Structural analysis of (S)-1-((1H-benzo[d][1,2,3]triazol-1-yl)oxy)-3-(4-(2-methoxyphenyl)piperazin-1-yl)propan-2-ol and binding mechanism with α1A-adrenoceptor: TDDFT calculations, X-ray crystallography and molecular docking

Abstract The title compound, (S)-1-((1H-benzo[d][1,2,3]triazol-1-yl)oxy)-3-(4-(2-methoxyphenyl)piperazi-n-1-yl)propan-2-ol ( 1 ), belongs to a class of arylpiperazine derivatives that exhibit good bioactivity against α 1A -adrenoceptor. The current study describes conformational analysis of five energy-minimized conformers obtained at the B3LYP/6-31G(d) level of theory. The characteristically positive rotatory strengths at an excitation energy of 256 nm were achieved using time-dependent density functional theory (TDDFT) calculations. Molecular orbital studies clearly elucidated the origins of electronic transitions at 256 nm. The absolute configuration of (S)- 1 was unambiguously determined by single crystal X-ray diffraction analysis. Molecular docking solved the binding mode of 1 -α 1A -adrenoceptor complex. This work can serve as a basis for better drug design of highly selective antagonists with chirality.