IRON COORDINATION BY CATECHOL DERIVATIVE ANTIOXIDANTS

Iron complexes of nitrocatechols with different substituent groups [1: -CH=CR(2); 2: -CH2-CHR(2); 3: -CH=CR'(R '')] were synthesized and the ir effects on iron-induced free radical reactions of biological import ance investigated. Catechol and nitrocatechol derivatives effectively inhibited iron-induced lipid peroxide dependent lipid peroxidation. In the Fenton like reaction, iron-catechol generated hydroxyl radicals m ore strongly than did iron citrate, and iron-nitrocatechol derivative 2 generated a small amount of hydroxyl radicals. The iron complexes of derivatives 1 and 3 did not generate hydroxyl radicals. Iron-catechol had the highest ratio of reduction to oxidation rate constants and th e second was iron-nitrocatechol 2, suggesting that iron chelated by ni trocatechols 1 and 3 may be most difficult to reduce. To elucidate the structure and physical properties of the iron complexes, UV/vis absor ption spectroscopic, ESR and H-1 NMR studies were performed in aqueous and DMSO solutions. In aqueous solution at pH 7.4, iron complexes of the nitrocatechol derivatives were high-spin tris(nitrocatecholato)fer rate(III) with a characteristic ligand-to-metal charge transfer absorb ance (pi --> d(pi)). The lambda(max) of iron nitrocatechol derivative 2 was shorter than those of iron-nitrocatechol derivatives 1 and 3, su ggesting that the reduction potential of iron-nitrocatechol 2 is highe r than that of iron-nitrocatechols 1 and 3. Nitrocatechol derivatives with a conjugation structure can sequester the chelated iron more effe ctively than catechol and the derivative without the conjugation again st free radical generation by keeping the iron in the ferric state, pr obably because of the reduction potentials.