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Background: Despite the application of various tools for the control of vectors of Plasmodium falciparum, malaria remains the major killer disease in sub-Saharan Africa accounting for up to 90% of deaths due to the disease. Due to limitations of the useage of chemical insecticides such as resistance, negative impact on the environment and to nontarget organisms, the World Health Organization (WHO) requires that affected countries find alternative vector control tools. This study evaluated the effectiveness of (+)-usnic acid (UA) as an insecticide through oral administration to male and female Anopheles gambiae as an alternative or additional active ingredient to be used in toxic sugar bait. Methods: (+)-usnic acid was diluted using acetone at 5, 10, and 15 mg/ml concentrations in three replicates. A 5 ml mixture of 2% food dye and 10% sugar using chlorine-free water mixed with the dilutions of the (+)-usnic acid and negative control was made containing 2% food dye and 10% sugar solution. The preparations were soaked on a ball of cotton wool and placed over the net of a cup. 5 male and 5 non-blood-fed female newly hatched starved An. gambiae Kisumu strain were introduced together into a cup and monitored for knockdown and mortalities after 4, 24 48, and 72 h. The data were analysed using a multiple linear regression model using the lm function, a base R function and a posthoc test were conducted on the significant main effects and interaction terms using the emmeans function from the emmeans R package. All analyses were performed in RStudio using base R (version 4.3.3). Results: There was high mortality of both male and female An. gambiae after ingestion of the toxic sugar bait. 15 mg/ml usnic acid caused the highest mortality (50%) within the first 4 h compared to 5 and 10 mg/ml (+)-UA. There was a decline in the mortality rate with increased exposure time from 24 to 72 h, however, there was a significant difference in mortality at 5, 10 and 15 mg/ml. Acute toxicity was associated with ingestion of 15 mg/ml after 24 h. 72 h post-mortality was lower in all concentrations than in the control. High mortality was observed among females over the first 4 h (60%) compared to males (40%) due to higher feeding rate of the toxic agent. The proportion of dead males and females was equal after 24 h while after 48 h, the proportion of dead males was high.There was a significantly lower mortality rate after 72 h for both males and females (0 to 13.3%). Compared to all the treatments, high mortality of males was observed. Conclusions: The results of this study indicate that (+)-UA when administered as oral sugar bait to An. gambiae has insecticidal properties and is a suitable ingredient to be used as a toxic agent in the novel attractive toxic sugar bait for the control of malaria vectors. (+)-UA may be an alternative active ingredient as toxic bait in the effort to reduce and eliminate the transmission of Plasmodium falciparum in Africa. [ABSTRACT FROM AUTHOR]

The aim of this study was to establish a simple, fast, and sensitive method with liquid chromatography–tandem mass spectrometry (LC–MS/MS) for simultaneously determining ibuprofen enantiomers using mouse blood in very small volumes. LC–MS/MS equipped with an electrospray ionization (ESI) source was used in negative ion mode and multiple‐reaction monitoring mode. Enantiomer chromatographic separation was carried out on a Lux® 5 μm Cellulose‐3 (250 × 4.6 mm, 5 μm) column at a flow rate of 0.6 mL/min. Samples were pretreated by extracting only 5 μL of blood with 40 μL of acetonitrile (containing 1.3% formic acid) so that a concentration‐time profile could be completed using a single mouse. 2‐(4‐Propylphenyl) propanoic acid was used as an internal standard. Standard curves for each enantiomer were linear from 0.04 to 80.00 μg/mL, demonstrating a lower limit of quantitation (LLOQ) than all previously reported methods. This method was completely validated and successfully executed to investigate the pharmacokinetics of ibuprofen enantiomers after intravenous administration of racemic ibuprofen, (S)‐(+)‐ibuprofen, and (R)‐(−)‐ibuprofen in Kunming mice, respectively. The results showed that the pharmacokinetic profiles of the (R)‐(−)‐ibuprofen and (S)‐(+)‐ibuprofen were significantly different, indicating the unidirectional inversion of R‐(−)‐ibuprofen to (S)‐(+)‐ibuprofen. [ABSTRACT FROM AUTHOR]

The significance and necessity of separating enantiomers in food, pharmaceuticals, pesticides, and other samples remains constant and unrelenting. The successful chiral separation usually includes the application of a chiral auxiliary compound, known also as a chiral selector (CS), that forms complexes with enantiomers of different physicochemical properties, enabling efficient separation. While both native and substituted cyclodextrins (CDs) are commonly used as CSs, β-CD is undoubtedly the most popular one among them. This review includes recent advancements in the application of β-CD as a CS. While the theoretical background behind the enantioseparation is also part of this work, the main emphasis is put on the factors that affect the efficacy of this process such as temperature, pH, solvent, and the choice of other additives. Also, the different analytical methods: Nuclear Magnetic Resonance (NMR) spectroscopy, Capillary Electrophoresis (CE), fluorescence spectroscopy (FS), High-Performance Liquid Chromatography (HPLC), Isothermal Titration Calorimetry (ITC), and UV–vis spectroscopy, used for enantioseparation with the aid of β-CD as CS, are thoroughly compared. Also, since some of the chiral compounds have been studied in the context of their enantioseparation more than once, those works are compared and critically analyzed. In conclusion, while β-CD can be in most cases used as CS, the choice of the experimental conditions and method of analysis is crucial to achieve the success. [ABSTRACT FROM AUTHOR]

Chiral pesticides account for about 40% of the total pesticides. In the process of using pesticides, it will inevitably flow into the surface water and even penetrate into the groundwater through surface runoff and other means, as a consequence, it affects the water environment. Although the enantiomers of chiral pesticides have the same physical and chemical properties, their distribution, ratio, metabolism, toxicity, etc. in the organism are often different, and sometimes even show completely opposite biological activities. In this article, the selective fate of different types of chiral pesticides such as organochlorine, organophosphorus, triazole, pyrethroid and other chiral pesticides in natural water bodies and sediments, acute toxicity to aquatic organisms, chronic toxicity and other aspects are summarized to further reflect the risks between the enantiomers of chiral pesticides to non-target organisms in the water environment. In this review, we hope to further explore its harm to human society through the study of the toxicity of chiral pesticide enantiomers, so as to provide data support and theoretical basis for the development and production of biochemical pesticides. [ABSTRACT FROM AUTHOR]

