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-degrees. The 1,4-dihydronicotinamide ring is slightly puckered and adopts a boat conformation. The calculated N-15 equilibrium isotope effect for hydride transfer is small, in agreement with experimental observations.