan.Results: Endpoint improvement in MADRS total score was observed on both the primary analysis for SEP-4199 200 mg/d (P = 0.054; effect size [ES], 0.31) and 400 mg/d (P = 0.054; ES, 0.29), and on the secondary (full ITT) analysis for SEP-4199 200 mg/d (P = 0.016; ES, 0.34) and 400 mg/d (P = 0.024; ES, 0.31). Study completion rates were 81% on SEP-4199 200 mg/d, 88% on 400 mg/d, and 86% on placebo. SEP-4199 had low rates of individual adverse events (<8%) and minimal effects on weight and lipids; median increases in prolactin were +83.6 μg/L on 200 mg/d, +95.2 μg/L on 400 mg/d compared with 0.0 μg/L on placebo.Limitations: The study excluded patients with bipolar II depression and serious psychiatric or medical comorbidity.Conclusion: Study results provide preliminary proof of concept, needing confirmation in subsequent randomized trials, for the efficacy of non-racemic amisulpride in bipolar depression. [ABSTRACT FROM AUTHOR]

Naturally occurring DNA, RNA, and proteins predominantly exist in only one enantiomeric form (homochirality). Advances in biotechnology and chemical synthesis allow the production of the respective alternate enantiomeric form, enabling access to mirror-image versions of these natural biopolymers. Exploiting the unique properties of such mirror molecules has already led to many applications, such as biostable and nonimmunogenic therapeutics or sensors. However, a 'roadblock' for unlocking the mirror world is the lack of biological systems capable of synthesizing critical building blocks including mirror oligonucleotides and oligopeptides to reducing cost and improve purity. Here, we provide an overview of the current progress, applications, and challenges of the molecular mirror world by identifying milestones towards mirroring life. In nature, DNA, RNA, and proteins exist in just one of two possible enantiomeric forms. The respective mirror image forms of DNA, RNA, and proteins are inert to natural enzymes, resulting in a multitude of promising applications in medicine and biotechnology. Although progress has been made with respect to the chemical synthesis of mirror proteins, the efficient generation of mirror proteins in sufficient purity and quantity is still a limiting factor for accessing the mirror world. Mirror versions of the required biomolecular machinery need to be accessible for the efficient synthesis of mirror biopolymers and their assembly into functional devices. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two undescribed secondary metabolites were isolated from endophytic fungus Stagonosporopsis oculihominis. • (±)-Stagonosporopsin A is a pair of enantiomer. • Stagonosporopsin C exhibited moderate inhibitory activity against Staphylococcus aureus subsp. aureus ATCC29213. A successive investigation of the endophytic fungus Stagonosporopsis oculihominis isolated from Dendrobium huoshanense led to the discovery of two undescribed secondary metabolites, (±)-stagonosporopsin A and stagonosporopsin B, and a new natural product, stagonosporopsin C. (±)-stagonosporopsin A is a pair of enantiomer. The structures of the isolated compounds, including their absolute configurations, were elucidated based on extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations and X -ray diffraction. Stagonosporopsin C exhibited moderate inhibitory activity against Staphylococcus aureus subsp. aureus ATCC29213 with an MIC 50 value of 41.3 μ M. [ABSTRACT FROM AUTHOR]

Human fatty acid synthase (FASN) is the sole cytosolic enzyme responsible for de novo lipid synthesis. FASN is essential for cancer cell survival and contributes to drug and radiation resistance by up-regulating DNA damage repair but not required for most non-lipogenic tissues. Thus, FASN is an attractive target for drug discovery. However, despite decades of effort in targeting FASN, no FASN inhibitors have been approved due to poor pharmacokinetics or toxicities. Here, we show that the FDA-approved proton pump inhibitors (PPIs) effectively inhibit FASN and suppress breast cancer cell survival. PPI inhibition of FASN leads to suppression of non-homologous end joining repair of DNA damages by reducing FASN-mediated PARP1 expression, resulting in apoptosis from oxidative DNA damages and sensitization of cellular resistance to doxorubicin and ionizing radiation. Mining electronic medical records of 6754 breast cancer patients showed that PPI usage significantly increased overall survival and reduced disease recurrence of these patients. Hence, PPIs may be repurposed as anticancer drugs for breast cancer treatments by targeting FASN to overcome drug and radiation resistance. [ABSTRACT FROM AUTHOR]

• A chiral ATPS was constructed using 4-arm PEG-DHAA as a phase-forming polymer and chiral selector. • Propranolol enantiomers were separated through liquid–liquid enantioselective extraction via the chiral ATPS. • The chiral ATPS can be reused, with potency in enantiomeric recognition and liquid–liquid enantioselective extraction. In this work, we successfully synthesized a chiral dehydroabietic acid-terminated tetra-arm PEG (4-arm PEG-DHAA) and utilized it to construct a chiral aqueous two-phase system (ATPS) alongside PEG2000 and (NH 4) 2 SO 4. The 4-arm PEG-DHAA served as both an assisted phase-forming polymer and a chiral selector. This ATPS can be employed for chiral recognition and liquid–liquid enantioselective extraction of the propranolol enantiomers. The effects of four primary factors, namely initial r ac-propranolol concentration, extraction temperature, system pH, and the concentration of 4-arm PEG-DHAA on enantioseparation, were thoroughly evaluated. Furthermore, the optimization of extraction conditions was conducted using the response surface methodology. The results indicated that the chiral ATPS has better and higher enantioselectivity, with a one-step chiral extraction achieving an e.e. up to 57% and a yield exceeding 73% for S-isomers under the optimized conditions. In addition, the chiral ATPS can be regenerated through simple back-extraction with diethyl ether and reused at least five times, achieving similar enantioselective extraction results. This research presents a valuable enantioseparation approach for propranolol enantiomers via liquid–liquid enantioselective extraction using the chiral ATPS. [ABSTRACT FROM AUTHOR]

Phenylalanine is an aromatic essential amino acid that exhibits the tendency to self-aggregate into fibrillar structures in its enantiomerically pure form. This observation was indicated as the underlying mechanism of phenylketonuria, which is a genetic condition associated with various neurological, physical, and developmental issues, characterized with phenylalanine buildup in the brain. The presence of D-phenylalanine was demonstrated previously to inhibit the formation of fibrils by L-phenlyalanine, indicating its potential use in phenylketonuria treatment. In this study, several combinations of D and L-phenylalanine were examined with the help of state-of-the-art deep learning methods for their fibril forming capacity, demonstrating the usefulness and accuracy of deep learning methods in distinguishing between different self-assembled structures. • This study addressed the classification of D- and L-phenylalanine images. • A total of 525 images for 7 different mixing ratios were collected with a Nikon ECLIPSE LV150N microscope at 500x. • An accuracy value of 99% was obtained by using deep learning models for classification. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel ELLME was established based on the principle of emulsification dilution. • ELLME is a non-toxic alternative to DLLME. • O/W emulsion prepared by pipette was added to samples to complete extraction in 1 s. • Rapid separation of extractant was achieved without using a centrifuge. • Chiral prothioconazole and its chiral metabolite were detected in food samples. Emulsive liquid–liquid microextraction (ELLME), a simple, rapid, and environmentally friendly technique, was established to identify chiral prothioconazole and its chiral metabolite in water, juice, tea, and vinegar using ultra-high-performance liquid chromatography (UPLC). Environmentally friendly extractant was mixed with pure water to prepare a high-concentration emulsion, which was added to samples to complete the emulsification and extraction in 1 s. Afterward, an electrolyte solution was added to complete the demulsification without centrifugation. ELLME did not use dispersants compared to the familiar dispersive liquid–liquid microextraction (DLLME), thus reducing the use of toxic solvents and avoiding the effect of dispersants on the partition coefficient. The linear range was from 0.01 to 1 mg/L. The limit of detection was 0.003 mg/L. The extraction recoveries ranged from 82.4 % to 101.6 %, with relative standard deviations of 0.7–5.2 %. The ELLME method developed has the potential to serve as an alternative to DLLME. [ABSTRACT FROM AUTHOR]

