Coordinatin Chemistry of Metallodrugs: Insights Into Biological Speciation from NMR Spectroscopy
There is much current interest in the design of metal compounds as drugs and diagnostic agents and in understanding the molecular mechanisms of action of metallopharmaceuticals already in clinical use. Central to progress in this area is investigation of the speciation of metal compounds, especially in biological media such as cells, body fluids and cell culture media. Modern multinuclear NMR approaches are very powerful for investigation of the thermodynamics and kinetics of reactions of metal compounds with both small and large biomolecules and it is possible to study the coordination chemistry of metallodrugs under physiologically relevant conditions. For example [1H, 15N] inverse detection methods allow studies of intermediates in the pathways of DNA platination by anticancer drugs and the direct detection of sulphur adducts of platinum drugs in urine. Other applications which are discussed include ligand exchange reactions of gold antiarthritic drugs, copper, silver, gold and ruthenium anticancer agents and bismuth antiulcer drugs. Resolution enhancement, specific isotopic labelling of amino acid side-chains and high field NMR studies of metal nuclei provide insight into the uptake and release of metallopharmaceuticals from the blood plasma proteins albumin (66 kDa) and transferrin (80 kDa). The use of 31P cross-polarization magic angle spinning NMR spectroscopy to investigate the structures of bioactive metal phosphine complexes in the solid state is also described.
Analytical Chemistry not elsewhere classified