**3. Obtained results**

It was found out novel *tautomerization pathways* for the formation of the *rare tautomers of the A or T DNA bases*:


Also, we found out new pathways of the *conformational transformations* of the *Watson-Crick А*�*Т(WC), reverse Watson-Crick А*�*Т(rWC), Hoogsteen А*�*Т(Н) and reverse Hoogsteen А*�*Т(rН) base pairs*:


*Where Quantum Biochemistry Meets Structural Bioinformatics: Excited Conformationally… DOI: http://dx.doi.org/10.5772/intechopen.94565*

So, on the potential energy surface of the classical AT/AU base pair it was received *28 various conformationally-tautomeric states* (**Figure 1**, **Table 1**):

• *Planar structures(Cs point symmetry) with wobble geometry:* WC & rWC – 2.A\*T (wWC), 3.AT\*O2(wWC), 4.AT\*(wWC), 6.AT\*O2(rwWC), 7.A\*C2T(rwWC), 8. AT\*(rwWC), 9.A\*T(rwWC) and H & rH – 16.AT\*(wH), 17.A\*C8T(wH), 18. AT\*O2(wH), 19.A\*N7T(wH), 21.AT\*O2(rwH), 22.A\*C8T(rwH), 23.AT\*(rwH), 24.A\*N7T(rwH);

**2.2 Bioinformatical analysis**

*DNA - Damages and Repair Mechanisms*

**3. Obtained results**

*tautomers of the A or T DNA bases*:

• <sup>A</sup>�T(wWC)\$A�T\*(w<sup>⊥</sup>

*reverse Hoogsteen А*�*Т(rН) base pairs*:

the "breathing" of DNA molecule [27];

the wobble conformers as intermediates [52];

H), A�T(wrH)\$A�T\*O2(w<sup>⊥</sup>

(w<sup>⊥</sup>

**6**

It was created original author's algorithm in order to reveal the unusual А�Т base pairs in the Nucleic Acid Database by Rutgers University [93, 94]. This algorithm is based on the comparison of the calculated structure of the А�Т base pairs at the ε = 4

It was found out novel *tautomerization pathways* for the formation of the *rare*

• A�T(WC)\$A\*�T(w)/A�T\*O2(w)/A�T\*(w) *via* the sequential proton transfer

• A�T(rWC)/A�T(H)/A�T(rH)\$A�T\*(rwWC)/A�T\*(wH)/A�T\*(rwH) mutagenic

WC), A�T(wrWC)\$A�T\*O2(w<sup>⊥</sup>

А�Т(rH)\$А\*N7�Т(rwH) / А\*N7�Т(wH) reactions *via* sequential proton transfer through the quasi-orthogonal transition states, as well as between the formed base pairs by the participation of the rare tautomers: А\*�Т(rwWC)\$А�Т\* (rwWC) and А\*�Т(wWC)\$А�Т\*O2(wWC), А\*N7�Т(rwН)\$А�Т\*(rwH) and А\*N7�Т(wН)\$А�Т\*O2(wH) through the double proton transfer (DPT) [50].

Also, we found out new pathways of the *conformational transformations* of the *Watson-Crick А*�*Т(WC), reverse Watson-Crick А*�*Т(rWC), Hoogsteen А*�*Т(Н) and*

• А�Т(WC)\$А�Т(wWC), А�Т(rWC)\$А�Т(wrWC), А�Т(Н)\$А�Т(wН) and А�Т(rН)\$А�Т(wrН) conformational transformations (Gibbs free energies of activation 7.13, 7.26, 7.67 and 7.44 in the continuum with ε = 4) [51], leading to the novel non-planar conformational states – *А*�*Т(wWC), А*�*Т(wrWC), А*�*Т(wН)*

understanding of the physico-chemical mechanisms of the opening of the base pairs, which precede the melting of DNA molecule and also describe in details

conformational transitions - *А*�*Т(WC)*\$А�Т(wWC)R,L\$А�Т(wH)L,R\$*А*�*Т(H)* and *А*�*Т(rWC)*\$А�Т(wrWC)R,L\$А�Т(wrH)L,R\$*А*�*Т(rH)*, occurring through

