Biophysical insights into the interaction of Ru(II) polypyridyl complexes with the RNA triplex poly(U)•poly(A)poly(U). Intercalative ligand shape effect on third-strand stabilization

To explore the correlating thermodynamic factors to the structural aspects that account for the stability of the RNA triplex, two functional Ru(II) complexes containing the same ancillary ligands and different intercalative ligands, [Ru(bpy)2(mip)]2+ (bpy=2,2′-bipyridine, mip=2′-(3″,4″-methylene-dioxyphenyl)imidazo[4′,5′-f][1,10]phenanthroline) and [Ru(bpy)2(bdip)]2+ (bdip=2-(1,3-benzodioxol-4-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) have been synthesized. The binding properties of [Ru(bpy)2(mip)]2+ and [Ru(bpy)2(bdip)]2+ to the RNA triplex poly(U)•poly(A)*poly(U) have been investigated by various biophysical techniques and quantum chemistry calculations. Compared with [Ru(bpy)2(bdip)]2+, remarkably higher binding and stabilization of the triplex RNA structure by [Ru(bpy)2(mip)]2+ is achieved upon changing the substituent positions on the intercalative ligand. The result reveals that the intercalative ligand shape plays a critical role in third-strand stabilization. The binding properties of [Ru(bpy)2(mip)]2+ (Ru1) and [Ru(bpy)2(bdip)]2+ (Ru2) to the RNA triplex poly(U)•poly(A)*poly(U) have been investigated by various biophysical techniques and quantum chemistry calculations. Compared with [Ru(bpy)2(bdip)]2+, remarkably higher binding and stabilization of the triplex RNA structure by [Ru(bpy)2(mip)]2+ is achieved upon changing the substituent positions on the intercalative ligand. [Display omitted] ► Properties of two Ru(II) complexes binding with the triple-stranded RNA are investigated. ► Remarkably higher stabilization of triple helix by [Ru(bpy)2(mip)]2+ is achieved. ► Results reveal that the intercalative ligand plays a critical role in the triplex stabilization.