Supramolecular chemistry, part 99 Affinity and nuclease activity of macrocyclic polyamines and their Cu-II complexes

The stability constants of Cu-II complexes that consist of either an oxaaza macrocycle with two triamine moieties linked by dioxa chains, or two macro cyclic ligands with a polyamine chain which are connecting the 2 and 9 posi tions of phonanthroline, have been determined by means of potentiometric me asurements. The results are compared to those reported for other ligands wi th a similar molecular architecture. Of the complexes that contain phenanth roline in their macrocycle, the Cu-II ion of the complex with the smallest and most rigid macrocycle (L3) has an unsaturated coordination sphere, whil e in the complex with the largest macrocycle (L5) the Cu-II ion is coordina tively almost saturated. These results are corroborated by the crystal stru cture of the [CuL5](ClO4)(2) complex. The affinity of the ligands and the c omplexes towards nucleic acids was studied by measuring the changes in the melting temperature, which showed that the affinity of the macrocyclic liga nds towards double-stranded DNA or RNA is generally smaller than that of th eir linear analogues that bear a similar charge, with a strong preference f or polyA-polyU, a model for RNA. However. the complexes of two of the chang ed macrocyclic ligands which contain a phenanthroline unit (L3, L5) showed a distinctly larger increase in their melting temperature DeltaT(m) with DN A (polydA-polydT), which is reversed again in favor of RNA upon metallation to the dinuclear copper complex with L5. Experiments with supercoiled plas mid DNA showed a particularly effective cleavage with a mononuclear Cu-II c omplex that contains a phenanthroline unit (L6). Related ligands showed les s activity towards DNA, but not so towards the biocidic bis(p-nitrophenyl)p hosphate (BNPP). In both cases (with DNA and BNPP) the activity seemed to i ncrease with decrease of coordinative saturation of the Cu-II ion, with the exception of one particular ligand (L6). Experiments with radical scavenge rs in the DNA experiments showed some decrease in cleavage, which indicates the participation of redox processes.