Ruthenium Complex Light Switches that are Selective for Different G-Quadruplex Structures

Recognition and regulation of G-quadruplex nucleic acid structures is an important goal for the development of chemical tools and medicinal agents. The addition of a bromo-substituent to the dipyridylphenazine (dppz) ligands in the photophysical light switch, [Ru(bpy)(2)dppz](2+), and the photochemical light switch, [Ru(bpy)(2)dmdppz](2+), creates compounds with increased selectivity for an intermolecular parallel G-quadruplex and the mixed-hybrid G-quadruplex, respectively. When [Ru(bpy)(2)dppz-Br](2+) and [Ru(bpy)(2)dmdppz-Br](2+) are incubated with the G-quadruplexes, they have a stabilizing effect on the DNA structures. Activation of [Ru(bpy)(2)dmdppz-Br](2+) with light results in covalent adduct formation with the DNA. These complexes demonstrate that subtle chemical modifications of Ru-II complexes can alter G-quadruplex selectivity, and could be useful for the rational design of in vivo G-quadruplex probes.