1718 planar aromatic heterocyclic ligands such as

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17,18 Planar aromatic heterocyclic ligands such as phenanthroline and terpyridine can stack in between the DNA base pairs, stabilized through dipole-dipole interactions. Here, depending on the complex and its extent of overlap with the base pairs, the free energy of stabilization can vary from ~2 to 10 kcal. Nonintercalative hydrophobic interactions of coordi- nated ligands in the DNA grooves also can occur, as we will see. Hydrogen- bonding interactions of coordinated ligands with the polynucleotide are quite common, and arise in particular with the phosphate oxygen atoms on the back- bone. With cobalt hexaammine, for example, hydrogen bonding to an oligonu- cleotide occurs between the ammine hydrogens and both phosphate oxygen atoms and purine bases. 19 A mix of covalent and noncovalent interactions is also possible. With cis- diammineplatinum(II) coordinated to the guanine N7 position, the ammine li- gands are well-poised for hydrogen-bonding interactions with the phosphate backbone. 12 The steric constraints on the molecule must be considered, how- ever. With Pt(terpy)CI +, both intercalation of the terpy ligand and direct coor- dination of the platinum center (after dissociation of the coordinated chloride) are available, but not simultaneously; coordination of the platinum to the base would likely position the terpyridylligand away from the base stack in the DNA major groove, precluding intercalation. 2o Sigel and coworkers 21 have studied the thermodynamics of noncovalent interactions coupled to direct coordination of simple first-row transition-metal complexes with mononucleotides, and these re- sults illustrate well the interplay of weak noncovalent interactions and direct coordination in generating geometric specificity in complex formation. C. Fundamental Reactions with Nucleic Acids The reactions of transition-metal complexes with polynucleotides generally fall into two categories: (i) those involving a redox reaction of the metal complex that mediates oxidation of the nucleic acid; and (ii) those involving coordination of the metal center to the sugar-phosphate backbone so as to mediate hydrolysis of the polymer. Both redox and hydrolytic reactions of metal complexes with nucleic acids have been exploited with much success in the development of tools for molecular biology.
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II. THE BASICS 463 1. Redox chemistry The simplest redox reaction with polynucleotides one might consider as an illustration is the Fenton reaction, which indirectly promotes DNA strand scis- sion through radical reactions on the sugar ring. The reaction with Fe(EDTA)2- is shown in Figure 8.5A. As do other redox-active divalent metal ions, ferrous ion, in the presence of hydrogen peroxide, generates hydroxyl radicals, and in the presence of a reductant such as mercaptoethanol, the hydroxyl radical pro- duction can be made catalytic. Although ferrous ion itself does not appear to interact appreciably with a nucleic acid, especially when chelated in an anionic EDTA complex and repelled by the nucleic-acid polyanion, the hydroxyl radi-
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