Nikolai S. Zefirov

Computer-aided search for high-density energetic compounds among hydrogen-free heterocycles

Abstract Our general strategy of a computer-aided search for compounds with the desired physicochemical properties includes three principal stages. The first stage is the selection of possible compositions (molecular formulas) and formulation of structural requirements that may ensure the necessary properties of target compounds. The second stage is computer generation of all molecules that conform to the set of structural constraints formulated at the first stage. The third stage includes the estimation of properties for the resultant compounds and selection of the most promising structures, which may be the targets of a subsequent synthetic search. This strategy was successfully applied to search for high-density energetic compounds among nitrogen-containing hydrogen-free aromatic heterocycles structurally similar to the highly stable energetic compound known as TACOT. A number of hypothetical substances with calculated energy content and density higher than those of TACOT were predicted, and certain qualitative structure–property relationships (which may assist in a further search for compounds with similar properties within other classes) were revealed among them. Some of the predicted compounds may be proposed for synthesis, experimental study and possibly for practical use.

On a quantum chemical interpretation of molecular connectivity indices for conjugated hydrocarbons

Abstract The topological indices (TIs)—invariants of weighted molecular graphs representing the chemical structures—are widely used as molecular descriptors in quantitative structure-property relationships (QSPR). The essential disadvantage of the TIs-method in QSPR is the absence of any physical-chemical interpretation of the majority of TIs used in QSPR. This leads to problems in the choice of TIs and justification of the obtained correlations, the “TIs-property”. In the present paper a quantum chemical interpretation of connectivity TIs widely used in QSPR for some classes of conjugated hydrocarbons is suggested. The results obtained justify using these TIs in QSPR for such compounds.

Quinone reductase 2 and antidepressant effect of melatonin derivatives

Melatonin and its immediate precursor, N‐acetylserotonin (NAS), exert antidepressant effects in experimental models and clinical studies. We reported that melatonin and NAS decreased immobility time (an indicator of antidepressant activity) in the mouse tail suspension test. Melatonin type 3 receptor (MT3) was identified as the same protein as quinone reductase 2 (QR2) detoxifying and antioxidant enzyme. To further elucidate the role of QR2/MT3 in antidepressant action of NAS and melatonin, we studied the effect of QR2/MT3 agonist and antagonist in a tail suspension test. QR2/MT3 agonist 5‐MCA‐NAT decreased, while the QR2/MT3 antagonist prazosin increased the duration of immobility in the tail suspension test in a dose‐dependent manner. Prazosin, in a dose that did not affect the duration of immobility, attenuated the antidepressant‐like effect of NAS, melatonin, and typical tricyclic antidepressant, amitriptyline, in the tail suspension test. Our results suggest that the modulation of QR2/MT3 might contribute to mechanism(s) of antidepressant effect. New antidepressants might be searched among the agonists of QR2/MT3.

Versatile computerized system for tracking and analysis of water maze tests

A crucial step in the estimation of properties of compounds in behavioral experiments is the quantification and description of the different effects observed. The goal of the present work was the automation of the Morris water maze test, one of the most popular behavioral methods for the study of animal memory. An original system was developed that provides fast and accurate tracking of animals, storage of the results in the database and video archive and a means of analyzing the results. This computerized version of the Morris water maze test permits the quantification of such vague characteristics of cognitive function as the “directionality” of search of the hidden platform after a standard training series. The suggestedparameters made it possible to discriminate cognitive properties of the novel compounds from other behavioral effects affecting escape latency. The effectiveness of this system was demonstrated in two experiments with neurochemically lesioned and drug-treated rats.

ALKENYLSULFENYLCHLORIDES : SYNTHESIS AND ADE REACTIONS OF 2-ALKOXY-2-OXO-3-R-4-CHLOROTHIO-1,2-OXAPHOSPHOL-3-ENES

Synthesis of titled representatives of alkenylsulfenylchlorides by the reaction of SCl2 with allenes 1 and 2 is described and their AdE reactions with some model olefins are discussed.

Computer simulation of thermal decomposition reactions of alkyl nitrates

An approach to the construction of models for thermal decomposition of organic compounds based onrecombination reaction networks was developed. Each species (molecule, ion, or radical) is considered as a potential reagent. It was suggested that the newly formed species can react with all other species which are already present in the reaction mixture. The results of reactions are represented as a bipartite graph whose vertices are formed either by species generated or by the descriptions of interactions, while the oriented edges determine the relations between the reagents and the reaction products. Based on analysis of the experimental data on the mechanisms of thermal decomposition, empirical rules were developed for simulating possible thermal decomposition reactions of the major classes of energetic compounds. The proposed approach allows one to describe the complete spectrum of reactions occurring in the course of thermal decomposition. The approach was realized in the CASB computer program and was exemplified by simulation of thermal decomposition of methyl, ethyl, and isopropyl nitrates. All stages of the mechanisms (some of which have been reported in the literature) were reproduced. A number of new decomposition reactions, which have not been studied experimentally, are suggested.

Approximate molecular electrostatic potential computations: applications to quantitative structure-activity relationships

Abstract Two new methods for calculating molecular electrostatic potentials are considered, taking into account QSAR requirements. The first of these is based on quantum chemical approximations; the other uses the topology of molecules. A program for displaying potential contour maps generated by various methods is presented. Examples of the successful use of these methods are given.

Physiologically active bis(dialkylamides) of phosphoryl-substituted α,ω-dicarboxylic acids

Bis(dialkylamides) of phosphoryl-substituted α,ω-dicarboxylic acids were synthesized and their biological activity was studied.

Hexadecapropyloxy-substituted diphthalocyanine complexes of rare-earth elements: synthesis, spectroscopic and electrochemical studies

Hexadecapropyloxy-substituted diphthalocyanine complexes of rare-earth elements (REE = Lu, Tm, Sm) were synthesized. The new symmetrically substituted diphthalocyanine complexes prepared starting from 4,5-dipropyloxyphthalodinitrile (phthalogen) are characterized by better solubilities compared to the known hexadecamethyl-substituted diphthalocyanine complexes of the same REE. Spectral and electrochemical characteristics of the complexes were studied. The compounds can be used as materials for high-contrast electrochromic devices.

Synthesis of novel non-natural conformationally restricted cyclopropane amino acids of spirane series

New conformationally rigid spirane analogues of γ-aminobutyric acid, namely, 4-aminospiro[2.2]pentanecarboxylic and 1-aminospiro[2.3]hexane-5-carboxylic acids were synthesized from the corresponding 4and 5-methoxycarbonyl-1-nitrospiro[2.n]alkane-1-carboxylic esters obtained in turn by the [1+2] cycloaddition of ethyl nitrodiazoacetate to methylidenecycloalkanecarboxylic esters.