From Chemistry Towards Technology Step-By-Step From Chemistry Towards Technology Step-By-Step От химии к технологии шаг за шагом 2782-1900 82571 10.52957/27821900_2021_03_66 Научные статьи Scientific articles Научные статьи Influence of the nature of N-alkylation of glycolurils on their solvation structural effects in H/D-isotopologues of water based on the results of thermodynamic study of solutions Influence of the nature of N-alkylation of glycolurils on their solvation structural effects in H/D-isotopologues of water based on the results of thermodynamic study of solutions Иванов Евгений Викторович Ivanov Evgeny Viktorovich evi@isc-ras.ru

кандидат химических наук;

candidate of chemical sciences;

 Лебедева Елена Юрьевна Lebedeva Elena Yurievna eyl@isc-ras.ru

кандидат химических наук;

candidate of chemical sciences;

 Институт химии растворов им. Г.А. Крестова Российской академии наук Institute of Solution Chemistry of G.A. Krestov of the Russian Academy of Sciences 23 09 2021 23 09 2021 2 3 66 86 26 04 2024 https://chemintech.ru/en/nauka/article/82571/view

This review is based on the analysis of data on the structural and thermodynamic properties of tetra-N-alkyl-substituted bicyclic bis-urea of the octane series (glycolurils), singly and dissolved in H2O and D2O, obtained by other authors. The paper discusses issues of the influence of the stereochemical nature of these bioactive compounds on their hydration processes. The researched substances are the low-toxic glycolurils with pharmacologically pronounced psychotropic effects, known under the commercial names Mebicar (tetra-N-methylanalog), Bicaret (tetra-N-ethylanalog), and the cis- and trans-N-diethyl-dimethyl-analogs, Mebicaret and Albicar. The last listed glycoluril, which is chiral in stereochemical nature, was investigated as racemate. The study also included the analysis of the available results of calorimetric, densitometric, and spectroscopic (for Mebicar) studies of glycolurils solutions in H/D isotopologues of water as well as quantum-chemical calculations of molecular parameters of these heterocyclic compounds in the ideal gas phase. It has been shown that the hydration of each of the studied tetra-N-alkyl-substituted glycolurils can be generally regarded as a superposition of two mechanisms – hydrophobic and hydrophilic. In the case of Bicaret, the former is dominant, while for Mebicar the latter obviously predominates. Regarding to the structural state and solvation in aqueous medium of glycolurils with mixed N-alkyl-substitution such as Albicar and Mebicaret, the stereochemical nature of their molecules predetermines a kind of "thermodynamic balance (dualism)" between the mentioned mechanisms. The paper outlines the distinctive features of the hydration process of racemic Albicar against the effects of intermolecular interaction in aqueous solution of achiral Mebicaret.

This review is based on the analysis of data on the structural and thermodynamic properties of tetra-N-alkyl-substituted bicyclic bis-urea of the octane series (glycolurils), singly and dissolved in H2O and D2O, obtained by other authors. The paper discusses issues of the influence of the stereochemical nature of these bioactive compounds on their hydration processes. The researched substances are the low-toxic glycolurils with pharmacologically pronounced psychotropic effects, known under the commercial names Mebicar (tetra-N-methylanalog), Bicaret (tetra-N-ethylanalog), and the cis- and trans-N-diethyl-dimethyl-analogs, Mebicaret and Albicar. The last listed glycoluril, which is chiral in stereochemical nature, was investigated as racemate. The study also included the analysis of the available results of calorimetric, densitometric, and spectroscopic (for Mebicar) studies of glycolurils solutions in H/D isotopologues of water as well as quantum-chemical calculations of molecular parameters of these heterocyclic compounds in the ideal gas phase. It has been shown that the hydration of each of the studied tetra-N-alkyl-substituted glycolurils can be generally regarded as a superposition of two mechanisms – hydrophobic and hydrophilic. In the case of Bicaret, the former is dominant, while for Mebicar the latter obviously predominates. Regarding to the structural state and solvation in aqueous medium of glycolurils with mixed N-alkyl-substitution such as Albicar and Mebicaret, the stereochemical nature of their molecules predetermines a kind of "thermodynamic balance (dualism)" between the mentioned mechanisms. The paper outlines the distinctive features of the hydration process of racemic Albicar against the effects of intermolecular interaction in aqueous solution of achiral Mebicaret.

 tetra-N-alkyl-substituted glycoluriles; H/D water isotopologues; standard molar volumes and dissolution enthalpies; solvent isotope effects; molecular parameters; hydrophilic and hydrophobic hydration The authors are grateful to Dr. Chem. Professor A.N. Kravchenko and PhD Chem. V.V. Baranov (IOC RAS, Moscow, Russia), as well as Dr. Chem. D.V. Batov (ICR RAS), Dr. Chem. V.V. Alexandriiskii and PhD Chem. Yu.A. Zhabanov (ISUCT, Ivanovo, Russia) for invaluable assistance in the synthesis and preparation of glycolurils for experiments as well as experimental and quantum-chemical investigation of their properties in dissolved, crystalline and gaseous states.

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