Tuning Reactivity of Platinum(II) Complexes

1.4 Kinetic Interest
The platinum-based drugs represent a unique and important class of anti-tumour
agents. The discovery of cisplatin in the 1970’s revolutionized the chemotherapy in
human cancer. Despite its unparalleled successes, the full therapeutic potential of
cisplatin has not been realized due to its severe side effects and the emergence of
cisplatin-resistant tumour cells. It is also clear from the increasing number of new
platinum complexes that synthetic possibilities for more effective platinum-based anti-
tumour agents are far from being exhausted. Hence there is need to investigate their
kinetic and thermodynamic behaviour in order to obtain a detailed mechanism of action
of these systems using appropriate biological nucleophiles. Information on the kinetic
parameters and products for the reactions of Pt(II) compounds with the anions of
bromides, iodides, thiocyanate and sulphur-donor nucleophiles such as thiourea and its
derivatives is of significance to understanding the mechanism of chemo-protection and
platinum metabolism in anticancer therapy. 94 This is of importance because the
platinum complexes can be systematically tuned through electronic and steric effects.
This is important for their application in drug design, C-H activation and homogeneous
catalysis. 95
1.5 Aim and Scope of This Study
Recent investigations by jaganyi et al. 73 have been limited to modification of the terpy
ligand by either varying the number of pyridine rings, through direct substitution of a
pyridine ring with electron-withdrawing or donating groups, 96 and by introducing an
aromatic ring substituent in 4’-position of the central pyridine ring. 97,98 Therefore, the
first case of this study was to look into the effect of changing the co-ligand on the
tridendate N-donor ligand of mononuclear Pt(II) complexes. The second case was
extended to new platinum anticancer drugs with cis geometry, similar to cisplatin, that
have been developed with the aim of decreasing the severe side effects of cisplatin and
exhibit enhanced stability to metabolic deactivation by coordinated S-donor
nucleophiles. 99 Studies by Jaganyi and his group 100 and van Eldik’s group 101 have been
limited to trans Pt(II) dinuclear complexes and only one cis-Pt(II) dinuclear complex
system was investigated by Van Eldik et al. 102 Which merits further studies on cis-
platinum(II) complexes. The main aim is therefore to extend the study into the kinetics
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