see designations in Table 2

Table 3. Basic thermodynamic and kinetic characteristics of tautomerisation of Watson-Crick DNA base pairs obtained at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory in vacuum #

Comparatively with the reverse barriers heights of tautomerisation of the Gua\*·Cyt\* and Ade\*·Thy\* mispairs (5.15 and 0.11 kcal/mol, respectively) the values of their interaction energies (22.94 and 33.80 kcal/mol , respectively) are high enough for mispairs dissociation into mutagenic tautomers (Table 6).

Although the equilibrium constants of tautomerisation of the Gua\*·Cyt\* (9.4210-7) and Ade\*Thy\* (1.4110-9) (Table 3) mispairs involving mutagenic tautomers fall within the range of the mutation frequency (Drake, 1991), their lifetimes (1.0410-12 s and 2.5710-14 s , accordingly, see Table 3) are negligible comparably with the time of one base pair dissociation during the enzymatic DNA replication (10-9 s) to cause spontaneous mutations. So, Löwdin's mispairs "escape from the hands" of replication apparatus.

These data indicate that Löwdin's mechanism is not sufficient to explain the mutagenic tautomers formation within AdeThy and GuaCyt base pairs of DNA.

#### **4.4 Tautomerisation of the DNA bases facilitated by an isolated water molecule**

It has been established quite some time ago that there is a shell of tightly bound water molecules at the surface of DNA with properties significantly different from those of bulk water and it seems that DNA interaction with water largely determines its conformation, stability, and ligand binding properties (J.H. Wang, 1955; Tunis & Hearst, 1968; Falk et al., 1970; Kubinec and Wemmer, 1992). The pure rotational spectra of the binary adducts of Ura and Thy with water were first observed by laser ablation molecular beam Fourier transform

dynamically unstable, moreover, the value of its reverse barrier (in terms of Gibbs free energy) is negative (-1.01 kcal/mol) indicating that Ade\*·Thy\* minimum completely disappears from the Gibbs free energy surface. Therefore, Ade\*·Thy\* mispair really doesn't exist (Fig. 3). By comparing the values of zero-point energy (Table 3, 7) and the reverse barrier (Tables 3, 7) of the Gua·Cyt↔Gua\*·Cyt\* tautomerisation, we came to the conclusion

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

Table 3. Basic thermodynamic and kinetic characteristics of tautomerisation of Watson-Crick DNA base pairs obtained at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of

Comparatively with the reverse barriers heights of tautomerisation of the Gua\*·Cyt\* and Ade\*·Thy\* mispairs (5.15 and 0.11 kcal/mol, respectively) the values of their interaction energies (22.94 and 33.80 kcal/mol , respectively) are high enough for mispairs dissociation

Although the equilibrium constants of tautomerisation of the Gua\*·Cyt\* (9.4210-7) and Ade\*Thy\* (1.4110-9) (Table 3) mispairs involving mutagenic tautomers fall within the range of the mutation frequency (Drake, 1991), their lifetimes (1.0410-12 s and 2.5710-14 s , accordingly, see Table 3) are negligible comparably with the time of one base pair dissociation during the enzymatic DNA replication (10-9 s) to cause spontaneous mutations.

These data indicate that Löwdin's mechanism is not sufficient to explain the mutagenic

It has been established quite some time ago that there is a shell of tightly bound water molecules at the surface of DNA with properties significantly different from those of bulk water and it seems that DNA interaction with water largely determines its conformation, stability, and ligand binding properties (J.H. Wang, 1955; Tunis & Hearst, 1968; Falk et al., 1970; Kubinec and Wemmer, 1992). The pure rotational spectra of the binary adducts of Ura and Thy with water were first observed by laser ablation molecular beam Fourier transform

**4.4 Tautomerisation of the DNA bases facilitated by an isolated water molecule** 

So, Löwdin's mispairs "escape from the hands" of replication apparatus.

tautomers formation within AdeThy and GuaCyt base pairs of DNA.

ΔG, kcal/mol <sup>K</sup>

2.3710-13 12.07 1.4110-9

9.6110-12 8.22 9.4210-7

4.6310-10 4.01 1.1410-3

4.1810-12 1.16 1.4210-1

that Gua\*·Cyt\* mispair is metastable.

Conversion Δ∆GTS,
