Affinity and Nuclease Activity of Macrocyclic Polyamines and Their Cu^IIComplexes

Abstract

The stability constants of CuII complexes that consist of either an oxa‐aza macrocycle with two triamine moieties linked by dioxa chains, or two macrocyclic ligands with a polyamine chain which are connecting the 2 and 9 positions of phenanthroline, have been determined by means of potentiometric measurements. The results are compared to those reported for other ligands with a similar molecular architecture. Of the complexes that contain phenanthroline in their macrocycle, the CuII ion of the complex with the smallest and most rigid macrocycle (L3) has an unsaturated coordination sphere, while in the complex with the largest macrocycle (L5) the CuII ion is coordinatively almost saturated. These results are corroborated by the crystal structure of the [CuL5](ClO4)2 complex. The affinity of the ligands and the complexes towards nucleic acids was studied by measuring the changes in the melting temperature, which showed that the affinity of the macrocyclic ligands towards double‐stranded DNA or RNA is generally smaller than that of their linear analogues that bear a similar charge, with a strong preference for polyA–polyU, a model for RNA. However, the complexes of two of the changed macrocyclic ligands which contain a phenanthroline unit (L4, L5) showed a distinctly larger increase in their melting temperature ΔTm with DNA (polydA–polydT), which is reversed again in favor of RNA upon metallation to the dinuclear copper complex with L5. Experiments with supercoiled plasmid DNA showed a particularly effective cleavage with a mononuclear CuII complex that contains a phenanthroline unit (L6). Related ligands showed less activity towards DNA, but not so towards the biocidic bis(p‐nitrophenyl)phosphate (BNPP). In both cases (with DNA and BNPP) the activity seemed to increase with decrease of coordinative saturation of the CuII ion, with the exception of one particular ligand (L6). Experiments with radical scavengers in the DNA experiments showed some decrease in cleavage, which indicates the participation of redox processes.

Cd(II) and Pb(II) Complexation by Dipyridine-Containing Macrocycles with Different Molecular Architecture. Effect of Complex Protonation on Metal Coordination Environment

“…The lower stability of the L1 and L2 complexes can be explained instead considering the formation of one or more large chelate rings due to the presence of some nitrogen donors not bound to the metal. Most likely, as previously found in phenanthroline-containing macrocycles, − the rigidity of the dipyridine unit does not allow the simultaneous involvement in metal binding of the heteroaromatic nitrogens and the adjacent benzylic amine groups. This hypothesis is supported by the high values of the equilibrium constants for successive addition of H + to the [Cd L1 ] 2+ and [Cd L2 ] 2+ complexes, which suggest that protonation takes place on uncoordinated nitrogen atoms.…”

DNA Interactions, Mutagenic, Anti-Mutagenic And Antimicrobial Activities of (E)-2-((3,5-Bis(Trifluoromethyl)Phenylimino)Methyl)-4,6- Dimethoxyphenol

“…Imine compounds are an important class of compounds and have many applications in medicine and pharmaceutical fields as antibacterial, antifungal, and chemotherapeutic agents [12][13][14]. Fluorine substitution is a widely used strategy for developing drugs that can change the conformation, membrane permeability, and electrical charge of a ligand [15].…”

Zn(II) Coordination to Polyamine Macrocycles Containing Dipyridine Units. New Insights into the Activity of Dinuclear Zn(II) Complexes in Phosphate Ester Hydrolysis

“…Polyamine macrocycles containing six or more nitrogen donors and cavities of appropriate shape and dimension may be able to hold two metal centers at short distances. − The distance between the two metal ions can be varied by an opportune synthetic modulation of the dimension of the macrocyclic cavity and of the ligand flexibility. At the same time, the chemical properties of the metal centers depend on the ligational properties of the chelating sites, and, therefore, an appropriate design of the metal binding unit may lead to polynuclear metal complexes with different reactivity and catalytic properties.…”