Reactivity Effects on Site Selectivity in Nucleoside Aralkylation: A Model for the Factors Influencing the Sites of Carcinogen-Nucleic Acid Interactions

Article abstract of DOI:10.1021/jo00372a015

Product distributions are described for 15 reactions between guanosine (1) and a series of p-Y-benzyl bromides (2a-e), p-Y-benzoyl chlorides (3a-e), and N-nitroso-N-(p-Y-benzyl)ureas (4a-e) where Y = a, O2N; b, Cl; c, H; d, CH3; e, CH3O.The yields of products from reaction at the 7-position of guanosine to produce 7-(p-Y-benzyl)guanosines (5a-e), at N² to produce N²-(p-Y-benzyl)guanosines (6a-e), at the O⁶-position to produce O⁶-(p-Y-benzyl)guanosines (7a-e), and at the 5-position to produce 4-(p-Y-benzyl)-5-guanidino-1-β-D-ribofuranosylimidazoles (8a-e) arecorrelated with the mechanism of the reaction (i.e., the S_N2 or S_N1 character) imposed by the para substituent and/or leaving group and the nature of the incipient charge density (i.e., the "hardness" or "softness") at the reaction center.These observations, coupled with the literature on sites of reaction of carcinogens with nucleic acid components, are used to rationalize the site selectivity differences exhibited by the alkylating and aralkylating classes of carcinogens in their nucleic acid reactions.