Nucleic base tautomer

The structures and energies of the tautomers of the bases of the nucleic acids have been subject to numerous computational studies. Since DNA is found in the aqueous environment of the cell interior, it is essential that the base tautomers, and the base pairs, be computed in the aqueous phase. In this section, we discuss the structures of the tautomers of each of the four DNA bases and uracil, found in RNA, focusing on the differences in the gas and solution phases. We then take on the structure of the base pairs in solution. 

The rare nucleic acid base tautomers, ordinarily present to the extent of 0.01% relative to the preferred tautomers, can be stabilized by metals via coordination of lone-pair electrons. For example, the 4-imino-2-oxo tautomer of cytosine has Pt + bound to its group, while the 4-hydroxy-2-oxo tautomer of U and T bases is platmated at N-3. ... 

Hydrogen-bonded nucleic acid base pairs containing unusual base tautomers Complete basis set calculations at the MP2 and CCSD(T) levels ... 

In conclusion to our work, it is now possible to predict the lifetimes of the nucleic acid-base tautomers. Since the abnormal lactim and imine forms are expected to be present in a ratio proportion of 10 to we expect, on the basis of the pKs,... 

The picture of prototropic trjinsformations of the nucleic acid base tautomers will never be completed without a knowledge of inter- and intramolecular proton transfer kinetics. The most general data describing the kinetics of proton transfer are the set of temperature dependent rate constants. These data for nucleic acid bases are not yet available from either experimental or theoretical studies except the very recent paper [ 134] where the authors attempt to estimate the water assisted proton transfer rate constant for adenine. However, the calculated values of proton transfer barrier for both non-water assisted and water assisted pathways are available for the adenine, guanine and eytosine [119, 123, 134]. These data are collected in Tables 12 - 16, where, for convenience, we have defined as forward reaction the proton transfer process from the normal (canonical) to the hydroxo- (imino-) form. 

It has been proposed that 8-aminodcoxyguanosinc is formed from the nitronate tautomer of 2-nitropropane either by base nitrosation followed by reduction, or via an enzyme-mediated conversion of the nitronate anion to hydroxyiam ine-O-sulfonate or acetate, which yields the highly reactive nitrenium ion NHj (Sodum et al., 1993). Sodum et al. (1994) have provided evidence for the activation of 2-nitropropane to an aminating species by rat liver aryl sulfotransferase in vitro and in vivo. Pretreatment of rats with the aryl sulfotransferase inhibitors pentachlorophenol or 2,6-dichloro-4-nitrophenol significantly decreased the levels of nucleic acid modifications produced in the liver by 2-nitropropane treatment. Partially purified rat liver aryl sulfotransferase activated 2-nitropropane and its nitronate at neutral pH to a reactive species that aminated guanosine at the position. This activation was dependent on the presence of the enzyme, its specific cofactor adenosine 3 -phosphate 5 -phosphosulfate, and mercaptoethanol. It was inhibited... 

The understanding of the tautomeric properties of the purine and pyrimidine bases of the nucleic acids and the determination of the electronic properties of the principal tautomers are of fundamental importance in molecular biology, in particular in connection with the theory of mutations (for general references see, e.g. refs. 1-6.) B. Pullman and A. Pullman have presented recently in these Advances3 a detailed review of the problem as it concerns the purine bases. The present paper... 

In general, the problem of tautomerism in nucleic acid bases has been approached by comparing the IR spectra of several isoelectronic model compounds. The model corresponding to the cytosine tautomers 4 or 5 have not yet been investigated. The IR spectroscopy studies cannot therefore definitely rule out these tautomers. It seems, however, that they do rule out form 6 for cytosine and cytidine and indicate that the dominant tautomer of the compounds in aqueous solution is the lactam-amino form 2, and that the protonated cations have the structure 7. 

A number of tautomeric forms of some fundamental purines have been studied quantum mechanically with the help of the standard, semiempirical Hiickel approximation of the molecular orbital method.57 58 Limited to ti electrons, these studies nevertheless enabled the determination of a number of electronic differences among the tautomers. Using some simplifying ideas, typical in 77-electron calculations, information has also been obtained, within the limits of this approximation, concerning the relative tendencies of the bases to undergo a given type of tautomerization, and this information has been used successfully for the prediction of the preferential mutagenic sites in the nucleic acids.50... 

Theoretical and experimental methods are complementary to each other. For example, computational methods have suggested that the amino groups of nucleic acid bases in the ground state are nonplanar [58], However, experimental evidence for amino group nonplanarity was obtained only recently when Dong and Miller [59] measured the vibrational transition moment angles in adenine and three tautomers of cytosine in helium droplets. 

A few chapters of the current volume describe different state-of-the-art experimental techniques used to unravel photophysical and photochemical properties of complex molecular systems. These chapters are especially tailored for the scholarly description of electronic excited state properties of nucleic acid bases and related species predicting different tautomeric distributions and possible nonra-diative deactivation processes. It is interesting to note that guanine provides particularly challenging case to discuss. Recent theoretical and experimental investigations show the existence of relatively significantly less stable imino tautomers in the... 

Fig. 15.1. The four bases found in the nucleic acids. Uracil occurs in RNA and is substituted by the analogous thymine (5-methyluracil) in DNA. Uracil is the keto tautomer of 2,4-dihydroxy pyrimidine with two donors N(1)H, N(3)H and two acceptors 0(2), 0(4). Cytosine is the keto tautomer of 4-amino, 2-hydroxy pyrimidine with three donors N(4)H2, N(1)H and two acceptors 0(2), N(3). Adenine is 6-aminopurine with three donors N(6)H2, N(9)H and three acceptors N(l), N(3), N(7). Guanine is the keto tautomer of 2-amino, 6-hydroxy purine with three donors N(2)H2, N(9)H and three acceptors, N(3), N(7), 0(6). In the nucleosides, pyrimidine N(l) and purine N(9) are substituted by ribose or deoxyribose (see Fig. 17.1)...

The crystal structure of isocytosine [ICYTIN] is interesting since it is a 1 1 complex of the 1,4- and 3,4-dihydro tautomers and has both triple and double hydrogen-bond self-association (Fig. 16.7). As outlined in Chapter 15, this tautomerism is not observed in the naturally occurring nucleic acid bases. 

In this section, we present the results of computational studies of the five nucleic acid bases cytosine 13, guanine 14, adenine 15, thymine 16, and uracil 17. The canonical structures, those that are involved in the Watson-Crick base pairing within DNA, are drawn below. Other tautomers for each base can be energetically competitive with the canonical structure, and these other tautomers are invoked in some models of DNA mutations and anomalous DNA structures. The ensuing discussion focuses on the relative energies of the tautomers, in both the gas and solution phases. Structural changes that accompany this phase change are also noted. 

An interesting feature of the gas-phase guanine tautomers is that their amino group is nonplanar. The sum of the angles about the amine nitrogen is less than 348° for the tautomers 14a-i, and specifically 340.4° and 337.4° in 14a and 14b, respectively. This is more pyramidal than for any of the other nucleic acid bases. 

Trygubenko, S. A. Bogdan, T. V. Rueda, M. Orozco, M. Luque, F. J. Sponer, J. Slaviek, P Hobza, P. Correlated ab initio study of nucleic acid bases and their tautomers in the gas phase, in a microhydrated environment and in aqueous solution. Part 1. Cytosine, Phys. Ghent. Ghent. Phys. 2002, 4,4192-4203. 

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