Purine tautomeric form

These relationships are general Hydroxyl substituted purines and pyrimidines exist in their keto forms ammo substituted ones retain structures with an ammo group on the ring The pyrimidine and punne bases m DNA and RNA listed m Table 28 1 follow this general rule Beginning m Section 28 7 we 11 see how critical it is that we know the cor rect tautomeric forms of the nucleic acid bases... 

FIGURE 11.4 The common purine bases—adenine and guanine—in die tautomeric forms predominant at pH 7. 

A hypothesis for the oxidation of purines in the presence of this enzyme has been elaborated by Bergmann and his colleagues. It postulates that the purine, often in one of its less prevalent tautomeric forms, is adsorbed on the protein, or the riboflavin coenzyme, of the enzyme then hydration occurs under the influence of the electronic field of the enz5rme, and this must involve a group that is not sterically blocked by the enzyme but which is accessible to the electron-transport pathway of the riboflavin moiety. Finally, the secondary alcohol is assumed to be dehydrogenated in this pathway to give a doubly... 

Most in vitro studies of xanthines have centered around the enzyme xanthine oxidase. Bergmann and co-workers 40-4)) have examined the main oxidative pathways in the xanthine oxidase catalyzed oxidation of purines. The mechanism proposed by these workers 41 > is that the enzyme binds a specific tautomeric form of the substrate, regardless of whether or not that form represents the major structure present in solution. It is then proposed that the purine, e.g., xanthine, undergoes hydration at the N7=C8 double bond either prior to or simultaneously with dehydrogenation of the same position. Accordingly, the process would involve either pathway a or b. Fig. 15. Route a would give a lactim form of the oxidized purine, while b would give the cor-... 

The tautomerisation of the purine bases adenine and guanine and of the pyrimidine bases thymine, cytosine, and uracil has important implications in molecular biology, and the occurrence of rare tautomeric forms of these bases has been suggested as a possible cause of spontaneous mutagenesis (Lowdin, 1965 Pullman and Pullman, 1971 Kwiatowski and Pullman, 1975). Three of the most likely tautomers for cytosine are shown in [87]—[89], together with the less likely imino forms [90] and [91] (Scanlan and Hillier,... 

Some of the impetus for studying tautomeric equilibria in heterocycles arises because of the postulate that point mutations in genetic material may be introduced when a given base exists in a tautomeric form during replication [279, 305-307], Cytosine, in particular, has imino and hydroxy tautomers that are within 3 kcal/mol of the global minimum illustrated above (because of the very large number of possible tautomers for the purines and pyrimidines, only the lowest energy tautomers are presented). This analysis has been made based on a... 

The bases are monocyclic pyrimidines (see Box 11.5) or bicyclic purines (see Section 11.9.1), and all are aromatic. The two purine bases are adenine (A) and guanine (G), and the three pyrimidines are cytosine (C), thymine (T) and uracil (U). Uracil is found only in RNA, and thymine is found only in DNA. The other three bases are common to both DNA and RNA. The heterocyclic bases are capable of existing in more than one tautomeric form (see Sections 11.6.2 and 11.9.1). The forms shown here are found to predominate in nucleic acids. Thus, the oxygen substituents are in keto form, and the nitrogen substituents exist as amino groups. 

Fluorescence and phosphorescence emission spectroscopy were employed to study the interaction of E. coli purine nucleoside phosphorylase (PNP) with its specific inhibitor, FA. The results show, for the first time, the application of phosphorescence spectroscopy to the identification of the tautomeric form of the inhibitor bound by the enzyme <2004MI377>. 

FIGURE 8-9 Tautomeric forms of uracil. The lactam form predominates at pH 7.0 the other forms become more prominent as pH decreases. The other free pyrimidines and the free purines also have tautomeric forms, but they are more rarely encountered. 

This paper presents quantum mechanical studies of the, 5N and, 3C chemical shifts in both the N7-H and N9-H tautomeric forms of purine. Quantum mechanical calculations of the chemical shifts were used to assign the NMR resonances and the spatial orientation of the principal axes of the chemical shift tensors. Calculations in purine and in a pyridine-methanol complex model provide insights on the importance of the intermolecular interactions on the chemical shifts of the nucleic acid bases. 

Purine can exist in two tautomeric forms, N7-H and N9-H depending on the state (9, 10). In the crystalline state, it exists in the N7-H form (11), but its N9-H form has been observed in the gas phase, matrix isolation, and in solution. Quantum... 

This paper presents a study of the i5N and, 3C chemical shifts in both tautomeric forms of purine. All the principal values of the, 5N and, 3C chemical shifts tensors were measured in a sample in which only the N7-H tautomeric form was present. In another sample, containing both tautomeric forms, the principal values of the quaternary carbons, the isotropic shifts of the remaining carbons and isotropic shifts of the nitrogens could also be obtained for the N9-H tautomeric form. The experimetal procedures are described in detail elsewhere. 

To explore the importance of the intermolecular interactions model systems were constructed for both the N7-H and the N9-H tautomeric forms. These models, labeled HB N9-H (1) and HB.N7-H (2) in the tables, are based on the X-ray structure of the N7-H tautomer partially surrounded by the nearest neighbor molecules. In the models the position of the nearest neighbor fragments was determined using the x-ray structure and the optimized X-H distances. The models and the numbering of the atoms in purine are shown in Figure 1. 

Figure 2 Quantum mechanically optimized structures of the N9-H (1) and N7-H (2) tautomeric forms of purine. All the interatomic distances are in A.

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... 

Let us start with the basic problem of the four fundamental tautomers of purine. As stated before, although the molecule of purine is generally represented in the form N(9)H, in which a hydrogen atom as attached to N-9, tautomeric forms may naturally be considered, in which the proton is attached to the other nitrogens of the molecule, yielding the tautomers N(7)H, N(3)H, and N(1)H. In fact, although the majority of biological purines exist essentially as derivatives of the N(9)H tautomer, the crystalline form of purine... 

Diamagnetic anisotropies have also been evaluated109 for the different tautomeric forms of purine. They, too, fall into two groups ... 

It therefore appears plausible to admit that the main reason for the occurrence of the N(7)H tautomer in the crystal of purine resides, at least to a large part, in the greater interaction energy that may be obtained with this tautomeric form. 

This paper has presented a discussion of a large number of tautomeric forms for the fundamental purines. It is obviously a rich field of study in which the conjunction of theory and experiment seems particularly fruitful. 

The essential possible interference of purine tautomerism in biochemistry and, in particular, in biochemical evolution concerns, as mentioned in the introduction to this chapter, its possible role in mutagenesis. This could occur through the mispairing of the bases when present in rare tautomeric forms. 

Figure 10.2 Tautomeric forms of uric acid. Although uric acid does not occur in nucleic acids (it is a degradation product of adenine and guanine), the tautomeric structures observed here are typical of all purine bases of this type. At pH 7, the keto forms predominate.

The chemical properties of the purine and pyrimidine bases include highly conjugated double bond systems within the ring structures. For this reason, nucleic acids have a very strong absorption maximum at about 260 nm, which is used for nucleic acid quantitation. Moreover, the bases can exist in two tautomeric forms, the keto and enol forms (Figure 10.2). In DNA and RNA, the keto forms are by far the more predominant, and this property makes it possible for the bases to form intermolecular hydrogen bonds (see Figure 10.18). 

It is important that we draw certain of the purine and pyrimidine bases in their preferred tautomeric forms. The correct pairings are given early in the chapter. What alternative pairings would be possible with these (minor) tautomers of thymine and guanine Suggest reasons (referring to Chapter 43 if necessary) why the major tautomers are preferred. 

---