Tuning Reactivity of Platinum(II) Complexes

Figure 1.3: Intracellular hydrolysis and bio-activation of cisplatin in aqueous solution leading
to binding at DNA in the cell nucleus. 33
The reactivity of the 1:1 complexes bearing Cl ¯ or H2O as the fourth ligand is, however,
controlled by the lability of the aqua ligand, which dramatically decreases with
increasing pH. 34 This study investigated the impact of the structure and chain-length of
the bridging ligand of square-planar Pt(II) dinuclear complexes of general formula [{cis-
Pt(NH3)2(OH2)}2–µ–L] +4 (L being α,ω-alkanediamine, diazine, and 4,4’-
dipyridinesulphide linkers) on the acid-base properties of the two water molecules in
the cis-position.
1.3.2.4 DNA Adducts and Cell Response
Once the active complex species enter the nucleus, they become attracted to the
negatively charged DNA. The electrostatic interaction complexation with nitrogen
atoms of purine bases, normally the N7 atoms of two vicinal guanine units, occurs via
the displacement of the two water molecules; leading to intrastrand cross-linking that
deforms the DNA tertiary conformation as shown Figure 1.4. This is key step in the
mechanism of action. 29a
k1 = 6.3 x 10 -5 s -1
6
k2 = 2.5 x 10 -5 s -1