Collect. Czech. Chem. Commun. 1988, 53, 1094-1101

Subcellular and cellular studies on relationship between structure and uncoupling effect of phenylhydrazonopropanedinitriles on oxidative phosphorylation

Ernest Šturdíka, Štefan Baláža, Edita Ďurčováa, Marián Antalíkb, Pavol Suloc, Maria Šturdíkováa and Vladimír Mikešd

a Department of Biochemical Technology, Slovak Institute of Technology, 812 37 Bratislava
b Laboratory of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, 040 11 Košice
c Section of Enzyme Technology, Institute of Biotechnology, Slovak Institute of Technology, 812 37 Bratislava
d Department of Biochemistry, J. E. Purkyně University, 611 37 Brno


The characterization of relations between the assumed activity-determining physico-chemical parameters (partition coefficients, dissociation constants, reactivity to thiol compounds) of o-, m-, and p-substituted phenylhydrazonopropanedinitriles and their uncoupling effect on oxidative phosphorylation in mitochondria isolated from rat liver, Paracoccus denitrificans bacteria and animal leukemia P 388 cells have shown that from the viewpoint of action mechanism the concept of proton-translocating (pH-gradient disturbing) effect is more plausible than the modification of the corresponding membrane proteins. The dependence of the activity of the compounds studied on their physicochemical characteristics is represented by a saturation curve with a plateau starting at log P 5-6 when the uncoupling effect is plotted versus lipophilicity and by a bell-shaped curve having a maximum at pKa 4·5-5·5 with respect to basicity.