Abstract Background Despite the application of various tools for the control of vectors of Plasmodium falciparum, malaria remains the major killer disease in sub-Saharan Africa accounting for up to 90% of deaths due to the disease. Due to limitations of the useage of chemical insecticides such as resistance, negative impact on the environment and to nontarget organisms, the World Health Organization (WHO) requires that affected countries find alternative vector control tools. This study evaluated the effectiveness of ( +)-usnic acid (UA) as an insecticide through oral administration to male and female Anopheles gambiae as an alternative or additional active ingredient to be used in toxic sugar bait. Methods ( +)-usnic acid was diluted using acetone at 5, 10, and 15 mg/ml concentrations in three replicates. A 5 ml mixture of 2% food dye and 10% sugar using chlorine-free water mixed with the dilutions of the ( +)-usnic acid and negative control was made containing 2% food dye and 10% sugar solution. The preparations were soaked on a ball of cotton wool and placed over the net of a cup. 5 male and 5 non-blood-fed female newly hatched starved An. gambiae Kisumu strain were introduced together into a cup and monitored for knockdown and mortalities after 4, 24 48, and 72 h. The data were analysed using a multiple linear regression model using the lm function, a base R function and a posthoc test were conducted on the significant main effects and interaction terms using the emmeans function from the emmeans R package. All analyses were performed in RStudio using base R (version 4.3.3). Results There was high mortality of both male and female An. gambiae after ingestion of the toxic sugar bait. 15 mg/ml usnic acid caused the highest mortality (50%) within the first 4 h compared to 5 and 10 mg/ml ( +)-UA. There was a decline in the mortality rate with increased exposure time from 24 to 72 h, however, there was a significant difference in mortality at 5, 10 and 15 mg/ml. Acute toxicity was associated with ingestion of 15 mg/ml after 24 h. 72 h post-mortality was lower in all concentrations than in the control. High mortality was observed among females over the first 4 h (60%) compared to males (40%) due to higher feeding rate of the toxic agent. The proportion of dead males and females was equal after 24 h while after 48 h, the proportion of dead males was high.There was a significantly lower mortality rate after 72 h for both males and females (0 to 13.3%). Compared to all the treatments, high mortality of males was observed. Conclusions The results of this study indicate that ( +)-UA when administered as oral sugar bait to An. gambiae has insecticidal properties and is a suitable ingredient to be used as a toxic agent in the novel attractive toxic sugar bait for the control of malaria vectors. ( +)-UA may be an alternative active ingredient as toxic bait in the effort to reduce and eliminate the transmission of Plasmodium falciparum in Africa.

DNA‐based tension probes with precisely programmable force responses provide important insights into cellular mechanosensing. However, their degradability in cell culture limits their use for long‐term imaging, for instance, when cells migrate, divide, and differentiate. This is a critical limitation for providing insights into mechanobiology for these longer‐term processes. Here, we present DNA‐based tension probes that are entirely designed based on the stereoisomer of biological D‐DNA, i.e., L‐DNA. We demonstrate that L‐DNA tension probes are essentially indestructible by nucleases and provide days‐long imaging without significant loss in image quality. We also show their superiority already for short imaging times commonly used for classical D‐DNA tension probes. We showcase the potential of these resilient probes to image minute movements, and for generating long term force maps of single cells and of collectively migrating cell populations. [ABSTRACT FROM AUTHOR]

In order to improve and replace the enantiomer method outlined in the olodaterol hydrochloride draft monograph (From the European Pharmacopoeia forum), one new, simple, and fast enantioselective normal phase high‐performance liquid chromatography chiral method was developed on polysaccharide‐based Chiral MX (2) (4.6 × 250 mm, 5 μm) column. n‐Hexane, ethanol, and diethylamine in the ratio of 40:60:0.1 (V/V/V) were selected as mobile phase at a flow rate of 0.8 mL/min, and the detection was performed on a photodiode array detector at 225 nm with 5 μL injection volume. The column temperature was set at 40°C for better peak shape and sensitivity. The analysis time can be shortened to 15 min, whereas the resolution between enantiomer and olodaterol was found to be even more than 10.0, which was far better than that obtained with the reported method in this draft monograph. The developed chiral method was validated in accordance with ICH Q2 (R1), including specificity, LOD&LOQ, precision, linearity, accuracy, and robustness. Thereby, the proposed method was demonstrated to be suitable for the determination of enantiomer in olodaterol hydrochloride bulk drug and drug product. Besides, the thermodynamic parameters were evaluated on the basis of Van't Hoff plots that was used to explain correlative chiral recognition mechanisms with the chiral stationary phase. [ABSTRACT FROM AUTHOR]

2-Keto-3-deoxy-galactonate (KDGal) serves as a pivotal metabolic intermediate within both the fungal d-galacturonate pathway, which is integral to pectin catabolism, and the bacterial DeLey-Doudoroff pathway for d-galactose catabolism. The presence of KDGal enantiomers, l-KDGal and d-KDGal, varies across these pathways. Fungal pathways generate l-KDGal through the reduction and dehydration of d-galacturonate, whereas bacterial pathways produce d-KDGal through the oxidation and dehydration of d-galactose. Two distinct catabolic routes further metabolize KDGal: a nonphosphorolytic pathway that employs aldolase and a phosphorolytic pathway involving kinase and aldolase. Recent findings have revealed that l-KDGal, identified in the bacterial catabolism of 3,6-anhydro-l-galactose, a major component of red seaweeds, is also catabolized by Escherichia coli, which is traditionally known to be catabolized by specific fungal species, such as Trichoderma reesei. Furthermore, the potential industrial applications of KDGal and its derivatives, such as pyruvate and d- and l-glyceraldehyde, are underscored by their significant biological functions. This review comprehensively outlines the catabolism of l-KDGal and d-KDGal across different biological systems, highlights stereospecific methods for discriminating between enantiomers, and explores industrial application prospects for producing KDGal enantiomers. Key points: • KDGal is a metabolic intermediate in fungal and bacterial pathways • Stereospecific enzymes can be used to identify the enantiomeric nature of KDGal • KDGal can be used to induce pectin catabolism or produce functional materials [ABSTRACT FROM AUTHOR]

