Theoretical study of the possibility of L-tryptophan with thiotriazoline complex formation

Introduction. For the joint use of L-tryptophan with tiotriazoline, it is necessary to solve the problem of the possibility of formation of sufficiently stable intermolecular complexes of these compounds. Therefore, it seemed interesting to consider the possible structure and energetic characteristics of complexes formed by L-tryptophan, 3-methyl-1,2,4-triazolyl-5-thioacetate (MTTA) and morpholine to create a dosage form. Purpose of the study. To investigate the structure and evaluate the energy formation of three-component complexes of L-tryptophan, 3-methyl-1,2,4-triazolyl-5-thioacetate and morpholine quantum chemistry methods have been used. This study allows to estimate the possibility of combining these substances into a single dosage form. Materials and methods. Thiotriazoline and L-tryptophan were used as objects of the study. The initial approximation to the geometry of the complexes was obtained using the molecular docking technique using the AutoDock Vina program. At the first stage the docking was carried out for MTTA and morpholine, according to the results of which 50 most stable complexes were selected for the construction of three-component complexes. Further, docking of obtained complexes of MTA and morpholine with the L-tryptophan molecule was carried out, and also the 50 most stable complexes were selected. Thus, 2500 initial geometries were obtained for each of the three-component complexes. Study results. Quantum-chemical calculations show that L-tryptophan and thiotriazoline are capable to form three-component complexes, the molecules in which are connected by a lot of intermolecular hydrogen bonds. Each of the molecules is linked by intermolecular hydrogen bonds to the other two in one complex only. All other complexes contain the components which are linked sequentially: morpholine – MTTA – tryptophan. The results of quantum-chemical calculations make it possible to assume that the studied complexes are thermodynamically unstable in an infinitely dilute solution. The formation energies of the complexes are positive, despite the presence of a lot of charge assisted intermolecular hydrogen bonds. This can be caused by the high conformational flexibility of the molecules in which the groups participating in the formation of hydrogen bonds are separated by bridge containing several methylene groups and a fairly easy transfer of protons participating in the formation of hydrogen bonds. Findings. The results of quantum-chemical study of a system consisting of three components (L-tryptophan, MTTA and morpholine) showed that the most thermodynamically stable three-component complexes have a positive energy of formation in infinitely dilute solutions. Despite the possibility of the formation of intermolecular hydrogen bonds between the components, some of which are charge-assisted, the L-tryptophan, MTTA and morpholine system is a mixture of substances, which makes it possible to use it in a single dosage form