A.E. Arbuzov Institute of Organic and Physical Chemistry

ABSTRACT Conjugated nitroalkenes, particularly 1‐aryl‐3‐nitroprop‐2‐en‐1‐ones, represent a valuable class of electrophilic substrates due to the presence of electron‐withdrawing groups that enable selective nucleophilic attacks. This study explores the reactivity of these nitropropenones and their brominated analogs with benzohydrazide, phenylsemicarbazide, and semicarbazide. The reactions predominantly proceed via aza‐Michael addition, yielding adducts that can be further transformed through elimination of HNO 2 or HBr to monohydrazones of α‐diketones with good to excellent yields. Structural studies, including NMR and x‐ray crystallography, revealed the E‐s‐trans configurations of the synthesized compounds. Importantly, in silico PASS analysis predicts high potential biological activities for the synthesized compounds, notably as inhibitors of various enzymes. These findings highlight the synthetic accessibility and promising pharmacological profile of nitroalkene‐derived hydrazone compounds, encouraging their further exploration for therapeutic applications.

The structure of two nitrogen-containing heterocyclic analogs of mucochloric and mucobromic acids - 3,4-dichloro- and 3,4-dibromo-5-hydroxy-1,5-dihydro-2H-pyrrol-2-ones - is studied. It is established by XRD that the crystals of the two pyrrolinones are not isostructural, despite their similar molecular geometries and the same space group P21/c. On the contrary, the type of stereoisomeric recognition and, consequently, the crystal lattice architecture can be controlled by varying the halogen nature.

The high catalytic power of cholinesterases results from an efficient interplay between optimised structure, molecular dynamics and fine adjustment of substrates in the active site. Kinetic and molecular modelling investigations of the catalysis of 'inverse' ester substrates compared to 'normal' ester substrates by butyrylcholinesterase (BChE) were performed to shed light on the effect of isomeric inversion of the ester bond on binding and catalytic steps. The substrates used were phenyl-acetate (PhA), -propionate (PhPr), -butyrate (PhBu). The 'inverse' substrates used were benzoic acid methyl ester (BAME), phenyl acetic acid methyl ester (PAAME) and phenyl propionic acid methyl ester (PPAME). Inversion of the ester bond dramatically affected catalytic efficiency. Comparative analysis of the kinetics of both types of substrates showed that hydrolysis of 'inverse' substrates was only possible at high enzyme concentrations, and the rates were first-order, indicating (S)max << Km. The ratio of specific activity (kcat/Km) between normal and 'inverse' substrates increased 12-fold from PhA/BAME to PhPr/PAAME. PhBu was the best substrate, while PPAME was not hydrolysed by BChE. Thus, introduction of methylene group(s) in the acyl moiety of substrates progressively increased kcat/Km, while introduction of methylene group(s) in phenol/alcohol moiety of 'inverse' substrate considerably decreased kcat/Km, indicating dramatic loss of substrate complementarity to the active site. QM/MM and molecular dynamics simulations revealed the molecular basis for altered kinetics of 'inverse' substrate hydrolysis. The observed effects stemmed from reduced stability of reaction intermediates and transition states, along with inversion of the productive complex conformation. BChE exhibited no selectivity for this conformation or alternative binding modes.

A one‐step, one‐pot method for the preparation of dihydroacridine bisphosphonates at room temperature by Fc/Fc + ‐mediated electrochemical synthesis using (RO) 3 P (R=alkyl) and acridines in good yields at room temperature is proposed. This is the first example of twofold C–P formation via synchronous aromatic C–H phosphorylation. 9,10‐Dihydroacridine derivatives are commonly found as privileged structural motifs in OLEDs, bioactive substances, photocatalysts, and various materials for useful applications. However, synthesis of these compounds from starting materials usually involves multiple stages. To date, no examples have been reported of the formation of geminal bisphosphonates on a single carbon atom through the phosphorylation of a C(sp 2 )–H aromatic fragment. The proposed method is also applicable for xanthene and acridine orange derivatives, but the yields of the bisphosphonates are lower. The products were characterized using X‐ray crystallography. Their redox properties were determined through cyclic voltammetry. Paramagnetic compounds formed under oxidation conditions were analyzed using the electron paramagnetic resonance method.

