Uracil pyrimidine structure

Another property of pyrimidines and purines is their strong absorbance of ultraviolet (UV) light, which is also a consequence of the aromaticity of their heterocyclic ring structures. Figure 11.8 shows characteristic absorption spectra of several of the common bases of nucleic acids—adenine, uracil, cytosine, and guanine—in their nucleotide forms AMP, UMP, CMP, and GMP (see Section 11.4). This property is particularly useful in quantitative and qualitative analysis of nucleotides and nucleic acids. 

Nucleotides can be linked together into oligonucleotides through a phosphate bridge at the 5 position of one ribose unit and the 3 position of another. The purine bases, adenine and guanine, have two heterocyclic rings, while the pyrimidines cytosine, thymine, and uracil have one. The structure of adenosine monophosphate is shown in Figure 11. 

Figure 11-6. Structures of representative conical intersections Sj/Sq in the pyrimidine bases, uracil, thymine, and cytosine. Uracil structures (a,d) are taken from Ref. [147, 210]. Thymine structures (b,e) are taken from Ref. [152], Cytosine structures (c,f) are taken from Ref. [157]...

Figure 1.43 indicates major sites of reactivity within the ring structures for nucleophilic displacement reactions. Cytosine, thymine, and uracil all react toward nucleophilic attack at the same two sites, the C-4 and C-6 positions. The presence of powerful nucleophiles, even at neutral pH, can lead to significant base modification or cleavage with pyrimidine residues (Debye, 1947). For instance, hydrazine spontaneously adds to the 5,6-double bond, initiating further ring reactions,... 

As in the case of pyrimidine bases discussed previously, adenine and guanine are subject to nucleophilic displacement reactions at particular sites on their ring structures (Figure 1.50). Both compounds are reactive with nucleophiles at C-2, C-6, and C-8, with C-8 being the most common target for modification. However, the purines are much less reactive to nucleophiles than the pyrimidines. Hydrazine, hydroxylamine, and bisulfite—all important reactive species with cytosine, thymine, and uracil—are almost unreactive with guanine and adenine. 

Platination of the N3 position in 1-substituted uracil and thymine derivatives requires proton abstraction and usually occurs only at high pH, but the Pt-N3 bond, once formed, is thermodynamically stable (log K 9.6) [7]. Platinum binding to N3 increases the basicity of 04, which becomes an additional binding site leading to di- and trinuclear complexes. A list of X-ray structurally characterized species is given by Lippert [7]. Pt complexes of uracil and thymine can form intensely colored adducts (e.g. platinum pyrimidine blues), which show anticar-cinogenic activity analogously to the monomeric species [7]. 

Nitrogenous base plus sugar moiety are called nucleosides. Ribonucleic acids (RNA) resemble DNA in that nucleoside monophosphates are joined through phosphodiester bonds. RNAs differ in that the sugars are p-D-ribose units and the pyrimidine uracil is found in place of thymine. Molecular structures and nomenclature for nitrogenous bases, nucleosides, and nucleotides are delineated in Table 2.2. 

Fluorouracil (5FU) is 5-fluoropyridrimidine-2,4(1/7, 3H)-dione. Its structure is illustrated in Figure 11. The hydrogen in the naturally occurring pyrimidine, uracil, is substituted by fluorine in the 5 position. The presence of the heteroatoms in the structure imparts hydrophilicity to the compound as they are capable of hydrogen bonding. 

There are five common bases found in nucleic acids. Adenine (A), guanine (G) and cytosine (C) are found in both DNA and RNA. Uracil (U) is found only in RNA and thymine (T) only in DNA. The structures of these bases are shown in Figure 13.2. Adenine and guanine are purine bases while uracil, thymine and cytosine are the pyrimidine bases. 

Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nudeic add constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH]... 

The nitrogen-containing bases that occur in DNA and RNA fall into two structural categories the purines and the pyrimidines. The former contain a five-membered ring fused to a six-membered ring, while the latter contain a six-membered ring only. The two purines are common to both DNA and RNA adenine (A) and guanine (G). The pyrimidine cytosine (C) occurs in both DNA and RNA. The other pyrimidine is thymine (T) in DNA but uracil (U) in RNA. 

