Theoretical study of the reaction of vitamin B6 with 1O2.

Singlet oxygen is known to cause oxidative stress in cells, leading to severe damage (e.g., lipid peroxidation, membrane degradation, mutagenic alterations to DNA, protein misfunctionality). Recently, pyridoxine has been discovered to be capable of quenching singlet oxygen, however, the mechanism of this reaction remains essentially unknown. In this work, we have investigated four sets of reactions: 1) 1,3-addition to a double bond connected to a hydrogen-carrying group, resulting in the formation of allylic hydroperoxides; 2) [pi2+pi2] 1,2-cycloaddition to an isolated double bond, resulting in the formation of 1,2-peroxides; 3) 1,4-cycloaddition to a system containing at least two conjugated double bonds, resulting in the formation of the so-called 1,4-peroxides; 4) 1,4-addition to phenols and naphthols with the formation of hydroperoxide ketones. Thermodynamically, reaction 4 and the 6(9), 3(8), and 5(8) cases of reaction 1 are the most exergonic ones, with energies ranging from -16 to -18 kcal mol(-1). Furthermore, reaction 4 shows the lowest barrier through the reaction path, and is predicted to be the preferred mechanism for the pyridoxine + singlet-oxygen reaction, which is in agreement with previous experimental results.