Redox properties and activity of iron-citrate complexes: evidence for redox cycling.

Iron in iron overload disease is present as non-transferrin-bound iron, consisting of iron, citrate, and albumin. We investigated the redox properties of iron citrate by electrochemistry, by the kinetics of its reaction with ascorbate, by ESR, and by analyzing the products of reactions of ascorbate with iron citrate complexes in the presence of H2O2 with 4-hydroxybenzoic acid as a reporter molecule for hydroxylation. We report -0.03 V < E°' > +0.01 V for the (Fe(3+)-cit/Fe(2+)-cit) couple. The first step in the reaction of iron citrate with ascorbate is the rapid formation of mixed complexes of iron with citrate and ascorbate, followed by slow reduction to Fe(2+)-citrate with k = ca. 3 M(-1) s(-1). The ascorbyl radical is formed by iron citrate oxidation of Hasc(-) with k = ca. 0.02 M(-1) s(-1); the majority of the ascorbyl radical formed is sequestered by complexation with iron and remains EPR silent. The hydroxylation of 4-hydroxybenzoic acid driven by the Fenton reduction of iron citrate by ascorbate in the presence of H2O2 proceeds in three phases: the first phase, which is independent of the presence of O2, is revealed as a nonzero intercept that reflects the rapid reaction of accumulated Fe(2+) with H2O2; the intermediate oxygen-dependent phase fits a first-order accumulation of product with k = 5 M(-1) s(-1) under aerobic and k = 13 M(-1) s(-1) under anaerobic conditions; the slope of the final linear phase is ca. k = 5 × 10(-2) M(-1) s(-1) under both aerobic and anaerobic conditions. Product yields under aerobic conditions are greater than predicted from the initial concentration of iron, but they are less than predicted for continuous redox cycling in the presence of excess ascorbate. The ongoing formation of hydroxylated product supports slow redox cycling by iron citrate. Thus, when H2O2 is available, iron-citrate complexes may contribute to pathophysiological manifestations of iron overload diseases.

Models of the iron-only hydrogenase: structural studies of chelating diphosphine complexes [Fe2(CO)4(micro-pdt)(kappa2P,P'-diphosphine)].

Six chelating diphosphine complexes, [Fe2(CO)4(micro-pdt)(kappa2P,P'-diphosphine)], have been crystallographically characterised allowing differences between basal-apical and dibasal conformations to be analysed.

Breast cancer in black African women: a changing situation.

Black African women in rural South Africa have a very low incidence rate of breast cancer, 5-10 per 100,000. The rate, however, is rising in the considerably increasing urban population. During the period 1994 to 1999 in Durban, enquiries revealed an average of 57 urban patients admitted to hospital each year, from a population of about 600,000 African women, indicating an age-adjusted annual incidence rate of 15.1 per 100,000. This incidence rate is very low in comparison with those in developed populations, which range from 40 to 89 per 100,000. In the African patients studied, the mean age on admission was relatively young, 54.1 +/- 10.9 years, almost a decade earlier than patients of developed populations. Moreover, the disease was very far advanced; 21.1% were at Stage III and 63.1% at Stage IV. As to exposure to risk factors, African women in general are characterised by certain protective factors. These factors, which closely resemble those of importance in patients in developed populations are, late menarche, early age at birth of first child, high parity (with usually prolonged lactation), and being physically active. However, with ongoing changes in the lifestyle of urban African women, the protective factors are decreasing in their intensity. Changes in these respects have been associated with rises in the disease's incidence rate. Clearly, because of the late stage of the disease at the time of the patients' admission to hospital, and hence their poor survival rate, intensive efforts should be made to educate women to seek help at an early stage of their disease. For its avoidance, feasible protective or restraining measures are primarily to adopt a 'prudent' lifestyle, in respect of both dietary and non-dietary components. However, the chances of these measures being meaningfully adopted in African urban communities, unfortunately, are negligible. In consequence, further increases in incidence rate would seem inevitable.