Alkylation of nucleic acids and their components

Guanosine, cytidine, inosine, and thymine react with 4-[N-(-chloroethyl)-N-methylamino]-benzaldehyde to give 7-alkylguanosine, 3-alkylcytidine, 1-alkylinosine, and 1-alkylthymine, respectively. The order of reactivities of the nucleosides with respect to 4-[N-(-chloroethyl)-N-methylamino] benzaldehyde in 36% aqueous dioxane at 50°C and pH 5–6 is guanosine > inosine > cytidine > thymine. Inosine, cytidine, and thymine are 36%, 21%, and 13% as reactive as guanosine. Adenosine and uridine do not react under these conditions. The ratio of the rate constant for the alkylation of guanosine by 4-[N-(-chloroethyl)-N-methylamine]-benzaldehyde and the rate constant for the hydrolysis of the latter in 17% aqueous dioxane at 50° and pH 5–6 is 10.5±0.5 mole^–1. The alkylation of guanosine at pH 7.5 is accompanied by cleavage of the imidazole ring of the 7-alkylguanosine, which proceeds at a higher rate than the rate of the limiting step — ionization of 4-[N-(-chloroethyl)-N-methylamino]benzaldehyde. The transformations of the alkylated nucleosides in acids and alkalis were studied, and the rate constants of these transformations were determined.See [26] for communication III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 109–116, January, 1972The authors thank D. G. Knorre for discussing the kinetic results of this research.