150 years of the periodic table: New medicines and diagnostic agents

Abstract 150 years after Mendeleev created his periodic table of 63 elements, now is the time to explore its impact on our understanding of life itself and the discovery of new medicines and diagnostic agents. We illustrate that currently 76 elements have compounds either approved for clinical use or in clinical trials for therapy or diagnosis. Modern analytical techniques and the methods of modern cell and molecular biology, including proteomics and genomics, can now be used to guide the design and application of both essential and non-essential elements in therapy and diagnosis, including stable and radioactive elements. In particular, there is potential for the target sites and mechanisms of action of metallodrugs to be identified. However, the speciation of the elements in biological environments presents enormous challenges. The biological activity of metal coordination complexes is highly dependent on the metal plus its ligands, and also on both thermodynamics (strengths of metal-ligand bonds), and kinetics (timescales of the making and breaking of coordination bonds), as well as metal- and ligand-based redox processes. Notably, biological systems/metabolic pathways are inherently dynamic. Using examples from our recent research, we illustrate how ligands exert fine control over the chemical reactivity and biological activity of metal complexes. Elucidation of the spatial and temporal coordination chemistry of metals in biological systems is likely to add exciting new dimensions to the periodic table.