Tuning Reactivity of Platinum(II) Complexes

4.1 Introduction
Platinum compounds play an important role in the treatment of many cancers 1-4 , as well
as nucleic acid probes 5, 6 and DNA molecular light switches. 7 It is estimated that 50-70 %
of cancer patients are treated with a platinum drug. 8 The complex cis-[PtCl2(NH3)2],
cisplatin, remains the most widely used anticancer drug against ovarian, testicular and
non-small cell lung cancers. 1-4 Driven by the impressive success of cisplatin and despite
its limited spectrum of activity due to the development of high toxicity and cross-
resistance in many cell lines, 8,9 thousands of new platinum containing compounds have
been developed and screened for anti-cancer activity. Only a small fraction has shown
sufficient promise during pre-clinical evaluation. 10
Recently, many multinuclear Pt(II) complexes that incorporate flexible diamine chains
or rigid aromatic bridging ligands such as azoles and diazine molecules 10,11 have been
synthesized and tested with the aim of obtaining better anti-tumour activity through
increased solubility and lower toxic effects. These di-and tri-nuclear Pt(II) complexes
are well suited for the anti-tumour activity compared to their mononuclear analogues
because they are ionic, more soluble and exhibit a high degree of cellular uptake.
Secondly, they possess Pt---Pt distances that are flexible enough to offer minimal
distortion of the DNA molecule. In addition their 1,3- and 1,4-GG interstrand cross-links
persist longer than the intrastrand cross-links and are less susceptible to repair. 12
A number of ligand substitution reactions involving dinuclear Pt(II) complexes have
been reported in literature. 12-17 Studies have shown that the reactivity of the complexes
is dependent on the Pt---Pt distance separating the centres. 18 The electronic and steric
properties of the complexes as well as the symmetry of the complexes have been put
forward to explain reactivity at the metal centres. Kinetic studies have also shown that
some dinuclear complexes undergo ring opening of their chelate during the substitution
reactions involving strong trans-influencing donor ligands such as TU, PPh3 and
I ¯ . 15,16,18,19 Despite this, there is evidence that complexes such as [{cis-PtCl(NH3)2-µ-y] n+
(where y = NH2(CH2)6NH2), 20 which has a cis-geometry at the Pt(II) centre does not
undergo degradation by strong sulphur donor nucleophiles. However, some studies
have demonstrated the release of the bridge in complexes of similar geometry following
2