Structural, spectroscopic, and in silico studies of 3-(dimethylamino)-1-(thiophen-2-yl)propan-1-ol: A potential antidepressant agent

Abstract The present study reports structural, spectroscopic signatures, reactivity parameters, and in silico anti-depressant activity of the title compound 3-(dimethylamino)-1-(thiophen-2-yl)propan-1-ol (DMATP). The structure of the DMATP compound has been unambiguously obtained through single crystal X-ray diffraction, vibrational spectroscopy, and thermal (TGA-DTA) analysis. DMATP is a chiral molecule containing a chiral methine carbon with S configuration and because of its chirality the compound crystallizes in the non-centrosymmetric orthorhombic P212121 space group. The thiophene ring and the attached nearly-planar side chain (excluding hydroxyl and one of the methyl group) are oriented to each other making a dihedral angle of 11.2(3)°. The –CH2 CH2 bond at the center of the side chain has a staggered conformation. In the crystal structure, the molecules are linked via O H…N hydrogen bonds forming C(6) chains propagating along a-axis resulting in a one dimensional architecture. The intermolecular interactions were analysed qualitatively as well as quantitatively with the aid of 3D-Hirshfeld surface and 2D-fingerprint plot analysis. The optimization of the geometry of the DMATP molecule was performed at DFT/B3LYP/6–311G(d,p) basis set and showed good agreement with the experimental results. The assignment of each vibrational wavenumber was done according to potential energy distribution (PED) analysis. Furthermore, frontier molecular orbital analysis (FMO's), global reactivity parameters, nonlinear optical (NLO) properties, and nonbonding orbital (NBO) analysis were carried out by the same method. Local reactive properties of the title compound were explained by molecular electrostatic potential (MEP), and Fukui functions. The dissociation energies of hydrogen and other single bonds have been also estimated in order to understand the autoxidation mechanism and degradation properties. An anti-depressant study of the DMATP compound was carried out with human serotonin carriers (PDB ID: 5I73 ) and compiled a binding mechanism with standard anti-depressant drugs such as duloxetine, desvenlafaxine, and atomoxetine.