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

The complexation properties of Cu2+ ions with the cyclophane receptors 2,6, 9, 13-tetraaza[14]metacyclophane (L1), 2,6,10,13, 17,21-hexaaza[22]metacycl ophane (L2) and 2,6,10,13,17,21 -hexaaza[22]paracyclophane (L3) are present ed. Formation of mononuclear complexes in the case of L1 and of mono- and b inuclear complexes in the case of the hexaaazcyclophane ligands L2 and L3 i s observed. The coordination numbers around each Cu2+ in the binuclear comp lexes 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 aff inity of the acyclic and macrocyclic polyamines towards DNA and RNA models, measured by changes in their melting temperature DeltaT(M), increases prog ressively with the average number of charges present on the amine, with hig her stabilisation for RNA. Unusually large differences of up to Delta(Delta T(M))= 30 degreesC 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 wit h a record value of Delta DeltaT(M) =41 degreesC, and a small destabilisati on 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). E xperiments with hydroxyl radical quenchers indicate a predominant redox cle avage mechanism. (C) 2001 Elsevier Science B.V. All rights reserved.