Purines metal complexes

In general the pyrimidines show a much lower reactivity towards the metal ions. Apparently no reaction was observed with uracil while the stability constants of Cu-cytosine are even lower than the lgJCi and gK% values of Cu(NH3)62+ (79). The high stability of the purine metal complexes can be attributed to the binding site at the imidazole residue. There the imino proton competes with the metal ion. Fig. 1 presents a model of the 2 1 complex of Cu-(adenine)%. 

Photoreactions of Metal Complexes with DNA closer to the purine strand than to the pyrimidine strand in the major groove. 

The following Table (Table 1) shows the values of the stability constants of some purines and pyrimidines with a number of transition metal ions (7, 2, 36, 69). Procedures for the synthesis of Cu, Co and Ni complexes with pyrimidines have been reported (65, 92, 93). The preparation of purine-metal compounds are described elsewhere (94, 95). There seem to be great difficulties in the quantitative study of metal complex formation, especially with the free purines, since the resulting metal chelates are almost insoluble in aqueous solution. Therefore, dioxane-water mixtures have been employed in a number of experiments. 

Table 1. Stability constants of some purine and pyrimidine metal complexes (1, 2, 69)...

Lappert developed the thermolysis of an electron-rich olefin in the presence of a transition metal complex as another way to synthesise these compounds [4], When, in 1975, Clarke and Taube published their findings on carbon coordinated purine transition metal complexes [5], transition metal NHC complexes with functionalised NHC made their debut in biochemistry. The chemistry of carbenes from natural products became firmly established following the discovery that the catalytic activity of thiamine (vitamin Bl) is based on the intermediate formation of a carbene derived from thiazole [6-9] (see Figure 1.2). 

Figure 11 Four types of metal complexes involving N-7 of purine nucleosides ...

Metal complexes of pyrimidine nucleotides have been studied much less intensively than those involving purines, undoubtedly reflecting the weaker coordination ability of the pyrimidine N-3 atom, relative to atoms N-7 and N-1 of purines. Nonetheless, the principal structures of such complexes have been determined. " Some of these are described below. 

Metal Complexes of Purines, Purine Nucleosides, Nucleotides,... 

Although, being an integral part of purine chemistry, discussion of their ligand properties in metal complex formation would expand the frame of this section. For an excellent overview the reader is referred to ref 82 and literature cited therein. 

The evidence of the effect of complexation was established by the absence of an absorption band at 3191 cm (N-H stretching characteristic of a purine function in Azathioprine) e.g., the aminogroup is involved in the formation of the metal complex. The anticancer action of purine derivatives was discovered in 1949. This cytostatic drug biotransforms to 6-mercaptopurine in the body. ... 

There has been considerable interest in recent years in the formation of condensed films of purine and pyrimidine bases at the solid-liquid interface. It is well recognised that non-covalent affinities between base pairs play a prevalent role in determining nucleic acid conformation and functionality. Likewise, there has been interest in the role of substrate and non-covalent intermolecular interactions in the configuration of ordered monolayers of purine and pyrimidine bases. There is also more general interest in the interaction of bases with metal surfaces and metal complexes. In the latter case it is noted that the biological role of nucleic acids and certain nucleotides are dependent on metal ions, particularly Mg, Ca, Zn, Mn, Cu and Ni. " Also certain metal complexes, notably of platinum, have the anti-tumour activity, which is linked to their ability to bind to bases on DNA. On a different note, the possibility that purine-pyrimidine arrays assembled on naturally occurring mineral surfaces might act as possible templates for biomolecular assembly has been discussed by Sowerby et al. 

While a substantial amount of structural information has been collected on metal complexes of purine and pyrimidines, much less is known about their reactivities. Of particular interest are the effects of the metal ion on the organic chemistry of nucleosides and the reactions of the metal ion when coordinated to the heterocyclic base, since these may contribute to either oncogenesis or anticancer activity. 

Building towards models relevant for polymeric DNA and RNA, nucleotides contain a phosphate attached at the 5 or 3 position. The 5 -nucleotides are most commonly studied, for which the phosphate has a pAa 6 for the first protonation step. Unless otherwise noted, throughout this chapter nucleotide will refer to the 5 -phosphate linkage. In nucleotides, metal-phosphate coordination competes with metal-base interactions. Chelate complexes with both phosphate and base coordination can occur when sterically allowed. Thus, transition metal complexes with purine monophosphates tend to exhibit metal coordination to the base N7 position, with apparent hydrogen bonding of coordinated waters to the phosphate. By contrast, more ionic Mg" binds preferentially to the phosphate groups in nucleotide monophosphates. In di- and tri-phosphate complexes such as metal-ATP compounds, the proximity of multiple phosphates generally favors polyphosphate chelate complexes with metal ions. 

Metal Complexes of Sulfur-Containing Purine Derivatives Erich Dubler... 

---