Coligand tuning of the DNA binding properties of half-sandwich organometallic intercalators: Influence of polypyridyl (pp) and monodentate ligands (L = Cl, (NH2)2CS, (NMe2)2CS) on the intercalation of (η5-pentamethylcyclopentadienyl)-iridium(III)- dipyrid

The DNA binding of polypyridyl (pp) (η5-pentamethylcyclopentadienyl)iridium(III) complexes of the type [(η5-C5Me5)IrCl(pp)](CF3SO3) (pp = dpq, dppz, dppn) (1–3) and [(η5-C5Me5)Ir(L)(pp)](CF3SO3)2 (L = (NH2)2CS, pp = dpq, dppz, dppn) (4–6), (L = (NMe2)2CS, pp = dpq, dppz, dppn) (7–9) has been studied by UV/Vis spectroscopy, circular dichroism and viscosity measurements. Modest increases ΔTm of 2–7 °C in the thermal denaturation temperature (for r = [complex]/[DNA] = 0.1) and the effectively unchanged values or decreases in viscosity observed for CT DNA after incubation with complexes 1–3 for 60 min are in accordance with thermodynamically preferred coordinative Ir-N (nucleobase) binding to the biopolymer. However, kinetically favoured intercalation for 2 and 3 leads to large initial hypochromic UV/Vis shifts for the π–π∗ transitions of their polypyridyl ligands in the range 300–450 nm. As indicated by the large ΔTm value of 14 °C and the marked increase in viscosity for 5/CT DNA mixtures, dppz appears to present an optimum surface area for side-on intercalation for L = (NH2)2CS. Whereas lower values for these parameters suggest partial intercalation for the smaller dpq ligand of complex 4, the ΔTm value of only 2 °C and a decrease in DNA viscosity are in accordance with surface binding for the dppn complex 6. In contrast, replacement of L = (NH2)2CS in 6 by L = (NMe2)2CS in 9leads to very strong intercalative binding of the larger polypyridyl ligand with a binding constant Kb = 1.0(6) × 107 M−1 following a possible change in the DNA structure from B to A, as suggested by CD spectroscopy. Viscosity studies and ΔTm values for complexes 7 and 8 are in accordance with, respectively, partial and strong intercalative binding of these complexes into DNA. Circular dichroism measurements suggest that the presence of the bulky (NMe2)2CS ligand causes significant distortions of the DNA structure for the larger dppz and dppn ligands.

The DNA binding of novel organoiridium(III) polypyridyl (pp) complexes of the types [(η5-C5Me5)IrCl(pp)](CF3SO3) (1–3) and [(η5-C5Me5)Ir(L)(pp)](CF3SO3)2 (L = (NH2)2CS, (NMe2)2CS) (4–9) has been studied by UV/Vis spectroscopy, CD and viscosometric titrations. The mode of binding (coordinative, surface or intercalative) can be tuned by the nucleophilicity and bulkiness of the monodentate ligand L. For L=(NH2)2CS, dppz presents an optimum aromatic surface area for side-on intercalation into DNA.Figure optionsDownload as PowerPoint slide