INFLUENCE OF σ DONATION AND π ACCEPTANCE PROPERTIES OF SPECTATOR LIGANDS ON SUBSTITUTION REACTIONS IN BIFUNCTIONAL MONONUCLEAR PLATINUM(II) COMPLEXES: EXPLORING REACTIVITY PATTERN OF ANTITUMOR COMPOUNDS

Kinetics and mechanism of ligand substitution reactions on square planar platinum (II) complexes have been explored continuously over the last few decades. This was after the fortuitous discovery of the antiproliferative activity of cisplatin by Barnett Rosenberg in 1965, which attracted much attention from various other investigators to design new Pt(II) drugs with better activity and fewer side effects. Cisplatin's clinical success as a chemotherapeutic drug has promoted the discovery of succeeding generations with efficacy and less toxicity. The focal aim of these investigations was based on tailoring the steric and electronic properties of spectator ligands to influence the solubility, pKa, and molecular association or reactivity of the platinum complexes to promote the potential of the antitumor drugs. This mini-review provides accounts on: i) the mechanisms of substitution at the Pt(II) complexes in general and the key factors that control the reactivity, and ii) the trends in experimentally measured rate data and how they are controlled by varying the 6-donation and it-acceptance abilities of the spectator ligand. Furthermore, the reactivity patterns of platinum complexes are analyzed, highlighting how 6-donating and it-accepting ligands influence their biological activities. The insights gained from kinetic and mechanistic studies are essential for the development of more effective and less toxic platinum-based anticancer drugs.