Redox and binding equilibria of some biologically-interesting metal-ligand systems

Redox equilibria are important in biology. They determine, for example, the physiological fate of both iron and copper. Given that the redox potential of blood plasma may be as low as -200 mV and that the potential in cells is likely to be considerably lower, the dominant low-molecular-mass species of copper and iron in biological fluids might be Cu(I) and Fe(II) rather than the commonly-assumed Cu(II) and Fe(III). However, this has proved difficult hitherto to investigate due to the absence of reliable formation constants of Cu(I) with complexing agents of likely biological significance and the uncertainty in the previously reported biologically important formation constants of Fe(III) and Fe(II) with citrate. In this work, the formation constants of Fe(III) and Fe(II) with citrate and the complexation of Cu(I) with the thioamino acids, cysteine, glutathione and penicillamine, have been studied by potentiometric titration using specially developed techniques. The formation of mixed complexes of Cu(I) with thioamino acids was investigated for the first time. These formation constants were used in a computer simulation of copper and iron speciation in blood plasma. In contrast to all previous blood plasma models, the redox relationships were taken into account. The resulting models, incorporating about 7200 chemical species, show that Cu(I) and Fe(II) species are indeed likely to predominate in the low-molecular-mass fraction of blood plasma. In this way, cysteine is suggested to be the most important naturally-occurring low-molecular-mass ligand for copper. The blood plasma models were also used to investigate the role of penicillamine in the treatment of Wilson's disease. a condition of copper toxicity