Metal-binding substances

5 The various modes of biological action of chelating agents (an introduction). 464 

6 Diminution, by chelation, of the toxic effect of a metal. Antidotes. 466 

9 Substances whose biological action is at least partly due to chelation. 481 

11 Fundamental considerations in designing new chelating agents. Promising avenues of application. 488 

Heavy metals, in traces, are essential for all forms of life. They are taken up by the living cell as cations, and their uptake is strictly regulated because most (or all) of them are toxic in excess. A remarkable specificity has been found seldom can an excess of one essential metal prevent the damage caused by a deficiency of another. In fact, such an excess often increases the injurious effect of the deficiency. 

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Some metal binding substances, including 8-hydroxyquinoline and sodium dimethyldithiocarbamate, damage the islets of Langerhans and cause diabetes in experimental animals181). 

Metal-binding substances, many of which function by chelation, have furnished many useful drugs and other substances of value in selective toxicity. They are manufactured in huge quantities for this purpose, particularly those that are used in agriculture as fungicides. They function by upsetting the delicate balance that exists between the cations of heavy metals in nature. Some of them withdraw metals from living tissues, but many others reinforce the natural toxicity of a heavy metal. 

Apart from their use as agricultural fungicides, metal-binding substances... 

Apart from amino acids, peptides and proteins, many other metal-binding substances play essential roles in all living cells. Firstly, there are the pteridines (including folic acid) and purines, whose stability constants have been determined (Albert, 1953 Albert and Serjeant, 1960). Riboflavine is most avid in the partly reduced state (Hemmerich, Veeger and Wood, 1965). Spermine 11 A), and the diamines spermidine 11.5) and putrescine 11.6) also compete. 

Many biologically active chelating agents are unsuited for internal therapy in Man simply because they are not selective enough. One must always proceed cautiously with metal-binding substances because some of them, such as sodium dimethyldithiocarbamate (Kadota and Midorikawa, 1951), injure the islets of Langerhans and thus cause diabetes in experimental animals. The 5-amino-, also the 2-methyl-derivatives of oxine act similarly (Kadota and Abe, 1954). 

Fischer T (1989) Occupational nickel dermatitis. In Maibach HI, Menne T (eds) Nickel and the skin immunology and toxicology. CRC Press, Boca Raton, pp 117-132 Fischer T, Rystedt I (1990) Influence of topical metal binding substances, vehicles, and corticosteroid creams on the allergic patch test reactions in metal-sensitive patients. Dermatol Clin 8 27-31... 

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