Coenzyme F430 from Methanogenic Bacteria: Mechanistic studies on the reductive cleavage of sulfonium ions catalyzed by F430 pentamethyl ester

Mechanistic questions regarding the reductive cleavage of sulfonium ions by the Ni I form of coenzyme F430 pentamethyl ester (F430M) were addressed in a series of kinetic studies and isotope labeling experiments. In neat DMF, methane formation from dialkyl(methyl)sulfonium ions consistently showed a delay time of ca. 1 h. In the presence of excess propanethiol, no delay was observed and methane formation followed pseudo‐first‐order kinetics with a logarithmic dependence of the initial rate on the concentration of propanethiol. From the temperature dependence of the reaction rate, an estimate for the activation parameters of Δ H # = 49 kJ mol −1 and (apparent) Δ S # = –114 J K −1 mol −1 was derived. The observation of deuterium incorporation into methane from (CH 3 ) 2 CHOD, but not from (CH 3 ) 2 CDOH, indicates that the fourth H‐entity is introduced into CH 4 as a proton, and that free CH 3 radicals are not involved. In contrast to the reaction with the homogeneous one‐electron reductant sodium naphthalide, the F430M‐catalyzed reduction of mixed dialkyl(methyl)sulfonium ions showed a pronounced selectivity for the cleavage of MeS over that of alkyl‐S (alkyl ≠ Me) bonds. Mechanisms that are consistent with these results, as well as possible explanations for the time delay and the apparent highly negative entropy of activation, are discussed.