title: Protonophoric properties of fluorinated arylalkylsulfonamides. Observations with perfluidone.
abstract: The acidity and lipophilicity of the fluorinated arylalkylsulphonamides are determined by the nature of the substituents on their aromatic rings. Herbicidal and anti-inflammatory effects of these compounds appear to increase with their lipophilicity. According to Mitchell's chemiosmotic theory, lipophilic weak-acid uncoupling agents act by transporting protons across the inner mitochondrial membrane and thus destroying the proton-electrochemical potential gradient required for ATP synthesis and ion transport. 1:1:1-Trifluoro-N-[2-methyl-4-(phenylsulphonyl) phenyl]methanesulphonamide (Perfluidone), a pre- and post-emergence herbicide (at 20 microM concentration), in isolated rat-liver mitochondria caused (1) a 2-fold stimulation of metabolic state-4 respiration, (2) a reduction of respiratory control ratio (RCR) by at least 50%, (3) an enhancement of latent ATPase activity by 40%, (4) a significant passive swelling of mitochondria in 0.15 N NH4Cl(delta A520 = -0.46 +/- 0.003), (5) proton intrusion during state-4 respiration (356 ng H+/min/mg protein; ng H+/min/mg protein with 5 microM perfluidone), and (6) at least 100% stimulation of oligomycin-inhibited respiration. These profiles are qualitatively comparable with those of the classical lipophilic weak-acid uncoupler, carbonylcyanide-trifluoro-methoxyphenylene hydrazone (FCCP), which acts by promoting the electrogenic transport of H+ ions across mitochondrial membrane.
authors.forename: O O
authors.initials: OO
authors.lastname: Olorunsogo
authors.forename: S O
authors.initials: SO
authors.lastname: Malomo
authors.forename: E A
authors.initials: EA
authors.lastname: Bababunmi
mesh_terms: D000251:Adenosine Triphosphatases / Q000032:analysis; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D006540:Herbicides / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008930:Mitochondria, Liver / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D006540:Herbicides; D009840:Oligomycins; D011522:Protons; D013449:Sulfonamides; D013450:Sulfones; D014475:Uncoupling Agents; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; C011062:perfluidone; D000251:Adenosine Triphosphatases