Regioselective addition of 2-nitropropane anion to NAD⁺ analogues

Various NAD⁺ analogues have been reduced regioselectively by the tetramethylammonium salt of 2-nitropropane anion in acetonitrile at 298 K to yield the corresponding 4-alkylated NADH analogues. The one-electron oxidation potential of the tetramethylammonium salt of 2-nitropropane anion has been determined as 0.10 V (vs. SCE) by using second harmonic ac voltammetry as well as by analysing the cyclic voltammograms at various sweep rates. The rate constants for the reduction of NAD⁺ analogues by 2-nitropropane anion (>1 × 10⁶ dm³ mol^-1 s^-1) are much larger than those estimated for outer-sphere electron transfer from 2-nitropropane anion to NAD⁺ analogues based on the one-electron oxidation potential of 2-nitropropane anion and the one-electron reduction potentials of NAD⁺ analogues. The origin of the regioselectivity is discussed in terms of the HSAB (hard and soft acids and bases) principle.