1H NMR studies of tris(phenanthroline) metal complexes bound to oligonucleotides: structural characterizations via selective paramagnetic relaxation.

The selective paramagnetic relaxation of oligonucleotide protons of d(GTGCAC)2 by delta- and lambda-Ni(phen)3(3+) and delta- and lambda-Cr(phen)3(3+) has been examined to obtain some structural insight into the noncovalent binding of tris(phenanthroline) metal complexes to DNA. The experiments demonstrate that the relative rate of relaxation of different oligonucleotide protons by the paramagnetic metal complex varies with the chirality of the metal complex and, to a lesser extent, the metal charge. The proton most efficiently relaxed in all cases is the adenosine AH2, which is situated in the minor groove of the oligonucleotide helix. For both lambda-Ni(phen)3(2+) and lambda-Cr(phen)3(3+), the order of relaxation rates varies as AH2 much greater than AH8 greater than G3H8 = TMe = C4H5. For delta-Ni(phen)3(2+) it varies as AH2 greater than G3H8 greater than AH8 greater than TMe = C4H5 and for delta-Cr(phen)3(3+) as AH2 greater than TMe = G3H8 = AH8 greater than C4H5. Distances between the metal center and oligonucleotide protons were calculated on the basis of the relaxation data, and these distances were used to generate a set of models to describe the interactions of the rigid metal complex with the helix. For lambda-isomers, the data are consistent with a predominant surface-bound association in the minor groove of the DNA helix. The results of delta-isomers correlate better with models that incorporate also a major groove intercalative mode. Despite the absence of hydrogen-bonding groups in the metal complex, the surface-bound model of the phenanthroline complex in the minor groove of DNA resembles the noncovalent association seen with other DNA groove binding molecules.