Thirdly, at high pH values (i.e. Complex III), dimers of GA or EGCG might be involved in the complexes. However, many of the spectra are derived from more than one complex, the spectra of which are not resolved from one another at RT, so it is inappropriate to discuss these details further. Characterisation of the EPR silent species that are formed at weakly acidic pH values is problematic. With the Cu/GA system, Ferreira Severino et al. [9] showed that the loss of signal was not the result of reduction of Cu(II) to Cu(I), and proposed

that the EPR silent species involved the formation of di- or polymeric complexes with coordination of the carboxyl group, as seen with simple carboxylic acids. However, coordination of carboxyl groups is not an option with EGCG, and any extended structure PI3K inhibitor with this polyphenol must be based on click here coordination of pyrogallol groups. However, the similarity of the results with GA and EGCG indicates that the chemistry of the reactions with Cu(II) of both phenols is similar, and suggests that the EPR silent species involve extended structures in which the Cu is coordinated to the pyrogallol moiety. The complexation

chemistry of EGCG is further complicated by the presence of two pyrogallol groups in the same molecule. In previous work on the oxidation of EGCG [29], it was shown that the site of oxidation is dependent on the experimental conditions, and that the relative reactivities of the B and D rings is not always the same. The pH of the solution could be a factor in determining this, since it also determines the degree of proton dissociation. 5-FU Thus it is possible that the products of reaction between Cu(II) and EGCG are not discrete molecules, but a group of closely related complexes. Nevertheless, the EPR results are consistent with those from the Cu(II)/GA system, and are consistent

with the formation of extended structures at acidic pH values, with the formation of mononuclear Cu(II) complexes gaining in importance at higher pH values and EGCG concentrations. Furthermore, as stated by Ferreira Severino et al. [9] for the Cu(II)/GA system, there is no convincing evidence for any redox reaction between Cu(II) and either of the polyphenols. The chemistry of the reactions of Cu(II) with the polyphenols EGCG and GA is similar, although the molecular mass of EGCG is four times that of GA with several more phenolic groups, but lacking any carboxyl group. With both polyphenols, EPR silent species are formed at weakly acidic pH values, and strong evidence is presented for these having extended structures rather than being the consequence of reduction of Cu(II) to Cu(I). The polyphenols, therefore, result in the removal of Cu from solution at an appreciably lower pH than is observed in the absence of the polyphenol (by ~ 2 pH units).