A chelate is a complex formed between a metal and a compound that contains two or more potential ligands. The product of such a reaction is a heterocyclic ring. Five- and six-membered chelate rings are the most stable, and polydentate (multiligand) chelators typically form more stable chelates than chelators with only one ligand atom.
The stability of chelates varies with the metal and the ligand atoms. For example, lead and mercury have greater affinities for sulfur and nitrogen than for oxygen ligands; calcium, however, has a greater affinity for oxygen than for sulfur and nitrogen. These differences in affinity serve as the basis for selectivity of action of a chelating agent in the body.
The effectiveness of a chelating agent for the treatment of poisoning by a heavy metal depends on numerous factors: the relative affinity of the chelator for the heavy metal as compared with essential body metals, the distribution of the chelator in the body as compared with the distribution of the metal, and the capacity of the chelator to remove the metal from the body once chelated. Consider the properties of an ideal chelating agent: high solubility in water, resistance to biotransformation, ability to reach sites of metal storage, capacity to form nontoxic complexes with toxic metals, ability to retain chelating activity at the pH of body fluids, and ready excretion of the chelate. A low affinity for Ca2+ also is desirable because Ca2+ in plasma is readily available for chelation, and a drug might produce hypocalcemia despite high affinity for heavy metals. A therapeutic chelating agent must bind the metal more avidly than endogenous ligands bind the metal. The large number of endogenous ligands is a formidable barrier to the effectiveness of a chelating agent. Observations in vitro on chelator-metal interactions provide only a rough guide to the treatment of heavy-metal poisoning. Empirical observations in vivo are necessary to determine the clinical utility of a chelator.
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