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 DT M , increases progressively with the average number of charges present on the amine, with higher stabilisation for RNA. Unusually large differences of up to D(DT 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 DDT 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.