Nucleobases pyrimidine

C. Lipschitz, H. Iith, G. J. de Jong, U. A. Th Brinkman and R. W. Frei, Trace emich-ment of pyrimidine nucleobases, 5-fluoro-uracil and bromacil on a silver-loaded tliiol stationaty phase with on-line reversed-phase high-perfomance liquid cliromatography , J. Chromatogr. 471 321-334 (1989). 

Merchan M, Gonzalez-Luque R, Climent T, Serrano-Andres L, Rodriuguez E, Reguero M, Pelaez D (2006) Unified model for the ultrafast decay of pyrimidine nucleobases. J Phys Chem B 110 26471-26476... 

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. 

Figure 7. Schematic structures of common pyrimidine nucleobases with the numbering scheme.

Guanine is a preferential DNA target to several oxidants it shows the lowest ionization potential among the different purine and pyrimidine nucleobases and it is the only nucleic acid component that exhibits significant reactivity toward singlet oxygen ( O2) at neutral pH. ... 

Each WCP dimer model consists of two purine bases (G and A) and two pyrimidine bases (C and T). According to the calculations, the two highest-lying orbitals HOMO and HOMO-1 of each duplex are mainly locahzed on the purine nucleobases, whereas the two occupied MOs following at lower energies, HOMO-2 and HOMO-3, are locahzed on pyrimidine nucleobases. Therefore, the purine-purine electronic coupling provides the dominant contribution to the hole transfer matrix elements, irrespective whether the bases belong to the same or to opposite strands. 

Comparing matrix elements of simple models of two purine nucleobases with those calculated for WCP dimers (Table 3), one wonders about the effect of pyrimidine nucleobases on the electronic coupling matrix elements of hole transfer in DNA [14, 73]. 

Detailed analysis [74] of the pertinent molecular orbitals shows that it is impossible to identify any orbital-based direct involvement of the pyrimidine nucleobases in the hole transfer (see Fig. 2). Therefore, hole transfer always proceeds via purine bases, irrespective of whether they are arranged in the same or in opposite strands. However, the electronic coupling is notably... 

Like purine nucleotides, pyrimidine nucleotides can be synthesized either de novo or by the salvage pathways from nucleobases or nucleosides. However, salvage is less efficient because, except in the case of utilization of uracil by bacteria, and to some extent by mammalian cells, pyrimidine nucleobases are not converted to nucleotides directly but only via nucleosides. 

Several blue tetra- and octanuclear Pt complexes, prepared upon reaction of cis-[Pt(NH3)2(H20)2]2+ with open and cyclic amides, as well as cyclic imides and a uracil nu-cleobase, and comprised of binuclear building blocks interacting through Pt-Pt bond formation, have been isolated and structurally characterized in recent years. Without exception, the average Pt oxidation state in these compounds is 2.25. Nevertheless, the structure and mode of action as antitumor agents of the Platinum Pyrimidine Blues , as prepared by Rosenberg in the early 70 s, remain elusive. This account represents a summary of our present knowledge on cationic Platinum Blues , with a focus on those blues obtained from cis-[Pt(NH3)2(H20)2]2+ and pyrimidine nucleobases, and presents speculations on reasonable alternative structures. 

Although blues prepared from unsubstituted uracil, thymine and related bases (e.g., 6-methyluracil, 5,6-dihydrouracil etc.) were the first to be prepared and tested, their composition is the least clear. The author suspects that there is still long way to go to fully understand the nature of these blues . It is possible that there are even blues built on different principles. A main obstacle to the elucidation of Pt blues derived from the unsubstituted pyrimidine nucleobases lies in their versatility as ligands. Not only is there the possibility that these ligands bind to metal ions, specifically Pt, via N(l) or N(3) or (only with uracil) C(5), but also many possible combinations of two or more binding sites, e.g., N(l),0(2) N(3),0(2) N(3),0(4) N(1),N(3) N(3),0(2),0(4) N(1),0(2),N(3),0(4) etc. (Scheme 6). A series of these binding patterns has been established by X-ray crystal-structure analyses [68-70], and others are likely on the basis of spectroscopic studies [71] [72] or from comparison with results obtained for N(l) substituted derivatives. The possibility of different tautomers of platinated forms being... 

Pyrimidine Nucleobases as Metal Ligands in Neutral and Anionic Forms... 

Table. Shorthands for Neutral, Mono-, and Dianionic Forms of Pyrimidine Nucleobases a)...

Fig. 3. Pyrimidine nucleobase anions acting as tri- and tetradentate ligands...

The work by Lippard and coworkers [2][24][25][88][95][98-100] derives its chief motivation from the understanding of the interaction between the anticancer drug cA-[PtCl2(NH3)2] and pyrimidine nucleobases. Unfortunately, the reaction of c7v-[PtCl2(NH3)2] with molecules such as uracil or thymine leads to non-crystalline dark blue materials ( platinum blues ) which are difficult to characterize. The use of a ligand with similar but more restricted number of donor sites, such as a-pyridone (hp), allowed isolation and full characterization of relevant platinum complexes. Related work has used 1-methyluracil (1-Me-urac) and 1-methylthymine (1-Me-thym) in which one of the pyrimidine nitrogens has been blocked [101]. 

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