6533b870fe1ef96bd12cfaa2

RESEARCH PRODUCT

Copper complexes of polyaza[n]cyclophanes and their interaction with DNA and RNA

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Abstract The complexation properties of Cu 2+ ions with the cyclophane receptors 2,6,9,13-tetraaza[14]metacyclophane ( L1 ), 2,6,10,13,17,21-hexaaza[22]metacyclophane ( L2 ) and 2,6,10,13,17,21-hexaaza[22]paracyclophane ( L3 ) are presented. Formation of mononuclear complexes in the case of L1 and of mono- and binuclear complexes in the case of the hexaaazcyclophane ligands L2 and L3 is observed. The coordination numbers around each Cu 2+ in the binuclear complexes involve at most three nitrogen donors for each metal ion. Cyclophanes L1 – L3 and several acyclic polyamine ligands are tested for their affinity towards double-stranded nucleic acid models of RNA and DNA. The binding affinity of the acyclic and macrocyclic polyamines towards DNA and RNA models, measured by changes in their melting temperature Δ T M , increases progressively with the average number of charges present on the amine, with higher stabilisation for RNA. Unusually large differences of up to Δ(Δ T M )=30°C were observed with tripropylenetetraamine ( L15 ) and with the macrocyclic amines ( L2 and L3 ). Introduction of copper in the ligands leads to considerable affinity variations. One macrocyclic copper complex (with L3 ) shows a strong discrimination between the RNA and DNA polymers with a record value of ΔΔ T M =41°C, and a small destabilisation of the DNA. The copper complexes exhibit nuclease activity; with plasmid DNA nicking was increased by one complex by a factor of k / k un =10 7 . Experiments with hydroxyl radical quenchers indicate a predominant redox cleavage mechanism.