Chiral pollutants often pose significant differential environmental health risks. In this study, the biotransformation of chiral dinotefuran (DIN) and its enantioselective metabolic toxicity mechanisms have been systemically investigated. Firstly, reversed-phase chromatography-high resolution mass spectrometry was developed to quantify the content of DIN R/S chiral enantiomer with pg level sensitivity, revealing a lower elimination rate constant (Ke) of S-DIN (0.730 h−1) than R-DIN (0.746 h−1). Secondly, the interaction mechanism between DIN metabolism and important endogenous bioactive molecules, such as aldehyde oxidase (AOX) and neurotransmitters, was revealed. The DIN nitro-group was converted into a guanidine group by the reducing site of nearby flavin adenine dinucleotide (FAD) in AOX with the preferred higher affinity of S-configuration. Meanwhile, the endogenous tryptophan (Trp) aldehyde metabolic intermediate, 5-hydroxyindoleacetaldehyde (5-HIAL), provides a persistent electron donor for DIN reduction via the oxidation-catalyzed site in AOX, resulting in remarkable up-regulation of monoamine neurotransmitters such as serotonin and dopamine. Thirdly, the higher level of neurotransmitters further mediated dysregulation of oxylipin homeostasis via the serotonergic pathway, where S-DIN exhibited more pronounced liver lipid damage and environmental health risk with the accumulated lipid biomarkers, oxidized triglyceride (OxTG) and oxidized sphingomyelin (OxSM). This study elucidates the AOX-mediated enantioselectivity metabolic pathway of DIN, providing a new analytical method for chiral pollutants and paves the way for their health risk assessments. [ABSTRACT FROM AUTHOR]

The tobacco-specific nitrosamines N ʹ-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are considered 'carcinogenic to humans' by the International Agency for Research on Cancer (IARC) and are believed to be important in the carcinogenic effects of both smokeless tobacco and combusted tobacco products. This short review focuses on the results of recent studies on the formation of NNN and NNK in tobacco, and their carcinogenicity and toxicity in laboratory animals. New mechanistic insights are presented regarding the role of dissimilatory nitrate reductases in certain microorganisms involved in the conversion of nitrate to nitrite that leads to the formation of NNN and NNK during curing and processing of tobacco. Carcinogenicity studies of the enantiomers of the major NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and the enantiomers of NNN are reviewed. Recent toxicity studies of inhaled NNK and co-administration studies of NNK with formaldehyde, acetaldehyde, acrolein and CO2, all of which occur in high concentrations in cigarette smoke, are discussed. [ABSTRACT FROM AUTHOR]

Chiral pesticides have one or more enantiomers, and their biological activity, toxicity, environmental behavior, degradation and metabolism may be different. Tea, as one of the three major beverages, has attracted much attention in terms of quality and safety. However, more attention is currently paid to the total amount of pesticide racemate residues. With the development of analytical techniques, it is particularly crucial to fully understand the stereoselective behavior of the chiral pesticide enantiomer in tea, as well as to examine residue degradation in tea and to set the maximum residue limits for enantiomers. This would help to improve the efficacies of chiral pesticides and reduce their residues and toxicities to non-target organisms. In this paper, the current status of chiral pesticide separation and residue detection technology in tea were reviewed, such as liquid chromatography, gas chromatography and supercritical fluid chromatography. In addition, it provided a summary of the residue degradation behaviors and risk assessment of chiral pesticide enantiomers in tea, which would be useful as a guide for further in-depth studies on chiral pesticide enantiomers in tea. [ABSTRACT FROM AUTHOR]

A pair of new quinolone alkaloid enantiomers, (Ra)-(-)-viridicatol (1) and (Sa)-(+)-viridicatol (4), and seven known compounds, namely, 2, 3 and 5–9, were isolated from Penicillium christenseniae SD.84. The structures of 1 and 4 were determined using NMR and HRESIMS data. Theoretical calculations through CD and ECD confirmed 1 and 4 as a pair of enantiomers. The MIC values of 4 against Staphylococcus aureus and methicillin-resistant S. aureus were 12.4 and 24.7 μM, respectively, compound 1 had no inhibitory activity. Antimicrobial assays of 2, 3, and 5–7 showed a moderate activity against S. aureus and methicillin-resistant S. aureus. This study demonstrated the remarkable potential of Penicillium sp. to produce new drug-resistant leading compounds, thereby advancing the mining for new sources of antimicrobial agents. [ABSTRACT FROM AUTHOR]

AbstractTwo pairs of cyclohexene amide alkaloid enantiomers were obtained from the root of Piper nigrum. Their plane structures were established by NMR and HRESIMS spectra. The absolute configurations of 1a/1b and 2a/2b were determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. All identified compounds were tested for inhibitory effects on acetylcholinesterase (AChE) in vitro. Notably, compounds 1b and 2b showed strong inhibitory effects on AChE and the interaction between proteins and compounds was discussed by molecular docking studies. [ABSTRACT FROM AUTHOR]

Optical Activity, Or Chirality, Is an Important Characteristic of Many Chemical Compounds. Various Industries Use Organic Compounds with Stereo Genic Centers, Which Can Affect Their Properties. Investigating The Attributes of Each Drug Enantiomer Is Crucial, As Only One Typically Exhibits Activity. Enantioselective Chromatography Plays a Valuable Role in Producing Pure Compounds and Developing Chiral Drugs. Advancements In Chiral Methods Within the Pharmaceutical Industry, Traditionally Reliant on Liquid Chromatography, Should Be Assessed. [ABSTRACT FROM AUTHOR]

