Tautomers, cytosine

The proton transfer in these clusters via the water bridge was found to be about three times as fast as a nonassisted transfer, underscoring the importance of the solvent for the reaction mechanism [98IJQ855]. In addition to the relative stabilities of the cytosine tautomers, the structures and properties of some cytosine derivatives have been investigated, mainly those of 5-hydroxycytosine 111 and 5,6-dihydroxycytosine 112 (Scheme 73) [99JST1, 99JST49]. 

Shukla MK, Leszczynski J (2002) Interaction of water molecules with cytosine tautomers An excited-state quantum chemical investigation. J Phys Chem A 106 11338... 

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. 

Table VII contains the results of the CNDO/2 calculation158 on the energy of cytosine tautomers 2, 3 or 6 and of some derivatives. It can be seen that the calculated energy shifts are in agreement with the effect of substitution on the tautomeric equilibrium of cytosine discussed in Section II, B. Thus, a 5-fluoro substituent causes a small tautomeric shift toward forms 3 (dB i3F Cyt - di ,3t = 2.98 kcal/mole) or 6 (JB l8F Cyt — = 4.87 kcal/mole), while a 6-fluoro substituent...

Fig. 6. Net total electronic charges in N4-amino and N4-hydroxy substituted cytosine tautomers calculated by the CNDO/2 method. The numbers in parentheses indicate w-charges.

All-valence and all-electron methods (except IEHT) predict that the first ionization potential of cytosine and of several derivatives of a cytosine is of the w-type (Tables XIV and XV). An ionization potential of the n-type is the first one in all tautomers of cytosine. Similarly, the electron affinities in all cytosine tautomers should be of the ir-type. 

Cytosine, protonated at N3 Proton nuclear magnetic resonance Metal complex of rare cytosine tautomer 9 -Methy ladenine... 

Figure 7.10 Structures and relative energies (kcal mor ) of mono- and dihydrated cytosine tautomers 13a and 13b. ...

TABLE 7.12 Relative Energies (in kcal mol of Cytosine Tautomers (13a-h)... 

Sambrano, J. R. de Souza, A. R. Queralt, J. J. Andrds, J. A theoretical study on cytosine tautomers in aqueous media by using continuum models, Ghent. Phys. Lett. 2000, 317, 437-443. 

Tautomeric Constants and Thermodynamic Parameters FOR Cytosine Tautomers... 

The effect of the solvent is usually modelled either by the use of the Onsager s self consistent reaction field (SCRF) [20] or by the polarizable continuum method (PCM) [21]. With regard to the relative stability of cytosine tautomers in aqueous solution, these methods provided results [14,15] which, in spite of some discrepancies, are in reasonable agreement with experimental data [3]. However, continuum-based methods do not explicitly take into consideration the local solvent-solute interaction which is instead important in the description of the proton transfer mechanism in hydrogen-bonded systems. A reasonable approach to the problem was recently proposed [22,23] in which the molecule of interest and few solvent molecules are treated as a supermolecule acting as solute, while the bulk of the solvent is represented as a polarizable dielectric. 

In the present paper the thermodynamic and kinetic aspects of the proton transfer reactions among cytosine tautomers assisted by specific solvent molecules was theoretically investigated. For the time being, bulk solvent effects were not considered and attention was only focused on the influence of hydrogen bonding on both (i) tautomers relative stability and (ii) the catalytic process occurring between adjacent positions of cytosine. The computational results on point (i) are compared with those of PCM calculations [15]. The results on point (ii) are discussed with reference to the conclusions of other theoretical studies available in the literature [16,17]. 

Figure 2. Scheme of the simulated proton transfer reactions occurring among mono- and dihydrated cytosine tautomers. 

Figure 3. Mono- and dihydrated adducts of cytosine tautomers relevant for stability calculations.

Table 1. Selected geometric parameters (distances in A, angles in degrees) for monohydrated cytosine tautomers and transition states optimized at the HF/3-2IG level.

Figure 4. Relative stability of mono- and dihydrated cytosine tautomers compared with PCM [15] and in vacuo [19] relative stability.

A comparison of the lowest singlet mi transition of cytosine tautomers presented in Tables 19 and 20 suggests that, widi respect to the keto-NlH tautomer, the transition in the keto-N3H tautomer is appreciably red-shifted for both the isolated and hydrated forms. While in the case of the enol and imino tautomers, the isolated forms show a blue-shift with respect to the isolated form of the keto-NlH tautomer for hydrated species, the imino form shows a slight blue-shift, and the enol form does not show any shift (Tables 19 and 20). The observed red-shift in the first mt transition of the keto-N3H tautomer is in accordance with the experimental fact that the absorption spectrum of 3-methylcytosine in aqueous media shows a significant red-shift with a peak near 289 nm (4.29 eV) compared to the corresponding transition of cytosine observed near 266 nm (4.66 eV). The observ transitions of 3-methylcytosine near 4.29 and 5.47 eV can be explained in terms of the computed transitions of hydrated forms of the keto-N3H tautomer near 4.25 and 5.68 eV, respectively (Table 20). The computed transitions of the imino form can be compared with the observed transitions of 3-methylcytidine in a water solution. Table 20 shows that the observed transition near 4.64 and 5.59 eV of 3-methylcj4idine can be explained in terms of the computed transitions of the imino form of cytosine within an error of about 0.3 eV. Therefore, it appears that the absorption spectra of aqueous solutions of cytosine would be mainly dominated by the keto-NlH tautomer and contributions fix>m other tautomers will not be significant. 

Figure 9. Structure and hydrogen bond lengths of hydrated cytosine tautomers (a) keto-NlH tautomer in the ground state, (b) keto-NlH tautomer in the S2(njt ) excited state, (c) keto-N3H tautomer in the ground state (top indices) and Sitnn" ) excited state (bottom indices), (d) keto-N3H tautomer in the 82(031 ) excited state, (e) enol tautomer in the groimd state (top indices) and Si(7nc ) excited state (bottom indices), and (f) imino tautomer in the ground state.

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