STRUCTURAL EXAMINATION OF ENANTIOSELECTIVE INTERCALATION - H-1-NMR OFRH(EN)(2)PHI(3+)ISOMERS BOUND TO D(GTGCAC)(2)

The enantioselective recognition of d(GTGCAC)(2) by Delta- and Lambda- Rh(en)(2)phi(3+) (en = ethylenediamine; phi = 9,10-phenanthrenequinone diimine) has been examined in a series of one-dimensional (1D) and tw o-dimensional (2D) 500 MHz H-1 NMR experiments both to extend our unde rstanding of the basis for the enantioselective DNA binding and to gai n structural information concerning intercalation by the octahedral me tal complexes. Delta-Rh(en)(2)phi(3+) forms a symmetric 1:1 complex wi th d(GTGCAC)(2), and the metal complex is in slow exchange with the ol igodeoxynucleotide bound form at 295 K. The strong upfield shifts of t he phi ligand's aromatic protons (0.6-1.3 ppm) are consistent with ful l intercalation of the phi ligand into the DNA base stack. 2D-NOESY ex periments reveal a loss in internucleotide connectivity between G(3) a nd C-4 bases, while new NOE cross peaks are observed between the phi l igand and the G(3) deoxyribose sugar. In contrast to binding by Delta- Rh(en)(2)phi(3+), the 1:1 Lambda-Rh(en)(2)phi(3+)-d(GTGCAC)(2) complex shows much broader resonances, and both metal complex and DNA protons appear to be in the intermediate exchange regime. The loss of C-2 sym metry in the 1:1 complex is consistent with binding by Lambda-Rh(en)(2 )phi(3+) at the T(2)G(3) step. Although the enantiomeric metal complex es display different sequence selectivities and exchange characteristi cs, Lambda- and Delta-Rh(en)(2)phi(3+) interact with the oligonucleoti de duplex in a fundamentally similar manner, through the full intercal ation of the phi ligand. Upfield movements in chemical shifts of phi p rotons are nearly identical for the two enantiomers, and both Lambda- and Delta-Rh(en)(2)phi(3+) stabilize the duplex to melting by 5-10 deg rees C. Given the common binding mode of the two enantiomers, the diff erences in their binding characteristics emanate from interactions wit h the ancillary nonintercalating Ligands. Thus, as a general strategy, intercalation may provide an anchor for sequence-selective interactio ns of octahedral metal complexes in the groove of duplex DNA.