Tuning Reactivity of Platinum(II) Complexes

5.1 Introduction
Multinuclear platinum(II) complexes containing heterocyclic amine carrier ligands
represent a novel class of anticancer drugs 1–7 that can overcome both acquired and
intrinsic resistance to cisplatin, cis-PtCl2(NH3)2. In addition, they also form different
binding modes to DNA. 6,8 One of the advantages of these dinuclear platinum(II)
complexes compared to cisplatin, is their strong binding affinity for intracellular
polyanionic DNA due to their relatively large positive charge (+4/+2). 9 Studies in this
area of multinuclear complexes are motivated by the tenet that bridging ligands play
important roles in regulating reactivity of the metal ions by controlling the geometric
symmetry, distance separating the coordinated metal ions, steric and electronic features
at the metal centre. 3,10–12 However, systematic investigation of the kinetic and
thermodynamic properties of the dinuclear platinum (II) complexes in which the
aromatic diazine ligands act as linkers is relatively unexplored with only one paper
reported in literature. 13
Most of the studies that are available in the public domain involve α,ω-alkanediamine 10
and bis-(2-pyridylmethyl) amine-bridged dinuclear platinum(II) complexes. 12–18 The
results from these investigations show that as the aliphatic-chain separating the two
platinum centres increases the extent of reactivity reaches a maximum. 17,18 Such
behaviour is consistent with the decrease in charge additions as well as the steric
influences, which decrease proportionally as the chain length increases in dinuclear
complexes. 18 However, it is unclear whether such metal-to-metal interactions would be
mediated by direct binding between the platinum atoms or by the bridging ligands
when the distance is shortened using rigid aromatic bridging ligands like azoles and
diazines. In most cases, long distance metal-to metal interactions are transmitted
through conjugated π-systems. 19–21 In fact, the rate of substitution decreases by a factor
of 60, if communication between aromatic rings is destroyed. 22
Recent studies in our research group involving dimethypyrazine and pyridyl-bridging
ligands have shown degradation of the linker; which is contrary to the commonly
accepted knowledge that the cis geometry, in the species such as [{cis–PtCl(NH3)2}2–µ–
H2N(CH2)6NH2] +2 , is less susceptible to metabolic decomposition by the sulphur
2