Interaction of novel metal complexes with DNA: synthetic and structural aspects

Metal ions bind to nucleic acids at various positions. This binding can be modulated by using metal complexes with appropriate ligands. Novel mono- and especially dinuclear metal complexes could be a powerful tool to detect rare, but still physiologically relevant, forms of DNA, e.g. the left-handed Z-DNA. In this review, our recent research activities in this area of bioinorganic chemistry are summarized. A special emphasis is laid on the synthetic challenges that arose upon the synthesis of the polyamine ligands. Further, some rather unusual approaches to elucidate the solution structure of copper bound to guanosine monophosphate with the help of pulsed EPR techniques like ENDOR and HYSCORE are described

Structural analysis of Cu(II) ligation to the 5'-GMP nucleotide by pulse EPR spectroscopy

Simple copper salts are known to denature poly d(GC). On the other hand, copper complexes of substituted 1,4,7,10,13-pentaazacyclohexadecane-14,16-dione are able to convert the right-handed B form of the same DNA sequence to the corresponding left-handed Z form. A research program was started in order to understand why Cu(II) as an aquated ion melts DNA and induces the conformational change to Z-DNA in the form of an azamacrocyclic complex. In this paper, we present a continuous wave and pulse electron paramagnetic resonance study of the mononucleotide model system Cu(II)-guanosine 5'-monophosphate . Pulse EPR methods like electron-nuclear double resonance and hyperfine sublevel correlation spectroscopy provide unique information about the electronic and geometric structure of this model system through an elaborate mapping of the hyperfine and nuclear quadrupole interactions between the unpaired electron of the Cu(II) ion and the magnetic nuclei of the nucleotide ligand. It was found that the Cu(II) ion is directly bound to N7 of guanosine 5'-monophosphate and indirectly bound via a water of hydration to a phosphate group. This set of experiments opens the way to more detailed structural characterization of specifically bound metal ions in a variety of nucleic acids of biological interest, in particular to understand the role of the metal-(poly)nucleotide interaction