The effect of benzenediols and benzenetriols on the nitrosation of propranolol depends on the position of hydroxyl groups on the benzene ring

Abstract

Nitrosation of propranolol under the standard conditions recommended by the World Health Organization (10 mM propranolol hydrochloride, 40 mM sodium nitrite, pH 3.5) was carried out in the absence and in the presence of phenol, benzenediols and benzenetriols added to the nitrosation mixture in concentrations ranging from 2 to 40 mM. The yield of N-nitrosopropranolol (NOP) was reduced, with potency decreasing in the following order, by 1,2-benzenediol > 1,2,3-benzenetriol > 1,4-benzediol; their inhibiting effect was dose-dependent. 1,2,4-Benzenetriol displayed a significant inhibitory activity only at 20–40 mM concentrations. The maximum reduction of NOP formation (7% of the yield obtained under control conditions) was produced at 120 min by 40 mM 1,2-benzenediol. In contrast, the yield of NOP was increased by 1,3-benzenediol and 1,3,5-benzenetriol, but this effect was inversely related to the concentration. The effect of the various phenols on the time course of propranolol nitrosation was dependent on both the test phenol and its concentration. 1,2-Benzenediol and 1,3-benzenediol displayed on the nitrosation of proline effects qualitatively of the same type, but quantitatively different, as compared with those observed on the nitrosation of propranolol. Taken as a whole, the results of this study indicate that depending on the positions of hydroxyl groups on the benzene ring benzenediols and benzenetriols may inhibit or hasten nitrosation reactions.