Ethylene glycol (EG) is commonly found as the main organic contaminant in airport runoff water during the cold season due to its use in the composition of de-icing fluids. Despite relatively low acute and chronic toxicity, EG may lead to a rapid growth of undesirable microbial biofilms in water bodies, thus reducing the concentration of dissolved oxygen and suppressing biodiversity. EG degradation using hydrogen peroxide activated with UV‑C light (H2O2/UV‑C) is a promising method of solving this problem because H2O2 serves as a cheap and green oxidant and provides complete EG mineralization in aqueous solutions. This paper describes the results of the in-depth study on the effect of adding Fe2+ ions and saturating the reaction solution with oxygen on EG degradation in the H2O2/UV system, showing the synergistic effect of both these factors on boosting the rate of EG removal and the depth of its mineralization. Comprehensive analysis of EG degradation and individual oxidation of key EG intermediates using TOC and HPLC methods revealed the roles of Fe2+ ions and dissolved oxygen in the synergistic effect and allowed us to clarify the main pathways of EG degradation in this system.

The intercellular contact between a motor neuron and a skeletal muscle fiber is a common model for electrophysiological studies of the mechanisms underlying chemical synapse function. However, data on the features of the neuromuscular synaptic transmission process in animals during early postnatal development are extremely scarce, and no systematic study of changes in electrophysiological parameters during ontogeny has been conducted. Using a relatively recently proposed model, namely the mouse m. levator auris longus neuromuscular preparation, and the classical method of muscle fiber dissection used to block contractions, we performed for the first time a detailed analysis of the most frequently used electrophysiological parameters characterizing the processes of spontaneous and evoked quantal acetylcholine release from motor nerve endings: amplitude-temporal parameters of spontaneous and evoked endplate potentials, miniature endplate potential frequency, quantal content, and latency of evoked responses. We described the dynamics of changes in the recorded parameters throughout the entire period of the mouse life. Particularly pronounced changes were identified precisely in the first days after birth, but it also turned out that neuromuscular signaling in two-week-old animals still differs significantly from that in the synapse of a sexually mature organism in a number of parameters. The obtained data can be used in the future to study the ontogenetic features of various neuroregulatory processes.

This review is devoted to research in the field of photodynamic and photothermal therapies for malignant tumors. Special attention in the review is given to photosensitizers based on compounds with a tetrapyrrole ring system, their metal complexes, BODIPY and aza-BODIPY derivatives, squaraines, and photoactivators based on metal complexes with other ligands such as phenanthroline and its derivatives, metronidazole, pyridine, and imidazole derivatives. Additionally, the review considers nanosized carriers for photosensitizers, such as organic and inorganic nanoparticles, liposomes, and extracellular vesicles. This review also discusses the dark toxicity and phototoxicity of these compounds and the processes of free oxygen radical formation, mitochondrial dysfunction, and induction of apoptosis in cancer cells. It has been established that nanoscale delivery systems are more promising for use in photodynamic and photothermal therapy compared to molecular photosensitizers. This is due to their improved solubility in physiological environments, selective accumulation in tumors, prolonged photoactivity, and lower therapeutic dose, which allows for the minimization of the side effects of treatment. Among the molecular photosensitizers under consideration, amphiphilic tetrapyrroles appear to be the most promising. Specifically, tetrapyrrole complexes of indium (III) and iridium (III) with non-porphyrin ligands exhibit favorable photophysical and biological characteristics. The review also indicates that photosensitizers tend to localize in the mitochondria of tumor cells, contributing to oxidative stress and apoptosis activation. This review may be of interest to biochemists and oncologists.

This study describes synthesis and biological evaluation of a new phosphonamidate and a series of α-aminophosphonates, employing propargylamine as a key NH-nucleophilic synthon. Two synthetic approaches were successfully implemented: (i) the reaction with O-ethyl (3,5-di-tert-butyl-4-hydroxybenzyl)phosphonоchloridate to form a P–N bond; (ii) a 1,6-aza-Michael addition to dialkyl/diphenyl [(3,5-di-tert-butyl-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]phosphonate, affording the α-aminophosphonate scaffold via C–N bond formation. Initial in vitro cytotoxicity screening against a panel of human cancer cell lines using the MTT assay revealed that the phosphonamidate derivative exhibited the highest activity within the synthesized series.