Structural Studies Reveal Enantiospecific Recognition of a DNA G-Quadruplex by a Ruthenium Polypyridyl Complex

By using X-ray crystallography, we show that the complexes L/ D-[ Ru(TAP) 2(11-CN-dppz)] 2+ (TAP= 1,4,5,8tetraazaphenanthrene, dppz= dipyridophenazine) bind DNA G-quadruplex in an enantiospecific manner that parallels the specificity of these complexes with duplex DNA. The L complex crystallises with the normally parallel stranded d(TAGGGTTA) tetraplex to give the first such antiparallel strand assembly in which syn-guanosine is adjacent to the complex at the 5' end of the quadruplex core. SRCD measurements confirm that the same conformational switch occurs in solution. The D enantiomer, by contrast, is present in the structure but stacked at the ends of the assembly. In addition, we report the structure of L-[ Ru(phen) 2(11-CN-dppz)] 2+ bound to d(TCGGCGCCGA), a duplex-forming sequence, and use both structural models to provide insight into the motif-specific luminescence response of the isostructural phen analogue enantiomers.