Copper nucleoside complexes

Deoxyribonucleo-functionalised oligo-bipyridyl ligands and their copper(l) complexes, such as the pentahelicate 31, have been synthesised. In these, the substituents are orientated on the periphery of the double helix such that they point outwards. In contrast to DNA, these helical structures thus have positive charges located inside the strands of the helix while the nucleic acid bases are on the outside. Although the presence of the chiral nucleosides could lead to preferential induction of one helical sense, whether this is the case or not was not determined in this study. 

Copper(I) tends towards a tetrahedral coordination geometry in complexes. With 2,2 -bipyr-idine as a chelate ligand a distorted tetrahedral coordination with almost orthogonal ligands results. 2,2 -Bipyridine oligomers with flexible 6,6 -links therefore form double helices with two 2,2 -bipyridine units per copper(I) ion (J. M. Lehn, 1987,1988). J. M. Lehn (1990 U. Koert, 1990) has also prepared such helicates with nucleosides, e.g., thymidine, covalently attached to suitable spacers to obtain water-soluble double helix complexes, so-called inverted DNA , with internal positive charges and external nucleic bases. Cooperative effects lead preferentially to two identical strands in these helicates when copper(I) ions are added to a mixture of two different homooligomers. 

Two different terpyridine-modified dU nucleosides have been incorporated into a 2 -0-methyl modified oligonucleotide antisense to an RNA target. In the presence of Cu(II) ions the terpyridine modified oligonucleotide cleaved the target RNA in a site-specific manner. Copper(I)-adenylates have also been shown to cleave DNA, and a europium complex conjugated at the end of a uniformly modified 2 -0-methoxyethyl oligonucleotide cleaved an RNA target in a site-specific manner. " ... 

Chelex-100 (Whatman) resin was suspended in 1 M CuCl2 overnight, washed repeatedly in water and suspended in 1 N ammonia overnight. A column (0.9 x 45 cm) was packed with a small volume of non-CuCl2 treated resin at the bottom followed by the copper complexed resin above. After washing the column, the nucleic acid components were loaded in a small volume of water and eluted with water (nucleotides followed by weakly basic nucleosides), 1 N ammonia (other nucleosides) and/or 2.5 N ammonia (bases). The nucleotides are not bound by the column and so are not fractionated. The nucleosides and bases are, however, well fractionated. Several minor components are well separated. The method is relatively quick and the eluants are volatile. 

In the presence of A and adenosine, the copper(II)/copper(Hg) couple split to the copper(II)/copper(I) and copper(I)/copper(Hg) couples [179, 180]. Sparingly soluble compounds of copper(I) with A and its ribonucleoside were accumulated on the electrode, either by reduction of the Cu(II) ions or by oxidation of the copper amalgam electrode. The copper(I) A deposit was stripped either cathodically or anodically. The stripping peaks obtained for copper complexes had higher detection limits, but appeared over a wider range of pH and at more negative potentials than the peaks related to mercury compounds [161]. It was shown that in addition to A, other purine bases, such as G, hypoxanthine, xanthine, and their nucleosides (guanosine and inosine) [181-183],... 

Methylhypoxanthine, which has structural similarities with nucleosides, forms a centrosymmetric complex (71) in which the imidazole nitrogen atom is bonded to copper, the Cu-N distance being 2.055 A. The square-bipyramidal co-ordination of the metal is completed by Cu-0(HaO) and Cu-Cl bonds of 1.971 and 2.785 A, respectively. The complex is stabilized by an intramolecular C-O H-0(water) hydrogen-bond. 

In contrast to Mg + and Mn +, which stabilize secondary structures in DNA and RNA, Cu + destabilizes DNA and RNA double helices, and this is attributed to the ability of copper to bind to the nucleic acid bases. Chao and Kearns have recently explored the possibility that this binding, as detected by electron and nuclear magnetic resonance spectroscopy, might be used to probe certain structural features of nucleic acid molecules, such as the looped out regions of tRNAs. The nature of the Cu complexes formed with nucleosides and nucleotides varies with the specific nucleic acid derivatives used and also the pH. Thus, in the pH range 8.5—10.0, copper forms a water-soluble complex with the ribose OH groups of the ribonu-cleosides and 5 -ribonucleotides, but these complexes cannot form with any of the deoxynucleosides or the 2 - and 3 -ribonucleotides. It is suggested that copper(ii) could stabilize unusual polynucleotide structures or interactions in certain enzymatic systems the latter could, for example, be responsible for translational errors in the RNA,DNA polymerase system which are known to be induced by transition metals. 

Finally, De Munno et al. reported the one-pot synthesis of a stable polynuclear copper(n)-cytidine complex, entitled as the nucleoside-wheel . Surprisingly, despite the positive charges from eight copper(II) centers the complex is able to act as a host for [Cu(H20)6] cations. These unique complexes provide new opportunities for specific molecular recognition in the broad field of host-guest chemistry [67]. 

Kobayashi Y, Yamamoto K, Asai T, Nakano M, Kumadaki I (1980) Studies on organic fluorine compounds. Part 35. Trifluoromethylation of pyrimidine and purine nucleosides with trifluoromethyl-copper complex. 1 Chem Soc Perkin Trans 1 2755-2761... 

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