Binding Studies of Metal-Salphen and Metal-Bipyridine Complexes towards G-Quadruplex DNA.

The proposed in vivo formation of G-quadruplex DNA (G4 DNA) in promoter regions of oncogenes and in telomeres has prompted the development of small molecules with high affinity and selectivity for these structures. Herein we report the synthesis of a new di-substituted bipyridine ligand and the corresponding complexes with Ni2+ and VO2+ . Both these new complexes have been characterized spectroscopically and by X-ray crystallography. Detailed DNA binding studies of these two complexes, together with three previously reported metal salphen complexes, are presented. Using FRET melting assays, the binding affinity and selectivity of the five metal complexes against six different G4 DNA structures as well as a duplex DNA have been determined. In addition, we present detailed ITC and UV/Vis studies to characterize the interaction of the complexes with human telomeric G4 DNA. Finally, we show via a polymerase stop assay that these complexes are able to stabilize a G4 DNA structure (from the c-Myc oncogene promoter) and halt the activity of Taq polymerase.

Phototoxic Activity and DNA Interactions of Water-Soluble Porphyrins and Their Rhenium(I) Conjugates.

In the search for alternative photosensitizers for use in photodynamic therapy (PDT), herein we describe two new water-soluble porphyrins, a neutral fourfold-symmetric compound and a +3-charged tris-methylpyridinium derivative, in which either four or one [1,4,7]-triazacyclononane (TACN) units are connected to the porphyrin macrocycle through a hydrophilic linker; we also report their corresponding tetracationic Re(I) conjugates. The in vitro (photo)toxic effects of the compounds toward the human cell lines HeLa (cervical cancer), H460M2 (non-small-cell lung carcinoma), and HBL-100 (non-tumorigenic epithelial cells) are reported. Three of the compounds are not cytotoxic in the dark up to 100 µm, and the fourfold-symmetric couple revealed very good phototoxic indexes (PIs). The intracellular localization of all derivatives was studied in HeLa cells by confocal fluorescence microscopy. Although low nuclear localization was observed for some of them, it still prompted us to investigate their capacity to bind both quadruplex and duplex DNA; we observed significant selectivity in the tris-methylpyridinium derivatives for G-quadruplex interactions.

A cyclometallated platinum complex as a selective optical switch for quadruplex DNA.

Hits the spot: A cyclometalled platinum(II) complex with a substituted phenanthroline ligand is reported. The complex has high in vitro affinity for quadruplex DNA and upon binding its emission is switched on. The complex can be easily delivered to the cell by using a metallo-cage as a carrier (see illustration). By means of confocal microscopy, it is shown that the complex is released inside the cell, penetrates the nucleus and localises in the nucleoli.

Hexakis(1H-imidazole-κN)cobalt(III) tris-(hexa-fluoridophosphate) hexa-hydrate.

In the crystal structure of the title compound, [Co(C(3)H(4)N(2))(6)](PF(6))(3)·6H(2)O, the Co(III) atom lies on a special position with site-symmetry and the P atom is located on a special position with site symmetry . The Co(III) atom has an almost ideal octa-hedral coordination formed by the N atoms of six imidazole ligands. The water mol-ecules form hydrogen-bonded helical chains propagating in [001] by O-H⋯O inter-actions with a distance of 2.913 (2) Å. They simultaneously inter-act as hydrogen-bond acceptors and donors with the cations and anions, respectively, resulting in the formation of a three-dimensional assembly. Weak C-H⋯F inter-actions further stabilize the crystal structure.

Ruthenium polypyridyl complexes and their modes of interaction with DNA: is there a correlation between these interactions and the antitumor activity of the compounds?

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy)L(1)L(2)]((2-n)+), and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}(2){mu-H(2)N(CH(2))(6)NH(2)}](4+). The ligand tpy is 2,2':6',2''-terpyridine and the ligand L(1) is a bidentate ligand, namely, apy (2,2'-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L(2) is a labile monodentate ligand, being Cl(-), H(2)O, or CH(3)CN. All six species containing a labile L(2) were found to be able to coordinate to the DNA model base 9-ethylguanine by (1)H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure-activity relationships that might be used to guide optimization of the activity of agents of this class of compounds.