Controlling the Lability of Square-Planar Pt(II) Complexes Through Electronic and π-Conjugation: Correlation Between Kinetics and Theoretical Parameters

In this chapter, we report on some of the highlights of the research work which has been carried out in our laboratories on the role and influence of nitrogen-/carbondonor tridentate ligands (N<^>C/N<^>N/C) on the rate of substitution of labile ligands from model square-planar Pt(II) complexes. This work was founded on the hypothesis that tailored kinetic control of substitution reactions through changing the electronic properties of the spectator ligand backbone of Pt(II) complexes can be an insightful avenue toward the optimization of the efficacy of future antitumor Pt(II) drugs. Focusing on the nitrogen-/carbon-donor tridentates (N<^>C/N<^>N/C), several Pt(II) complexes were synthesized and used to study systematically the mechanisms and rates of substituting the labile coligand from the complexes using biorelevant nucleophiles. The trends in reactivity as the nonleaving ligands in the complexes were systematically changed were used to understand the electronic and steric roles of the coordinated tridentate/bidentates on the lability of their complexes. Our kinetic data source can be used for the tailor-designing of future metal-based drugs with rigid nonleaving ligands, given that the lability of such complexes in biological systems plays a role on their ultimate in vivo pharmacokinetics (i.e., toxicity, deactivation and development of resistance, and cytotoxicity).