An ab initio study on the structure and splitting of the uracil dimer anion-radical (see Scheme 3.72, R = H) gives preference to the one-step mechanism (Voityuk and Roesch 1997). Anion-radical anions of the pyrimidine dimers cleave with rate constants in excess of 10 s ... 

Additionally, nucleic acid bases have been used in the dynamic assembly of mixed-metal, mixed-pyrimidine metallacalix[n]arenes [47]. In this approach, Lippert and coworkers investigated the dynamic assembly of metallacalixarenes based on platinum (Pt ), palladium (Pd°), uracil, and cytosine assemblies with mixed amines. These combinations form cyclic metallacalix[n]arenes structures with n = A and = 8. Of the metallacalix[4]arenes, compounds were formed with five, six, and eight bonded metals, and a variety of nucleobase coimecfivities (UCUC and UCCU). The dynamic nature of this assembly allows access to novel and structurally diverse set of nucleobase metallacalixarenes. 

The probable structures of the dimers and hydrates are illustrated below for a uracil derivative. The constraints imposed upon the orientation of the pyrimidine residues in the dinucleotide should restrict the number of geometrical isomers possible, relative to the number of possibilities for a derivative containing only a single pyrimidine residue. 

A series of pyrido[2,3-rf pyrimidine-2,4-diones bearing substituents at C-5 and/or C-6 were synthesized using palladium-catalyzed coupling of uracil derivative 417 with vinyl substrates or allyl ethers to give the regioisomeric mixtures of 418/419 and 420/421, respectively. The ratio of the isomeric structures was dependent on the substituent R. In the case of the reaction with -butyl vinyl ether, only the product 419 was obtained. However, the reactions with acrylonitrile, ethyl acrylate, 2-trifluoromethylstyrene, and 3-nitrostyrene afforded only 418. Also, reaction with allyl phenyl ether gave only 420. The key intermediate 417 was prepared by the reaction of 6-amino-l-methyluracil with DMF-DMA (DMA = dimethylacetamide), followed by N-benzylation with benzyl chloride and vinyl iodination with iV-iodosuccinimide (NIS) (Scheme 15) <2001BML611>. 

Cytosine, thymine, and uracil are pyrimidines along with adenine and guanine they account for the five nucleic acid bases. Pyrimidines are heterocyclic single-ringed compounds based on the structure of pyrimidine. Cytosine, thymine, and uracil, like adenine and guanine, form nucleosides and nucleotides in RNA and DNA. When the bases combine with ribose, a ribo-nucleoside forms and when it attaches to deoxyribose, a deoxyribosenucleoside is formed. Names of the nucleoside are summarized in Table 29.1. These in turn combine with phospho-ryl groups, in a process called phosphorylation, to form their respective nucleotides that form nucleic acids. The nucleotides can be tri, di, and mono phosphate nucleotides similar to the way in which adenine forms ATP, ADP, and AMP. 

As active transport uses a carrier system, it is normally specific for a particular substance or group of substances. Thus, the chemical structure of the compound and possibly even the spatial orientation are important. This type of transport is normally reserved for endogenous molecules such as amino acids, required nutrients, precursors, or analogues. For example, the anticancer drug 5-fluorouracil (Fig. 3.6), an analogue of uracil, is carried by the pyrimidine transport system. The toxic metal lead is actively absorbed from the gut via the calcium transport system. Active uptake of the toxic herbicide paraquat into the lung is a crucial part of its toxicity to that organ (see chap. 7). Polar and nonionized molecules as well as lipophilic molecules may be transported. As active transport may be saturated, it is a zero-order rate process in contrast to passive diffusion (Fig. 3.3). 

Both DNA and RNA contain two major purine bases, adenine (A) and guanine (G), and two major pyrimidines. In both DNA and RNA one of the pyrimidines is cytosine (C), but the second major pyrimidine is not the same in both it is thymine (T) in DNA and uracil (U) in RNA Only rarely does thymine occur in RNA or uracil in DNA The structures of the five major bases are shown in Figure 8-2, and the nomenclature of their corresponding nucleotides and nucleosides is summarized in Table 8-1. 

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