Medicinal Applications of Metal Complexes Binding to Biological Macromolecules

Abstract Biological macromolecules present in living organisms, like proteins, DNA, have many metal‐binding sites. As a consequence, coordination compounds can react with such cellular components, displaying possible toxic effects, or they also may have beneficial applications. So metal ions and compounds not only are essential for life in e.g. dioxygen transport, or biocatalysis, but they can also be used for controlled toxicity in medicinal applications. Well‐known examples are the application of gold compounds in arthritis treatment, bismuth compounds for ulcer healing, and silver compounds for open skin protection. However, only in a few cases details of the mechanist are known, and if so, the biological macromolecules play a key role. Transition‐metal coordination compounds that have metal‐ligand exchange rates comparable to cell‐division processes, i.e. in particular Pt and Ru, often appear to be highly active in killing cancers, as seen from the study of several cancer cell lines. Classical examples, like cisplatin, and new examples of Pt and Ru compounds will be discussed in some detail, with a focus on their binding to the DNA biomacromolecule. The classical compound cis ‐diamminedichloridoplatinum(II), often abbreviated as cisplatin, and its first‐generation derivatives are known to bind to several biomacromolecules in a specific way, and eventually bind at DNA. Four important examples are shown in the figure. However, on its way to DNA other cellular components, like proteins and peptides might be intermediates before the final target is reached. Other metal‐containing drugs, like Ru compounds, that show anti‐cancer activity have a less well‐known mode of action. Molecular‐based mechanistic studies may result in improved clinical administration protocols.