[Display omitted] • Innovative synthesis approach for the creation of molecularly imprinted GO/Fe 3 O 4 composites. • The synthesized MIP-GO/Fe 3 O 4 for advanced chiral amino acids separation. • The developed material demonstrates high selectivity with enantiomeric excess (%ee) of 97.86% • The materialshas a good stability and reusability. Enantiomeric compounds have been reported to exhibit different biological and pharmacological activities. MIP-GO/Fe 3 O 4 has been synthesized with L-glutamic acid (L-Glu) as template molecules and developed to separate amino acids enantiomeric compounds (AAs) especially for DL-glutamic acid (DL-Glu). The MIP-GO/Fe 3 O 4 adsorbent material was synthesized in several stages, namely electrochemically synthesizing GO, co-precipitation for GO/Fe 3 O 4 , and surface imprinting polymerization to obtain MIP-GO/Fe 3 O 4. The characterization results of MIP-GO/Fe 3 O 4 show that the composite system has been successfully created with saturation magnetization (Ms) values of 49.37 emu/g. Adsorption tests are carried out on the racemic mixture of DL-Glu and show that the material worked effectively and selectively to separate D- and L-Glu with a %ee value of 97.86 % and an adsorption capacity for L of 9.9 mg g−1 on optimum conditions. In addition, the adsorbent developed shows good reusability values with a decreasing performance of no more than 2.0 % after 10-time use cycles and is easily separated in less than 15 s. This research contributes to developing advanced materials with extraordinary selectivity and efficiency, paving the way for advances in enantiomer separation technology. [ABSTRACT FROM AUTHOR]

• An easy-to-use LC–MS method to quantify racemic MDMA and MDA was developed. • An enantioselective LC–MS method for MDMA and MDA was developed using a chiral column. • Both bioanalytical methods allow sensitive and rapid sample measurement. • Chiral pharmacokinetics were assessed in subjects dosed with MDMA or its enantiomer. 3,4-Methylenedioxymethamphetamine (MDMA) is an entactogen with therapeutic potential. The two enantiomers of MDMA differ regarding their pharmacokinetics and pharmacodynamics but the chiral pharmacology of MDMA needs further study in clinical trials. Here, an achiral and an enantioselective high performance liquid chromatography–tandem mass spectrometry method for the quantification of MDMA and its psychoactive phase I metabolite 3,4-methylenedioxyamphetamine (MDA) in human plasma were developed and validated. The analytes were detected by positive electrospray ionization followed by multiple reaction monitoring. The calibration range was 0.5–500 ng/mL for the achiral analysis of both analytes, 0.5–1,000 ng/mL for chiral MDMA analysis, and 1–1,000 ng/mL for chiral MDA analysis. Accuracy, precision, selectivity, and sensitivity of both bioanalytical methods were in accordance with regulatory guidelines. Furthermore, accuracy and precision of the enantioselective method were maintained when racemic calibrations were used to measure quality control samples containing only one of the enantiomers. Likewise, enantiomeric calibrations could be used to reliably quantify enantiomers in racemic samples. The achiral and enantioselective methods were employed to assess pharmacokinetic parameters in clinical study participants treated with racemic MDMA or one of its enantiomers. The pharmacokinetic parameters assessed with both bioanalytical methods were comparable. In conclusion, the enantioselective method is useful for the simultaneous quantification of both enantiomers in subjects treated with racemic MDMA. However, as MDMA and MDA do not undergo chiral inversion, enantioselective separation is not necessary in subjects treated with only one of the enantiomers. [ABSTRACT FROM AUTHOR]

In Korea and China, ilaprazole is a widely used proton pump inhibitor in the treatment of gastric ulcers. In this study, a specific and sensitive LC-MS/MS method has been developed and validated for the quantification of ilaprazole enantiomers in the rat plasma, using R -lansoprazole as the internal standard. The enantioseparation was achieved on a CHIRALPAK AS-RH column (4.6 mm × 150 mm, i.d. 5 μm), with a mobile phase composed of 10 mM ammonium acetate aqueous solution and acetonitrile (60:40, V/V), at a flow-rate of 0.5 mL/min. The method was validated over the concentration range of 0.5–300 ng/mL for both, R - and S -ilaprazole. The lower limit of quantification was 0.5 ng/mL for both enantiomers. The relative standard deviation (RSD) of intra- and inter-day precision of R -ilaprazole and S -ilaprazole was less than 10.9%, and the relative error accuracy (RE) ranged from −0.5%–2.0%. Finally, the method was successfully evaluated in rats in a stereoselective pharmacokinetic study of the ilaprazole racemate. Image 1 • The enantioseparation of ilaprazole enantiomers was achieved on Chiralpak AS-RH column. • The LC-MS/MS was specific and sensitive. • The PK profiles of ilaprazole enantiomers showed significant difference. [ABSTRACT FROM AUTHOR]

• High-pressure melting behavior of 3 chiral mandelic acid derivatives is presented. • 10−20 °C melting point depressions were observed at 16 MPa and 20 MPa CO 2 pressure. • The Schröder–van Laar and Prigogine–Defay equations are applicable at high-pressure. • The compounds' chiral eutectic composition remained unaffected by carbon dioxide. Chiral molecules pose great research potential related to their wide applications in various industries due to the different biological effects of enantiomers. Chiral temperature-composition (melting) phase diagrams are widely available for atmospheric pressure, and those are frequently applied to predict the maximal efficiency of enantioseparation. However, self-disproportionation of enantiomers has already been observed in gas antisolvent fractionation as well. Here, we present the first chiral temperature-composition phase diagrams under carbon dioxide pressure. Chiral temperature-composition phase diagrams of 2-, 3- and 4-chloromandelic acids were determined experimentally. High pressure differential scanning calorimetry and the visual first and last melting point method were used simultaneously to determine the temperature-composition phase diagrams of the compounds. Results were compared to the atmospheric phase diagrams. At 16 and 20 MPa pressures modest melting point depressions of 10−18 °C were observed for any enantiomeric compositions, while the eutectic composition remained practically unaffected. The Schröder–van Laar and Prigogine–Defay equations, widely accepted for the prediction of atmospheric temperature-composition phase diagrams of enantiomeric mixtures, were proved to be applicable also in the presence of a soluble pressurized gas. [ABSTRACT FROM AUTHOR]

Investigation on the chemical constituents of Artemisia scoparia resulted in the isolation of sixteen compounds, including undescribed six pairs of diprenylated phenolic enantiomers (±)-scopacoumaricin A-F, and two pairs of cis-trans isomers cis / trans -scopacoumaricin G and cis/trans -artepillin A. Trans -artepillin A was obtained from this plant for the first time. The structures of the isolates were proposed by analysis of their 1D, 2D-NMR and HRESIMS spectroscopic data. Their absolute configurations were determined by comparison of their experimental and calculated electronic circular dichroism spectra. Evaluations of the anti-inflammatory activity revealed that (−)-scopacoumaricin D, (+)-scopacoumaricin F and cis -scopacoumaricin G showed moderate anti-inflammatory activity on lipopolysaccharide-induced nitric oxide production in RAW264.7 cell. Sixteen compounds, including six pairs of diprenylated phenolic enantiomers and two pairs of cis - trans isomers, were isolated and identified from Artemisia scoparia. 1a/1b-6a/6b , 7 – 9 were previously undescribed, and 10 was obtained from A. scoparia for the first time. Anti-inflammatory activity and cytotoxicity of the isolates were studied. [Display omitted] • Fifteen undescribed diprenylated phenolic isomers were identified from A. Scoparia. • Structures were determined by extensive spectroscopic analyses. • Anti-Inflammatory and cytotoxicity of the isolates were tested. [ABSTRACT FROM AUTHOR]

