Influence of water hydrogen bonding on the reactions of arylnitrenium ions with guanosine: Hydrogen-bonding effects can favor reaction at the C8 site

Abstract

A computational study was done for the reactions of the 2-fluorenylnitrenium ion (2FN) with guanosine (G) and its monohydrate tautomer (G·H 2O) to form the key N7 or C8 intermediates that may then proceed to produce the C8 adduct product. The 2FN + G·H 2O reactions with the transition state of the C8 pathway being noticeably lower than that of the N7 pathway are very different from those found for the 2FN + G reactions where the transition states for the N7 pathway are lower than those for the C8 pathway. This is due to the lone pair of N7 being protected by hydrogen bonding in a protic solvent (G·H 2O in our case), so the C8 position of guanosine will become more nucleophilic than position N7. Computational results for the 2FN + G·H 2O reactions predict that the C8 intermediate, rather than the N7 intermediate, is the predominant intermediate formed from the reaction. Our results are consistent with time-resolved absorption and time-resolved resonance Raman experiments that found a very fast reaction of 2FN with guanosine to produce a "C8 intermediate" with a common time constant for the decay of 2FN and the formation of the C8 intermediate. The results here suggest that explicit hydrogen-bonding effects on the chemical reactivity of guanosine may contribute to arylnitrenium ions reacting with guanine derivatives to produce predominantly C8 adducts rather than N7 adducts. © 2009 American Chemical Society.