A QUANTUM CHEMICAL STUDY OF THE TYPE-IV NUCLEOPHILIC-SUBSTITUTION REACTION AND DISSOCIATION OF THE BETA-NICOTINAMIDE GLYCOSYL BOND IN THE GAS-PHASE USING SEMIEMPIRICAL PM3 CALCULATIONS

The type IV nucleophilic substitution reaction at the anomeric carbon of beta-nicotinamide riboside+ was studied in the gas phase using the semiempirical PM3 method. Because there are few computational studies of displacement reactions on a positively charged substrate, the isoenergetic displacements of dimethyl ether on the trimethyloxonium cation and trimethylamine on the tetramethylammonium cation were studied to provide base line comparisons. The results are compared to the thermodynamics of the unimolecular dissociation reaction and to prototype reactions of the extensively studied S(N)2(type I) reaction. The experimentally determined dissociative character of the hydrolysis of beta-nicotinamide riboside+ can be rationalized in terms of the gas-phase-calculations; the results suggest that the nitrogen-carbon bond must be broken almost entirely before either external nucleophile or solvent can react with the oxocarbenium ion intermediate. The structures for the inversion and retention reactions are different, in contrast to a suggestion made by Sinnott and Jencks (Sinnott, M. L.; Jencks, W. P. J. Am. Chem. Soc. 1980, 102, 2026-2032) that inversion and retention should proceed through a single activated complex. General differences between nucleophilic displacement reactions on neutral and positively charged substrates are discussed.