Theoretical investigation of the molecular structure, vibrational spectra, and molecular docking of tramadol using density functional theory

Abstract

AbstractThe optimized molecular structures, harmonic vibrational wavenumbers, and the corresponding vibrational assignments of (1S,2S)‐tramadol and (1R,2R)‐tramadol are computationally examined using the B3LYP density functional theory method together with the standard 6–311++G(d,p) and def2‐TVZP basis sets. The optimized structures show that phenolic rings of both 1R,2R and 1S,2S tramadol adopt planar geometry, which are slightly distorted due to the substitution at the meta‐position; and the six‐membered cyclohexane adopts a slightly distorted chair conformation. The 1S,2S enantiomer is energetically more favorable than 1R,2R with the energy differences of 1.32 and 1.03 kcal/mol obtained at B3LYP/6–311++G(d,p) and B3LYP/Def2‐TVZP levels, respectively. The analysis of the binding pocket in the silico molecular docking with the m‐opioid receptor shows that it originated two clusters with the 1S,2S enantiomer and one cluster with the 1R,2R enantiomer of tramadol. The results point to a more stable complex of the m‐opioid receptor with the 1R,2R enantiomer of tramadol.