Mechanisms of reductive methylation of NAD⁺ analogues by a transdimethylcobalt(III) complex

Various NAD⁺ analogues are readily reduced by a trans-dimethylcobalt(III) complex, trans-[CoMe₂(L)] (L=11-hydroxy-2,3,9,10-tetramethyl-1,4,8,11-tetraazaundeca-1,3,8, 10-tetraene-1-olate), to yield the corresponding methylated NADH analogues, while cis-dialkyl- or monoalkylcobalt(III) complexes show no reactivity towards NAD⁺ analogues. The charge distribution of the NAD⁺ analogues, as well as the thermodynamic stability of the products, is shown to be an important factor in determining the isomer distribution of the methylated products. The observed second-order rate constants for the reduction of NAD ⁺ analogues by trans-[CoMe₂(L)] in acetonitrile at 298 K are much larger than those estimated for outer-sphere electron transfer from trans-[CoMe₂(L)] to NAD⁺ analogues.