Azamat Z. Temerdashev

The determination of amino acid enantiomers plays an important role in addressing a wide range of analytical challenges. Chiral chromatographic columns are commonly used for this purpose; however, they are expensive and require highly qualified personnel. This study optimizes the derivatization conditions using the chiral derivatizing reagent Marfey’s reagent, which enables the determination of amino acid enantiomer derivatives by reversed-phase UHPLC–HRMS with a C₁₈ column. The D- and L-forms of the analytes exhibited identical ionization efficiencies, an important prerequisite for accurate quantitative chemical analysis. The results also demonstrate that gabapentin can serve as an internal standard instead of isotope-labeled analytes. Under the optimized conditions, the method achieved detection limits of 20 ng/mL for the compounds investigated.

2-hydrazinyl-1,3-benzothiazole (HBT), 4-amino-4H-1,2,4-triazole (AT) and 2-hydrazinyl-1H-benzimidazole (HBI) were evaluated in this study as novel derivatization agents for the determination of steroid hormones in urine. The derivatization reactions were based on the interaction between the carbonyl group of steroids and the primary amino group of novel reagents. Optimal conditions for the derivatization of steroid hormones with novel agents, including pH, agent concentration, temperature and time of reaction were established. The resulting derivatives were separated and detected using reversed-phase ultra-high performance liquid chromatography–quadrupole time-of-flight mass spectrometry. The methods developed for achieved detection limits of 0.015–0.15 ng/mL for HBT derivatives, 0.15 ng/mL for AT derivatives and 0.075–0.15 ng/mL for HBI derivatives, respectively. During the reaction with these new agents, both syn- and anti-forms of derivatives of steroid hormones are formed, similar to other hydrazines. Based on the molecular properties of the obtained derivatives, the influence of substituents on the chromatographic characteristics was studied. The procedure was successfully applied to the analysis of authentic urine samples, and the results were compared with those obtained from hydroxylamine-based and Girard’s reagent T-based derivatization, demonstrating the prospects for further study of new reagents.

Triethylammonium (E)-2-oxo-1-(2-oxoindolin-3-ylidene)-2-phenylethane-1-thiolate, readily obtained from phenacyl thiocyanate and isatin, undergoes efficient S-alkylation with alkyl halides in refluxing DMF. When ethyl 4-chloroacetoacetate is employed, the reaction affords (E)-3-[2-oxo-1-{(2-oxopropyl)thio}-2-phenylethylidene]indolin-2-one via in situ Krapcho decarboxylation of the intermediate β-keto ester; the structure was confirmed by X-ray crystallography. Quantum chemical calculations (ωB97X-3c/CPCM) reveal that the (E)-isomer of the starting thiolate is thermodynamically favored by ~18 kJ/mol over the (Z)-form in EtOAc. In silico ADMET profiling and protein-ligand docking studies indicate favorable bioavailability parameters and potential interactions with targets such as stromelysin-1 (MMP-3), FABP4, and PPAR-γ, suggesting possible anti-inflammatory and antidiabetic applications. Under laboratory conditions, the starting thiolate exhibits significant protective (antidote) activity against the herbicide 2,4-D in sunflower seedlings, increasing hypocotyl and root lengths by up to 126 and 154%, respectively.

Background/Objectives: The dysregulation of thiol metabolites is strongly linked to hepatocellular carcinoma (HCC) pathogenesis. However, quantifying these highly polar and oxidation-prone thiols in clinical serum samples via conventional liquid chromatography–mass spectrometry (LC-MS) remains challenging due to their poor sensitivity and reproducibility. Methods: We developed a sensitive and robust iodoacetamine-alkyne (IAM) derivatization–based LC-MS method for quantification of seven trans-sulfuration pathway thiols in human serum. Results: IAM derivatization markedly improved the method’s specificity due to enhanced chromatographic retention and diagnostic MS/MS fragments containing both the alkyne tag and analyte backbone. Sensitivity increased 33-to-160-fold versus underivatized analytes, with limits of detection of 0.02–0.1 nM. All analytes exhibited good linearity, acceptable precision with intra-day and inter-day relative standard deviations in the range of 1.2–13.8%, and high recovery from 88.6% to 102.9%. Conclusions: From the thiol quantification in human serum from 40 HCC patients and 40 healthy controls, it was found that levels of cysteine, homocysteine, glutathione, and cysteinylglycine were significantly lower in HCC patients (p < 0.05). A two-variable logistic regression model using cysteine and cysteinylglycine achieved 90.0% specificity and 80.0% sensitivity for robust HCC discrimination between HCC patients and healthy controls to some extent, with an area under the receiver operating characteristic curve of 0.88 (95% confidence interval: 0.792–0.968).

This work aimed to synthesize new derivatives of 2-hydrazinylpyridine-3-carbonitrile and to investigate their biological activity as safeners for the 2,4-D herbicide. The new 2-hydrazinylnicotinonitriles were obtained in high yields (up to quantitative) under mild conditions (25 °C, dioxane) by treating 4,6-diaryl-2-bromo-3-cyanopyridines with hydrazine hydrate. The latter were synthesized by brominating 2-(3-oxo-1,3-diarylpropyl)malononitriles, the Michael adducts, which are readily available from 1,3-diarylpropenones (chalcones) and malononitrile. An unusual side product of the bromination/carbocyclization was isolated and characterized; it consisted of co-crystals of 3-benzoyl-4-hydroxy-4-phenyl-2,6-di-(p-tolyl)cyclohexane-1,1-dicarbonitrile and 3-benzoyl-5-bromo-4-hydroxy-4-phenyl-2,6-di-(p-tolyl)cyclohexane-1,1-dicarbonitrile at a ~4:6 ratio. The new 2-hydrazinylnicotinonitriles react with halogen-containing aromatic aldehydes to form the corresponding hydrazones. The biological activity of the new nicotinonitriles was examined for their function as 2,4-D antidotes. It was found that, under laboratory conditions, eight of the synthesized compounds exhibited a notable antidote effect against 2,4-D on sunflower seedlings.

Cyanoselenoacetamide reacted with 1-aryl-2-bromoethanones in ethanol or DMF to give 4,6-di­amino-2-[(2-aryl-2-oxoethyl)selanyl]pyridine-3-carbonitriles in 68–93% yields.