Tuning Reactivity of Platinum(II) Complexes

Chapter Two
2.0 Ligand Substitution at Pt(II) Square-planar Centre
2.1 Introduction
In order to understand how a metal such as Pt achieves the desired anticancer activity,
the kinetics underlying the interaction of the Pt-based drugs with their target, the DNA
and S-donor ligands present in biological fluids is important. 1 The prime target of Pt is
thiols (RS - ) like glutathione and cysteine. These are known to bind irreversibly to Pt(II)
under the conditions obtained in the body fluids at a neutral pH. This renders the
anticancer Pt(II) agent inert and ineffective.
These Pt(II) complexes in comparison to other d 8 square-planar complexes such as
Pd(II), Rh(I), Ir(I) and Au(III) are characterised by similar in ionic radii due to the
lanthanide contraction. However, the rate of metal-ligand exchange is slow in Pt(II)
complexes. This gives it high kinetic stability and results in ligand-exchange reactions of
a longer duration than the other metals. The Pt(II) compounds exhibit ligand-exchange
kinetics in the same order of magnitude as the division of tumour cells, 2
which makes them suitable to stop mitosis and promote cell death before the Pt(II)
centre could be inactivated by non-target binding sites like the soft S-donor ligands.
Moreover, Pt(II) complexes containing N and S donor atom ligands are both kinetically
stable (slow ligand exchange) and thermodynamically stable. 3 The analogous complexes
of Au(III) are effective as anticancer drugs, but are thermodynamically unstable since
they are readily reduced to Au(1) and Au(0). 4 Therefore, continued investigation into
ligand-exchange kinetics of Pt(II) complexes remains an important area in
contemporary drug design and synthesis. The varying of parameters such as steric and
electronic effects to tune solubility, acidity and reactivity of these complexes may
improve the therapeutic efficacy of the anticancer drugs as well as tune the reactivity of
the complexes. In the last few decades, an appreciable amount of research has been done
on the kinetic and the mechanistic behaviour of substitution reactions of Pt(II)
complexes. 5,6,7,8 Due to the similarity in the reaction mechanisms of platinum(II)
complexes with the other square planar complexes, the information collected on
platinum(II) complexes can be applied to the other square planar complexes.
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