The objective is to investigate kinetics and mechanisms of interaction of superoxide with some selected aliphatic and aromatic halogenated hydrocarbons (halocarbons) of proven toxicity in some aprotic reaction media. It is proposed that the cytotoxicity of halocarbons involves a series of chemical and biochemical events. The process starts at the hydrophobic region of cell membrane, where superoxide reacts with halocarbons to produce active free radicals which cause toxicity through lipid peroxidation. The purpose of this proposal is to investigate the mechanism of the initial chemical reaction between superoxide and halocarbon in simulated aprotic environment such as DMSO and DMF. The methodology involves determination of the rate of reaction between superoxide and halocarbon, isolation and identification of reaction products such as halocarbon peroxides, polymeric products, free halide and oxygen, and to establish the mechanism of the overall reaction. The halocarbons of interest are open chain aliphatic compounds (chloroform, carbon tetrachloride, 1,1-dichloroethane and 1,1-dichloroethene), alicyclic compounds (various isomers of hexachlorocyclohexanes) and aromatic compounds (varous chlorinated congeners of polychlorinated biphenyls). It is anticipated that the rate of these reactions will vary considerably according to the degree of chlorination and conformation of halocarbons, and the results can be correlated with their relative toxicities. Various analytical techniques, such as chronoamperometry, coulometry, GC, GC-MS, HPLC, UV-VIS and NMR will be employed to achieve our goal.
| Safe, S; Wang, F; Porter, W et al. (1998) Ah receptor agonists as endocrine disruptors: antiestrogenic activity and mechanisms. Toxicol Lett 102-103:343-7 |