This study aimed to assess the comparative bioavailability between ibuprofen acid orodispersible tablets (Test product) and ibuprofen acid oral tablets (Reference product). This was a randomized, single-dose, 3-way crossover, open-label, pharmacokinetic study in 36 healthy male and female volunteers. Blood samples were taken periodically over a 12-h period after dosing to derive total plasma ibuprofen and S(+)/R(−) ibuprofen enantiomer pharmacokinetic parameters; safety profile and tolerability were evaluated throughout the study. After a single-dose administration of ibuprofen acid oral tablets (2 × 200 mg), the total ibuprofen C max and AUC 0–t (geometric least square [LS] mean) for the Test product was 29.4 μg/mL and 100.6 h/μg/mL, respectively, and for the Reference product it was 30.6 μg/mL and 98.7 h/μg/mL. The geometric LS mean Test/Reference ratio 90% CI for both total ibuprofen C max (90.71–101.77) and AUC 0-t (98.72–105.23) was contained entirely within the predefined 80.00%–125.00% lower and upper limits; in addition, no statistically significant difference was found in T max (P = 0.1819) after fasted administration of the Test and Reference products. There were 4 mild treatment emergent adverse events, considered unrelated to the study drug, reported by 2 volunteers during the study; no serious adverse events, no suspected unexpected serious adverse events. and no clinically significant changes in laboratory safety, vital signs, or 12-lead ECG measurements were reported. The enantiomer-specific analysis mirrored that of total ibuprofen, with the C max and AUC 0–t LS mean Test/Reference ratio 90% CI for both ibuprofen S(+) and R(−) enantiomers contained entirely within the predetermined 80%–125.00% limits. This study found that ibuprofen acid 200 mg orodispersible tablets and ibuprofen acid 200 mg tablets met the regulatory criteria for bioequivalence for AUC 0–t and C max. Post hoc analysis of ibuprofen both S(+) and R(−) enantiomers mirrored the findings for total ibuprofen. All investigational products were found to be well tolerated. Clinicaltrials.gov identifier: NCT03180879. Image 1 [ABSTRACT FROM AUTHOR]

Hexabromocyclododecane (HBCD), a commonly used flame retardant, causes public concern due to its potential negative effects on organisms. Microplastics are suspected to contain certain amounts of HBCD. Wastewater treatment plants (WWTPs) are believed to be one of the largest sources of microplastics and a sink for micropollutants, providing opportunities for interactions between them, especially for hydrophobic micropollutants such as HBCD. There is a lack of studies focusing on the prevalence of microplastics and HBCD they carry. The present study investigated two typical WWTPs in Hong Kong, Stonecutters Island WWTP (SCI) and Shek Wu Hui WWTP (SWH), which employ different treatment technologies. The abundance of microplastics decreased with the treatment flow, and the microplastic concentrations in effluent were at intermediate levels (0.40 and 0.27particles/L) compared with the levels reported in previous studies. The concentrations of HBCD transported by microplastics reached 4184.4 ng/g in the effluent, whereas that in sewage water (dissolved phase) was 0.8 pg/L. For microplastics, 7.32 × 107 and 2.24 × 107 particles per day were estimated to be released from SCI and SWH, respectively into the environment; the release of HBCD carried by microplastics potentially reached 15.5 g per day, whereas the dissolved HBCD in the effluent may reach 0.067 g per day. A preliminary risk assessment of HBCD transported by microplastics showed that HBCD posed negligible risk; nevertheless, attention should be paid to the continual discharge of microplastics from WWTPs. Unlabelled Image • The removal efficiencies varied among different shapes of microplastics. • HBCD was detected from microplastics collected in the WWTPs in Hong Kong. • The enantiomeric patterns of HBCD differed between microplastics and sewage. • HBCD carried by microplastics posed negligible risk. [ABSTRACT FROM AUTHOR]

• Enantiomeric change of chiral BFRs in wastewater treatment processes was observed. • Seasonal fate of chiral BFRs from various wastewater treatments was compared. • Secondary treatment yielded higher removals of HBCD and TBECH. • Biodegradation and preferential sorption of γ -HBCD and β -TBECH may occur. • Sludge sorption may help the elimination of (+)- α - and (+)- γ -HBCD and E 2 - β -TBECH. This study investigated the occurrence and fate of 1,2,5,6,9,10-hexabromocyclododecane (HBCD) and 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH), two chiral brominated flame retardants (BFRs) with sixteen different stereoisomers, in four Hong Kong wastewater treatment plants (WWTPs) featuring diverse treatment processes during a two-year sampling campaign. More effective HBCD removal was achieved via biodegradation as compared to sludge sorption, whereas both chemically enhanced primary treatment and secondary treatment yielded high TBECH elimination (>90%). α -HBCD (54–75%) predominated in all samples, and its proportions were increased in effluent as compared to influent and sludge. α - and β -TBECH (72.3–84.4% in total) were the predominant TBECH diastereomers, with a proportional shift from the latter to the former diastereomer mostly observed after treatment. More rapid biodegradation and preferential sorption of γ -HBCD as compared to α -HBCD as well as β -TBECH as compared to α -TBECH might account for this changing pattern. This is the first study to report the enantiomer-specific behavior of chiral BFRs in different wastewater treatment processes. A preferential elimination of (+)- α - and (+)- γ -HBCD and E 2 - β -TBECH (the second enantiomeric elution order) took place consistently after biological treatment, possibly due to enantioselective adsorption and microbial degradation. Our results highlight the importance of conducting enantiospecific analysis for chiral pollutants in wastewater samples. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The long acting anti-coagulant brodifacoum has 4 isomers, however their relative toxicities are not known. • HPLC was used to obtain 2 pairs of BDF diastereomers. • In adult male rats BDF-cis diastereomers are more toxic than the BDF-trans forms. • BDF-cis has a longer half-life than BDF-trans, which could contribute to increased toxicity. Abstract Brodifacoum (BDF) is a potent, long-acting anticoagulant rodenticide that can cause fatal poisoning in humans. The chemical structure of BDF includes 2 chiral carbons, resulting in 2 pairs of diastereomers, BDF-cis (R/S and S/R) and BDF-trans (R/R and S/S). However, the relative potency of these molecules is not known. The purpose of this study was to compare the in vitro and in vivo toxic effects of the 2 BDF diastereomer pairs. In adult Sprague-Dawley rats BDF-cis was significantly more toxic than BDF-trans (LD 50 values of 219 versus 316 μg/kg, respectively) while racemic BDF had intermediate potency (266 μg/kg). In adult New Zealand white rabbits, BDF-cis had a longer half-life than BDF-trans which could contribute to its observed increased toxicity. Lastly, BDF-cis (10 μM), but not BDF-trans, damaged cultured SH-SY5Y human neuroblastoma cells by attenuating mitochondrial reductive capacity. Taken together, these data suggest that different toxic manifestations of BDF poisoning in mammals could be attributed, in part, to differences in relative enantiomer concentrations present in racemic formulations of this commercially-available toxicant. [ABSTRACT FROM AUTHOR]

