The effects of conformation on the acidity of ascorbic acid: a density functional study

Ascorbic acid (AsA; ascorbate; vitamin C; C6H8O6) is a potent antioxidant in both the cytosolic and membrane components of the human body. AsA serves a protective function as a free radical scavenger and plays a non-direct antioxidam role by aiding in the reduction of the alpha-tocopheroxy radical back to alpha-tocopherol. Two hydroxyl moieties (defined as chi(1) and chi(2)) are paramount to the conformational profile of AsA. One hydroxyl group, chi(1), is initially deprotonated in AsA's antioxidant mechanism. To explore AsA's acidic character, selected conformations were optimized at the B3LYP/6-31G(d) level of theory and their adiabatic energies of deprotonation calculated. The lowest and highest energies of deprotonation were found to occur in the conformers aa3h-p (chi(1) = g(+), chi(2) = g(+), chi(3) = g(-), chi(4) = anti, chi(5) = g(-), chi(6) = g(-)) at 320.92 kcal mol(-1) and aall-p (chi(1) = g(-), chi(2) = anti, chi(3) = anti, chi(4) = g(+), chi(5) = g(-), chi(6) = anti) at 343.84 kcal mol(-1) respectively. Conformers with minimal intramolecular stabilization had the lowest energies of deprotonation while conformers exhibiting multiple hydrogen bonds had larger energies of deprotonation. In light of these findings, it is hypothesized that higher energy conformations will be favoured in the deprotonation of AsA antioxidant mechanism of action. (C) 2003 Elsevier B.V. All rights reserved.