• A�T(wH)\$А�Т(wrWC), A�T(wWC)\$A�T(wrH), A�T(wWC)\$A�T(wrWC), A�T (wH)\$А�Т(wrH) conformational transitions (Gibbs free energies of activation

T = 298.15 K), which define the conformational interconversions: A�T(WC)\$

3.20, 3.70, 12.04 and 10.69 kcal�mol�<sup>1</sup> in the continuum with <sup>ε</sup> = 1 at

A�T(rWC) / A�T(rH) and A�T(H)\$A�T(rH) / A�T(rWC) [53].

and *А*�*Т(wrН)* (**Figure 1**). This opens up new perspectives for the

• А�Т(wWC)\$А�Т(wH) and А�Т(wrWC)\$А�Т(wrH), which define the

rH) reactions of tautomerization [49];

rWC), A�T(wH)\$A�T\*

with structure of the analogical base pairs in the Nucleic Acid Database.

and shifting of the bases relatively each other [47];

tautomerization *via* the sequential proton transfer [48];

• А�Т(WC) / А�Т(rWC)\$А\*�Т(rwWC) / А\*�Т(wWC), А�Т(H) /

#### **Figure 1.**

*Unusual AT base pairs formed through the newly discovered conformationally-tautomeric transformations at the MP2/6–311++G(2df,pd)//B3LYP/6–311++G(d,p) level of QM theory. Graphs of the AT base pairs are presented for the data in the continuum with ε = 4. Definitions: ΔG relative Gibbs free and ΔE electronic energies (in kcalmol<sup>1</sup> ) in vacuum, ε = 1 (upper row) and also in the continuum with ε = 4 (lower row); ΔEint electronic and ΔGint Gibbs free energies of the interaction in free state (MP2/6–311++G(2df,pd)//B3LYP/6– 311++G(d,p) level of QM theory, in kcalmol<sup>1</sup> ). Intermolecular AH … B H-bonds are designated by dotted lines, their lengths H … B are presented in angstroms. Number of the unusual AT base pairs, which have been identified in the Nucleic Acid Database [62, 63] by structural bioinformatics, is presented in brackets in bold.*

• *Non-planar structures (C1 point symmetry):* WC & rWC – 10.AT(wWC), 11.AT (wrWC), 12.AT\*(w<sup>⊥</sup> WC), 13.AT\*O2(w<sup>⊥</sup> rWC); and H & rH – 25.AT(wH), 26.AT (wrH), 27.AT\*(w<sup>⊥</sup> H), 28.AT\*O2(w<sup>⊥</sup> rH).

Notably, that Gibbs free and electronic energies of the AT/AU base pairs are in the wide range of values, which insignificantly decrease at the transition from the continuum with ε = 1 to the continuum with ε = 4, while dipole moment increases at this (**Table 1**).

We have carefully scanned all 28 unusual conformationally-tautomeric states of the АТ DNA base pairs in the Nucleic Acid Database by Rutgers University using original author's methodology for structural bioinformatics analysis. It was identified most part of the theoretically investigated by us excited conformationallytautomeric states of the classical АТ DNA base pair (**Figure 1**, **Table 1**).

#### **4. Discussion of the obtained results**

Let us start the discussion and more detailed analysis of the obtained results from the consideration of the traditional area of the biological applications of the prototropic tautomerism of the DNA bases [54], as well as their role in the origin of the spontaneous point mutations – transitions and transversions at the DNA biosynthesis – so-called replication errors [58–63]. This physico-chemical model should satisfy strict conditions. Saying shortly, in order to point on the most important things, from one side – barriers of the mutagenic tautomerization of the base pairs should not be quite high in view of the quite rigid kinetic requirements for the incorporation into the double strand of DNA by the DNA-polymerase during the one act of replication (<sup>10</sup><sup>4</sup> s) [54]. At this, the lifetime of the tautomerized states of the pairs should exceed characteristic time of the inertial DNA-polymerase machinery (<sup>10</sup><sup>9</sup> s). Only at this condition the inertial replicational DNApolymerase machinery would successfully dissociate tautomerized base pairs into the monomers, in particular into the rare tautomeric forms.

