ELECTROCHEMICAL THEORY OF THE TRANSFER OF PROTONS ACROSS A BIOLOGICAL MEMBRANE FACILITATED BY WEAK ACID UNCOUPLERS ADDED TO THE MEDIUM

An electrochemical theory of the transport of protons across a biological membrane facilitated by uncouplers of oxidative phosphorylation added to the medium has been developed. The interfacial potential differences at the two membrane/solution interfaces are explicitly taken into account. The derived equations are applied to explain the uncoupling activity of uncouplers like 2,4,6-trinitrophenol, 2,4-dinitrophenol, carbonylcyanide p-trifluoromethoxyphenylhydrazine, and 3,5-di(tert-butyl)-4-hydroxybenzylidenemalononitrile, in terms of their protonic dissociation constants in aqueous solution (K(W)) as well as in the membrane medium (K(M)) and their standard ion-transfer potential (of anionic form) at the membrane/solution interface (DELTA-PHI(A)-degrees); the (relative) values of K(M) and DELTA-PHI(A)-degrees are estimated from data determined by ion-transfer voltammetry of the uncouplers at the nitrobenzene/water interface. The equations can also explain the unique behaviour of picrate as uncoupler that it is ineffective when added to intact mitochondria but effective when added to submitochondrial particles with inside-out mitochondrial inner membranes.