Syntheses of biologically active ubiquinone derivatives

Abstract

Various 6-alkylubiquinone or 6-(omega-haloalkyl)ubiquinone derivatives were synthesized through a radical coupling reaction between alkanoyl or omega-haloalkanoyl peroxides and ubiquinone 0. The latter was synthesized from 2-methoxy-4-methylphenol via nitration, methylation, reduction, and oxidation by modifications of the reported methods. 6-(omega-Haloalkyl)ubiquinones were converted to 6-(omega-hydroxyalkyl)ubiquinones by a mercuric-assisted solvolysis technique. The 6-(omega-hydroxyalkyl)ubiquinones were then esterified with carboxylic acid anhydrides or carboxylic acid bearing reporting groups, such as a photoaffinity label, N-(4-azido-2-nitrophenyl)-beta-alanine, or a spin-label, 3-carboxy-2,2,5,5-tetramethyl-3-pyrrolinyl-1-oxy. The esterification was catalyzed by dicyclohexylcarbodiimide and pyridine, and the esters were purified by preparative silica gel thin-layer chromatography, developed by 3% ethanol in benzene. The spectral properties and biological functions of the synthesized ubiquinone derivatives were studied. The biological function of the synthesized compounds was followed by the ability to serve as an electron acceptor, donor, or mediator in the isolated mitochondrial electron transfer complexes of succinate-Q reductase, ubiquinol-cytochrome c reductase, and succinate-cytochrome c reductase, respectively. The concentration effect of these ubiquinone derivatives on the electron transfer reaction was compared with that of ubiquinone 10. The study of the inhibitory effect of synthesized arylazidoubiquinone on succinate-cytochrome c reductase after photolysis confirmed the existence of specific Q-binding proteins in this segment of the respiratory chain. The specific interaction between ubiquinone and protein has also gained support from the immobilization of the spin-label of a synthesized spin-labeled ubiquinone derivative.