Bromobenzene epoxidation leading to binding on macromolecular protein sites

S. S. Lau, V. G. Zannoni

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Bromobenzene is metabolized via the hepatic mixed-function oxygenase system to reactive intermediates; i.e., 2,3- and 3,4-bromobenzene epoxides. These metabolites presumably bind to tissue macromolecules evoking cytotoxicity. However, the specific sites of macromolecular proteins are not known and this was investigated using microsomal protein and hemoglobin. The results indicate that 2,3- and 3,4-epoxide bind to macromolecules at different rates. The 3,4-epoxide is more reactive, binding covalently to microsomal protein at the site of its synthesis, whereas bromobenzene 2,3-epoxide is more stable, leaving the microsomal protein compartment and binding covalently to soluble protein, i.e., the hemoglobin β chain. Structural analysis with fingerprint mapping of the hemoglobin β chain after pretreatment with cysteine and histidine blocking agents such as p-nitrophenacyl bromide, 2-bromoethylamine hydrobromide and diethylprocarbonate indicated that the 2,3-epoxide preferentially binds to the cysteinyl residue, whereas the 3,4-epoxide binds to the histidinyl residue. This difference in binding of the 2,3- and 3,4-bromobenzene epoxides may be an important factor in determining the degree of their cytotoxicity.

Original languageEnglish (US)
Pages (from-to)563-572
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
StatePublished - 1981

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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