Regarding the torsional flexibility of the dihydrolipoic acid's pharmacophore: 1,3-propanedithiol

Abstract

The conformational space of antioxidant dihydrolipoic acid has been explored through the investigation of its pharmacophore, 1,3-propanedithiol. Five of the possible 25 non-equivalent isomers (namely: gGGg′, gGGg, g′AGg, gAGg and g′AGg′) were observed in the 59.6–74.4 GHz frequency region using free-jet absorption rotational spectroscopy. Furthermore, for three of them, the ³⁴S mono-substituted isotopologues were also detected in natural abundance. Theoretical simulations show that the balance of steric and electronic intramolecular interactions arises on a shallow conformational potential energy surface and suggest that in polar solvents the flexibility of the dithiol chain is greater than that in the isolated phase.