Sequence‐Selective Organoiridium DNA Bis‐Intercalators with Flexible Dithiaalkane Linker Chains

Abstract

AbstractThe rapid DNA intercalation by dinuclear polypyridyl (η5‐C5Me5)IrIII complexes of the type [{(η5‐C5Me5)Ir(dppz)}2(μ‐L)](CF3SO3)4 1–4 has been studied by UV/Vis spectroscopy, circular dichroism, viscosity measurements and nuclear magnetic resonance. Whereas the Ir atoms of compounds 1–3 are linked by flexible dithiaalkanes of the type L = CH3S(CH2)nSCH3 (n = 4–6), compound 4 contains cyclic 1,4‐dithiane as a shorter more rigid bridging ligand. Stable intercalative binding into CT DNA is indicated for 1–3 by large increases in the DNA thermal denaturation temperature and by induced negative CD bands at about 300 nm. Viscositymeasurements show that the DNA lengthening induced by the bis‐intercalators 1–3 is about twice that caused by the monointercalator 4. An analysis of the NOE cross‐peaks for a 1:1 mixture of 3 with the double‐strand decanucleotide d(5′‐GCGCATCGGC‐3′) demonstrates that 3 intercalates in a sequence‐specific manner from the minor groove between the base pairs C4–G17 and A5–T16, and T6–A15 and C7–G14.