Figure 4.18: (a) NMR solution structure of the DNA duplex and BP showing classical intercalation between the G13G14 base step of the opposite strand. (b) X-ray structure showing threading intercalation of 9-amino-6-bromo-DACA (space-filling model) into the DNA duplex.
Metal complexes that can have intercalative interactions with DNA form two classes. For relatively inert square-planar Pt(II) complexes and octahedral complexes with aromatic ligands, intercalation into DNA mainly involves the aromatic ligands. Metal complexes containing σ-bonded ligands with aromatic side arms as intercalators or organometallic complexes with π-bonded arenes as intercalators can be dual-function complexes: the aromatic side arms or arene ligands can intercalate between DNA bases while the metal coordinates directly to a DNA base. Intercalative interactions between metal complexes and DNA have novel features that can influence biological activity. Square-planar complexes containing aromatic fragments can bind to DNA by intercalation without direct metal coordination to DNA bases. Lippard et al. have shown that square-planar platinum(II) complexes containing heterocyclic aromatic ligands, such as terpy, quaterpy, phen, bipy, and phi, bind to DNA duplexes noncovalently, intercalating between the base pairs (Figure 4.19 a-c).
Figure 4.19: (a) Some examples of platinum metallointercalators. (b) Structures of ACRAMTU, Pt-ACRAMTU and model of a DNA duplex containing with the Pt-ACRAMTU adduct (c) Molecular structure of [Pt(terpy)(HET)] and Crystal structure of [Pt(terpy)(HET)]þ3 d(CpG)2 showing HET intercalated between two GC base pairs.(d) Some examples of Rh and Ru based metallointercalators.