oa Editorial [Hot Topic: Metal Based Agents with Potential for Therapeutic and Diagnostic Applications (Guest Editors: Shigenobu Yano & Michael Gottschaldt)]

Metal based agents are continuously gaining increasing attention as potential drug candidates or as tools in diagnostic applications. Combination of unique intrinsic properties of metal ions and complexes, e.g. redox-properties, radioactivity, magnetism or reactivity, with the multiplicity of various organic and bioorganic ligands afforded an inconceivable number of potential molecules. The known activities of several metal ions in biology have stimulated further developments of metal-based therapeutics and diagnostics. The present issue of Current Topics in Medicinal Chemistry deals with some of the unique aspects associated with recent results regarding the therapeutic and diagnostic potential of metal based agents. First of all, the ligands employed for metal ion coordination play an integral role in tailoring the resulting agent for specific application, allowing for fine tuning of important drug parameters. Besides the classical ligand design aiming for optimized complex formation, metal binding, complex stability, water solubility, overall charge, secretion pathway, complex dissociation and related toxicity, recent research has centered on including added functionalities to ligands. With this approach multifunctional ligands with enhanced targeting, reporting and overall efficacy have been developed. A comprehensive overview of new developments of such multifunctional ligands and their application is given by Tim Storr and co-workers (Simon Fraser University, Canada). Introduction of biologically derived functionalities onto metal based agents in order to use specific binding or transport phenomena is currently widely studied for the design of novel drugs and diagnostics. Among others, much effort has been spend to conjugate carbohydrates to various metal complexes. Sugars are key-substances in many biological events, e.g. transport and recognition processes. Recent attempts for the synthesis of sugar-based metal complexes are discussed by S. Yano & Y. Mikata (Kyoto University and Nara Women' University, Japan) with special emphasis on palladium complexes, the synthesis of Cglycosides, C-glycoside-amino acid hybrid molecules, sugar-dipicolylamine conjugates as well as introduction of oligosaccharides to photofunctional porphyrine derived molecules. From the view of the constitutive basic ligand system certainly oligopyridines as well as porphyrines have achieved major impact on current developments of metal based agents. This is due to the often unique photophysical properties of their metal complexes. Therefore, a major part of the issue will focus on or at least deal with polypyridyl-derived metal complexes from different points of view, e.g. the type of polypyridyl ligands used, photophysical or toxicological properties, interaction with biomolecules or focused on particular metal centers. One of the widespread groups of polypyridyl metal complexes is derived from terpyridine. So far, the majority of results for biomedical application of these types of complexes were published for heavy second or third row transition metal ions (like PtII and RuIII complexes as anti tumor agents and IrIII, PtII and EuIII for biolabeling). In recent years terpyridine based complexes from first row transition metals, which are naturally more abundant and intrinsically less toxic, have been reported to possess biological activities as, e.g., anti tumor agents or DNA oxidants. The review from Winter and co-workers (Friedrich-Schiller- University of Jena, Germany) emphasizes developments in this particular area. The current status of functional terpyridines and terpyridine-like ligands and their complexes with Zn, Cu, Fe, Cr, Co and V in different oxidation states is presented and their cytotoxic and nuclease activities as well as their properties in terms of labeling biomolecules and in self-assembly processes is evaluated.....