Alkylation of guanosine and 4-(p-nitrobenzyl)-pyridine by styrene oxide analogues in vitro

Abstract

In vitro alkylation activity of styrene oxide (SO) and three of its analogues, 4-vinyltoluene oxide (VTO), 3,5-dimethylstyrene oxide (DMSO), and 4-nitrostyrene oxide (NSO) was assayed using 4-(p-nitrobenzyl) pyridine (NBP) and guanosine as nucleophiles. Hydrolysis rates were also determined. The half-lives of VTO, DMSO, SO, and NSO were 8, 11, 40, and 60 h, respectively in aqueous solution. The rate of NBP alkylation correlated with the rate of hydrolysis. By contrast, the rates of guanosine alkylation were quite different: SO > VTO > DMSO. NSO did not react with guanosine. Fluorescence and ultraviolet spectroscopic data on the guanosine adducts indicated that SO, VTO, and DMSO formed main alkyl products at N-7.