Highlights • LC/MS/MS method for determining the enantiomers of α-lipoic acid in human urine. • Urine samples of six healthy volunteers were collected. • Oasis® MAX cartridge was able to remove many contaminants in urine sample. • Each enantiomer was affected by some pharmacokinetic effects in vivo. Abstract An analytical method for the enantiomeric determination of α-lipoic acid in human urine was developed to evaluate the pharmacokinetics of α-lipoic acid, an ingredient in health food. Urine samples were collected over time after administering α-lipoic acid dietary supplement to healthy subjects. The samples were cleaned up by solid-phase extraction using an Oasis® MAX cartridge. In the LC/MS/MS method, CHIRALPAK AD-3R was used as the chiral separation column and acetonitrile-methanol-formic acid (10 mM) (25:25:50, v/v/v) was used as the mobile phase. 13C 4 1,2,5,6- d - l -α-Lipoic acid was used as the internal standard. MS/MS was performed by electrospray ionization (ESI) in the negative ion mode using two monitoring ion transitions (m/z 205.0 → 170.9 and m/z 209.0 → 174.9). A calibration curve was prepared in the concentration range of 0.5–100 ng/mL for each enantiomer (r > 0.9999). The limit of detection (LOD, S/N = 3) and the limit of quantification (LOQ, S/N > 10) were 0.1 ng/mL and 0.5 ng/mL, respectively. The intra-day and inter-day accuracy of α-lipoic acid enantiomers at the LOQ level (0.5 ng/mL), the low concentration level (5 ng/mL), the middle concentration level (50 ng/mL), and the high concentration level (100 ng/mL) ranged from 93.7 to 103.1%. The intra-day and inter-day precision were ≦ 6.94% and ≦ 7.05%, respectively. Calculating the mean values of pharmacokinetic parameters revealed that the AUC and C max values of d -α-lipoic acid were statistically significantly higher than those of l -α-lipoic acid (p < 0.05). It was suggested that l -α-lipoic acid is more bioavailable than d -α-lipoic acid despite individual differences in excretion rate. [ABSTRACT FROM AUTHOR]

Abstract Acetochlor (ACT) is a chiral chloroacetamide pesticide that has been heavily used around the world, resulting in its residues being frequently found in surface waters. It has been reported that ACT is an endocrine disrupting chemical (EDC) with strong thyroid hormone-disrupting activity in aquatic organisms. However, the enantioselectivity underlying thyroid disruption has yet to be understood. In this study, using a zebrafish embryo-larvae model, the enantioselective thyroid disruption of ACT was investigated at a series of environmentally relevant concentrations (1, 2, 10 and 50 μg/L). Our results showed that both racemic ACT and its enantiomers significantly increased the malformation rates of embryos at 72 h postfertilization (hpf). Decreased thyroxine (T 4) contents and increased triiodothyronine (T 3) contents were found in larvae at 120 hpf, with (+)- S -ACT exhibiting a greater effect than (−)- R -enantiomer. Similarly, (+)- S -ACT also showed a stronger effect on the mRNA expressions of thyroid hormone receptors (TR α and TR β), deiodinase2 (Dio2) and thyroid-stimulating hormone- β (TSH β) genes. The observed enantioselectivity in TR expressions was consistent with that of in silico binding analysis, which suggested that (+)- S -enantiomer binds more potently to the TRs than (−)- R -enantiomer. In general, ACT enantiomers showed different influences on the secretion of THs, expression of TH-related key genes and binding affinity to TRs. Considering the different toxicity of different enantiomers, our study highlights the importance of enantioselectivity in understanding of thyroid disruption effects of chiral pesticides. Graphical abstract Unlabelled Image Highlights • (+)- S -acetochlor had stronger thyroid disruptive effect in zebrafish larva. • Acetochlor exposure increased T3 contents and decreased T4 contents. • (+)- S -acetochlor could induce developmental toxicity at 2 μg/L. [ABSTRACT FROM AUTHOR]

Abstract New water soluble and optically active cyclopentadienyl titanium derivatives [(η5-C 5 H 5) 2 Ti{(1 R, 4 S)-ĸON,(R)NH}Cl] (R = Bn (Benzyl) 1a ', 2-pic (2-picolylamine) 1b ') have been synthesized. The novel compounds along with those previously described [(η5-C 5 H 5) 2 Ti{(1 S, 4 R)-ĸON,(R)NH}Cl] (R = Bn 1a , 2-pic 1b) were evaluated by polarimetry, ultra-violet and circular dichroism spectroscopy. The structure of 1b was determined by single crystal X-ray crystallography and showed a unique terminal monohapto Ti O disposition of the oximato ligand. All enantiomers have been tested against several cancer cell lines in vitro : prostate PC-3 and DU-145, lung A-549, pancreas MiaPaca-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. In addition, 1a , 1b and 1b ' were tested against non-tumorigenic prostate RWPE-1 cell line. After 24 h of incubation, 1b and 1b ' were moderately active against Jurkat and A-549 cells. The anti-proliferative effect of titanium compounds on prostate PC-3, DU-145 and RWPE-1 cell lines was also assessed after 72 h of drug exposure. The cytotoxic profile of the enantiomers was similar, exception made for the PC-3 cells, with S,R- isomers exhibiting cytotoxicities 2 to 3 times higher than R,S -compounds. Under these conditions, derivative 1b showed calculated IC 50 values better than those of Tacke's Titanocene-Y (bis-[(p -methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride) on both the prostate PC-3 and DU-145 cells. 1a and 1b cytotoxic behaviour shows certain selectiveness, with activities 2–4 times lower on normal prostate RWPE-1 than on cancer PC-3 cells. Furthermore, 1b produces higher cytotoxicity on prostate PC-3, DU-145 and RWPE-1 cells than the additive dose of titanocene dichloride and pro-ligand b·HCl. Additionally, compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, which suggest that these metal complexes and/or their hydrolysis products bind DNA either in the minor groove or externally. Graphical abstract Image 1 Highlights • Synthesis of novel enantiopure titanocene amino-oximato compounds is reported. • The X-ray crystal structure of one of the compounds shows a unique monohapto Ti-ON coordination. • One enantiomer shows IC 50 values lower than Titanocene-Y on both PC-3 and DU-145 cells. • One enantiomer is more active than additive doses of Ti(η5-C 5 H 5)Cl 2 and oxime pro-ligand. [ABSTRACT FROM AUTHOR]

Abstract Concern about the presence of chiral pharmaceuticals in the environment from wastewater discharge is mounting. In this work, the occurrence and fate of atenolol, metoprolol, venlafaxine, and chloramphenicol, including 10 different stereoisomers, were investigated in sewage and sludge from diverse treatment processes in 4 sewage treatment plants (STPs) in Hong Kong via 4 sampling campaigns over a period of 2 years. The average amounts of individual pharmaceuticals entering the STPs ranged from 4.91 g/d to 6290 g/d, with sludge carrying much lower amounts than the discharged effluent. Mass balance analysis revealed that: larger quantities of these pharmaceuticals were released during the dry seasons, biodegradation was the primary removal mechanism for atenolol and chloramphenicol, and the removal via primary sedimentation and disinfection processes was insignificant (<30%). Selectivity toward R -(+)-atenolol, S -(−)-metoprolol, and R -(−)-venlafaxine was mostly found across secondary-treated effluent samples. Sold as an enantiopure pharmaceutical in R , R - para -form, chloramphenicol was preferentially eliminated after biological process. This is the first study on the occurrence of chloramphenicol enantiomers in the aquatic environment. Ecotoxicological assessment indicated that atenolol and metoprolol could pose risks to marine fish in effluent-receiving waters (i.e., the western waters and Victoria Harbor) of Hong Kong, while R -(+)-atenolol could pose a risk to protozoans five times higher than the S -(−)-enantiomer. Graphical abstract Image 1 Highlights • The fates of chiral pharmaceuticals after various sewage treatments were compared. • Secondary treatment enriched (+)-atenolol, (−)-metoprolol, and (−)-venlafaxine. • Biological process resulted in the selective elimination of R , R -chloramphenicol. • This is the first study on enantiomeric chloramphenicol in aquatic environments. • An excess of (+)-atenolol could pose a risk to protozoans in receiving waters. [ABSTRACT FROM AUTHOR]

