Protonophoric properties of fluorinated arylalkylsulfonamides. Observations with perfluidone.
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.
Olorunsogo
O O
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Malomo
S O
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Bababunmi
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EA
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
D006540:Herbicides; D009840:Oligomycins; D011522:Protons; D013449:Sulfonamides; D013450:Sulfones; D014475:Uncoupling Agents; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; C011062:perfluidone; D000251:Adenosine Triphosphatases