From the other side, these barriers should be quite high in order to overcome resistance of the stacking interactions and sugar-phosphate backbone of DNA on the way of the incorporation of the tautomerizing base pair into the double structure of DNA [54].

**AT pair**

**9**

**1. AT(WC) [47]**

**2. A\*T(wWC)**

**3.** 

**4. AT\*(wWC)**

**5. AT(rWC)**

**6.**  **7.**  **8.**  **9.** 

**10. AT(wWC)** **11. AT(wrWC)**

**12.**  **13.** 

**14. A\*T\*(WC)**

**15. AT(H) [48]** **16. AT\*(wH) [48]**

**17. A\*C8T(wH)**

**18.** 

**19. A\*N7T(wH)**

**20. AT(rH) [48]**

**21.**  **22.** 

**A\*C8T(rwH)**

 **[48]**

30.77

 31.21

 6.47

 29.87

 30.07

 7.89

**22.** 

**A\*C8U(rwH)**

31.18

 31.49

 6.68

 30.62

 30.66

 8.88

**AT\*O2(rwH)**

 **[48]**

14.13

 15.55

 5.10

 12.84

 14.17

 6.76

**21.** 

**AU\*O2(rwH)**

14.82

 16.10

 5.40

 13.25

 14.52

 7.11

 **[48]**

24.82

0.69

0.87

 5.67

0.21

0.44

 7.14

**20. AU(rH)**

0.40

0.74

 5.38

0.19

0.38

 6.79

 24.97

 10.35

 21.53

 20.99

 13.93

**19.** 

**A\*N7U(wH)**

25.32

 25.39

 10.79

 21.66

 21.25

 14.40

**AT\*O2(wH)**

 **[48]**

11.20

 11.26

 8.23

 10.05

 10.15

 11.00

**18.** 

**AU\*O2(wH)**

11.91

 11.91

 8.65

 10.23

 10.62

 11.46

 **[48]**

30.25

 30.60

 6.08

 29.87

 30.07

 7.89

**17.** 

**A\*C8U(wH)**

30.17

 30.50

 5.80

 29.91

 30.06

 7.52

 **[50]**

12.10

0.95

10.20

 11.52

 4.74

 9.24

 10.72

 6.04

**16. AU\*(wH)**

1.08

 6.16

0.48

0.66

 7.91

**15. AU(H)**

0.59

9.32

 10.97

 4.45

 9.19

 10.34

 5.67

0.96

 6.34

0.18

0.57

 8.12

 12.31

 0.78

 12.63

 12.67

 0.93

**14. A\*U\*(WC)**

**AT\*O2(w**⊥**rWC)**

 **[49]**

20.67

 21.68

 5.56

 17.93

 18.92

 8.04

**13.** 

**AU\*O2(w**⊥**rWC)**

21.38

11.96

 12.04

 0.73

 12.42

 12.45

 0.83

 22.32

 6.21

 18.58

 19.40

 8.85

**AT\*(w**⊥**WC)**

 **[49]**

16.52

 17.40

 4.16

 14.64

 15.19

 5.71

**12.** 

**AU\*(w**⊥**WC)**

16.02

 16.86

 3.67

 14.24

 14.87

 5.20

 **[49]**

6.02

 8.07

 2.68

 4.92

 6.54

 3.71

**11. AU(wrWC)**

 **[49]**

6.16

 7.84

 2.57

 4.45

 6.41

 3.97

**10. AU(wWC)**

**A\*T(rwWC)**

 **[48]**

9.55

 9.12

 3.23

 9.17

 8.49

 4.25

**9.** 

**A\*U(rwWC)**

9.55

6.12

6.25

 8.18

 2.63

 5.31

 6.52

 3.50

 8.15

 2.50

 5.06

 6.39

 4.10

*Where Quantum Biochemistry Meets Structural Bioinformatics: Excited Conformationally…*

