Mechanism of the mutagenic action of hydroxylamine: VI. Reaction of hydroxylamine with the uracil nucleus

Abstract

1. 1. The major direction of the first stage of the reaction of hydroxylamine with uridine and UMP (pH optimum approx. 8) is the addition of the neutral reagent molecule to the C-5-C-6 double bond of the neutral uracil nucleus. 2. 2. The structures of the adducts of uridine and uridine 5′-phosphate with hydroxylamine, that are the major reaction products over the pH range 6–8 at low temperatures, have been proved. 3. 3. In aqueous solution the adducts either eliminate the hydroxylamine molecule to give the starting compounds (the rate of this reaction does not depend on pH over the range 0–8), or, alternatively, give rise to isoxazolone and ribosylurea (ribosylurea phosphate) by fission of the uracil nucleus. The rate of the latter reaction becomes considerable at pH > 7 and increases with increasing concentration of hydroxyl ions. The adducts also enter another, most probably oxidative, transformation in alkaline medium in the absence of versene.