The pinyon pines, Pinus edulis (two-needle pinyon pine) and Pinus monophylla (single-leaf pinyon pine) are conspicuous trees in the pinyon-juniper woodlands of the Great Basin. The purpose of this study is to examine the volatile phytochemicals in the leaf essential oils of P. edulis and P. monophylla, including enantiomeric distribution of the chiral monoterpenoids. Leaves (needles) of P. edulis and P. monophylla were collected in Utah and the essential oils were obtained by hydrodistillation. Gas chromatographic analysis revealed the major components to be α-pinene (13.1-36.5% and 27.8-29.0%, respectively), β-pinene (6.2-34.8% and 11.2-23.4%), β-phellandrene (9.5-20.2% and 11.9-14.7%), and α-terpineol (3.8-6.8% and 6.2-9.2%). Enantioselective gas chromatography showed (–)-β-pinene (> 95%), (–)-β-phellandrene (> 98%), and (–)-α-terpineol (53.6-93.0%) to be the dominant enantiomers while α-pinene showed some variability (39.5-88.9% (+)-α-pinene). The enantiomeric distributions of chiral terpenoids are presented for these essential oils for the first time and adds to our understanding of Pinus essential oils. However, additional research is needed to investigate the enantiomeric distributions of chiral terpenoids of Pinus essential oils more fully. [ABSTRACT FROM AUTHOR]

Three pairs of enantiomers (1–3)—the new 12R-aloesol (1a) and two new fatty acids (2 and 3)—and one new natural product (4) together three known compounds (5–7) were isolated from a coral-reef-derived Streptomyces sp. SCSIO 66814. Their structures were determined through extensive spectroscopic analysis, chiral analysis, and single-crystal X-ray diffraction data. Compounds 2 and 3 were presumed to be intermediates for further generating homononactic acid (5) and nonactic acid, and the latter two molecules were able to act as precursors to form macrotetrolides with remarkable biological activity. The isolation of related precursors, compounds 2–5, provided more evidence to support the proposal of a plausible biosynthetic pathway for nonactic acid and its homologs. Additionally, (+)-1 exhibited a weak activity against DPPH radicals. [ABSTRACT FROM AUTHOR]

Tofacitinib citrate (RR-isomer) is a janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis (RA) in adults who have had an inadequate response or intolerance to methotrexate. The presence of the enantiomer of tofacitinib citrate (SS-isomer) is monitored for quality control as a possible impurity in the final product. In this study, a reversed-phase high-performance liquid chromatography (RP-HPLC) method based on a chiral recognition mechanism for the separation of tofacitinib citrate and its enantiomer was established based on the principles of green analytical chemistry. A CHIRALPAK IH column was used with a mobile phase of ammonium acetate buffer (pH 8.0) and acetonitrile in a gradient elution at a detection wavelength of 285 nm. The calibration curve exhibited excellent linearity over the range of 0.1002–20.04 μg/mL (r = 0.9999). The average recovery of the enantiomer was 98.6% with a relative standard deviation (RSD) of 0.7%. The limit of detection (LOD) and the limit of quantitation (LOQ) were 0.04 and 0.1 μg/mL, respectively. This RP-HPLC method was suitable for detecting the enantiomers of tofacitinib citrate in tablets. Furthermore, the method proved to be environmentally friendly based on the evaluation by Analytical Eco-Scale, Analytical GREEnness (AGREE) and Green Analytical Procedure Index (GAPI). [ABSTRACT FROM AUTHOR]

We herein present for the first time the phosphylated (*) tetrapeptide (TP)-adduct GlyGluSer198*Ala generated from butyrylcholinesterase (BChE) with proteinase K excellently suited for the verification of exposure to toxic organophosphorus nerve agents (OPNA). Verification requires bioanalytical methods mandatory for toxicological and legal reasons. OPNA react with BChE by phosphonylation of the active site serine residue (Ser198) forming one of the major target protein adducts for verification. After its enzymatic cleavage with pepsin, the nonapeptide (NP) PheGlyGluSer*AlaGlyAlaAlaSer is typically produced as biomarker. Usually OPNA occur as racemic mixtures of phosphonic acid derivatives with the stereocenter at the phosphorus atom, e.g. (±)-VX. Both enantiomers react with BChE, but the adducted NP does not allow their chromatographic distinction. In contrast, the herein introduced TP-adducts appeared as two peaks when using a stationary reversed phase (1.8 µm) in micro-liquid chromatography–electrospray ionisation tandem-mass spectrometry (µLC–ESI MS/MS) analysis. These two peaks represent diastereomers of the (+)- and (−)-OPNA adducted to the peptide that comprises chiral L-amino acids exclusively. Concentration- and time-dependent effects of adduct formation with (±)-VX and its pure enantiomers (+)- and (−)-VX as well as with (±)-cyclosarin (GF) were investigated in detail characterising enantioselective adduct formation, stability, ageing and spontaneous reactivation. The method was also successfully applied to samples from a real case of pesticide poisoning as well as to samples of biomedical proficiency tests provided by the Organisation for the Prohibition of Chemical Weapons. [ABSTRACT FROM AUTHOR]

The significance and necessity of separating enantiomers in food, pharmaceuticals, pesticides, and other samples remains constant and unrelenting. The successful chiral separation usually includes the application of a chiral auxiliary compound, known also as a chiral selector (CS), that forms complexes with enantiomers of different physicochemical properties, enabling efficient separation. While both native and substituted cyclodextrins (CDs) are commonly used as CSs, β-CD is undoubtedly the most popular one among them. This review includes recent advancements in the application of β-CD as a CS. While the theoretical background behind the enantioseparation is also part of this work, the main emphasis is put on the factors that affect the efficacy of this process such as temperature, pH, solvent, and the choice of other additives. Also, the different analytical methods: Nuclear Magnetic Resonance (NMR) spectroscopy, Capillary Electrophoresis (CE), fluorescence spectroscopy (FS), High-Performance Liquid Chromatography (HPLC), Isothermal Titration Calorimetry (ITC), and UV–vis spectroscopy, used for enantioseparation with the aid of β-CD as CS, are thoroughly compared. Also, since some of the chiral compounds have been studied in the context of their enantioseparation more than once, those works are compared and critically analyzed. In conclusion, while β-CD can be in most cases used as CS, the choice of the experimental conditions and method of analysis is crucial to achieve the success.

