Iron complexes of gallocatechins. Antioxidant action or iron regulation?

Abstract

Iron(III) complexes of gallocatechins were studied in aqueous solutions by UV–VIS spectrometry, HPLC, cyclic voltammetry, laser photolysis and pulse radiolysis techniques. The blue–violet colored complexes are readily formed in water. The Job plots indicate 1∶2 stoichiometry for the reaction of iron(III) with gallocatechins and methyl gallate, and 1∶3 for that of iron(III) and catechin. This suggests that the three phenol groups of the gallate moiety play a role in complex formation. The formation constants of the complexes are found to be pH dependent, as expected for polyhydroxybenzene derivatives. pKa1 = 4.3 and pKa2 = 7.4 for the polyphenols with the gallate ester moiety (epigallocatechin gallate and epicatechin gallate) are lower than those of epigallocatechin (EGC) and catechin (pKa1 = 4.9 and pKa2 = 8.4), very probably because of the electron-withdrawing effect of the ester. Apparent stability constants of iron(III) gallocatechin complexes are high at pH 7, log K ≈ 27, comparable to those of the catechol derivatives. Photoionization of the iron complexes by the 248 nm laser is more efficient at higher pH, ϕ = 0.13 at pH 7 vs. ϕ = 0.26 at pH 11.5. The absorption spectra, which resemble those of ligand phenoxyl radicals, indicate that photoionization yields unstable phenoxyls, t1/2 ≈1 ms. Similar spectra are recorded when one-electron oxidation by the azide radical, N3˙, is used to generate the ligand radicals. The reduction potential of Fe(III)gallocatechins is –0.325 V vs. NHE, which is ≈0.45 V less negative than the reduction potential of the Fe(II)/Fe(III) couple. In the case of the catechins with the gallate ester moiety, namely EGCG and ECG, the high pH cyclic voltammograms exhibit a quasi-reversible oxidation–reduction not seen in the other derivatives. The relevance of these findings for the physiological function and antioxidant and chemopreventive action of gallocatechins is discussed.