POTENT NON-PROTONOPHORE UNCOUPLERS ACTING ON NATURAL AND ARTIFICIAL MEMBRANES

The uncoupling properties of 10 new symmetrical phenylureas, including N,N'-bis-(4-trifluoromethylphenyl)-urea, were investigated. Four comp ounds were shown to be powerful uncouplers. The result is a proton tra nsfer across the organelle's membrane. These symmetrical phenylureas c annot be classified among the main class of uncouplers (acting through a protonophoric mechanism), due to their inability to exchange proton s in a range of pHs between 2 and 9. The most potent uncouplers of the series induced permeabilization of artificial bilayer membranes (with out protein) to both H+ and monovalent cations (K+, Na+) and did not i ncrease the rate of diffusion of a small uncharged molecule (urea). Th e uncoupling properties for such molecules are due neither to their ab ility to induce conformational changes in membrane protein nor to thei r effect on phospholipid bilayer fluidity. They seem to change the reg ular organization of the polar lipid bilayer.