Highlights • Review of recent publications in the field of bioanalysis. • Enantioselective chromatography using supercritical fluids as mobile phase constituents (SFC). • Method development in bioanalytical SFC with strongest impact of chiral stationary phases for success. • Method validation showing fitness for purpose in routine applications. Abstract This review covers literature investigating methods for enantioselective chromatography using supercritical fluids as mobile phase constituents (SFC) in the field of bioanalysis. It provides an overview on method development and screening approaches published in scientific literature 2014-2018. Chiral stationary phases are used to create a chiral environment that allows for discrimination of enantiomers. Especially polysaccharide-based stationary phases are used in methods of recent investigations. In comparison to HPLC chiral SFC separation provides more selective cavity effects of inclusion-type chiral separation phases. Modifier and additive choices as well as further operating conditions like backpressure, temperature and flow rate are summarized and critically discussed. Further on, observed sample pretreatment and possible detection techniques are presented. SFC hyphenated to mass detection was found of major relevance and is therefore further discussed. Coupling of SFC with different detectors allows for straightforward use in bioanalysis. Interfacing MS detectors is generally performed including a make-up pump. Thus, applied make-up conditions were also reviewed. While most of the chiral separations in HPLC are performed in normal phase mode, and thus, challenge MS hyphenation, SFC-MS hyphenation can be easily achieved. This allows for convenient application in chiral trace analyses, often required in bioanalysis. Even worse in enantioseparation than in achiral chromatography, method development in SFC suffers from a lack of knowledge in separation mechanisms and thus approaches are often quite unique and most often achieved by screening using a One-Factor-at-a-Time (OFAT) design. Broad screening experiments with methodical approaches still appear as method of choice for now. [ABSTRACT FROM AUTHOR]

Abstract Chiral pesticides can exert stereospecific toxicity in contaminated environmental compartments. Therefore, measuring pesticides at the enantiomeric level is essential to assess the risk posed to exposed organisms, including humans. In recent years, there has been rapid progress on the development and application of stereoselective liquid chromatography–tandem mass spectrometry (LC–MS/MS) methodologies for monitoring pesticides in the environment. Coupling chiral LC separations with MS/MS detection enables trace enantiomeric determination of pesticides in complex environmental matrices. The intent of this review is to provide an up-to-date synopsis on recent advances of stereoselective LC–MS/MS methodologies for pesticide analysis. Key aspects of these methodologies discussed include sample storage and extraction method, stationary phases for separation, multi-residue separations, and method of quantitation. Finally, future trends in this rapidly growing field of analytical chemistry research are outlined. Highlights • Progress on development of stereoselective LC–MS/MS pesticide methods reviewed. • Possible enantiomer changes by (a)biotic processes during sample storage overlooked. • Polysaccharide derivative phases offer wide scope for pesticide separations. • Stereoselective LC–MS/MS methods for multi-residue analysis now being developed. • Lack of deuterated surrogates and metabolites available for monitoring studies. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Method was developed for screening enzymes or strains producing L-Phosphinothricin. • Method has good detection range, precision and accuracy. • Strain K. cryocrescens ZJB-17005 was newly isolated by the screening method. • 45% of conversion and >99.9% of e.e. were achieved at 100 g L−1 substrates. Abstract A novel and simple methodology for the detection of phosphinothricin produced by a biosynthesis approach in 96-well microtiter plates was developed based on the fluorometric determination of an isoindole derivative. The assay method to determine the generation of L-phosphinothricin was conducted with the help of a derivatization reaction. The linear detection range of the method was demonstrated to be from 0.74 to 100 μg ml−1 for the catalysis by resting cells and from 1.6 to 100 μg ml-1 for the catalysis by secretory enzymes. Meanwhile, the value of the relative standard deviation was less than 2.2% and the recovery was 99–101% of true value. Based on the method constructed in this study, one bacterial strain, Kluyvera cryocrescens ZJB-17005, with high stereoselectivity (>99%) and excellent yield (45%) was isolated from 13,284 strains in the production of L-phosphinothricin by a biosynthesis approach. [ABSTRACT FROM AUTHOR]

Eleven alkaloids, including five previously undescribed indolizidine alkaloids (1 , 2a , 2b , 3a , and 3b) and four new pyrrolidine alkaloids (5 − 8), were isolated from the roots of Anisodus tanguticus. Of these, two new pairs of enantiomeric alkaloids (2a / 2b and 3a / 3b) are the first examples of alkaloids containing both indolizidine and pyrrolidine structural fragments. The one-carbon bridge connections with two pyrrolidine rings (6) or with a pyrrolidine ring and a pyridine ring (8) are the first reported from nature. Extensive spectroscopic techniques were used to elucidate their structures, and NMR and ECD calculations were used to determine the absolute configurations. The viability of human umbilical vein endothelial cells (HUVECs) was inhibited by compounds 2a , 2b , 3a , 4b , and 5 , and compound 2b exhibited a potential anti-angiogenic effect by inhibiting the proliferation, migration, and tube formation of HUVECs. A chorioallantoic membrane assay also demonstrated the anti-angiogenic activity of 2b. In addition, compounds 2a , 2b , 3a , and 4b exhibited moderate cytotoxicity against A2780 cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights • Efficient optical resolution of ibuprofen by gas antisolvent fractionation. • Phenylglycinol is an excellent resolving agent of ibuprofen. • Purification of scalemic mixtures by repeated resolution to >99% in 3 steps. • Thin fibers with diameters in the nanometer range (400–800 nm) were produced. Abstract Optical resolution is still the dominant route to obtaining enantiopure active ingredients. The traditional methods require large organic solvent quantities and long processing times. Antisolvent fractionation with supercritical carbon dioxide offers intensified processing by drastically reducing the time requirement of the diastereomeric salt precipitation. A novel optical resolution of ibuprofen was developed and optimized with phenylglycinol as a resolving agent and gas antisolvent fractionation as the separation method. Above the critical values of certain operational parameters (carbon dioxide to methanol ratio, apparent diastereomeric salt concentration, equilibration time, the relative volume of the extracting fluid) the selectivity was roughly constant, the optical resolution is robust. The scalemic mixtures were purified by repeated resolution and enantiomeric purities above 99% were reached in three consecutive steps. [ABSTRACT FROM AUTHOR]

The rate that amino acids are removed from the soil solution is poorly known but vitally important. It is possible to determine the time course of soil solution concentrations by extracting soils at different time points after adding labelled compounds, but this approach either lacks sufficient temporal resolution or generates large number of samples that require subsequent offline analysis. The aim of this study was to develop online microdialysis-mass spectrometry to enable the minimally invasive measurement of the time-course of isotope labelled amino acid added to soil. The method was subsequently tested by examining the fate of isotope labelled L- and d -alanine added to sterile and non-sterile soils. One concern with application of microdialysis to soil is if calibrations are affected by inorganic ion composition of the perfusate and the external (soil) solution. Tests showed that the presence/absence of inorganic ions in perfusate and external solution did not affect dialysate concentrations, suggesting that perfusing with an artificial soil solution matching the inorganic ion composition of the external solution does not convey any benefits. Hence water was used as perfusate for development of online microdialysis-mass spectrometry. The online system took around one minute to equilibrate to step-changes in concentration and had detection limits around 0.5 μmol L −1 for alanine. Addition of isotope labelled alanine to soils led to an almost instantaneous increase and subsequent decrease in dialysate alanine concentration. With sterile soils there was a slow abiotic decrease in dialysate concentrations, presumably due to development of a depletion shell around the microdialysis probe and adsorption of alanine to the soil. For non-sterile soils there was an additional more rapid biotic decrease in dialysate concentrations that presumably reflected microbial uptake. For l -alanine added to non-sterile soil much of the compound was taken up before it reached the probe surface and concentrations decreased to below detection limits within 5–20 min. Thus microdialysis afforded a graphic illustration of the ephemeral nature of intact l -alanine in non-sterile soil, while parallel measurements showed that added d -alanine was removed from soil solution several times more slowly. [ABSTRACT FROM AUTHOR]

