Conformation of exocyclic amino groups in purines and pyrimidines: crystal structure and conformation of 1-methyl-N4-hydroxycytosine hydrochloride

Abstract

The hydrochloride salt of 1-methyl-N4-hydroxycytosine crystallizes in the triclinic space group [Formula: see text] with cell dimensions: a = 8.232(1), b = 9.293(1), c = 5.416(1) Å (1 Å = 0.1 nm); α = 91.95(1), β = 91.72(2), γ = 71.56(1)° (SE in parentheses). The structure was solved by direct methods and refined to R = 3.7% for 1514 reflections. Despite the absence of an intramolecular hydrogen bond in the solid state, the N4-hydroxy substituent is syn to the ring N(3). This conformation, which probably prevails also in the neutral form, is of relevance to the mechanism of attack of cytosine by hydroxylamine, known to involve predominantly the cytosine cation, as well as to the mechanism of hydroxylamine mutagenesis. Such conformational aspects are also relevant to other phenomena, including translation and restriction.