Purine 8-metallation

Although not a purine, the ligand properties of 7-azaindole (81) strongly resemble those of deprotonated purines. Metal binding of this anionic ligand may occur to one or two metal ions, just as with 1,8-naphthyridine (Scheme 8).158... 

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. 

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)%. 

While metal-nitrogen and metal-oxygen bonded compounds dominate nucleobase coordination chemistry, examples in which metal-carbon bonds are formed have been identified. Early studies on the synthesis of metal-labeled DNA demonstrated that nucleotide-triphosphates, UTP, CTP, dUTP, and dCTP, can undergo mercury modification at C5 (82,83). The UTP derivative was also shown to act as a substrate for RNA polymerase in the presence of mercaptans (83). Later, guano-sine was shown to undergo mercury modification at C8 though, in this case, the purine was multiply substituted, 21 (84). 

There have been few reports of purine derivatives1 that contain metal-carbon nucleobase binding (75), and those that have been described are often polymetalated (84). Quite recently mononuclear complexes of adenine and guanine have been prepared that contain... 

There are a few reports of C8-metalated purine derivatives that are not nucleobases (92-94). 

The availability of different metal ion binding sites in 9-substituted purine and pyrimidine nucleobases and their model compounds has been recently reviewed by Lippert [7]. The distribution of metal ions between various donor atoms depends on the basicity of the donor atom, steric factors, interligand interactions, and on the nature of the metal. Under appropriate reaction conditions most of the heteroatoms in purine and pyrimidine moieties are capable of binding Pt(II) or Pt(IV) [7]. In addition, platinum binding also to the carbon atoms (e.g. to C5 in 1,3-dimethyluracil) has been established [22]. However, the strong preference of platinum coordination to the N7 and N1 sites in purine bases and to the N3 site in pyrimidine bases cannot completely be explained by the negative molecular electrostatic potential associated with these sites [23], Other factors, such as kinetics of various binding modes and steric factors, appear to play an important role in the complexation reactions of platinum compounds. 

Phenyl metallation, 16 91 Af-Phenyl-lV -(l,3-dimethylbutyl)-p-phenylenediamine, 3 107 Ar-(Phenylmethylj-9-(tetrahydro-2i7-pyran-2-yl)-9H- purin-6-amine, 13 261 as a plant growth regulator, 13 37-38 4-Phenylol anchoring groups, 8 683t 4-Phenylphenol, chemiluminescence reagent enhancer, 5 845 o-Phenylphenol, antimicrobial used in cosmetics, 7 831t... 

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

Nudeobases have pyrimidine and purine (a combination of pyrimidine and imidazole) heterocyclic nuclei which have two ligating nitrogens placed in angular directions. The angular dispositions of pyrimidine, imidazole, and 1,7-purine nitrogens respectively being 120°, 150°, and 90° impart to these bases, heteroatom-induced endocyclic donor ability towards metals which drive self-assembly processes to form macrocyclic systems. The metallacalixarenes formed from nudeobases and various metal salts are discussed with respect to each base. 

A comparison of these nucleobase-derived metallacalixarenes with natural nucleobase-derived tetrands may be advisable. In the non-natural quartets formed by interconnection of uracil, purine or its derived nucleobases with coordinative metals, the cationic character lies on the metals in the periphery and anions are bound in the cavity. In natural tetrands of these nucleobases, the hydrogen bonds interconnect the bases and the structures are stabilized by a cation located in the centre whereas phosphate groups located in the periphery carry negative charge (2005AGE668). As against the existence of only natural... 

Other 1,3-diazaheterocycles related to the benzimidazole system that can be lithiated include purine nucleosides 53-55 and the related cordy-cepin analogs 56, which undergo lithiation with LDA at the 8-position when the ribose or deoxyribose hydroxy groups, are suitably protected (87CPB72 89JHCI89). Some aspects of the nucleoside metalation work have been recently reviewed (89MII). 

---