Chelating agents in biological systems.

Abstract

Chelation enables metals to be transported to or from vulnerable target sites, and to hinder or facilitate their carcinogenic potential. In the reverse sense, metals are capable of ligand scavenging via complexation or mixed complex formation-the latter being the result of interaction with binary complexes. Consequently, metal complexes can be utilized for the transport of selected organic chemotherapeutic drugs to target organs, or for the decorporation of those toxic organic compounds which are able, before or after metabolic activation, of reacting with metals or 1:1 metal complexes. It is emphasized that the degree to which metal ions interact in vivo should employ the conditional constants which take into account competition from other ions, especially Ca2 +, H +, and OH-. The genotoxic consequences ofthe various chemical factors involved in chelation, along with examples: kinetics, stabilization of oxidation states, lipophilicity, and mixed ligand formation, are discussed.

The management of embedded metal fragment patients and the role of chelation Therapy: A workshop of the Department of Veterans Affairs—Walter Reed National Medical Center

“…The heme molecule offers a quadridentate chelate; others can be hexadentate. Generally, the more coordination bonds, or “claws,” the more stable the metal‐ligand complex 30 …”

“…However, it was during World War II, faced by the enemy use of the arsenical gas, lewisite, that British scientists developed dimercaprol (British Anti‐lewisite or BAL) to chelate arsenic and also recognized the value of EDTA (as calcium disodium EDTA [CaNa 2 EDTA]) to treat lead poisoning 32 . It was observed that to be an effective chelator, the drug must bind to the toxic metal with higher affinity than to endogenous biomolecules, and therefore, outcompete biomolecules for metal binding 30 …”

“…Generally, the more coordination bonds, or "claws," the more stable the metal-ligand complex. 30 The first synthetic chelator, ethylenediaminetetraacetic acid (EDTA), was synthesized in Germany as a replacement for citrate used as a water softener. 31 The citrate effectively bound calcium and magnesium which contribute to water hardness.…”

“…32 It was observed that to be an effective chelator, the drug must bind to the toxic metal with higher affinity than to endogenous biomolecules, and therefore, outcompete biomolecules for metal binding. 30 One of the by-products of the penicillin revolution in the post-1945 period was the development of penicillamine, another compound rich in sulfur with a high affinity for copper. Although sometimes used in cases of mercury poisoning, it is the drug chelator of choice in treating the copper excess of Wilson's disease.…”