Solvent polarity effects and limited acid catalysis in rearrangements of model radicals for the methylmalonyl-CoA mutase- and isobutyryl-CoA mutase-catalyzed isomerization reactions

The kinetics of reactions of models for the intermediate radicals formed in the methylmalonyl-CoA mutase- and isobutyryl-CoA mutase-catalyzed rearrangements were studied by laser flash photolysis methods. The aldehyde-containing model analogous to the propanal-3-yl radical reacted via 3-exo cyclization with rate constants that varied with solvent polarity (k in the range 2 x 105 to 1 x 107 s-1). The analogous methyl ketone-containing radical reacted 2 orders of magnitude less rapidly, and the ethylthiocarbonyl-containing radical analogue reacted too slowly for kinetic measurements. No acid catalysis was observed in acetic acid, but the CF3CO2H-complexed radicals reacted 1 order of magnitude faster than the uncomplexed radicals. The results indicate that catalysis of the 3-exo radical cyclizations of the radicals formed in the enzymes by hydrogen bonding to an acid, so-called "partial protonation", is not adequate for acceleration of the reactions to the point of kinetic competence. A dissociative mechanism for the radical rearrangements in nature is considered as an alternative.