Chiral pesticides have the special chiral structures, so enantioselective biological effects are usually observed in living organisms. Current study used paclobutrazol as a case study and explored the enantioselective degradation and oxidative stress effect on wheat. The results demonstrated that the degradation of R‐paclobutrazol was faster than S‐paclobutrazol significantly and improved the content of MDA and O2− in wheat plants, which proved that the R‐paclobutrazol induced oxidative damage in wheat, showing selective biological effects, and S‐paclobutrazol was friendly to wheat. This study provided a theoretical basis for the selective activity of chiral pesticides and the development of chiral pesticide monomers. [ABSTRACT FROM AUTHOR]

Enantiomerically enriched phosphorus‐containing α‐amino acids were synthesized by the method of asymmetric synthesis, using Ni(II) square planar complex of dehydroalanine as an initial complex. After acidic hydrolysis, α‐amino acids with high enantiomeric purity were isolated. At the next stage, Fmoc derivatives of the obtained α‐amino acids were synthesized (ee >99 %). Synthesized α‐amino acids and their Fmoc derivatives exhibited anticholinesterase activity, inhibiting AChE and BuChE. At the same time, the antiacetylcholinesterase activity ranged from 14 to 77 %, and (S)‐2‐((((9H‐fluoren‐9‐yl)methoxy)carbonyl)amino)‐3‐(diisopropoxyphosphoryl) propanoic acid showed relatively high activity (77.9 %). In the case of studying the antibutyrylcholinesterase properties, the activity ranged from 4 to 71 %, and (S)‐2‐amino‐3‐(diisopropoxyphosphoryl)propanoic acid showed high activity (71 %). [ABSTRACT FROM AUTHOR]

Germacrene D, a sesquiterpenoid compound found mainly in plant essential oils at a low level as (+) and/or (−) enantiomeric forms, is an ingredient for the fragrance industry, but a process for the sustainable supply of enantiopure germacrene D is not yet established. Here, we demonstrate metabolic engineering in yeast (Saccharomyces cerevisiae) achieving biosynthesis of enantiopure germacrene D at a high titer. To boost farnesyl pyrophosphate (FPP) flux for high-level germacrene D biosynthesis, a background yeast chassis (CENses5C) was developed by genomic integration of the expression cassettes for eight ergosterol pathway enzymes that sequentially converted acetyl-CoA to FPP and by replacing squalene synthase promoter with a copper-repressible promoter, which restricted FPP flux to the competing pathway. Galactose-induced expression of codon-optimized plant germacrene D synthases led to 13–30 fold higher titers of (+) or (−)-germacrene D in CENses5C than the parent strain CEN.PK2.1C. Furthermore, genomic integration of germacrene D synthases in GAL80, LPP1 and rDNA loci generated CENses8(+D) and CENses8(−D) strains, which produced 41.36 µg/ml and 728.87 µg/ml of (+) and (−)-germacrene D, respectively, without galactose supplementation. Moreover, coupling of mitochondrial citrate pool to the cytosolic acetyl-CoA, by expressing a codon-optimized ATP-citrate lyase of oleaginous yeast, resulted in 137.71 µg/ml and 815.81 µg/ml of (+) or (−)-germacrene D in CENses8(+D)* and CENses8(−D)* strains, which were 67–120 fold higher titers than in CEN.PK2.1C. In fed-batch fermentation, CENses8(+D)* and CENses8(−D)* produced 290.28 µg/ml and 2519.46 µg/ml (+) and (−)-germacrene D, respectively, the highest titers in shake-flask fermentation achieved so far. Key points: • Engineered S. cerevisiae produced enantiopure (+) and (−)-germacrene D at high titers • Engineered strain produced up to 120-fold higher germacrene D than the parental strain • Highest titers of enantiopure (+) and (−)-germacrene D achieved so far in shake-flask [ABSTRACT FROM AUTHOR]

The chiral media is crucial to the chiral recognition and separation of enantiomers. In this study, we report the preparation of novel chiral carbon nanoparticles (CCNPs) via surface passivation using glucose as the carbon source and S‐(−)‐α‐methylbenzylamine as the chiral ligand. The structures of the obtained CCNPs are characterized via FT‐IR, Raman spectroscopy, DLS, XPS, XRD, TEM, and zeta potential analysis. These CCNPs could be employed as the chiral adsorbent and used for the enantioselective adsorption of the ibuprofen enantiomers. The results demonstrated that the CCNPs could selectively adsorb R‐enantiomer from ibuprofen racemate solution and give an enantiomeric excess (e.e.) of about 50% under an optimal adsorption condition. Moreover, the regeneration efficiency of the CCNPs remained above e.e. of 43% after the fifth cycle. The present work confirmed that the prepared CCNPs show great potential in the enantioselective separation of ibuprofen racemate. [ABSTRACT FROM AUTHOR]

Four new 2-pyrone derivatives, two pairs of enantiomers, (±)-egypyrone A [(±)-1] and (±)-egypyrone B [(±)-2], together with a new benzophenone analogue, orbiophenone B (3), were isolated from the endophytic fungus Penicillium egyptiacum. The enantiomeric mixtures (±)-1 and (±)-2 were separated through chiral HPLC, respectively. Their structures were elucidated by extensive analysis of spectroscopic data and the absolute configuration was determined by comparing the optical rotation of structurally similar molecule. Subsequently, the cytotoxic activities of (±)-1, (±)-2, and 3 against the U87 cell line were tested and no activity was observed at a concentration of 10 µM. [ABSTRACT FROM AUTHOR]

