Methanol Solvation Effect on the Proton Rearrangement of Curcumin’s Enol Forms: An Ab Initio Molecular Dynamics and Electronic Structure Viewpoint

The recognition of the solvent effect on the enol–enol tautomerism in curcumin can guide the rationalization of systems of chemical and biological interest. Although the phenomenon is widely studied, the nature of the proton rearrangement involving the explicit solvation remains an important issue. In this study, we describe the phenomenon by an ab initio approach in gas-phase and methanol solution. The mechanism involved in the proton rearrangement has been investigated by Car–Parrinello molecular dynamics and the static M062X/DFT method. The free-energy landscape and potential energy surface in the methanol environment were explored and compared with the gas-phase one. The energy profile in methanol medium shows asymmetrical proton distribution in the curcumin enol forms and, inversely, a symmetrical behavior in the gas phase. The Gilli π-delocalization index and the HOMO orbital shape show a slight decrease in the resonance-assisted hydrogen bond (RAHB) in the solvated enol forms, different from the gas-phase system. The thermal rate constant of the intramolecular proton transfer indicated that the tunneling effect plays an important role when the curcumin molecule is under the influence of methanol. These results suggest a criterion to characterize the symmetry of the potential energy profile for the intramolecular proton transfer.