# Estimating stability and mean life of anomalous tautomers

A pair of bases in the DNA, say, A-T, have a tautomerized form A*-T* (resulting from switching the sides of both protons along the hydrogen bridges).

I have studied how, by means of DFT computations, one can compute the energy difference between the normal and the anomalous forms. But, another point of interest is the stability of the tautomer.

I have read several times that those anomalous tautomers "decay" to the normal A-T form very quickly (much quicker than the time it lasts a round of DNA replication), which is interesting because it implies that tautomerization is not likely to be a source of spontaneous mutations.

What I would like to learn is how can one compute this expected life-time of the anomalous tautomer

I have an idea (which I don't know if it could be rigth or if maybe is completely worthless), which involves making a Born-Oppenheimer separation for the two protons (''after'' the DFT computation of the electronic ground state) and then study the non-adiabatic transitions between the different vibronic states of the couple of protons. I am happy to provide details, if someone whises so.

But perhaps "my method" is too messy, or naive (or both) and / or there are other standar approaches to compute approximately the expected mean life of anomalous tautomers such as the mentioned A*-T*.

I would be very grateful if someone could apport some insigth and/or references into how are these expected life-times calculated typically in computational chemistry!

• I am by no means an expert, but molecular dynamics simulations are sometimes used to study lifetimes. A lot of force fields exist, both for unreactive and reactive systems. Seeing as how tautomerism involves breaking and reforming of bonds, perhaps the ReaxFF could be fitted, validated, and then used?
– Yoda
May 10 '16 at 22:09
• find TS for tautomerizarion -> compute rate constant using TS theory -> compute half-life for tautomer May 11 '16 at 5:49
• I had not heard of the ReaxFF, thanks for the note. @Jan Jense: could you elaborate further your answer, if you have time to spare?
– user28429
May 11 '16 at 9:55
• Have a look at molecularmodelingbasics.blogspot.dk/2009/08/… May 11 '16 at 10:19
• The protons might tunnel, so kinetics vs. barrier height might have a different relationship. Jan 4 '19 at 22:23