Synthesis and PMR spectra of 7-hydroxyalkylguanosinium acetates

Guanosine and 9-methylguanine treated with epoxides in glacial acetic acid are hydroxyalkylated stereoselectively at the N₇ position of the guanine moiety. Previously unreported 7-(hydroxyalkyl)guanosinium acetates from the reactions of six epoxides with guanosine and 7-(hydroxyalkyl)-9-methylguaninium acetates from the reactions of two epoxides with 9-methyl guanine in glacial acetic acid have been prepared and characterized by their pmr spectra. By using an excess of epoxide, quantitative conversion of guanosine or 9-methylguanine to the corresponding 7-hydroxyalkylguanosinium or 7-hydroxyalkyl-9-methylguaninium acetate was achieved. Comparisons of the pmr spectra of the 7-(hydroxyalkyl)guanosinium acetates in DMSO-d₆ to the spectrum of guanosine reveal that the H₈ and amino group proton absorptions common to guanosine are shifted to a lower field, the absorptions of the H₁ proton is absent, and the coupling constant of the H′₁-H′₂ protons of the ribosyl group is decreased from about 5.7 ± 0.1 Hz in guanosine to about 3.5 ± 0.1 Hz in the products. The use of the pmr spectral features of 7-(hydroxyalkyl)-9-methylguaninium compounds in characterizing 7-hydroxyalkylguanosinium compounds is discussed. Evidence is presented which suggests that extensive delocalization of positive charge exists in both the pyrimidine and imidazole rings of N₇-hydroxyalkylated guanosine and N₇-hydroxyalkylated-9-methylguanine. The possible effects of charge delocalization upon the hydrogen bonding potential of 7-hydroxyalkylated guanine moieties in DNA is discussed.