Tautomers double proton transfer

Although the calculations of the transition energies of different tautomeric forms of molecules have been performed in a few cases, the discussion has been restricted to the difference in electronic absorption band positions and not to the change in relative stabilities of the tautomers caused by electronic excitation. The latter problem, however, has been the subject of a few theoretical considerations for nucleic acid base pairs. Most of these studies were motivated by the need for a potential function for double proton transfer between nucleic acid bases that would allow calculation of proton tunneling probabilities for the Lowdin model of mutagenesis (Lowdin, 1965). 

As any coupling term between the two protons of a dimer is negligible compared to the barrier height, concerted double proton transfer can be ignored. Interconversion between tautomers I and II (see Fig. 9) occurs via III and III corresponding to the transfer of a single proton along coordinates x or x2. 

The double proton-transfer reactions of 7-hydroxyquinoline with water at both gates of cyclodextrins have been studied (98CPL(296)335). It was shown that whereas in neutral water both tautomers coexist (85% of 31a and 15% of 31b Kj — 5.7 +1), addition of /1-cyclodextrin results in their conversion into the encapsulated hydroxy tautomer thus shifting the tautomeric equilibrium entirely to 31a. 

Although there is a very fast (on the NMR time scale) double proton transfer in quinoline 123, the enaminone/enolimine tautomers 123a and 123b are the only ones present in the chloroform solution. Ab initio calculations of the relative stabilities of tautomers using the PCM solvation model produced results contradictory to the experimental data (03CEJ2710). 

Figure 9. The interchange between the two tautomers of BA dimers, labeled L and R, is mediated by a double proton transfer in the hydrogen bonds. At low temperature, translational quantum tunneling dominates the dynamics.

Another aspect of the thio substitution of nucleobases and uracil in particular arises due to a highly probable link between the spontaneous point mutations developing during the RNA replication and likely describing by the Lowdin mechanism of double proton transfer [19] and the occurrence of the rare enol tautomers of uracil viewed as a major factor responsible for the formation of the nucleobase pairing mismatches (see Ref. [20] and references therein). This aspect addresses to the question of how thio substitution alters the order of stability of tautomers (see also Refs. [21, 22]). 

Table 4 presents the proton affinities PA and deprotonation enthalpies DPE of thiouracils calculated at the B3LYP/6-31+G(d,p) computational level. Inspecting this Table, we find that first, the thio substitution of uracil systematically increases its PAs by 3-6 kcal/mol and second, it decreases the DPEs of uracil by 6-13 kcal/mol. As far as the base pair A thioU is considered, it particularly implies a lowering, on the one hand, of the potential well at the Sio atom of thiouracil corresponding to the proton transfer from the N8 atom of adenine to the Sio of thiouracil and, on the other one, a raising of the potential well at the N3 atom of thiouracil involved in the proton transfer from the N3-H bond to the Ni atom of adenine. Therefore, summarizing, the thio substitution of uracil is in a favor to the double proton transfer mechanism of the occurrence of the spontaneous point mutations proposed by Lowdin [19]. Table 4 also includes the PAs of the T2 tautomer of uracil and thiouracils. A comparison with the corresponding PAs of the parental normal nucleobases shows that their tautomerization to the T2 form is accompanied by an increase of the proton affinity by 20-23 kcal/mol. 

The lactim-lactam phototautomerization was studied by means of 2-(6 -hydroxy-2 -pyridyl)benzimidazolium in water [61]. It was found that two pathways exist, namely, a water-assisted proton translocation by probably a double proton transfer, and a two-step process during which the molecule dissodates and forms a zwitteri-onic species which is protonated at the pyridine nitrogen. The disappearance of the lactim tautomer after optical excitation takes less than 1 ns, while the zwitterionic form and the lactam tautomer have an exdted-state Hfetime of a few nanoseconds. Studies on 5-(4-fluorophenyl)-2-hydroxypyridine revealed that, after optical excitation of the lactim form, a tautomeric equiHbrium is established by proton transfer processes, again on a subnanosecond timescale [62]. 

On the other hand, with the intermolecular hydrogen bonding formed by self-dimerization in the concentrated solutions, a double proton transfer is known to take place converting dimer D to tautomer T, as shown in Scheme 2 this is confirmed by observing the cryogenic effects (10 to 293 K) on the steady-state and time-resolved fluorescence spectroscopic techniques. ... 

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