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

The rapid DNA intercalation by dinuclear polypyridyl (eta(5)-C5Me5)Ir-III complexes of the type [{(eta(5)-C5Me5)Ir(dppz)}(2)(mu-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)(n)-SCH3 (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. Viscosity measurements 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.