STRUCTURAL EXAMINATION OF ENANTIOSELECTIVE INTERCALATION - H-1-NMR OF RH(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 two-dimensional (2D) 500 MHz H-1 NMR experiments both to extend our understanding of the basis for the enantioselective DNA binding and to gain structural information concerning intercalation by the octahedral metal complexes. Delta-Rh(en)(2)phi(3+) forms a symmetric 1:1 complex with d(GTGCAC)(2), and the metal complex is in slow exchange with the oligodeoxynucleotide bound form at 295 K. The strong upfield shifts of the phi ligand's aromatic protons (0.6-1.3 ppm) are consistent with full intercalation of the phi ligand into the DNA base stack. 2D-NOESY experiments reveal a loss in internucleotide connectivity between G(3) and C-4 bases, while new NOE cross peaks are observed between the phi ligand 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 symmetry 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 complexes display different sequence selectivities and exchange characteristics, Lambda- and Delta-Rh(en)(2)phi(3+) interact with the oligonucleotide duplex in a fundamentally similar manner, through the full intercalation of the phi ligand. Upfield movements in chemical shifts of phi protons 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 degrees C. Given the common binding mode of the two enantiomers, the differences in their binding characteristics emanate from interactions with the ancillary nonintercalating Ligands. Thus, as a general strategy, intercalation may provide an anchor for sequence-selective interactions of octahedral metal complexes in the groove of duplex DNA.