A novel metabolic pathway of 3,6-anhydro-l-galactose (l-AHG), the main sugar component in red macroalgae, was first discovered in the marine bacterium Vibrio sp. EJY3. l-AHG is converted to 2-keto-3-deoxy-galactonate (KDGal) in two metabolic steps. Here, we identified the enantiomeric nature of KDGal in the l-AHG catabolic pathway via stereospecific enzymatic reactions accompanying the biosynthesis of enantiopure l-KDGal and d-KDGal. Enantiopure l-KDGal and d-KDGal were synthesized by enzymatic reactions derived from the fungal galacturonate and bacterial oxidative galactose pathways, respectively. KDGal, which is involved in the l-AHG pathway, was also prepared. The results obtained from the reactions with an l-KDGal aldolase, specifically acting on l-KDGal, showed that KDGal in the l-AHG pathway exists in an l-enantiomeric form. Notably, we demonstrated the utilization of l-KDGal by Escherichia coli for the first time. E. coli cannot utilize l-KDGal as the sole carbon source. However, when a mixture of l-KDGal and d-galacturonate was used, E. coli utilized both. Our study suggests a stereoselective method to determine the absolute configuration of a compound. In addition, our results can be used to explore the novel l-KDGal catabolic pathway in E. coli and to construct an engineered microbial platform that assimilates l-AHG or l-KDGal as substrates. Key points: • Stereospecific enzyme reactions were used to identify enantiomeric nature of KDGal • KDGal in thel-AHG catabolic pathway exists in an l-enantiomeric form • E. coli can utilizel-KDGal as a carbon source when supplied withd-galacturonate [ABSTRACT FROM AUTHOR]

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To investigate the enantioselective behavior of chiral fungicide penthiopyrad in tomato under field and greenhouse conditions, a residue analytical method was developed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the determination of enantiomers of penthiopyrad in tomatoes based on an optimized QuEChERS approach. The proposed method was used for studying the behavior of residues, dissipation and accumulation of penthiopyrad enantiomers in tomato system under two cultivate patterns. The results indicated that at the range of 0.002-1 mg/L, the linearity of the penthiopyrad enantiomers was good with R ² > 0.99. At the spiked levels of 0.005, 0.1 and 1 mg/kg, the average recoveries of the R-(−)-PEN and S-(+)-PEN in different matrices were 77%-98% and 81%-101%, and the relative standard deviations (RSDs) were 1.6%- 5.1%and 1.6%-4.2%, respectively. The limit of quantification (LOQ) was 0.005 mg/kg. The degradation rates of the residues were < 30% in tomato samples stored at −20 ℃ for 100 d. The dissipation trend in tomato was fitted with the first-order kinetic equation in both the open field and greenhouse planting modes, and the correlation coefficients (r) were 0.9315-0.9400. The half-lives of R-(−)-PEN and S-(+)- PEN were 5.43 and 5.10 d in the open field, and were 8.09 and7.80 d in the greenhouse modes, respectively. The dissipation of S-(+)-PEN was faster than that of R-(−)-PEN, and the enantiomers of penthiopyrad was accumulated in tomato after repeated spraying. The results of residue distribution also showed that penthiopyrad enantiomers were mainly distributed in the leaves of tomato, and the concentration in tomato leaves, stems and fruits in greenhouse was higher than that in open field. On the 5th days after the last application, the residues of the penthiopyrad were lower than the maximum residue limit (MRL) in China, and the residues of its metabolite (PAM) were lower than the LOQ. The results indicated that the application of penthiopyrad on tomatoes in accordance with the recommended method complies with Good Agricultural Practices in China and meets the basic requirements for food safety [ABSTRACT FROM AUTHOR]

Drug isomers may differ in their proarrhythmia risk. An interesting example is the drug sotalol, an antiarrhythmic drug comprising d- and l- enantiomers that both block the hERG cardiac potassium channel and confer differing degrees of proarrhythmic risk. We developed a multi-scale in silico pipeline focusing on hERG channel - drug interactions and used it to probe and predict the mechanisms of pro-arrhythmia risks of the two enantiomers of sotalol. Molecular dynamics (MD) simulations predicted comparable hERG channel binding affinities for d- and l-sotalol, which were validated with electrophysiology experiments. MD derived thermodynamic and kinetic parameters were used to build multi-scale functional computational models of cardiac electrophysiology at the cell and tissue scales. Functional models were used to predict inactivated state binding affinities to recapitulate electrocardiogram (ECG) QT interval prolongation observed in clinical data. Our study demonstrates how modeling and simulation can be applied to predict drug effects from the atom to the rhythm for dl-sotalol and also increased proarrhythmia proclivity of d- vs. l-sotalol when accounting for stereospecific beta-adrenergic receptor blocking.

The crystal structure of (R,R)-4-bromo-2-{4-[4-bromo-1-(4-toluenesulfonyl)-1H-pyrrol-2-yl]-1,3-dinitrobutan-2-yl}-1-(4-toluenesulfonyl)-1H-pyrrole (1, C26H24Br2N4O8S2) is presented. The title compound was isolated in suitable yield as a by-product in our synthesis of geminal-dimethyl hydrodipyrrins. We observe an unforeseen enantiomeric resolution both in the bulk sample and the crystal of 1, with distinct C—H...O (Cmethyl—H...Onitro, Csp3—H...Osulfonyl) interactions observed in the enantiomers present, along with other interactions, namely C5-pyrrolyl—H...Osulfonyl, forming a polymer along the crystallographic c-axis direction. Whilst pyrrolic fragments are well documented in the literature, little data is found surrounding the 1,3-dinitrobutane scaffold.

Copyright of Journal of Shenyang Pharmaceutical University is the property of Shenyang Pharmaceutical University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Three pairs of enantiomers (1–3)—the new 12R-aloesol (1a) and two new fatty acids (2 and 3)—and one new natural product (4) together three known compounds (5–7) were isolated from a coral-reef-derived Streptomyces sp. SCSIO 66814. Their structures were determined through extensive spectroscopic analysis, chiral analysis, and single-crystal X-ray diffraction data. Compounds 2 and 3 were presumed to be intermediates for further generating homononactic acid (5) and nonactic acid, and the latter two molecules were able to act as precursors to form macrotetrolides with remarkable biological activity. The isolation of related precursors, compounds 2–5, provided more evidence to support the proposal of a plausible biosynthetic pathway for nonactic acid and its homologs. Additionally, (+)-1 exhibited a weak activity against DPPH radicals.

