Influence of Metals on DNA

Metals, as chemical agents, determine specific interactions based on ionization processes occurring at different levels of the DNA macromolecule, followed by the metal ions coordination (Eichhorn 1973, Sis-soeff et al. 1976, Gao et al. 1993). 

Investigations into the interaction of metal ions (M ) with DNA have importance in the elucidation of various biochemical and biomedical effects on humans and animals (Eichhorn 1973, Marzilli 1977, Haiduc and Silvestru 1989/1990, Littlefield etal. 1993, McFail-Isom etal. 1998). 

The interaction of DNA with metal ions is followed by changes in the double-stranded and even the single-stranded structure of the macromolecule. These changes are caused by destabilization of the biomacromolecule and the formation of various complexes, initially named molecular associations , and nowadays adducts (Grunberger and Weinstein 1979, Garban et al. 1980, Froystein et al. 1993). 

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To put in perspective the binding of metal ions to ligand-modified nucleic acid duplexes, we summarize the conclusions of these reviews on metal binding to DNA duplexes and emphasize those conclusions that are relevant for the influence of metal coordination on the secondary structure of DNA. These studies have been the prologue of today s efforts to use DNA or its synthetic analogues as scaffold for transition metal ions. 

DNA molecule. These authors proposed to evaluate the influence of Mg on the diminution of the toxic effects of Ni and Cd with respect to sustaining DNA damage. Their conclusions were that (i) Ni is not directly toxic to DNA (ii) Cd produces damage directly on the DNA molecule and (hi) Mg interacts with some of toxic heavy metals and alters the tumorigenic process. 

The influence of DNA on the photo-electron transfer process between a variety of donor-acceptor couples has been examined during the last ten years. For all the systems studied, the metal complex interacts with the DNA and plays the role of electron acceptor or donor in the hydrophobic DNA microenvironment, whereas the other partner of the process, i.e. the reducing or oxidising agent in the ground state, is localised either on the DNA double helix, or does not interact with the nucleic acid and remains in the aqueous phase. Thus three... 

The coordination chemistry of the purine-type ligands has been studied on a rather large scale during the last decade, due to its relevance in biological systems. Detailed reviews are available of the coordination chemistry aspects both in the solid state and in solution.146-149 Recently it has also been proposed that the role of metal-ion binding to purines influences the conversions between, for example, B-DNA and Z-DNA.150... 

Minasov G, Tereshko V, Egli M. Atomic-resolution crystal structures of B-DNA reveal specific influences of divalent metal ions 46. on conformation and packing. J. Mol. Biol. 1999 291 83-99. 

The coordination properties of the nucleobases have been reviewed by Houlton (40) and by Lippert (2). In a recent review, Lippert discussed the influence of the metal coordination on the piSTa of the nucleobases (41), which correlates with their coordination properties. While the coordination properties of nucleobases, nucleosides, and nucleotides have been extensively studied and reviewed, the number of articles dedicated to the coordination properties of nucleic acids is signihcantly smaller. DeRose et al. (42) recently published a systematic review of the site-specific interactions between both main group and transition metal ions with a broad range of nucleic acids from 10 bp DNA duplexes to 300 00 nucleotide RNA molecules as well as with some nucleobases, nucleosides, and nucleotides. They focused on results obtained primarily from X-ray crystallographic studies. Egli also presented information on the metal ion coordination to DNA in reviews dedicated to X-ray studies of nucleic acids (43, 44). Sletten and Fr0ystein (45) reviewed NMR studies of the interaction between nucleic acids and several late transition metal ions and Zn. Binding of metal complexes to DNA by n interactions has been reviewed by Dupureur and Barton (46). 

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