Theoretical study of the possibility of glycin with thiotriazoline complexes formation

Abstract

Brain strokes are widely spread all over the world and are among the most dangerous for the population. Often it leads to death, complete or partial loss of ability to work. The correction of imbalance of Excitatory and inhibitory neurotransmitter systems by activation of natural inhibitory processes is a promising direction of primary neuroprotection in cerebral ischemia. Particular attention is drawn to the natural inhibitory neurotransmitter – glycine and its role in the mechanisms of acute cerebral ischemia. There are data on the ability of the thiotriazoline antioxidant to potentiate the therapeutic effect of neurometabolic cerebroprotectors. Therefore, the creation of new combined preparation based on glycine with thiotriazoline is important today. Objective: to study the structure, and estimate the energy of formation and geometric characteristics of the intermolecular hydrogen bonds for complexes which are formed with glycine, 3-methyl-1,2,4-triazolyl-5-thioacetate (MTTA) and morpholine. Method of calculation. The initial approximation to the structure of the complexes was obtained with the help of molecular docking procedure using the AutoDock Vina program. The resulting three-component complexes were preliminarily optimized by the semiempirical PM7 method, taking into account the outward influences, which was simulated by the COSMO method. The calculations were carried out using the MOPAC2012 program. The complexes were optimized using the density functional method with the empirical dispersion correction B97-D3/SVP+COSMO (Water) using geometric correction for the incompleteness of the gCP basic set. A more accurate calculation of the solvation energy was carried out by SMD method. Calculations by the density functional method were carried out using the ORCA 3.0.3 program. The energy of formation of complexes in solution was calculated as the difference between the free Gibbs energies of the solvated complex and its individual solvated components. Results and its discussion. Quantum-chemical modeling of the complexes of thiatriazoline and glycine has showed the possibility of the formation of multiple hydrogen bonds in them. The results of calculations show that the multiplicity of charge-enhanced donor and acceptor sites for hydrogen bonding leads to the formation of complexes that are different in structure but close in energy formation. Conclusions. The conducted quantum-chemical study of system has shown the possibility of formation of three-component complexes with low stability in infinitely diluted solutions. The glycine molecule tends to form not only intermolecular hydrogen bonds, but also a charge-enhanced intramolecular hydrogen bond. It can be expected that in real solutions the enhancement of intermolecular interactions can lead to an increase in the stability of the complexes.

Keywords

• glycine
• thiotriazoline
• quantum chemical calculations
• molecular complexes