The nucleobases in DNA and RNA are generally present in the keto-form, and not in the enol-form. As an interesting historical note, James Watson and Francis Crick did initially believe them to adopt the enol-form, which isn't compatible with the correct model of the DNA they later proposed.

But there are some reports indicating that in certain RNA structures guanosine and uridine form essentially a Watson-Crick basepair where one of the two bases is present in the enol-form, instead of the usual G-U wobble base pair.

Is there anything known on how large the energy difference between the keto- and the enol-form of those bases actually is?

  • $\begingroup$ Do you mean in situ (i.e. in a BP) or on their own? $\endgroup$ – Richard Terrett Apr 27 '12 at 5:41
  • $\begingroup$ Both alternatives would likely answer my question, but I was mainly wondering about the nucleobases on their own. $\endgroup$ – Mad Scientist Apr 27 '12 at 5:45

I am not an expert in the field, but a quick literature check turns up a good amount of papers on the topic. In particular, I found this paper [1] which nicely answers the question for guanine:

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So, in the gas phase, the most stable enol tautomer has a 0.9 kcal/mol free energy difference with the most stable keto tautomer. That free energy difference is very exacerbated in aqueous solution, with now a ∆G° = 8.7 kcal/mol. We also notice that the most stable keto tautomer is not the same in the gas phase and in solution, and that both keto and enol have many tautomers close in free energy, showing the limits of the simple keto vs. enol line of thought.

Regarding uracil, the first reference that comes up in a bibliographic search is this paper [2]. I only quote the abstract:

The effects of the solvent on the tautomeric equilibria of cytosine and uracil are studied using Onsager's reaction field model in the framework of density functional theory. […] Our results are in good agreement with available experimental results and confirm that the polarization of the solute by the continuum has important effects on the absolute and relative solvation energies.

  1. pKa Values of Guanine in Water: Density Functional Theory Calculations Combined with Poisson-Boltzmann Continuum-Solvation Model, Y. H. Jang et al., J. Phys. Chem. B 2003, DOI: 10.1021/jp020774x

  2. Solvent effects in density functional calculations of uracil and cytosine tautomerism, L. Paglieri et al, Quantum Chem., 2004, DOI: 10.1002/qua.560560517

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    $\begingroup$ The large difference between gas phase and aqueous solution is very interesting, as the inside of a complex RNA structure is likely closer to the former. $\endgroup$ – Mad Scientist Apr 27 '12 at 20:55
  • $\begingroup$ What I don't understand is why they did not include the tautomer, which is protonated at the external amine group. That should be prone to protonation. $\endgroup$ – Martin - マーチン Aug 21 '17 at 8:55

The data provided by @F'x are very helpful towards answering the question. But the relative stabilization of the bases when hydrogen bonded to each other is germane to the question. Because the role of stacking is still being worked out, I don't think this question has a simple answer.

Since wobble pairs are observed, but I haven't seen them outside a context where conventional base pairs are also present in the same molecule, I'm not even sure their formation is exergonic.


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