Figure 1. Structures of some metallodrugs which interact with DNA via coordination, groove binding, intercalation, insertion, or dual function binding (coordination and intercalation).

Figure 2. X‐ray structure showing threading intercalation of 9‐amino‐6‐bromo‐DACA (space‐filling model) into the DNA duplex 5′‐d(C|G(5‐BrU)AC|G) 2‐3′ (wireframe), where | indicates intercalation [ 17].

Figure 3. Schematic representation adducts known to form on DNA upon treatment with cisplatin.

Figure 4. (a) Average solution structure of the dodecamer DNA duplex d(CCTCAGGCCTCC)·d(GGAGTCCGGAGG) platinated by cisplatin (kinked by 60°) and (b) the native DNA duplex with AGGC sequence. The platinum atom in the cisplatin–DNA adduct is shown as a sphere [ 31]. (c–d) Chemical shift differences for NMR resonances of platinated and unplatinated DNA duplexes (d(ATACATG*G*TACATA)·(TATGTACCATGTAT), III* or III, respectively). Chemical shift differences, Δδ, measured as (δ III * − δ III) for (c) aromatic and (d) H1′ resonances. Shift changes are indicated for the platinated GG strand (▪) and for the complementary CC strand (▿) [ 28].

Figure 5. Schematic drawings of the L1 and R2 rotamers of [Pt(R‐tmen){d(GpG)}] + and [Pt(S‐tmen){d(GpG)}] + [ 30].

Figure 6. (a) Molecular structure of [Ru(bpy) 2(pqx)] 3+. (b) A molecular model showing the binding of Λ‐[Ru(bpy) 2(pqx)] 2+ to d(CGCGAATTCGCG) 2 in the major groove [ 44]. (c) Selected NOEs between [{Pt(dien)} 2µ‐H 2N‐(CH 2) 6‐NH 2] 4+ and a single strand of the dodecanucleotide d(CGCGAATTCGCG) 2 (dotted lines), indicative of minor groove binding [ 46].

Figure 7. (a) Molecular structure of [Pt(terpy)(HET)] +. (b) Molecular structure of [Rh(bpy) 2chrysi] 3+. (c) Crystal structure of [Pt(terpy)(HET)] + d(CpG) 2 showing the intercalation of HET between two GC base pairs [ 47]. (d) Structural model for insertion binding of the Rh complex at the mismatched site in the 9mer duplex (5′‐CGGACTCCG‐3′) 2 based upon an NMR study, viewed from the major groove [ 50]. (e) Molecular structure of Δ‐α‐[Rh(R, R‐Me 2trien)Phi] 3+. (f) Crystal structure of Δ‐α‐[Rh(R, R‐Me 2trien)Phi] 3+ bound to 5′‐d(GTTGCAAC) 2‐3′ duplex DNA [ 49].

Figure 8. (a) Structures of ACRAMTU, (b) Pt‐ACRAMTU, and (c) adduct of DNA duplex 5′‐CCTCG*TCC‐3′/3′‐GGAGCAGG‐5′, with Pt‐ACRAMTU (right, the acridine chromophore is depicted in space‐filling form) [ 16].

Figure 9. Molecular models of two conformers of duplex d(ATACATGGTACATA)·(TATGTACCATGTAT) ruthenated at N7 of G18 with {(η 6‐bip)Ru(en)} 2+. In (a) the biphenyl arene is intercalated and in (b) stacked on T17 as a flipped‐out base. The bip is in green [ 14].

Figure 10. Molecular models of the DNA hexamer duplex d(CGGCCG) 2 ruthenated at N7 of G3 (a–c) or N7 of G6 (d–f) with {(η 6‐tha)Ru(en)} 2+, showing a novel penetrative intercalation [ 64]. The tetrahydroanthracene ligand tha is in green.

Figure 11. Two‐dimensional HSQC NMR spectra of the duplex d(CGGCCG) 2 (II) (bottom), and a 1 : 1 equilibrium mixture of duplex II and Ru‐tha (top) in 90% H 2O/10% D 2O, showing the (−1.2 to −0.70 ppm) to sugar ring H3′ and H4′ (5.2–4.1 ppm) connectivities. Significant changes are observed for , H3′, and H4′ resonances of bases G3, C4, C5, and G6, minor changes are observed for the corresponding resonances of bases C1/C7 and G2/G8 [ 64].