INTERACTION OF BINUCLEAR TRANSITION-METAL COMPLEXES WITH DNA

A series of binucleating tetrakis(methylimidazole) ligands of the gene ral type (MeIm)(2)C(OH)-spacer-C(OH)(MeIm)(2) were prepared, where MeI m = 1-methylimidazol-2-yl and the spacer was one of several different rigid (5 = 1,4-C6H4, 6 = trans-C2H2, 14 = (2 alpha,3a beta,5 alpha,6a beta)-octahydro-3a,6a-dimethylpentalene 15 = (2 alpha,3a alpha,5 alpha ,6a alpha)-octahydro-3a,6a-dimethylpentalene, 16 = 2 alpha,3a alpha,5 beta,6a alpha)-octahydro-3a,6a-dimethylpentalene) or flexible ((CH2)(n ) 7, n = 0; 8, n = 1; 9, n = 2; 10, n = 3; 11, n = 8) spacers. A highl y rigid binucleating ligand, (3a alpha,6a ylimidazol-2-yl)methylene)-3 a,6a-dimethylpentalene (17), was also prepared and characterized. The effectiveness of the rigid binuclear complexes of Cu(II), Ni(II), and Zn(II) as catalysts for the hydrolysis of the phosphate diester sodium bis(4-nitrophenyl) phosphate was similar to corresponding mononuclear complexes with ligand 4 = (MeIm)(2)C(OH)CH3 or bipyridine. A signific ant DNA binding ability was observed for the binuclear complexes, whic h was not evident with the mononuclear compounds. In gel electrophores is mobility studies, the cationic dimetal complexes with the tetrakis( methylimidazole) ligands significantly retarded the migration of super coiled plasmid DNA. The binucleating ligands with flexible organic spa cer groups and the mononuclear metal complexes did not show this effec t. In ultrafiltration experiments with tritium labeled ligands, all th e cationic dimetal complexes showed evidence for DNA binding, whereas the mononuclear complexes of 4 did not. Similar results were obtained for DNA precipitation studies. Without added metal ions, none of the l igands evidenced a significant DNA binding ability. Simple amine polyc ations and mononuclear cations, such as Mg(II), were not able to disru pt the binding of the binuclear complexes to DNA, unless added in a la rge excess. Nickel(II) complexes that contained ligands 7, 9, and 15 w ere crystallized and characterized by X-ray crystallography. In additi on, the Zn(II) complexes present in solution with ligands 4, 14, and 1 5 were studied by H-1 NMR spectroscopy. Reasons for the enhanced bindi ng ability of dimetal complexes to DNA and the role of a flexible or r igid spacer group are discussed.