Substituent effects on the interactions of ruthenium(II) polypyridyl complexes [Ru(bpy)2(6-R-dppz)]2+ (R = hydroxy and fluorine) with the RNA triplex poly(rU)·poly(rA) × poly(rU)

Abstract

Two new ruthenium(II) polypyridyl complexes, [Ru(bpy)2(6-OH-dppz)]2+ (Ru1, bpy = 2,2′-bipyridine, 6-OH-dppz = 6-hydroxydipyrido[3,2-a:2′,3′-c]phenazine) and [Ru(bpy)2(6-F-dppz)]2+ (Ru2, 6-F-dppz = 6-fluorodipyrido[3,2-a:2′,3′-c]-phenazine), have been synthesized and characterized in this work. The interactions of Ru1 and Ru2 with the RNA triplex poly(rU)·poly(rA) × poly(rU) have been investigated by spectroscopic and viscometric techniques. Spectral titrations and viscosity experiments show that the binding modes of Ru1 and Ru2 to the triplex are intercalation, with the binding affinity for Ru2 being greater than that for Ru1. Fluorescence titrations indicate that Ru2, unlike Ru1, can act as a “molecular light switch” for the triplex. Furthermore, thermal denaturation experiments suggest that Ru1 and Ru2 stabilize the Hoogsteen base-paired strand (third-strand) of the triplex without significant differences, while the two complexes exhibit different selective stabilizing effects toward the triplex. In contrast to Ru1, Ru2 shows a preference for stabilizing the template duplex under the conditions used in this study. Results of the present work demonstrate that the electronic effects of substituents on the main ligands can significantly affect the binding and stabilization effects of Ru(II) polypyridyl complexes toward the RNA triplex poly(rU)·poly(rA) × poly(rU).