Binding of delta- and lambda-[Ru(phen)3]2+ to [d(CGCGATCGCG)]2 studied by NMR.

The interactions of the delta and lambda enantiomers of the chiral metal complex [Ru(phen)3]2+ (phen = 1,10-phenanthroline) with the oligonucleotide duplex [d(CGCGATCGCG)]2 have been studied with NMR and CD spectroscopy. From NOESY data it is shown that the interaction primarily takes place in the minor groove of the oligonucleotide which remains in a B-like conformation. The observed NOEs also provide evidence that the metal complexes preferentially bind to the central AT region. The observed AT specificity is more pronounced with the delta as compared to the lambda enantiomer, which interacts with a larger part of the oligonucleotide. Furthermore, the NOESY data show that neither of the enantiomers binds by classical intercalation. This is also supported by a comparison study of the analogue [Ru(phen)2DPPZ]2+ (DPPZ = dipyrido[3,2-a:2',3'c]phenazine) which intercalates in DNA. The NMR as well as the CD results show that the delta and lambea enantiomers of [Ru(phen)3]2+ bind in different modes to [d(CGCGATCGCG)]2. Comparison of CD spectra of the metal complex in the presence of [d(CGCGATCGCG)]2, poly(dAdT).poly-(dAdT), poly(dGdC).poly(dGdC), and calf thymus DNA suggests that these binding modes are independent of DNA sequence. The results are found to be compatible with binding of delta-[Ru(phen)3]2+ by insertion of two phenanthroline ligands into the minor groove, causing minor distortions of the DNA structure, whereas the lambda enantiomer binds in a mode that leaves the DNA structure unaffected.