 9.05

 2.69

 20.29

 19.36

 2.69

**AT\*(rwWC)**

 **[48]**

7.44

 7.38

 2.52

 7.03

 7.01

 3.43

**8.** 

**AU\*(rwWC)**

6.99

 6.94

 1.97

 17.73

 17.25

 1.97

**A\*C2T(rwWC)**

 **[48]**

46.79

 49.27

 5.20

 16.30

 17.88

 12.49

**7.** 

**A\*C2U(rwWC)**

46.71

 49.42

 5.85

 16.66

 17.76

 13.23

**AT\*O2(rwWC)**

 **[48]**

16.27

 18.49

 6.38

 13.44

 15.28

 8.64

**6.** 

**AU\*O2(rwWC)**

16.95

 19.02

 6.98

 10.15

 10.41

 6.32

 **[48]**

0.14

 0.24

 2.40

0.14

 0.20

 3.34

**5. AU(rWC)**

 **[47]**

12.46

 14.23

 4.57

 10.01

 11.80

 6.05

**4. AU\*(wWC)**

**AT\*O2(wWC)**

 **[47]**

10.40

 10.75

 3.96

 9.69

 9.99

 5.60

**3.** 

**AU\*O2(wWC)**

10.96

11.82

0.34

 0.42

 2.78

 0.26

 0.28

 3.77

*DOI: http://dx.doi.org/10.5772/intechopen.94565*

 13.53

 4.09

 9.57

 11.38

 5.42

 11.33

 4.59

 10.15

 10.41

 6.32

 **[47]**

9.97

 9.66

 4.29

 9.43

 8.89

 5.93

**2. A\*U(wWC)**

**Δ**

**Gε=1a**

0.00

 0.00

 1.87

 0.00

 0.00

 2.48

**1. AU(WC)**

**ΔEε=1b**

**με=1c**

**Δ**

**Gε=4a**

**ΔEε=4b**

**με=4c**

**AU pair**

**Δ**

**Gε=1a**

0.00

10.35

 9.92

 4.83

 9.67

 9.04

 6.52

 0.00

 1.69

 0.00

 0.00

 2.25

**ΔEε=1b**

**με=1c**

**Δ**

**Gε=4a**

**ΔEε=4b**

**με=4c**


*Where Quantum Biochemistry Meets Structural Bioinformatics: Excited Conformationally… DOI: http://dx.doi.org/10.5772/intechopen.94565*

• *Non-planar structures (C1 point symmetry):* WC & rWC – 10.AT(wWC), 11.AT

*Unusual AT base pairs formed through the newly discovered conformationally-tautomeric transformations at the MP2/6–311++G(2df,pd)//B3LYP/6–311++G(d,p) level of QM theory. Graphs of the AT base pairs are presented for the data in the continuum with ε = 4. Definitions: ΔG relative Gibbs free and ΔE electronic*

*electronic and ΔGint Gibbs free energies of the interaction in free state (MP2/6–311++G(2df,pd)//B3LYP/6–*

*lines, their lengths H … B are presented in angstroms. Number of the unusual AT base pairs, which have been identified in the Nucleic Acid Database [62, 63] by structural bioinformatics, is presented in brackets in bold.*

*) in vacuum, ε = 1 (upper row) and also in the continuum with ε = 4 (lower row); ΔEint*

rH).

Notably, that Gibbs free and electronic energies of the AT/AU base pairs are in the wide range of values, which insignificantly decrease at the transition from the continuum with ε = 1 to the continuum with ε = 4, while dipole moment increases at

We have carefully scanned all 28 unusual conformationally-tautomeric states of the АТ DNA base pairs in the Nucleic Acid Database by Rutgers University using original author's methodology for structural bioinformatics analysis. It was identified most part of the theoretically investigated by us excited conformationallytautomeric states of the classical АТ DNA base pair (**Figure 1**, **Table 1**).

