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

Abstract

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.

Keywords: G-quadruplexes; light switch; photochemistry; photophysics; ruthenium.