Cytosine, computational studies

Cytosine was the first nucleobase whose radiationless decay was studied with quantum mechanical methods. Nevertheless, its first excited states are not so clearly separated as in uracil and thymine, and this causes complications in the computational studies of the photophysics. So, many computational studies have been reported to elucidate the mechanisms for radiationless decay to the ground state but, not always with the same conclusions. 

Dqbkowska I, Rak J, Gutowski M (2005). DNA strand breaks induced by concerted interaction of H radicals and low-energy electrons A computational study on die nucleotide of cytosine. Eur Phys J D 35 429 135. 

In this section, we present the results of computational studies of the five nucleic acid bases cytosine 13, guanine 14, adenine 15, thymine 16, and uracil 17. The canonical structures, those that are involved in the Watson-Crick base pairing within DNA, are drawn below. Other tautomers for each base can be energetically competitive with the canonical structure, and these other tautomers are invoked in some models of DNA mutations and anomalous DNA structures. The ensuing discussion focuses on the relative energies of the tautomers, in both the gas and solution phases. Structural changes that accompany this phase change are also noted. 

Hunter, K. C. Rutledge, L. R. Wetmore, S. D. The hydrogen bonding properties of cytosine A computational study of cytosine complexed with hydrogen fluoride, water, and ammonia, J. Phys. Ghent A 2005,109, 9554-9562. 

Experimental data on the gas phase stability of monohydrated bases are not available. Nevertheless, the computational study provides the justification for the predicted tendencies. The observed change of the relative stability displays the tendency (for isolated bases) to approach the stability of fully hydrated complexes upon the interaction with water molecules. This conclusion is especially important for the tautomers of guanine and cytosine where the relative stability of the tautomers is completely different in the gas phase compared to the polar medium. So, one can conclude that even the interaction with one water molecule in the case of cytosine and the interaction with two water molecules in the case of guanine is sufficient to reverse the gas-phase relative stability order into the order which corresponds to the stability found in a water solution. 

The confidence in the accuracy of the computational studies allows one to elucidate the role of water molecules in the structure of the DNA. The hydration of the DNA, even by a limited number of water molecules, additionally stabilize the canonic structures both for the isolated bases and for the hydrogen bonded pairs. This means that the hydration is the supplementary source of the stability of the normal structures of the DNA bases. Such effect is especially important for cytosine and guanine which, without the interactions with solvent, exist as the mixture of normal and rare tautomers. 

A comprehensive review of excited-state calculations for the nucleobases is outside of the scope of this chapter. Instead we will focus on cytosine as an example to present some general traits of the potential energy surfaces that determine the excited state behavior of these systems, and also the methodological challenges encountered in their study. While the calculations on the isolated bases allow for an interpretation of the gas phase experiments, we will also show how external effects (water solvent or the DNA environment) can be included in the computations to move towards a more realistic computational description of the experiments in solution and/or DNA oligomers. 

The CASPT2 vertical excitations (see Ref. [29] for details of the computations), displayed in Table 17-1, are approximately 4.5 eV (tt, tt state), 5.3 eV (nN,ir state), and 5.6 eV (nQ, tt state). For comparison, the experimental absorption maximum of the tt, tt state in the gas phase is 4.65 eV, and it is reproduced reasonably well by the calculations. In consequence, the study of the photophysics of gas-phase cytosine centers on the three low-lying states of tt, tt, nN, tt and nQ, tt character. In the past years, we have published several studies on this subject, where the level of theory has been improved gradually, and here we will refer mainly to the results obtained with the highest level of theory [29],... 

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