Tofacitinib citrate (RR-isomer) is a janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis (RA) in adults who have had an inadequate response or intolerance to methotrexate. The presence of the enantiomer of tofacitinib citrate (SS-isomer) is monitored for quality control as a possible impurity in the final product. In this study, a reversed-phase high-performance liquid chromatography (RP-HPLC) method based on a chiral recognition mechanism for the separation of tofacitinib citrate and its enantiomer was established based on the principles of green analytical chemistry. A CHIRALPAK IH column was used with a mobile phase of ammonium acetate buffer (pH 8.0) and acetonitrile in a gradient elution at a detection wavelength of 285 nm. The calibration curve exhibited excellent linearity over the range of 0.1002–20.04 μg/mL (r = 0.9999). The average recovery of the enantiomer was 98.6% with a relative standard deviation (RSD) of 0.7%. The limit of detection (LOD) and the limit of quantitation (LOQ) were 0.04 and 0.1 μg/mL, respectively. This RP-HPLC method was suitable for detecting the enantiomers of tofacitinib citrate in tablets. Furthermore, the method proved to be environmentally friendly based on the evaluation by Analytical Eco-Scale, Analytical GREEnness (AGREE) and Green Analytical Procedure Index (GAPI).

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.

Barbituric acid derivative (TDPT) is an achiral molecule, and its adsorption on a surface results in two opposite enantiomerically oriented motifs, namely TDPT-Sp and Rp. Two types of building blocks can be formed; block I is enantiomer-pure and is built up of the same motifs (format SpSp or RpRp) whereas block II is enantiomer-mixed and composes both motifs (format SpRp), respectively. The organization of the building blocks determines the formation of different nanoarchitectures which are investigated using scanning tunneling microscopy at a liquid/HOPG interface. Sophisticated, highly symmetric "nanowaves" are first formed from both building blocks I and II and are heterochiral. The "nanowaves" are metastable and evolve stepwisely into more close-packed "nanowires" which are formed from enantiomer-pure building block I and are homochiral. A dynamic hetero- to homochiral transformation and simultaneous multi-scale phase transitions are demonstrated at the single-molecule level. Our work provides novel insights into the control and the origin of chiral assemblies and chiral transitions, revealing the various roles of enantiomeric selection and chiral competition, driving forces, stability and molecular coverage. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium responsible for severe nosocomial infections and is considered a critical pulmonary pathogen for both immunocompromised and cystic fibrosis patients. Planktonic cells of P. aeruginosa possess intrinsic and acquired resistances, inactivating several classes of conventional antibiotics. Additionally, this bacterium can grow, forming biofilms, and complex structures, further hampering the action of multiple antibiotics. Here, we report the biological properties of D-Q53 CecB, an all-D enantiomer of the silkworm natural peptide Q53 CecB. Compared to the L-variant, D-Q53 CecB was resistant to in vitro degradation by humans and P. aeruginosa elastases and showed an enhanced bactericidal activity against P. aeruginosa planktonic bacteria. D-Q53 CecB was thermostable and maintained its antimicrobial activity at high salt concentrations and in the presence of divalent cations or fetal-bovine serum, although at reduced levels. Against different types of human cells, D-Q53 CecB showed cytotoxic phenomena at concentrations several folds higher compared to those active against P. aeruginosa. When L- and D-Q53 CecB were compared for their antibiofilm properties, both peptides were active in inhibiting biofilm formation. However, the D-enantiomer was extremely effective in inducing biofilm degradation, suggesting this peptide as a favorable candidate in an anti-Pseudomonas therapy. [ABSTRACT FROM AUTHOR]

The separation on the enantiomers of thirteen newly synthesised liquid crystalline racemic mixtures obtained on the basis of (R,S)-2-hexanol was studied in HPLC on a chiral column prepared by covalent immobilisation of the chiral selector, namely amylose tris(3-chloro-5-methylphenylcarbamate) on silica. The mobile phases (MPs) consisting of n-heptane/isopropanol (IPA) or acetonitrile (ACN)/water (H2O) at different volume ratios were used. All measurements were made at room temperature. The order of the elution was also determined. The chromatographic parameters such as: resolution - (R), selectivity - (α) and number of theoretical plates - (N) were determined. On the basis of the obtained results, optimal conditions were indicated for the best separation of the tested racemic mixtures. [ABSTRACT FROM AUTHOR]

One new nonadride enantiomer, ent-epiheveadride, along with five known dioxopiperazine derivatives were isolated from the marine-derived fungus Aspergillus chevalieri PSU-AMF79. Their structures were identified by extensive spectroscopic analysis. The absolute configuration of ent-epiheveadride was determined by comparison of the specific rotation and electronic circular dichroism data with those of related known compounds. It exhibited antifungal activity against Cryptococcus neoformans ATCC90113 flucytosine–resistant and Candida albicans NCPF3153 with the MIC values of 128 and 200 µg/mL, respectively. In addition, the known L-alanyl-L-tryptophan anhydride displayed TMEM16A inhibitory activity with 65.0% inhibition at a concentration of 5 µg/mL. [ABSTRACT FROM AUTHOR]

