Physicochemical properties of SF 6847, a potent uncoupler of oxidative phosphorylation in mitochondria in relation to its activity

Abstract

AbstractThe steric and electronic structure of the most potent uncoupler of oxidative phosphorylation, SF 6847, was studied. From 1H NMR measurements, it was found that the benzylic protons meta to the hydroxyl group are equivalent in neutral form, and that these protons tend to become non‐equivalent on acid dissociation of the phenolic proton. The CNDO/2 calculation of the dimethyl derivative of SF 6847 showed that in the most stable conformation the angle of the malononitrile group with respect to the benzene ring is about 40° and that the planar form is quite unstable. Results on electronic absorption of SF 6847 in various media showed that the acid dissociation of its phenolic group is affected very much by small changes in the nature of the surrounding environment. It was also found that the calculated total energy differences between the anionic and neutral forms are correlated well with the uncoupling activities of 4‐substituted 2,6‐di‐tert‐butylphenol derivatives.