C-H bond activation in ribonucleotide reductases - Do short, strong hydrogen bonds play a role?

The hydrogen-transfer reactions between methyl thiyl radical and methanol, ethylene glycol, and 3,4-dihydroxytetrahydrofuran have been studied as mode l systems for the C-H bond activation step in ribonucleotide reductases wit h DFT methods. In all three cases, the overall reaction is endothermic. The lowest reaction barrier and the smallest endothermicity has been found for the tetrahydrofuran substrate. The influence of hydroxide, formate, hydron ium, and neutral formic acid on the C-H bond activation in ethylene glycol has also been studied. Taking the reduction of the intrinsic barrier height as a measure of catalytic activity, the negatively charged formate group i s the most effective catalyst. This catalytic effect is based on the format ion of a strong anionic hydrogen bond, which achieves its maximum strength in the transition state of the C-H bond activation step. The observed modul ation of the hydrogen bond strength along the reaction pathway is ultimatel y traced back to the electrophilic nature of the methyl thiyl radical.