Tautomers water interaction with

Kryachko, E. S. Nguyen, M. T. Zeegers-Huyskens, T. Theoretical study of uracil tautomers. 2. Interaction with water, 7. Phys. Chem. A 2001,105, 1934-1943. 

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

Amino acids, the building blocks of proteins, can exist in two principal tautomeric forms. In aqueous solution, the naturally occurring a-amino acids are found in their zwitterionic form 42Z, but in the gas phase, the neutral form 42N is the only structure observed. This substantial solvent effect is understood in terms of the dipole moments of the tautomers. The dipole moment of the zwitterion is very large and is favorably stabilized by electrostatic interactions with the polar water molecules. In the absence of the polar environment (the gas phase), the charge separation of the zwitterion is unsustainable and only the neutral form exists. 

A related study was undertaken by Zeng and Ren who examined the tautomer-ization of 2-aminothiazole in the gas phase and in solution. They considered more different scenarios, including the isolated molecules, the isolated molecules interacting with 1, 2, or 3 water molecules, and two interacting molecules. In all cases, they considered a gas phase tautomerization as well as reactions occurring in water or... 

It is also well known that the keto-enol equilibrium is modified fundamentally in aqueous solution due to the specific interaction of solvent molecules with the substrates through hydrogen bonds Calculated results summarized in Figure 39a indicate that the keto-enol equilibrium is markedly modified in the bimolecular neutral systems in which each tautomer interacts with one water molecule. In particular, the energy barrier for hydrogen transfer from oxygen to carbon is reduced appreciably, in going from... 

The present work discusses some properties of thiouracil nucleobases calculated at the B3LYP/6-31+G(d,p) computational level, namely, their structures, most stable tautomers, proton affinities and deprotonation enthalpies, hydrogenation, interaction with water, and base pairing, in order to shed a certain light on the problem of why their functioning in RNA and modified DNA base pairs is so unusual. 

Before analysis of the interactions of the nucleic acid bases with the clay minerals in the presence of water and cation one needs to understand the individual interactions of NAs with isolated water and with a cation. Such theoretical study was performed for 1 -methylcytosine (MeC) [139]. The study revealed influence of water and cation in the proton transfer for this compound. This leads to the formation of imino-oxo (MeC ) tautomer. Topology of the proton transfer potential surface and thermodynamics of stepwise hydration of MeCNa+ and MeC Na+ complexes is further discussed. The one dimensional potential energy profile for this process followed by the proton transfer with the formation of hydrated MeC Na+ is presented in Fig. 21.2. One-dimensional potential energy profile for amino-imino proton transfer in monohydrated N1-methylcytosine (this represents the situation when tautomerization is promoted by a single water molecule without the influence of Na+ cation) and for the case of pure intramolecular proton transfer (tautomerization is not assisted by any internal interactions) is also included. The most important features of this profile do not depend on the presence or absence of Na+ cation. All the potential energy curves have local minima corresponding to MeC and MeC. However, the significant difference is observed in the relative position of local minima and transition state, which results in a different thermodynamic and kinetic behavior for all presented cases (see Fig. 21.2). 

The thermodynamic and kinetic parameters of the stepwise hydration of 1-methylcytosine and its imino-oxo tautomer in the presence of the Na" " cation have been investigated [139]. Hydrationof 1-methylcytosineby one water molecule leads to an increase of the concentration of its imino-oxo tautomer in the equilibrium mixture and decrease of the barrier of the tatutomer formation (to 15.6 kcal/mol). If the sodium cation is present the tautomeric form is much less favored and tautomerization barrier increases to 25.2 kcal/mol. The computationally predicted values of the rate constants suggest that the tautomerization of 1-methylcytosine to its imino-oxo form proceeds mainly due to a presence of the hydrated (MeCW) species. Based on the kinetic analysis of the tautomerization process in hydrated MeC in the presence of sodium ions it was concluded that complexes of hydrated MeC with Na+ are unlikely to contribute to the frequency of DNA point mutations caused by the tautomers. This is due to the fact that the interactions with Na" " lead to a decrease of both the rate and the equilibrium constants of the tautomerization reactions in hydrated 1-methylcytosine. 

Let us start the analysis of the influence of the hydration on the nonplanarity phenomena from the nonplanarity of the first type. There are two important observations here. First of all one may see that the nonplanarity of the first type (sp- hybradization of the amino group) does not depend significantly either on chemical structure of the tautomers or on the interaction with water molecules in the case of guanine and cytosine. 

Experimental data on the gas phase stability of monohydrated bases are not available. Nevertheless, the computational study provides the justification for the predicted tendencies. The observed change of the relative stability displays the tendency (for isolated bases) to approach the stability of fully hydrated complexes upon the interaction with water molecules. This conclusion is especially important for the tautomers of guanine and cytosine where the relative stability of the tautomers is completely different in the gas phase compared to the polar medium. So, one can conclude that even the interaction with one water molecule in the case of cytosine and the interaction with two water molecules in the case of guanine is sufficient to reverse the gas-phase relative stability order into the order which corresponds to the stability found in a water solution. 

There is a general pattern of the DNA base pair - water interaetions. One may see that the interaction with water molecules destabilize hydrogen-bonded rare tautomers. In other words, the interaction with water molecules makes more stable canonic base pairs. This is in complete correspondence with the above... 

The confidence in the accuracy of the computational studies allows one to elucidate the role of water molecules in the structure of the DNA. The hydration of the DNA, even by a limited number of water molecules, additionally stabilize the canonic structures both for the isolated bases and for the hydrogen bonded pairs. This means that the hydration is the supplementary source of the stability of the normal structures of the DNA bases. Such effect is especially important for cytosine and guanine which, without the interactions with solvent, exist as the mixture of normal and rare tautomers. 

---