Light-Activated Compounds

The presently-disclosed subject matter includes light-activated ruthenium compounds. In some embodiments the compounds release one or more ligands when exposed to light, and in specific embodiments the light includes a wavelength of about 500 nm to about 1000 nm. The present compounds can also comprise an overall charge, wherein the overall charge can be a positive overall charge or a negative overall charge. Further still, embodiments include methods of treating cancer in a subject by administering a compound and then exposing a site of the subject to light

Redox Couples of Inducible Nitric Oxide Synthase

We report direct electrochemistry of the iNOS heme domain in a DDAB film on the surface of a basal plane graphite electrode. Cyclic voltammetry reveals Fe^(III/II) and Fe^(II/I) couples at −191 and −1049 mV (vs Ag/AgCl). Imidazole and carbon monoxide in solution shift the Fe^(III/II) potential by +20 and +62 mV, while the addition of dioxygen results in large catalytic waves at the onset of Fe^(III) reduction. Voltammetry at higher scan rates (with pH variations) reveals that the Fe^(III/II) cathodic peak can be resolved into two components, which are attributable to Fe^(III/II) couples of five- and six-coordinate hemes. Digital simulation of our experimental data implicates water dissociation from the heme as a gating mechanism for ET in iNOS

A monoadduct generating Ru(ii) complex induces ribosome biogenesis stress and is a molecular mimic of phenanthriplatin

Ruthenium complexes are often investigated as potential replacements for platinum-based chemotherapeutics in hopes of identifying systems with improved tolerability in vivo and reduced susceptibility to cellular resistance mechanisms. Inspired by phenanthriplatin, a non-traditional platinum agent that contains only one labile ligand, monofunctional ruthenium polypyridyl agents have been developed, but until now, few demonstrated promising anticancer activity. Here we introduce a potent new scaffold, based on [Ru(tpy)(dip)Cl]Cl (tpy = 2,20:60,200-terpyridine and dip = 4,7-diphenyl-1,10-phenanthroline) in pursuit of effective Ru(II )-based monofunctional agents. Notably, the extension of the terpyridine at the 40 position with an aromatic ring resulted in a molecule that was cytotoxic in several cancer cell lines with sub-micromolar IC50 values, induced ribosome biogenesis stress, and exhibited minimal zebrafish embryo toxicity. This study demonstrates the successful design of a Ru(II ) agent that mimics many of the biological effects and phenotypes seen with phenanthriplatin, despite numerous differences in both the ligands and metal center structure

Abstract 4840: The role of the metal scaffold in the development of cytotoxic metal complexes

Abstract Multiple cytotoxic metal compounds are known, but structure activity relationships can be difficult to determine in these complex molecules. It is tempting to generalize the activity or off-target effects of the compounds to being related to the identity of the metal, or alternatively, to some specific “active” ligand features, but this is a misleading oversimplification that can slow the development of new therapeutics. In this presentation a systematic study of the impact of the metal center, one specific “active” ligand, and the inactive “coligands” that create the metal scaffold will be presented. There is clear evidence that each component plays a role in both desired and potentially deleterious off-target activities, providing the opportunity to adjust each of these three components independently to generate optimized potential anti-cancer agents. Citation Format: Edith C. Glazer. The role of the metal scaffold in the development of cytotoxic metal complexes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4840.</jats:p

Photodimerizable ditopic ligand.

International audience[reaction: see text] The synthesis, photophysical properties, and structural characterization of a photodimerizable ditopic ligand are described. Upon irradiation at 366 nm, ligand 1 dimerizes to the head-to-tail tetra-bpy ligand 2. This thermally stable photodimer can be dissociated back to 1 using higher energy irradiation (254 nm)