Theoretical study of conformational features of NAD+ and NADH analogs: protonated nicotinamide and 1,4-dihydronicotinamide

The conformations of nicotinamide (N + ) and 1,4-dihydronicotinamide (NH) have been studied by ab initio calculations at the MP2/6-31G * //6-31G * level. The amide group favors a cis conformation by about 1 kcal/mol for both N + and NH. The rotational barrier for cis to trans interconversion is about 4 and 7 kcal/mol for N + and NH, respectively. The amide group in the trans conformation is out of plane by about 20 o . The 1,4-dihydronicotinamide ring is slightly puckered and adopts a boat conformation. The calculated 15 N equilibrium isotope effect for hydride transfer is small, in agreement with experimental observations