Oxidative demethylation of methylcobalamin by hexachloroiridate(IV)

Article abstract of DOI:10.1021/om00073a022

The stoichiometries and kinetics of the demethylation of CH₃-B₁₂ by IrCl₆^2- in aqueous solution have been examined. In the presence of excess IrCl₆^2-, this reaction occurs with a 2:1 (IrCl₆^2-:CH₃-B₁₂) stoichiometry, producing H₂O-B₁₂⁺, CH₃Cl, and IrCl₆^3-/IrCl₅(H₂O)^2-. With deficient IrCl₆^2-, the reaction occurs with a ～ 1.3:1 (IrCl₆^2-:CH₃-B₁₂) stoichiometry, producing H₂O-B₁₂⁺, IrCl₆^3-, and C₂H₆ (the major demethylation product). The demethylation follows a second-order rate expression: first order in CH₃-B₁₂ and first order in IrCl₆^2-. This second-order rate constant is pH dependent in acidic solution, which is interpreted in terms of protonation of the 5,6-dimethylbenzimidazole moiety and its resulting base-on to base-off conversion. IrCl₆^3- inhibits the demethylation, while Cl^- pronouncedly enhances the rate. The mechanism is described as a one-electron transfer from CH₃-B₁₂ to IrCl₆^2- (rate-determining step), yielding a transient CH₃-B₁₂⁺ intermediate. This intermediate rapidly releases a methyl radical which either abstracts a chlorine atom from a second IrCl₆^2- molecule to produce CH₃CI or combines to yield C₂H₆.