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

• Published in: Inorganica Chimica Acta 2001-05, Vol.316 (1), p.71-78
• Main Authors: Chand, Dillip Kumar, Schneider, Häns-Jörg, Aguilar, Juan A, Escartı́, Francisco, Garcı́a-España, Enrique, Luis, Santiago V
• Format: Article
• Language: English
• Subjects: Copper complexes; Cyclophane complexes; DNA; RNA
• ISSN: 0020-1693; 1873-3255
• DOI: 10.1016/S0020-1693(01)00380-2

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.