Let us start the discussion and more detailed analysis of the obtained results from the consideration of the traditional area of the biological applications of the prototropic tautomerism of the DNA bases [54], as well as their role in the origin of the spontaneous point mutations – transitions and transversions at the DNA biosynthesis – so-called replication errors [58–63]. This physico-chemical model should satisfy strict conditions. Saying shortly, in order to point on the most important things, from one side – barriers of the mutagenic tautomerization of the base pairs should not be quite high in view of the quite rigid kinetic requirements for the incorporation into the double strand of DNA by the DNA-polymerase during the one act of replication (<sup>10</sup><sup>4</sup> s) [54]. At this, the lifetime of the tautomerized states of the pairs should exceed characteristic time of the inertial DNA-polymerase machinery (<sup>10</sup><sup>9</sup> s). Only at this condition the inertial replicational DNApolymerase machinery would successfully dissociate tautomerized base pairs into

From the other side, these barriers should be quite high in order to overcome resistance of the stacking interactions and sugar-phosphate backbone of DNA on the way of the incorporation of the tautomerizing base pair into the double struc-

rWC); and H & rH – 25.AT(wH), 26.AT

*). Intermolecular AH … B H-bonds are designated by dotted*

WC), 13.AT\*O2(w<sup>⊥</sup>

H), 28.AT\*O2(w<sup>⊥</sup>

(wrWC), 12.AT\*(w<sup>⊥</sup>

*311++G(d,p) level of QM theory, in kcalmol<sup>1</sup>*

*DNA - Damages and Repair Mechanisms*

**4. Discussion of the obtained results**

the monomers, in particular into the rare tautomeric forms.

(wrH), 27.AT\*(w<sup>⊥</sup>

this (**Table 1**).

**Figure 1.**

*energies (in kcalmol<sup>1</sup>*

ture of DNA [54].

**8**


**Table 1.** *Energetic and polar characteristics of the conformers and tautomers of the AT/AU nucleobase pairs obtained at the MP2/6–311++G(2df,pd) // B3LYP/6–311++G(d,p) level of QM/PCMtheory in the isolated state (<sup>ε</sup> = 1) and in the continuum with ε = 4 under normal conditions (see Figure 1).*

Nowadays, just one single model satisfies these strict conditions [47]. According to this model (**Figure 1**), mutagenic tautomerization of the bases in the A�T(WC) base pair is controlled by the transition states, which represent itself tight ion pairs

In this regard, it arises quite logical question – "Whether *Nature* uses prototropic

Biological role of the prototropic tautomerism of the DNA bases is not limited by

In the work [61] at the example of the hypoxanthine dimer it was revealed novel way of the conformationally-tautomeric transformations of the structures, which are joined by the neighboring antiparallel H-bonds, through the quasi-orthogonal transition state with the changing of the mutual orientation of the dimmers on 180 degree. Conformationally-tautomeric transitions of such a nature have been fixed in all without exception four configurations of the classical A�T DNA base pair [53].

the presented here examples. It is quite more complex and wider. Let us attract readers' attention to the one more so-called unusual role of the tautomericconformational transformations in the DNA structural transitions. However, their

tautomerization of the DNA bases beyond the borders of classical tautomeric hypothesis?" Let us say – for the supporting of the unusual DNA structures. Principle of economy of thinking (*Entia non sunt multiplicanda praeter necessitate*), which is quite often applied by the living nature, enables in principle, affirmatively answer on the quite interesting question. Below we would provide number of examples of the application in the structural biology of all without exception wobble configura-

tions of the A�T pair by the participation of the mutagenic tautomers.

mechanism of action could be explained only at the macroscopical level.

Combining these data with previous, concerning the WC/H\$wWC/wH

• A�T(WC)\$A�T\*(rwWC)\$A�T(rWC)\$A�T\*O2(wWC)\$A�T(WC);

• A�T(H)\$A�T\*(rwH)\$A�T(rH)\$A�T\*O2(wH)\$A�T(H),

the WC/H\$rWC/rH at the quantum level:

structures in real macromolecular biosystems.

