Double-helical metal complexes, the helicates H2-Hs, were found to bind to double-helical DNA by spectroscopic, DNA-melting, and electrophoretic-mobility measurements. The helicates also inhibited the cleavage of DNA by two restriction enzymes, SspI and EcoRV, a property which agrees with the binding occurring in the major groove of the double helix. Visible-light irradiation of solutions containing a helicate and the pBR322 plasmid led to single-strand cleavage, indicating that these complexes could be of interest as potential probes for nucleic-acid structure.
Introduction. -The study of the interactions of small molecules with DNA has been an actively growing research field, following closely the progress of knowledge on structure and function of nucleic acids. The goals are to better understand the interactions with nucleic acids through the analysis of model systems, and to develop drugs acting on nucleic acids. Metal complexes are frequently used as nucleic-acid ligands in these investigations.
We present here results relative to the reversible binding to double-stranded DNA of one class of such compounds: the helicates, double-helical copper(1) complexes that are formed by self-assembly between two ligand strands and Cu' ions [l]. These processes thus involve the interaction of the natural polyanionic double helix of DNA with the artificial polycationic double helix of the helicates.
The ligands L = dibp to pentabp used consist of a strand of binding subunits derived from 6,6'-dimethyl-2,2'-bipyridine linked by an oxybis(methy1ene) bridge (Fig. ). The Cu' ions are coordinated tetrahedrally to two bipyridine (bpy) units and act as the structure organizer. The complexes H,H, were characterized by UVjVIS and NMR spectroscopy and are represented schematically in Fig. . The double-helical geometry was confirmed by determination of the structure of the trinuclear complex by X-ray Such Cu' complexes could bind in multiple ways to DNA and even effect strand cleavage like other metal complexes . While interaction through H-bonding is very unlikely, electrostatic binding is expected to be important, because DNA is a large polyanion, and each helicate molecule bears multiple positive charges. Hydrophobic effects might also play a role since the trinuclear helicate H, has a hydrophobic surface CryStdllOgrdphy [ 11.