see designations in Table 2

Table 4. Basic thermodynamic and kinetic characteristics of water-assisted tautomerisation of DNA bases obtained at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory in vacuum #

It should be noted that in the works devoted to the water-assisted tautomerisation (Fogarasi & Szalay, 2002; Furmanchuk et al., 2011; Gu & Leszczynski, 1999; H.-S. Kim et al., 2007; López et al., 2010; Michalkova et al., 2008; Sobolewski & Adamowicz, 1995) the authors did not justify their choice of the Watson-Crick edges of nucleotide bases (Watson & Crick, 1953a, 1953b) for interaction with a water molecule. This can be explained by the absence of the experimental or theoretical data on hydration of the isolated DNA bases. Up to date, the reported data include only the analysis of hydration of DNA bases in crystal structures of oligonucleotides of A- (Schneider et al., 1992), B- (Schneider et al., 1992, 1993; Schneider & Berman, 1995) and Z-forms of DNA (Schneider et al., 1992, 1993) and wide angle neutron scattering study of an A-DNA fiber (Langan et al., 1992). These studies revealed that sites of the preferred hydration of base pairs are localized in the major groove of DNA. Later on Fogarasi et al. (Fogarasi & Szalay, 2002) have demonstrated that the preferable position for water binding to Cyt is the O=C2-N1-H (H-O-C2=N1 in the enol form) moiety.

The energy barriers for water-assisted tautomerisation are greatly reduced (by 21-27 kcal/mol) as compared with the corresponding ones in the gas phase. Therefore, the explicit water molecules could accelerate by several orders the tautomerisation process from canonical to mutagenic tautomer. Such significant reduction in the internal tautomerisation barriers could be explained by the formation of the H-bonds between the water molecule and nucleic acid bases, which stabilize the transition state.

changes in their complexes with water. So, equilibrium constants of tautomerisation for the AdeH2O and ThyH2O complexes (4.8910-8 and 3.3910-7, respectively) fall into the mutationally significant range, while for the CytH2O and GuaH2O complexes (4.1610-3

For comparison, computation results reported by Gorb and Leszczynski (Gorb & Leszczynski, 1998a, 1998b) are of a special interest. As part of their comprehensive study of water-mediated proton transfer between canonical and mutagenic tautomers of Cyt and Gua, the authors have shown that the interaction with water changes the order of relative

kcal/mol k, s-1 <sup>τ</sup>, s τ1/2, s τ99.9%, s

Table 4. Basic thermodynamic and kinetic characteristics of water-assisted tautomerisation of DNA bases obtained at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of

It should be noted that in the works devoted to the water-assisted tautomerisation (Fogarasi & Szalay, 2002; Furmanchuk et al., 2011; Gu & Leszczynski, 1999; H.-S. Kim et al., 2007; López et al., 2010; Michalkova et al., 2008; Sobolewski & Adamowicz, 1995) the authors did not justify their choice of the Watson-Crick edges of nucleotide bases (Watson & Crick, 1953a, 1953b) for interaction with a water molecule. This can be explained by the absence of the experimental or theoretical data on hydration of the isolated DNA bases. Up to date, the reported data include only the analysis of hydration of DNA bases in crystal structures of oligonucleotides of A- (Schneider et al., 1992), B- (Schneider et al., 1992, 1993; Schneider & Berman, 1995) and Z-forms of DNA (Schneider et al., 1992, 1993) and wide angle neutron scattering study of an A-DNA fiber (Langan et al., 1992). These studies revealed that sites of the preferred hydration of base pairs are localized in the major groove of DNA. Later on Fogarasi et al. (Fogarasi & Szalay, 2002) have demonstrated that the preferable position for

The energy barriers for water-assisted tautomerisation are greatly reduced (by 21-27 kcal/mol) as compared with the corresponding ones in the gas phase. Therefore, the explicit water molecules could accelerate by several orders the tautomerisation process from canonical to mutagenic tautomer. Such significant reduction in the internal tautomerisation barriers could be explained by the formation of the H-bonds between the water molecule

water binding to Cyt is the O=C2-N1-H (H-O-C2=N1 in the enol form) moiety.

and nucleic acid bases, which stabilize the transition state.

ΔG, kcal/mol <sup>K</sup>

1.1910-6 9.97 4.8910-8

3.8410-8 8.82 3.3910-7

2.1310-4 3.25 4.1610-3

3.3710-6 2.27 2.1610-2

and 2.1610-2, respectively)these values are considerably higher (Table 4).

Ade·H2O→Ade\*·H2O 18.53 3.8010-1 2.63 1.82

Ade\*·H2O→Ade·H2O 8.56 7.77106 1.2910-7 8.9210-8 Thy·H2O→Thy\*·H2O 15.51 8.12101 1.2310-2 8.5410-3

Thy\*·H2O→Thy·H2O 6.69 2.40108 4.1710-9 2.8910-9 Сyt·H2O→Сyt\*·H2O 15.00 1.80102 5.5710-3 3.8610-3

Сyt\*·H2O→Сyt·H2O 11.75 4.32104 2.3210-5 1.6110-5 Gua·H2O→Gua\*·H2O 11.63 5.78104 1.7310-5 1.2010-5

Gua\*·H2O→Gua·H2O 9.36 2.68106 3.7410-7 2.5910-7

energies of cytosine tautomers.
