The Interactions of Platinum Compounds with Biological Molecules

Abstract

This article describes the modes of interaction of anti-tumour and related platinum complexes with biomacromolecules and their components. We start with a brief review of the chemistry of the platinum compounds and proceed to illustrate where possible this chemistry as it is seen to occur in the interaction of platinum compounds with biological molecules. Our aim is to uncover this chemistry as it may apply to the transport of platinum compounds in a biological medium, to the attack by the platinum drugs at their site of action or to their role in causing toxicity. Such studies are only able to indicate possible modes of action and can never furnish proof of a mechanism of biological activity. However, we shall refer most often to four prototype compounds, namely cis- and trans-dichloro-diammine platinum(II) and cis- and trans-tetrachloro-diammine platinum(IV), whose stereo-chemistries are shown in Fig. 1. Of these four compounds only the cis isomers display appreciable anti-tumour activity, the trans isomers being largely ineffective. Thus a comparison of the reactions of these four complexes with biological molecules can provide an invaluable index of the relevance or otherwise of the chemistry to the biological effect. Therefore although the trans isomers are ineffective as anti-tumour drugs their reactions with macro-molecules are of great interest and comparative studies should always be made where possible.