Theoretical Studies on the Conformation of Protonated Dopamine in the Gas Phase and in Aqueous Solution

Abstract

A trans (T) and two gauche (G1 and G2) conformers have been identified for protonated dopamine in the gas phase upon ab initio calculations up to the QCISD(T)/6-31G*//HF/6-31G* and MP2/6-311++G**//MP2/6-311++G** levels and based on B3LYP/6-31G* optimizations in DFT. Free energy differences at 298 K and 1 atm were calculated to be 3.2−5.6 kcal/mol between T and G1, and about 0 kcal/mol between the G2 and G1 conformers. The OH groups are nearly coplanar with the benzene ring and form an O−H···O−H intramolecular hydrogen bond in their most stable arrangement. Using the free energy perturbation method through Monte Carlo simulations, relative solvation free energies were evaluated in aqueous solution at T = 310 K and 1 atm. Ab initio/Monte Carlo torsional potential curves were calculated along pathways where small rotations about the C(ring)−Cβ and Cβ−Cα axes were allowed. No stable rotamers but the gas-phase optimized structures were identified. The T − G1 and G2 − G1 relative solvation free energies were ca...