Quantitative structure activity relationships for dicoumarol antivitamins K in the uncoupling of mitochondrial oxidative phosphorylation

Article abstract of DOI:10.1021/jm00235a019

The dynamic structure of dicoumarol derivatives substituted on the methylene bridge was studied by nuclear magnetic resonance (nmr) spectroscopy. These molecules may be considered as dimers with restricted rotation around the methylene bridge, held by intramolecular hydrogen bonds; the presence of the substituent R modifies this dynamic process, mainly the facility of exchange of the 2 hydroxyl protons. These compounds were compared in respect of their potency in uncoupling oxidative phosphorylation in pig heart mitochondria; the data were correlated with constants used to characterize the substituent R; to make a potent uncoupler, R should be as small and as hydrophilic as possible. The results are discussed in consonance with the postulated mechanisms of action of the uncouplers, but no simple conclusion could be drawn, especially concerning the role of the dissociable protons.