Tautomers of nucleotide bases

Protons bound to heteroatoms in heterocyclic compounds are likely to be very mobile in solution and, where two or more heteroatoms are present in a structure, different isomers (tautomers) may be in equilibrium. As a case in point, consider the nucleotide bases (indicates the point of attachment to the sugar-phosphate backbone). 

Based on your analysis, is it likely that tautomeric equilibria involving the nucleotide bases will interfere noticeably with base pairing in DNA Explain. 

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Transient absorption experiments have shown that all of the major DNA and RNA nucleosides have fluorescence lifetimes of less than one picosecond [2—4], and that covalently modified bases [5], and even individual tautomers [6], differ dramatically in their excited-state dynamics. Femtosecond fluorescence up-conversion studies have also shown that the lowest singlet excited states of monomeric bases, nucleosides, and nucleotides decay by ultrafast internal conversion [7-9]. As discussed elsewhere [2], solvent effects on the fluorescence lifetimes are quite modest, and no evidence has been found to date to support excited-state proton transfer as a decay mechanism. These observations have focused attention on the possibility of internal conversion via one or more conical intersections. Recently, computational studies have succeeded in locating conical intersections on the excited state potential energy surfaces of several isolated nucleobases [10-12]. 

Nucleoside analogues do not always behave as expected. 5-Bromouracil (6.a) effectively forms base pairs with guanine nucleotides. This surprising observation has been explained by invoking a different tautomer of 6.a. Draw a different tautomer of 6.a and show how it can effectively base pair to a guanine nucleotide. (Tautomerization theory Topal, M. D., Fresco, J. R. Base Pairing and... 

Tautomeric enol and imino forms of bases occur only rarely, and can lead to mutations. It should be emphasized that in none of the above described mismatch base pairs is there any evidence for the existence of rare tautomeric forms. For the A-C pair, protonation at (adenine)N(l) appears more probable than the imino form (Fig. 20.6). However, conclusive evidence is still lacking because hydrogen atoms cannot be located at the attainable resolution of about 2 A. Moreover, in none of the crystal structures of the nucleosides and nucleotides or of the bases themselves is there any evidence of the enol-imino tautomers (Part II, Chaps. 15, 16, 17). 

Molecular modeling is now an industry standard technique and is gaining popularity in the academic world as a tool for modem analytical chemistry. It can be extremely useful in the prediction and interpretation of infrared and ultraviolet spectra, particularly in cases where the spectra are hard to interpret due to contamination by energetically equivalent tautomers, for example, cytosine and other nucleotide bases. Computational techniques can also be useful in elucidating reaction mechanisms and for 3D structural visualization. To this end, nearly one-quarter of the articles in the American Chemical Society s flagship publications, the Journal of the American Chemical Society and the Journal of Organic Chemistry, that are concerned with stmctural prediction or interpretation make use of molecular simulations in some way. 

A relatively large number of investigations reporting dynamics simulations for nucleobases, nucleobase tautomers, nucleotides, derivatives, WC pairs and quartets in different solvation conditions has been published in the last years. Recent overviews of the field can be found in Refs. (Alexandrova et al. 2010 Barbatti et al. 2010a). In this section, we shortly review the dynamics of isolated bases focusing on which relaxation mechanism these works have proposed for each molecular system. 

When attached to a sugar (ribose in RNA, 2-deoxyribose in DNA), the bases are converted to nucleosides. Nucleotide is the term used for phosphorylated nucleosides. Understanding the hydrogen bonding needed to form the double helix of DNA requires the determination that 2- and 4-hydroxypyridines and their nucleobase analogs exist as the keto tautomer. 

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