Solvent effects on the antioxidant activity of 3,4-dihydroxyphenylpyruvic acid : DFT and TD-DFT studies

In the human body, free radicals or reactive oxygen species (ROS) can be generated excessively and lead thereafter to many diseases. However, it was proved that 3,4-dihydroxyphenylpyruvic acid (3,4-DHPPA) presents an antioxidant activity sufficient to fight against these harmful molecules through different mechanisms. The antioxidant activity of this phenolic acid (PhA) was previously evaluated in the vacuum. Since most biological processes occur in solvent, in this work, solvent effects on the antioxidant activity of this PhA and its UV-Vis absorption spectrum were investigated using B3LYP/6-31+G*, 6-311++G** and Integral Equation Formalism Polarizable Continuum Model (PCM) methods. The solvation is described in a hybrid manner, since PCM methods fail in describing solute-solvent short range interactions. The antioxidant activity of four of the twelve conformers of this PhA is evaluated thermodynamically in different media and it is pointed out that, the less stable representative conformer of 3,4-DHPPA is the most responsible of the ROS scavenging. Solvent effects on bond dissociation enthalpy is very weak (0-25 kJ mol−1), but sufficient to influence hydrogen bonds and to invert the order of the preferential sites of hydrogen atom cleavage. In addition, solvent notably influences and changes the nature of the scavenging mechanism of ROS, favouring by this way the sequential proton loss electron transfer in polar solvents and the homolytic hydrogen atom transfer in non-polar solvents. Finally, it is worth mentioning that solvent induces a considerable red shift of the absorption maximum of 3,4-DHPPA going from the vacuum, and a slight blue shift of the transition S0 → S1 going from less polar to more polar solvents.