Over 300 chiral drug substances lack official United States Pharmacopeia (USP) methods for the enantiomeric purity determination. Because enantiomeric analysis typically requires specialized methods for each drug compound, developing protocols for each of these 300+ substances would be an expensive and laborious endeavor. Alternatively, if a detector capable of determining the enantiomeric composition without chiral separation could be used with certain drug compounds, this could be implemented relatively rapidly into official testing monographs. Circular dichroism (CD) detection following HPLC (HPLC-CD) has been proposed for this purpose but studies performed thus far have not prioritized its compatibility with validated regulatory methods. In this study, HPLC-CD was evaluated for enantiomeric purity determinations of 13 drug substances using HPLC methods consistent with assay protocols described in United States Pharmacopeia (USP) monographs. Of these selected substances, three (sitagliptin, timolol, and levalbuterol) showed no CD activity and one other (levofloxacin) could not be analyzed due to incompatibility of the mobile phase with the CD detector. For the remaining 9 substances, method validation was performed to determine the linearity, accuracy, precision and limits of quantitation of enantiomer impurities, which was compared to limits established by USP. It was found that enantiomeric impurities for four substances (pramipexole, levocetirizine, ( S )-citalopram, and tolterodine) could be quantitatively determined at levels suitable to USP specifications. This analysis demonstrated that HPLC-CD does provide an effective enantiomeric characterization strategy for compatible chiral compounds, and can be implemented quickly and economically compared to traditional column-dependent chiral separation or derivatization methods. [ABSTRACT FROM AUTHOR]

In this study, electrochemical sensors for the enantioselective recognition of d and l phenylalanine were prepared using a molecular imprinting technique in which the electro-polymerization of pyrrole was carried out by Chronopotentiometry(CP) with the target molecules being present on a Ag screen printed electrode's (SPE) surface. The sensing performance was evaluated by multi-potential steps at 0 and 2 V(vs. Ag/AgCl) held for 1 s and 2 s, respectively, for 20 cycles (with the two enantiomers being present at the same concentration). The individual selectivity's for l and d - phenylalanine on their respective imprinted films were estimated to be L/D = 23.480 ± 2.844/1 and D/L = 19.134 ± 1.870/1 respectively, based on the current change between 0 and 2 V (vs. Ag/AgCl) with the two enantiomers being present at the same concentration (10 mM). Several parameters affecting recognition ability were investigated including: cross-selectivity of d and l - phenylalanine imprinted film, phenylalanine concentration effects, interfering species, deactivation and the storage life of electrode. The phenylalanine imprinted films were also characterized by AC impedance, chronoamperometry, Fourier-transform infrared spectroscopy (FTIR), Scanning Electron Microscope(SEM), and Energy Dispersive X-Ray Spectroscopy (EDS). Finally, a recognition mechanism for the interaction of the polypyrrole film with its template under the influence of applied negative and positive potentials is proposed. [ABSTRACT FROM AUTHOR]

Drug impurity and degradation profiling mean the detection, structure elucidation and quantitative determination of impurities and degradation products in bulk drug materials and pharmaceutical formulations. This is today one of the most important fields of activities in pharmaceutical analysis. The reason for this is that unidentified, potentially toxic impurities are health hazards, and in order to increase the safety of drug therapy, impurities should be identified and determined by selective methods. The aim of this review is to characterise the state-of-art in the field of impurity and degradation profiling of drugs based on papers published in the last decade. The separation and determination of impurities and degradants with a known structure are discussed, but emphasis is placed on the structure elucidation and determination of new (unknown) impurities and degradation products by off-line and on-line chromatographic–spectroscopic methods. The analytical aspects of enantiomeric purity of chiral drugs are also discussed. [ABSTRACT FROM AUTHOR]

Pharmaceuticals such as racemate ketoprofen (RS-KP) and its enantiomer, dexketoprofen (S(+)-KP) are highly detectable non-steroidal anti-inflammatory drugs (NSAIDs) in the aquatic environment and therefore are designated as one of the most emerging groups of pollutants that can affect environmental and human health. The potential impact of these pharmaceuticals was assessed for the first time in vitro using a rat hepatocellular carcinoma cell line (H4IIE). Cells were exposed to low and high concentrations of these drugs. Cytotoxicity was determined by MTT reduction assay; CYP1A1 transcriptional and enzymatic levels together with canonical oxidative stress responsive markers (GPx, GR, GST and CAT) were also investigated. Cells exposed to RS-KP and S(+)-KP did not show cytotoxicity effect at the concentrations tested. However, this study highlighted differences between RS-KP and S(+)-KP in most of the evaluated markers, showing compound-, concentration- and time-specific effect patterns which suggest a potential stereo-selective toxicity of these drugs. [ABSTRACT FROM AUTHOR]

In this review, the chirality and stereoselectivity in photochromic reactions are broadly discussed. Stereoselectivity is categorized into the two main areas of enantioselectivity and diastereoselectivity. Enantioselective photochromism was discussed according to the methods of generating chirality, that is: (1) optical resolution of chiral and racemic compounds, (2) spontaneous separation of racemic compounds during crystallization, (3) chiral template-assisted photochromic reactions to preferentially generate an enantiomer or cause chirality-based events, and (4) the generation of a non-racemic mixture of the photoisomers by irradiation of circularly polarized light to the racemic starting photoisomer. Diastereoselective photochromism was discussed for each family of photochromic reactions, namely, (1) fulgides, (2) diarylethenes, (3) spiro-compounds, (4) azobenzenes, and (5) organometallic complexes. Chirality-related reactions in overcrowded alkenes are discussed in a separate chapter. These include: (1) the discovery of the light-driven molecular motor, (2) the first generation of light-driven molecular motors with unidirectional rotation, which have two chiral carbon atoms in a molecule, (3) the second generation of light-driven molecular motors with unidirectional rotation, which have a single chiral carbon atom in a molecule. Finally, two distinctive novel photochromic systems are introduced in which the reactions proceed stereoselectively, although their enantio- or diastereoselectivity during photochromic reactions have yet to be examined. [ABSTRACT FROM AUTHOR]

A pair of ruthenium(II) complex enantiomers, Δ - and Λ -[Ru(bpy) 2 PBIP] 2 + {bpy = 2,2′-bipyridine, PBIP = 2-(4-bromophenyl)imidazo[4,5- f ]1,10-phenanthroline} have been synthesized and characterized. The systematic comparative studies between two enantiomers on their DNA binding-behaviors with calf thymus DNA (CT DNA) were carried out by viscosity measurements, spectrophotometric methods and molecular simulation technology. Additional assays were performed to explore the cytotoxicity of the ruthenium(II) enantiomers against tumor cell lines. DNA-binding studies show that both the enantiomers can bind to CT DNA via intercalative mode, and the Δ form binds to CT DNA more strongly than the Λ form does. Molecular simulation further shows that both the two enantiomers intercalate between base pairs of DNA in minor groove, and that the Δ form intercalates into DNA more deeply than the Λ form does. In addition, the cell proliferation assays show that the Δ form induces a greater cytotoxicity than the Λ form on human cervical cancer HeLa cells, which is positive correlated with the results in DNA binding studies and molecular docking, and implies that the DNA binding affinities of ruthenium(II) polypyridyl complexes might be constitute to the part of their anticancer mechanisms. [ABSTRACT FROM AUTHOR]

