Conformational flipping of the N(6) substituent in diprotonated N6-(N-glycylcarbonyl)adenines: The role of N(6)H in purine-ring-protonated ureido adenines

Conformational transitions of the N(6) substituent, in hyyermodified nuclei c acid base N-6-(N-glycylcarbonyl)adenine, gc(6)Ade, on diprotonation of th e adenine ring at any two of N(1), N(3), and N(7) sites, are studied using the quantum chemical perturbative configuration interaction with localized orbitals (PCILO) method. The N(6) substituent retains the usual "distal" or ientation (alpha - 0 degrees) in (N(1), N(3)) diprotonated gc(6)Ade, but th e "proximal" orientation (alpha = 180 degrees) is preferred instead, for (N (3), N(7)) and (N(7), N(1)) diprotonated gc(6)Ade. The proximal orientation may alter the reading frame during translation. Intramolecular N(6)H ... O (13b) hydrogen bonding is the key common feature, present in the preferred structure, for each of these variously diprotonated gc(6)Ade. (C) 2000 John Wiley & Sons, Inc.