Facile C_sp²-C_sp² bond cleavage in oxalic acid-derived radicals

Oxalate decarboxylase (OxDC) catalyzes the Mn-dependent conversion of the oxalate monoanion into CO₂ and formate. Many questions remain about the catalytic mechanism of OxDC although it has been proposed that the reaction proceeds via substrate-based radical intermediates. Using coupled cluster theory combined with implicit solvation models we have examined the effects of radical formation on the structure and reactivity of oxalic acid-derived radicals in aqueous solution. Our results show that the calculated solution-phase free-energy barrier for C–C bond cleavage to form CO₂ is decreased from 34.2 kcal/mol for oxalic acid to only 9.3 kcal/mol and a maximum of 3.5 kcal/mol for the cationic and neutral oxalic acid-derived radicals, respectively. These studies also show that the C–C σ bonding orbital of the radical cation contains only a single electron, giving rise to an elongated C–C bond distance of 1.7 Å; a similar lengthening of the C–C bond is not observed for the neutral radical. This study provides new chemical insights into the structure and stability of plausible intermediates in the catalytic mechanism of OxDC, and suggests that removal of an electron to form a radical (with or without the concomitant loss of a proton) may be a general strategy for cleaving the unreactive C–C bonds between adjacent sp²-hybridized carbon atoms.