title: In vitro activation of lipophilic tributyltins by superoxide produces tributylstannyl superoxo radicals, proposed initiators of lipid peroxidation: an EPR model study.
abstract: Tri-n-butyltin(TBT) compounds having the chemical formula (C4H9)3SnX are broad-spectrum biocidal agents whose toxic effect is primarily at the membrane level. Red blood cells (RBC) exposed to micromolar concentrations of tributyltin compounds (TBTX) undergo morphological changes and hemolysis. Determination of the mechanism of action whereby TBT elicits membrane damage continues to be a challenging endeavor. Because xenobiotic TBT+ and endogenous O2.- have been found to penetrate and alter RBC membrane function, it is hypothesized that they may combine chemically within the RBC hydrophobic lipid bilayer during TBT insult to initiate lipid peroxidative processes. The present study has been designed (1) to determine if TBT+ and O2.- combine chemically in aprotic media and, if so, (2) to characterize any free-radical complex(es) generated. The reactions of the membrane-active TBTX compounds (X = OCH3, Cl, Br, or I) with O2.- have been investigated in the aprotic solvent system cis-dicyclohexano-18-crown-6 ether/DMSO using EPR techniques. When incremental amounts of each TBT halide were added to O2.- solutions at room temperature, the EPR signal characteristic of O2.- diminished in intensity and disappeared when a 1:1 O2.-/TBT+ mole ratio was attained. Although the same phenomenon was observed for all TBT halides used, only the KO2/TBTI reaction produced detectable amounts of a new oxygen-centered free-radical complex. The EPR spectral parameters calculated from the product anisotropic frozen glass spectra were gx = 2.054, a(x) = 31.7 G, gy = 2.021, gz = 2.002, gav = 2.026.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Naval Medical Research Institute Detachment (Toxicology), Wright-Patterson Air Force Base, Dayton, Ohio 45433.
authors.forename: J A
authors.initials: JA
authors.lastname: Rivera
authors.forename: S C
authors.initials: SC
authors.lastname: Cummings
authors.forename: D A
authors.initials: DA
authors.lastname: Macys
mesh_terms: D004121:Dimethyl Sulfoxide; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D015227:Lipid Peroxidation; D013481:Superoxides / Q000737:chemistry*; D014220:Trialkyltin Compounds / Q000737:chemistry*
chemical_list: D005609:Free Radicals; D014220:Trialkyltin Compounds; D013481:Superoxides; C011559:tributyltin; D004121:Dimethyl Sulfoxide