A helically distorted and polycondensed bisphenol [1,1′-bibenzo[c]phenanthrene]-2,2′-diol (HEBPOL) and its separated optically pure enantiomers were used to prepare thin films and to explore their optoelectronic properties. Due to both hydrophobic aromatic rings and hydrophilic −OH groups the compound possessed amphiphilic characters, which helps to form a stable layer at the air-water interface. The stable film from the air-water interface was then transferred to different types of solid substrates by Langmuir-Blodgett (LB) technique. In the atomic force microscopic (AFM) images, circular-shaped islands were observed for the films of racemic mixture and their enantiomers deposited at different surface pressures. Thin films of different thickness were also prepared by spin coating (SP) method. The information about thickness, roughness, and electron density of layers or films was determined through X-ray reflectivity (XR) experiments. The multilayer formation was observed in the LB film, which was suggested by the height of islands in AFM images and the thickness determined by the XR experiments. The generation of photocurrent was measured by a conventional three-electrode system with a light source of the Xenon lamp. The photocurrent generation was speculated higher for the films having a higher thickness and experimentally found above 0.4 μA/cm 2 for 100 Å. The compound is axially chiral and both the enantiomers respond to circularly polarized light irradiation in solution as well as in LB and SP films. [ABSTRACT FROM AUTHOR]

Free d -amino acids and amino acid isomers were differentiated using tandem mass spectrometry without chromatographic separation. Ultraviolet photodissociation and water adsorption of leucine (Leu) and isoleucine (Ile) enantiomers hydrogen-bonded with tryptophan (Trp) were investigated at 8 K in the gas phase. The enantiomer-selective C α –C β bond cleavage of Trp was observed in the product ion spectra obtained by 285 nm photoexcitation, where the abundance of NH 2 CHCOOH-eliminated ion of heterochiral H+(d -Trp)(l -Leu) was higher than that of homochiral H+(l -Trp)(l -Leu). When comparing water adsorption on the surfaces of the heterochiral and homochiral clusters in a cold ion trap, the number of water molecules adsorbed on the heterochiral cluster was greater than that adsorbed on the homochiral cluster. These results indicate that the stronger intermolecular interactions within the homochiral H+(l -Trp)(l -Leu) compared to the heterochiral cluster inhibit enantiomer-selective photodissociation. Leu and Ile were differentiated by the isomer-selective C α –C β bond cleavage of Trp in the clusters. Calibration curves for the differentiation of isomeric amino acids and their enantiomers were developed using monitoring isomer- and enantiomer-selective photodissociation, indicating that the molar fractions in solution could be determined from a single product ion spectrum. [Display omitted] • d -Amino acids were differentiated using tandem mass spectrometry. • Intermolecular interactions within homochiral clusters inhibit enantiomer-selective photodissociation. • Tryptophan recognizes amino acid isomers and their enantiomers via hydrogen bonding. [ABSTRACT FROM AUTHOR]

(+) and (−)-Eugenilones A−K, 11 pairs of undescribed enantiomeric sesquiterpenoids, together with three undescribed biogenetically related members eugenilones L−N, were discovered from the fruits of Eugenia uniflora Linn. (Myrtaceae). Structurally, eugenilones A−D were four caged sesquiterpenoids featuring 9,10-dioxatricyclo [6.2.2.02,7]dodecane, 11-oxatricyclo [5.3.1.03,8]undecane, and tricyclo [4.4.0.02,8]decane cores, respectively. Eugenilones E−K were eudesmane-type sesquiterpenoids, while eugenilones L−N were epoxy germacrane-type sesquiterpenoids. Notably, eugenilones A−K were efficiently resolved by chiral HPLC to give 11 pairs of optically pure enantiomers. The structures and absolute configurations of eugenilones A−N were determined through spectroscopic analyses, X-ray crystallography, and ECD calculations. The putative biosynthetic pathways for these undescribed isolates were proposed. Moreover, eugenilones A and E exhibited significant anti-inflammatory effects by inhibiting LPS-stimulated NO overproduction in RAW264.7 cells (IC 50 values of 4.89 ± 0.37 μM and 20.89 ± 1.49 μM, respectively) and TNF- α -induced NF- κ B activation in HEK293 cells (IC 50 values of 10.97 ± 1.03 μM and 28.63 ± 1.59 μM, respectively). Eugenilones A−N (1 − 14), 14 undescribed sesquiterpenoids, including four members with rare caged ring systems, were isolated and identified from the fruits of Eugenia uniflora. It is noteworthy that compounds 1 − 11 existed as 11 pairs of enantiomers and were successfully resolved by chiral HPLC. Furthermore, compounds 1 and 5 showed significant anti-inflammatory effects. [Display omitted] • Fourteen undescribed sesquiterpenoids, including four with rare caged ring systems, were isolated from Eugenia uniflora. • Eugenilones A−K existed as 11 pairs of enantiomers, which were uncommon in natural sesquiterpenoids. • Eugenilones A and E showed significant anti-inflammatory effects in RAW264.7 and HEK293 cells. [ABSTRACT FROM AUTHOR]

The absolute and relative concentration of small organic N compounds varies among soils, yet we have little idea what drives this variation among soils. Previous studies have noted differences in DON/DIN and amino acid profiles among sites differing in altitude and/or productivity, and thus it seemed plausible that similar factors would have broader effects on the molecular composition of the pool of small organic N. To test this idea we used an altitudinal transect that ranged from a low altitude forest of Eucalyptus regnans with a canopy height averaging 65 m through to coniferous shrubbery that was above the alpine treeline and had a canopy less than 50 cm high. From low to high altitude mean annual temperature decreased 7 °C such that turnover was likely twice as slow at the highest site than the lowest. Capillary electrophoresis-mass spectrometry was used to identify and quantify the main small organic N compounds in free, adsorbed and microbial fractions of the soil; while chiral liquid chromatography-mass spectrometry was used to quantify amino acid enantiomers in hydrolysed soil and the free, adsorbed and microbial fractions of soil. CE-MS detected 66 small (<250 Da) organic N compounds of which 63 could be positively identified. Protein amino acids were a large fraction of the pool of small organic N, but there were also large amounts of non-protein amino acids, quaternary ammonium compounds and alkylamines. There were differences among sites in the profile of small organic N, but these differences were not monotonically related to altitude and there was no evidence pools of small organic N were larger or enriched in recalcitrant compounds at cooler high altitude sites. Among sites there was only modest variation in the molecular composition of the protein amino acid pool probably because protein amino acids are primarily derived from a common source (i.e. depolymerisation of soil proteins). In contrast, there was substantially larger variation within pools of non-protein amino acids, alkylamines and quaternary ammonium compounds; which is probably because compounds from these classes are primarily products of de novo synthesis by specific organisms, and thus molecular composition varies among sites depending on composition of the microbial community. D-enantiomers of amino acids were at low concentrations relative to L enantiomers such that in soil extracts the summed concentration of d -amino acids was 0.5–0.6% of L amino acids, while in hydrolysates D-enantiomers were 0.99% of L-enantiomers. There was no evidence that absolute or relative concentrations of D-enantiomers in free solution, microbial biomass or hydrolysates were larger at high altitude sites, despite turnover likely being slower at the cooler high altitude sites. The absence of an effect of altitude on D/L probably indicates that the turnover of soil proteins is comparatively rapid and thus soil proteins are similarly young even among sites in which mean annual temperature differs by 7 °C. [ABSTRACT FROM AUTHOR]