The crystal structure of (R,R)-4-bromo-2-{4-[4-bromo-1-(4-toluenesulfonyl)-1H-pyrrol-2-yl]-1,3-dinitrobutan-2-yl}-1-(4-toluenesulfonyl)-1H-pyrrole (1, C26H24Br2N4O8S2) is presented. The title compound was isolated in suitable yield as a by-product in our synthesis of geminal-dimethyl hydrodipyrrins. We observe an unforeseen enantiomeric resolution both in the bulk sample and the crystal of 1, with distinct C--H--O (Cmethyi--H--Onitro, Csp3--H--Osulfonyi) interactions observed in the enantiomers present, along with other interactions, namely C5-pyrrolyl--H-«-Osulfonyl, forming a polymer along the crystallographic caxis direction. Whiist pyrroiic fragments are weii documented in the iiterature, little data is found surrounding the 1,3-dinitrobutane scaffold. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Petrochemical Universities / Shiyou Huagong Gaodeng Xuexiao Xuebao is the property of Journal Editorial Department Of Liaoning Shihua University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hop-derived linalool can substantially impact beer aroma. However, during the processing and storage of beer, the (R )-linalool predominating in hops can undergo racemisation to the less potent (S )-enantiomer. The aroma impact of the (S )-linalool was difficult to assess, because reliable threshold data were unavailable. To fill this gap, enantiopure (S )-linalool was isolated from the racemate by HPLC using a chiral column. This (S )-linalool was used in parallel to enantiopure (R )-linalool to determine enantiospecific odour threshold concentrations of linalool in water and unhopped beer with a trained sensory panel. Results revealed orthonasal odour detection threshold concentrations of 0.82 and 8.3 µg/kg in water and 6.5 and 53 µg/kg in beer, for (R )- and (S )-linalool, respectively. The higher odour potency of the (R )-linalool was thus confirmed, however, its odour threshold concentrations were found to be only 8 to 10 times lower than the odour threshold concentrations of the (S )-linalool and not 80 times as previously approximated from GC-O data. The data will help to better understand the aroma impact of (R )- and (S )-linalool in beer. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Food Safety & Quality is the property of Journal of Food Safety & Quality Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Enantiomers show different behaviors in interaction with the chiral environment. Due to their identical chemical structure and their wide application in various industries, such as agriculture, medicine, pesticide, food, and so forth, their separation is of great importance. Today, the term "nano" is frequently encountered in all fields. Technology and measuring devices are moving towards miniaturization, and the usage of nanomaterials in all sectors is expanding substantially. Given that scientists have recently attempted to apply miniaturized techniques known as nano‐liquid chromatography/capillary‐liquid chromatography, which were originally accomplished in 1988, as well as the widespread usage of nanomaterials for chiral resolution (back in 1989), this comprehensive study was developed. Searching the terms "nano" and "enantiomer separation" on scientific websites such as Scopus, Google Scholar, and Web of Science yields articles that either use miniaturized instruments or apply nanomaterials as chiral selectors with a variety of chemical and electrochemical detection techniques, which are discussed in this article. [ABSTRACT FROM AUTHOR]

The crystal structure of (R,R)-4-bromo-2-{4-[4-bromo-1-(4-toluenesulfonyl)-1H-pyrrol-2-yl]-1,3-dinitrobutan-2-yl|-1-(4-toluenesulfonyl)-1H-pyrrole (1, C26H24Br2N4O8S2) is presented. The title compound was isolated in suitable yield as a by-product in our synthesis of geminal-dimethyl hydrodipyrrins. We observe an unforeseen enantiomeric resolution both in the bulk sample and the crystal of 1, with distinct C--H⋯O (Cmethyl--H⋯Onitro, C...--H⋯Osulfonyl) interactions observed in the enantiomers present, along with other interactions, namely C5-pyrrolyl--H⋯Osulfonyl, forming a polymer along the crystallographic c-axis direction. Whilst pyrrolic fragments are well documented in the literature, little data is found surrounding the 1,3-dinitrobutane scaffold. [ABSTRACT FROM AUTHOR]

The efficacies and toxicities of chiral drug enantiomers are often dissimilar, necessitating chiral recognition methods. Herein, a polylysine–phenylalanine complex framework was used to prepare molecularly imprinted polymers (MIPs) as sensors with enhanced specific recognition capabilities for levo-lansoprazole. The properties of the MIP sensor were investigated using Fourier-transform infrared spectroscopy and electrochemical methods. The optimal sensor performance was achieved by applying self-assembly times of 30.0 and 25.0 min for the complex framework and levo-lansoprazole, respectively, eight electropolymerization cycles with o-phenylenediamine as the functional monomer, an elution time of 5.0 min using an ethanol/acetic acid/H2O mixture (2/3/8, V/V/V) as the eluent, and a rebound time of 10.0 min. A linear relationship was observed between the sensor response intensity (ΔI) and logarithm of the levo-lansoprazole concentration (l-g C) in the range of 1.0 × 10−13–3.0 × 10−11 mol/L. Compared with a conventional MIP sensor, the proposed sensor showed more efficient enantiomeric recognition, with high selectivity and specificity for levo-lansoprazole. The sensor was successfully applied to levo-lansoprazole detection in enteric-coated lansoprazole tablets, thus demonstrating its suitability for practical applications. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a method for simultaneously separating ibuprofen enantiomers using electrospray ionization (ESI) liquid chromatography with tandem mass spectrometry (LC–MS/MS). LC–MS/MS was operated with negative ionization and multiple reaction monitoring modes; transitions were monitored at m/z of 205.1 > 160.9 for ibuprofen enantiomers, 208.1 > 163.9 for (S)-(+)-ibuprofen-d3 [internal standard 1 (IS1)], and 253.1 > 208.9 for (S)-(+)-ketoprofen (IS2), respectively. In a one-step liquid–liquid extraction, 10 μL plasma was extracted with ethyl acetate:methyl tertiary-butyl ether of 7:3. Enantiomer chromatographic separation was carried out with an isocratic mobile phase consisting of 0.008% formic acid in water–methanol (v/v) at a flow rate of 0.4 mL/min on a CHIRALCEL® OJ-3R column (150 × 4.6 mm, 3 µm). This method was fully validated for each enantiomer and results were in compliance with the regulatory guidelines of the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. The validated assay was executed for nonclinical pharmacokinetic studies after oral and intravenous administration of racemic ibuprofen and dexibuprofen in beagle dogs. [ABSTRACT FROM AUTHOR]