**11**

conformationally-tautomeric transitions [50], we have obtained joined picture of

as well as experimental confirmation (see below) of the existence of these

*Bioinformatical analysis.* This data convincingly evidence on the real occurrence of these base pairs in the real biological systems [93, 94] and thus – on their biological importance. This situation remains for a long time the hidden side of the classical А�Т DNA base pair. However, it became successfully resolved in the current work.

�T�, and is realized through the step-by-step proton transfer along the intermolecular H-bonds and is assisted by the lateral changing of the configuration of the pair – its transition from the Watson-Crick configuration to the wobble or shifted [47]. In fact, complementary A base plays a role of catalysator of the intramolecular mutagenic tautomerization of the T base within the A�T(WC) base pair. Below it would be outlined experimental confirmations that wobble structures of the A�T base pair, containing mutagenic tautomeric forms of the T base, are real objects of the structural biology. This fact, in our opinion, experimentally confirms reality of the tautomeric mechanisms of the origin of the replication errors [47]. We have demonstrated for the first time, that others three biologically important configurations of the A�T base pair – A�T(rWC), A�T(H) and A�T(rH) [47] – tautomerises by the abovementioned and described mechanism of the tautomerization, forming wobble pairs by the participation of the mutagenic tautomers (**Figure 1**). Moreover, we have arrived to the conclusion by the comparison of their energetical characteristics, that *Nature* quite consciously choose evolutionary the most remote A�T(WC) base pair for the building of the carrier of the genetic

*Where Quantum Biochemistry Meets Structural Bioinformatics: Excited Conformationally…*

information in the form of the right-handed DNA [47].

*DOI: http://dx.doi.org/10.5772/intechopen.94565*

A+

#### *Where Quantum Biochemistry Meets Structural Bioinformatics: Excited Conformationally… DOI: http://dx.doi.org/10.5772/intechopen.94565*

Nowadays, just one single model satisfies these strict conditions [47]. According to this model (**Figure 1**), mutagenic tautomerization of the bases in the A�T(WC) base pair is controlled by the transition states, which represent itself tight ion pairs A+ �T�, and is realized through the step-by-step proton transfer along the intermolecular H-bonds and is assisted by the lateral changing of the configuration of the pair – its transition from the Watson-Crick configuration to the wobble or shifted [47]. In fact, complementary A base plays a role of catalysator of the intramolecular mutagenic tautomerization of the T base within the A�T(WC) base pair. Below it would be outlined experimental confirmations that wobble structures of the A�T base pair, containing mutagenic tautomeric forms of the T base, are real objects of the structural biology. This fact, in our opinion, experimentally confirms reality of the tautomeric mechanisms of the origin of the replication errors [47].

We have demonstrated for the first time, that others three biologically important configurations of the A�T base pair – A�T(rWC), A�T(H) and A�T(rH) [47] – tautomerises by the abovementioned and described mechanism of the tautomerization, forming wobble pairs by the participation of the mutagenic tautomers (**Figure 1**). Moreover, we have arrived to the conclusion by the comparison of their energetical characteristics, that *Nature* quite consciously choose evolutionary the most remote A�T(WC) base pair for the building of the carrier of the genetic information in the form of the right-handed DNA [47].

In this regard, it arises quite logical question – "Whether *Nature* uses prototropic tautomerization of the DNA bases beyond the borders of classical tautomeric hypothesis?" Let us say – for the supporting of the unusual DNA structures. Principle of economy of thinking (*Entia non sunt multiplicanda praeter necessitate*), which is quite often applied by the living nature, enables in principle, affirmatively answer on the quite interesting question. Below we would provide number of examples of the application in the structural biology of all without exception wobble configurations of the A�T pair by the participation of the mutagenic tautomers.