Phytochemical investigation on the fruiting bodies of Ganoderma resinaceum led to the isolation of five new meroterpenoids, namely ganoresinains A–E ( 1 – 5 ), and four known analogues ( 6 – 9 ). The new compounds were identified by extensive analyses of spectroscopic data (NMR, MS, UV, and IR) and comparison with the literature data. Compound 1 and 6 were isolated as enantiomeric mixture, which were separated over analytical chiral HPLC chromatography. Compounds 6–9 were isolated from G . resinaceum for the first time. [ABSTRACT FROM AUTHOR]

The marine-derived Aspergillus protuberus MF297-2 and the terrestrial A. amoenus NRRL 35600 produce enantiomeric prenylated indole alkaloids. Investigation of biological activities of the natural and synthetic derivatives revealed that (−)-enantiomers of notoamides A and B, 6- epi -notoamide T, and stephacidin A inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)–induced osteoclastogenic differentiation of murine RAW264 cells more strongly than their respective (+)-enantiomers. Among them, (−)-6- epi -notoamide T was the most potent inhibitor with an IC 50 value of 1.7 μM. [ABSTRACT FROM AUTHOR]

Mechanofluorochromic organic compounds have attracted increasing attention owing to their application in various fields. Here, dimethyl 1,3-bis(4-bromophenyl)-2-phenyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate (Me-THP-2Br), a racemic C6-unsubstituted tetrahydropyrimidine with highly sensitive mechanofluorochromic characteristics based on a new mechanism is reported. Me-THP-2Br has excellent aggregation-induced emission (AIE) characteristics, that is, no emission in solution but becomes highly emissive upon aggregation. It can unusually form four stable solid forms, namely, three polymorphic crystals PC, BC and CC emitting purple, blue, cyan fluorescence respectively, and one amorphous state AS with 18–52% fluorescence quantum yields. We find that all these as-prepared solid forms can emit the same green fluorescence (490 nm) when they are ground into powder, and revert to purple fluorescence (425 nm) upon fuming/heating. The green and purple emissions can be switched reversibly by grinding-fuming/heating process. In addition, the ground powder of Me-THP-2Br can be used as an excellent rewritable material. More importantly, its sensitive mechanofluorochromism proves to originate mainly from conversion between the paired RS -packing and unpaired RR/SS -packing of enantiomers, which is first reported. Since racemic organic compounds can be easily obtained by chemical synthetic methods, more racemic organic fluorophores with sensitive mechanofluorochromism are expected to be developed. [ABSTRACT FROM AUTHOR]

Background:S-equol, which is enantioselectively produced from daidzein by gut microbiota, has been suggested as a chemopreventive agent against type 2 diabetes mellitus (T2DM), but the underlying mechanisms remain unclear.Objective: We investigated the effects of S-equol on pancreatic β-cell function.Methods: β-Cell growth and insulin secretion were evaluated with male Institute of Cancer Research mice and isolated pancreatic islets from the mice, respectively. The mechanisms by which S-equol stimulated β-cell response were examined in INS-1 β-cells. The effect of S-equol treatment on β-cell function was assessed in low-dose streptozotocin-treated mice. S-equol was used at 10 μmol/L for in vitro and ex vivo studies and was administered by oral gavage (20 mg/kg, 2 times/d throughout the experimental period) for in vivo studies.Results:S-equol administration for 7 d increased Ki67-positive β-cells by 27% (P < 0.01) in mice. S-equol enantioselectively enhanced glucose-stimulated insulin secretion in mouse pancreatic islets by 41% (P < 0.001). In INS-1 cells, S-equol exerted stronger effects than daidzein on cell growth, insulin secretion, and cAMP-response element (CRE)-mediated transcription. These S-equol effects were diminished by inhibiting protein kinase A. The effective concentration of S-equol for stimulating cAMP production at the plasma membrane was lower than that for phosphodiesterase inhibition. S-equol-stimulated CRE activation was negatively controlled by the knockdown of G-protein α subunit group S (stimulatory) and positively controlled by that of G-protein-coupled receptor kinase-3 and -6. Compared with vehicle-treated controls, S-equol gavage treatment resulted in an increase in β-cell mass of 104% (P < 0.05), a trend toward high plasma insulin concentrations (by 118%; P = 0.06), and resistance to hyperglycemia after streptozotocin treatment (78% of AUC after glucose challenge; P < 0.01). S-equol administration significantly increased the number of Ki67-positive proliferating β-cells by 62% (P < 0.01) and decreased that of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic β-cells by 75% (P < 0.05).Conclusions: Our results show that S-equol boosts β-cell function and prevents hypoglycemia in mice, suggesting its potential for T2DM prevention. [ABSTRACT FROM AUTHOR]

Pyrethroids are the most popular drug against sea lice in salmon farming. Although they are more toxic to insects, they have toxic effects in mammals. Pyrethroids were detected in 100% of farmed salmon with a mean concentration of 1.31 ± 1.39 ng g −1 ww and in 50% of wild salmon with a mean of 0.02 ± 0.03 ng g −1 ww. Cypermethrin and deltamethrin, the active ingredients of anti-sea lice formulations, represented 77   ±  27% of the total contamination of farmed salmon. Although farmed salmon had higher concentrations than wild salmon, the daily intake of pyrethroids through salmon consumption was several orders of magnitude below the accepted daily intake (ADI). Thus, the pyrethroids treatment on salmon does not pose a threat on the health of the consumers. [ABSTRACT FROM AUTHOR]

During the early stages of ecosystem development there are increases in plant and soil microbial biomass, nutrient availability and rates of nutrient cycling; but little is known about how pools of small organic N vary during the initial stages of soil development. The aim of this study was to examine how the pool of small organic N compounds varies during the initial stages of soil development, and if age differentially affects D- and L-enantiomers of protein amino acids. Measurements were made at a soil chronosequence on the east coast of Tasmania that comprised a series of sub-parallel beach dunes and ridges varying in age from <100 years to 5500 years. Capillary electrophoresis-mass spectrometry was used to identify and quantify the main small organic N compounds in free, adsorbed and microbial fractions of the soil; while chiral liquid chromatography-mass spectrometry was used to quantify amino acid enantiomers in hydrolysed soil and the free, adsorbed and microbial fractions of soil. CE-MS detected 66 small (<250 Da) organic N compounds of which 63 could be positively identified. Small organic N was dominated by protein amino acids, while there were also large amounts of quaternary ammonium compounds and alkylamines. There were differences among chronosequence sites in the profile of small organic N, but these differences were not monotonically related to age and there was no evidence for a build-up of recalcitrant compounds over time. Differences were instead site-specific and related to presence/absence of particular non-protein amino acids which probably related to the presence/absence of specific plants and/or microbes that produce and/or can metabolise different non-protein amino acids. In free solution and microbial biomass D enantiomers of many amino acids were below detection limits (i.e. < 0.125 nmol g −1 ) and D-enantiomers were at low concentrations relative to L enantiomers such that across all ages and replicates the summed concentration of d -amino acids was 0-3-0.6% of L amino acids. There was no evidence that absolute or relative concentrations of D-enantiomers in free solution, microbial biomass or hydrolysates were larger at the older chronosequence sites. The consistent lack of an effect of soil age on D/L probably indicates that the turnover of soil proteins is comparatively rapid and thus soil proteins are similarly young even among sites in which soil age is vastly different. [ABSTRACT FROM AUTHOR]