Tuning Reactivity of Platinum(II) Complexes

1.3.4 Terpyridine Platinum(II) Complexes
Terpyridine-platinum(II) complexes are known to possess DNA intercalating activity
and have been regarded as potential anti-tumour agents. 66 Some of the selected
aromatic intercalators are listed in Figure 1.8.
N
N
Pt
S
OH
[Pt(terpy)(HET)] +
N
+
N
N
Pt
N
13
CH 3
N
[Pt(terpy)(4-picoline)] 2+
2+ 2+
H 2 N
Pt
NH 2
[Pt(phen)(en)] 2+
Figure 1.8: Selected Pt(II) metallo-intercalators: terpy = terpyridine, phen =
phenanthroline, 4-picoline = 4-methylpyridine, en = 1,2-diaminoethane,
and HET = 2-hydroxyethanethiolato ligand.
Intercalative binding, as most commonly studied, is the noncovalent stacking
interaction resulting from the insertion of a planar heterocyclic aromatic ring between
the base pairs of the DNA double helix. Intercalation stabilizes, lengthens, stiffens, and
unwinds the DNA double helix. 67 Previous studies have demonstrated (2,2’:6’,2’’–
terpyridine)platinum(II) complexes to be cytotoxic to human ovarian cancer and that
bis-[(2,2’:6’,2’’–terpyridine)platinum(II)] complexes with short and rigid linkers are
particularly effective. 68,69 The single charged complex {Pt(terpy)(HET)] + was found to
intercalate into DNA with a binding constant of 8.3 × 10 6 M -1 , whilst the [Pt(terpy)(4-
picoline)] +2 is a much stronger intercalator with a binding constant of 2.0 x 10 7 M -1,
which translates to more than two orders of magnitude greater. 70 This is due to the
double positive charge of the 4-picoline complex. However, their cytotoxic mechanism
remains unclear. These Pt(II) terpy metal complexes can also be used as probes of the
electronic and steric effects on the binding to DNA, as the ancillary ligand and nature of
the metal can be sterically and electronically tuned. 70,71,72 The π-acceptor effects of
terpyridine ligands have been shown to play an important role in the substitution
behaviour of Pt(II) complexes. 73 Systematic variation of π-bonding character of the