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Abstract

The stability constants of Cu(II) complexes that consist of either an oxaaza 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 Cu(II) 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 Cu(II) 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 deltaTm 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 Cu(II) 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 Cu(II) 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.

Mechanistic aspects of the interaction of intercalating metal complexes with nucleic acids

“…These systems, besides enabling selective sensing of metal ions [93], can be employed as probes for nucleic acids [94], both as free ligands and bound to metal ions. As the luminescence of the system depends on the coordinated metal and on the substrate with which the macrocycle undergoes interaction, this property makes these metallo-receptors especially suitable to react with nucleic acids by intercalation of the aromatic fluorophore between base pairs [95,96]. However, the action of azamacrocycle metallo-intercalators is not limited to probing polynucleotides; in some cases, once the complex anchored in the vicinity of the nucleic acid by the intercalating residue, there is the possibility of cleavage of the phosphodiester bond by the metal centre [97][98][99][100].…”

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

“…Burstyn and co-worker reported that copper(II)-macrocyclic triamine complexes promote the hydrolytic cleavage of plasmid DNA [21]. In recent years, there has been substantial interest in the design and study of Lewis acidic, potential redox and spectroscopically active Cu(II/I) complexes of synthetic and naturally occurring ligands as nuclease mimics [22][23][24][25] and in fact, a few copper(II) complexes have been shown to be capable of mediating non-random double-strand cleavage of plasmid DNA.…”

Mixed-ligand copper(II) complexes of dipicolylamine and 1,10-phenanthrolines: The role of diimines in the interaction of the complexes with DNA

“…Thus, a number of metal chelates are of current interest for important applications in nucleic acid chemistry as probes of DNA structure in solution, reagents for mediation of strand scission of duplex DNA under physiological conditions and chemotherapeutic agents and in genomic research. [1][2][3][4][5] Over the past decade, there has been substantial increase in interest in the design and study of DNA binding properties of potential redox and spectroscopically active Cu(II), Co (III) and Ru(II) complexes [6][7][8][9] as new chemical nucleases [10][11][12] as they appear to be less readily repaired by DNA repair mechanism. 13,14 Copper(II) complexes containing heterocyclic bases have received considerable current interest in nucleic acid chemistry due to their diverse applications following the discovery of the "chemical nuclease" activity of the [Cu (phen) 2 ] + (phen = 1,10-phenanthroline) complex in the presence of hydrogen peroxide and a reducing agent by Sigman and coworkers.…”