Mechanistic Study on the Photochemical “Light Switch” Behavior of [Ru(bpy)₂dmdppz]²⁺

[Ru­(bpy)₂dmdppz]²⁺ (bpy = 2,2′-bipyridine and dmdppz = 3,6-dimethyl dipyridylphenazine), a strained Ru­(II) polypyridyl complex, is a derivative of the well-known luminescent “light switch”, [Ru­(bpy)₂dppz]²⁺ (dppz = dipyridylphenazine). [Ru­(bpy)₂dmdppz]²⁺ is of interest because it acts as a photochemical sensor and metalating agent for DNA. Here we report a detailed study to elucidate the mechanism of ligand substitution by investigating the photochemical reaction in a variety of solvents and by determining the effects of different incoming ligands, the incoming ligand concentration, and the temperature dependence. Results from these studies indicate that the mechanism of substitution is associative or interchange associative, in contrast with the dissociative mechanism of other photolabile Ru­(II) polypyridyl complexes

Combining a Ru(II) “Building Block” and Rapid Screening Approach to Identify DNA Structure-Selective “Light Switch” Compounds

A chemically reactive Ru­(II) “building block”, able to undergo condensation reactions with substituted diamines, was utilized to create a small library of luminescent “light switch” dipyrido-[3,2-<i>a</i>:2′,3′-<i>c</i>] phenazine (dppz) complexes. The impact of substituent identity, position, and the number of substituents on the light switch effect was investigated. An unbiased, parallel screening approach was used to evaluate the selectivity of the compounds for a variety of different biomolecules, including protein, nucleosides, single stranded DNA, duplex DNA, triplex DNA, and G-quadruplex DNA. Combining these two approaches allowed for the identification of hit molecules that showed different selectivities for biologically relevant DNA structures, particularly triplex and quadruplex DNA

Photoactive Ru(II) Complexes With Dioxinophenanthroline Ligands Are Potent Cytotoxic Agents

Two novel strained ruthenium­(II) polypyridyl complexes containing a 2,3-dihydro-1,4-dioxino­[2,3-<i>f</i>]-1,10-phenanthroline (dop) ligand selectively ejected a methylated ligand when irradiated with >400 nm light. The best compound exhibited a 1880-fold increase in cytotoxicity in human cancer cells upon light-activation and was 19-fold more potent than the well-known chemotherapeutic, cisplatin

Photoactive Ru(II) Complexes With Dioxinophenanthroline Ligands Are Potent Cytotoxic Agents

Two novel strained ruthenium­(II) polypyridyl complexes containing a 2,3-dihydro-1,4-dioxino­[2,3-<i>f</i>]-1,10-phenanthroline (dop) ligand selectively ejected a methylated ligand when irradiated with >400 nm light. The best compound exhibited a 1880-fold increase in cytotoxicity in human cancer cells upon light-activation and was 19-fold more potent than the well-known chemotherapeutic, cisplatin

Photoactive Ru(II) Complexes With Dioxinophenanthroline Ligands Are Potent Cytotoxic Agents

Two novel strained ruthenium­(II) polypyridyl complexes containing a 2,3-dihydro-1,4-dioxino­[2,3-<i>f</i>]-1,10-phenanthroline (dop) ligand selectively ejected a methylated ligand when irradiated with >400 nm light. The best compound exhibited a 1880-fold increase in cytotoxicity in human cancer cells upon light-activation and was 19-fold more potent than the well-known chemotherapeutic, cisplatin