Biological role of the prototropic tautomerism of the DNA bases is not limited by the presented here examples. It is quite more complex and wider. Let us attract readers' attention to the one more so-called unusual role of the tautomericconformational transformations in the DNA structural transitions. However, their mechanism of action could be explained only at the macroscopical level.

In the work [61] at the example of the hypoxanthine dimer it was revealed novel way of the conformationally-tautomeric transformations of the structures, which are joined by the neighboring antiparallel H-bonds, through the quasi-orthogonal transition state with the changing of the mutual orientation of the dimmers on 180 degree. Conformationally-tautomeric transitions of such a nature have been fixed in all without exception four configurations of the classical A�T DNA base pair [53]. Combining these data with previous, concerning the WC/H\$wWC/wH conformationally-tautomeric transitions [50], we have obtained joined picture of the WC/H\$rWC/rH at the quantum level:

• A�T(WC)\$A�T\*(rwWC)\$A�T(rWC)\$A�T\*O2(wWC)\$A�T(WC);

• A�T(H)\$A�T\*(rwH)\$A�T(rH)\$A�T\*O2(wH)\$A�T(H),

as well as experimental confirmation (see below) of the existence of these structures in real macromolecular biosystems.

*Bioinformatical analysis.* This data convincingly evidence on the real occurrence of these base pairs in the real biological systems [93, 94] and thus – on their biological importance. This situation remains for a long time the hidden side of the classical А�Т DNA base pair. However, it became successfully resolved in the current work.

**AT pair**

**10**

**23. AT\*(rwH)**

**24.**  **25. AT(wH) [49]** **26. AT(wrH) [49]**

**27. AT\*(w**⊥

**28.** 

*aRelative Gibbs free energy of the base pair (T = 298.15 K), kcalmol1*

*bRelative electronic energy of the base pair, kcalmol1*

*cDipole moment of the base pair, Debay.*

**Table 1.**

*Energetic and polar*  *theory in the isolated state (<sup>ε</sup> = 1) and in the continuum*

*characteristics*

 *of the conformers*

 *and tautomers of the AT/AU nucleobase*

 *with ε = 4 under normal conditions (see Figure 1).*

 *pairs obtained at the* 

*MP2/6–311++G(2df,pd)*

 *//* 

*B3LYP/6–311++G(d,p)*

 *level of QM/PCM*

**AT\*O2(w**⊥**rH)**

 **[49]**

20.59

 21.73

 5.50

 17.93

> *.*

> > *.*

 18.78

 6.97

**28.** 

**AU\*O2(w**⊥**rH)**

21.28

 22.36

 5.88

 18.19

 19.25

 7.25

**H) [49]**

16.46

 17.40

 5.23

 14.19

 15.06

 6.33

**27. AU\*(w**⊥

**H)**

16.00

 16.90

 4.83

 14.01

 14.68

 5.97

**A\*N7T(rwH)**

 **[48]**

23.93

7.26

6.88

 8.55

 6.10

 4.84

 6.41

 8.26

**26. AU(wrH)**

 8.87

 5.88

 4.50

 6.28

 8.29

**25. AU(wH)**

7.35

6.88

 8.53

 6.02

 4.84

 6.54

 8.21

*DNA - Damages and Repair Mechanisms*

 8.12

 5.12

 4.75

 6.47

 7.92

 23.99

 9.42

 20.67

 20.32

 12.44

**24.** 

**A\*N7U(rwH)**

23.69

 23.83

 8.91

 20.77

 20.26

 11.75

 **[48]**

7.91

 7.59

 7.36

 7.49

 6.93

 9.52

**23. AU\*(rwH)**

**Δ**

**Gε=1a**

**ΔEε=1b**

**με=1c**

**Δ**

**Gε=4a**

**ΔEε=4b**

**με=4c**

**AU pair**

**Δ**

**Gε=1a**

7.48

 7.11

 6.88

 6.81

 6.62

 8.91

**ΔEε=1b**

**με=1c**

**Δ**

**Gε=4a**

**ΔEε=4b**

**με=4c**
