Box 12-1 Chelation Therapy and Thalassemia

To enhance iron excretion, intensive chelation therapy is used. The most successful drug is desferrioxamine B, a powerful Fe3+-chelator produced by the microbe Streptomyces pilosus,6 The formation constant for the Fe(III) complex, called ferrioxamine B, is 103afi. Used in conjunction with ascorbic acid—vitamin C, a reducing agent that reduces Fe3+ to the more soluble Fe2+— desferrioxamine clears several grams of iron per year from an overloaded patient. The ferrioxamine complex is excreted in the urine. 

Desferrioxamine reduces the incidence of heart and liver disease in thalassemia patients. In patients for whom desferrioxamine effectively controls iron overload, there is a 91% rate of cardiac disease-free survival after 15 years of therapy.7 There are negative effects of desferrioxamine treatment for example, too high a dose stunts a child s growth. 

Desferrioxamine is expensive and must be taken by continuous injection. It is not absorbed through the intestine. Many potent iron chelators have been tested to find an effective one that can be taken orally, but only the drug deferiprone is currently used orally.In the long term, bone marrow transplants or gene therapy10 might cure the disease. 

Structures above show the iron complex ferrioxamine B and the related compound, ferrioxamine E, in which the chelate has a cyclic structure. Graph shows success of transfusions and Ironsfusions plus chelation therapy. [Crystal structure kinrty provided by M. Neu, Los Alamos National Laboratory, based on D. Van der Helm and M. Poling. J. Am. Chem. Soc. 1976, 98,82. Graph from R S. Dobbin and R. C. Hider, Iron Chelation Therapy. Chem. Br. 1990,26.565.] 

The fraction of all free EDTA in the form Y4 is called aY4-. At pH 6.00 at a formal concentration of 0.10 M, the composition of an EDTA solution is 

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