We studied the photoionisation mechanisms of uracil and its 1-, 3- and 5-methylated derivatives. We found that substituting in 3- position in-between carbonyl sites has a significant effect in the photoionisation decay mechanisms.
Much is known in the study of photo-excited processes in DNA/RNA,[1] whereas little is currently understood regarding the effects of ionising radiation to our genetic material. This is a topic I have been working on over the last few years with Mike Bearpark, and where we have so far studied all pyrimidine nucleobases[2,3] as well as non-canonical bases like isocytosine.[4]
In this work we focussed on characterising the changes made to the decay pathways of photoionised and electronic excited uracil derivatives upon chemical substitution, starting with simple methylation.[5] DNA/RNA methylation has an important and pronounced role in epigenetic modifications, the most known case being 5-methyl-cytosine, but more species are believed to feature in sizeable yields in our genetic material and their study is therefore timely.
We find methylation in any position other than 3' (i.e. in either 1', or 5') does not significantly change things: photoelectron signals are slightly blue-shifted compared to uracil, the conical intersections mediating decay display the same topography, and the potential energy barrier mediating decay to the cation ground state is very slightly (almost negligibly) increased.
3'-methylation, on the other hand, shows very close electronic excited state cations and an overall cation manifold much more compact in energy: this produces significant changes in the expected photoelectron spectrum compared with uracil, and also closes in the energetic gap between states leading to the appearance of an effective 3-state conical intersection (see scheme above). This 3-state intersection is similar to the one previously suggested by Matsika in uracil.[6] The potential energy barrier mediating decay to the cation ground state vanishes for this system, which suggests it might be the fastest decaying uracil species we have studied to date, even thought dynamics studies are underway to validate this point. We expect 3-methyl-uracil to have both a step-wise (like uracil and the other derivatives) as well as a concerted (through the 3-state intersection) competitive decay channels.
We find the treatment of electron correlation is very important for describing correctly the photophysics of 3-methyl-uracil: the 3-state intersection is only present when including dynamic electron correlation in the model, and the inclusion of this correlation also changes the resulting optimised geometry and the topography of the conical intersection mediating decay to the ground state.
This work continues our exploration of DNA's potential photostability beyond UV radiation.[4] This study has been recently featured in the selected 2022 HOT article section in Phys. Chem. Chem. Phys. and is available free of charge until the end of February 2023!
References
[1] S. Boldissar and M. S. de Vries, "How nature covers its bases", Phys. Chem. Chem. Phys. 2018, 20, 9701-9716.
[2] J. Segarra-Martí, T. Tran and M. J. Bearpark, "Ultrafast and radiationless electronic excited state decay of uracil and thymine cations: computing the effects of dynamic electron correlation", Phys. Chem. Chem. Phys. 2019, 21, 14322-14330.
[3] J. Segarra-Martí, T. Tran and M. J. Bearpark, "Computing the ultrafast and radiationless electronic excited state decay of cytosine and 5-methyl-cytosine cations: uncovering the role of dynamic electron correlation", ChemPhotoChem 2019, 3, 856-865. [4] J. Segarra-Martí and M. J. Bearpark,"Modelling photoionisation in isocytosine: potential formation of longer-lived excited state cations in its keto form", ChemPhysChem 2021, 22, 2172-2181. Also highlighted in a previous post here.
[5] J. Segarra-Martí, T. Tran and M. J. Bearpark, "3-methylation alters excited state decay in photoionised uracil", Phys. Chem. Chem. Phys. 2022, 24, 27038-27046.
[6] S. Matsika, "Two- and three-state conical intersections in the uracil cation", Chem. Phys. 2008, 349, 356-362.