Ligands that can bind with more than one donor atom to the same central metal ion are called chelate ligands or chelators. Chelators or their complexes have found applications as chemical decontamination and decorporation agents, MRI contrast agents, chelating agents for radiopharmaceutical applications, luminescent probes and in vivo NMR shift reagents.
Metal ions in solution form complexes in which the central metal ion is surrounded by ligands. A ligand that can bind to the metal ion through two or more coordinative bonds to form rings is called a chelating agent or chelator. Binding of a multidentate chelator to a metal ion results in an increased stability of the complex as compared to the monodentate analog (chelate effect). Organic chelating agents have great practical importance. Chemical decontamination agents: Chemical decontamination uses chelating agents to remove toxic or radioactive metal contaminats from the environment. Some of the most frequently used chelating agents include ethylenediaminetetraacetic acid (EDTA), picolinic acid, oxalic acid, citric acid, diethylenetriaminepentaacetic acid (DTPA). Decorporation agents: Decorporation therapy uses chelating agents to remove toxic and radioactive metal ions from living organisms. This is an efficient way to reduce the radiation dose to persons who have been internally contaminated with radionuclides. The most commonly used ligand for this purpose is diethylenetriamine pentaacetic acid (DTPA). It is effective for mobilizing transuranium ions such as plutonium (Pu) as well as heavy metal ions. Other complexing agents such as cryptand based ligands are very promising and are currently under development. Chelating agents in biological systems: Porphyrine based chelating agents and their chelates play important roles in oxygen transport and in photosynthesis or they act as the active sites of enzymes. MRI contrast agents. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and DTPA and their derivatives are used as chelating agents for magnetic resonance imaging applications. The Gd(III) (gadolinium) complex of these ligands is administered to patients to enhance the image contrast and visualize organ function or blood flow. There is a continuing need for the design and synthesis of more efficient chelating agents for MRI. Current research focuses on new, high performance contrast agents that have specific in vivo biodistribution or are able to respond to biochemical stimuli and visualize biological events at the cellular level (smart or responsive MRI contrast agents).
Chelating agents for radiopharmaceutical applications. Radiopharmaceuticals are radioactive drugs that are used for diagnosis or therapy. They deliver small doses of radiation to a specific site in the body. A radiopharmaceutical can be targeted to a receptor through a targeting vector such as antibodies, antibody fragments, peptides, peptidomimetics, or small organic molecules. Since many metallic elements have medically useful radioisotopes, metalloradiopharmaceuticals play a very important role in nuclear medicine. Targeted metalloradiopharmaceuticals are constructed by attaching the radioactive metal ion to a targeting molecule using a bifunctional ligand. DTPA-based bifuctionals are commonly used for diagnostics. Due to the exceptionally high thermodynamic and kinetic stability of DOTA-metal complexes, bifunctional ligands based on DOTA are frequently used for therapeutic applications. There is an ongoing research to develop bifunctional ligands that form complexes with improved kinetic stability.