The five-coordinate high-spin (S = 1) Ni2+ complex [Ni(tmc)CH3](+) (1) (tmc = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) serves as a model for a viable reaction intermediate of the A cluster of acetyl-CoA synthase (ACS) in which the distal nickel center is methylated. Spectroscopic and density functional theory (DFT) computational studies afford a quantitative bonding description for 1 that reveals a highly covalent Ni-CH3 bond. From a normal coordinate analysis of resonance Raman data obtained for 1, a value of k(Ni-C) = 1.44 mdyn/&ANGS; is obtained for the Ni-C stretch force constant of this species. This value is smaller than k(Co-C) = 1.85 mdyn/&ANGS;, which is reported for the Co-C stretch in the methylcobinamide cofactor (5) that serves as the methyl donor to the A cluster in the ACS catalytic cycle. Experimentally calibrated DFT computations on viable methylated A cluster models reveal that the methyl group binds to the proximal (Ni-p) rather than the distal (Ni-d) nickel center and afford a simple electronic argument for this preference. By correlating the experimental force constants with the computed bond orders of the M-C bonds in 1 and 5, the Ni-p(2+)-CH3 bond strength for an A cluster model with a square-planar Nip conformation, which is the most probable structure of the methylated A cluster on the basis of steric and energetic considerations, is predicted to be similar to the Co3+-CH3 bond strength in CH3-CoFeSP, This similarity could be a crucial thermodynamic prerequisite for the reversibility of the enzymatic transmethylation reaction.