Based on CASPT2 results, the present contribution establishes for the first time that cytosine photodimer formation (C< >C) is mediated along the triplet and singlet manifold by a singlet-triplet crossing, (T1/S0)X, and by a conical intersection, (S1/S0)CI, respectively. The former can be accessed in a barrierless way from a great variety of photochemical avenues and exhibits a covalent single bond between the ethene C6-C6' carbon atoms of each monomer. The efficiency of the stepwise triplet mechanism, however, would be modulated by the effectiveness of the intersystem crossing mechanism. The results provide the grounds for the understanding of the potential photogenotoxicity of endogenous and exogenous compounds via triplet-triplet sensitization, with a lower bound for cytosine oligonucleotides predicted to be 2.70 eV, and give support to the traditional view of the primary role of triplet excited states in the photochemistry of DNA, a well-known source of photoproducts in solution under triplet photosensitization conditions. The function played by singlet excimers (excited dimers) to explain both the red-shifted fluorescence and photoreaction is highlighted. A rationale on the pronounced wavelength dependence of the observed fluorescence is offered. Geometrical arrangements at the time of light irradiation close to, but energetically above, (S1/S0)CI are suggested as reactive orientations that become prone to produce C< >C directly, with no energy barrier. Because of the outstanding intrinsic ability of cytosine to form stable relaxed excimers, the system located near the bound relaxed excimer has to accumulate enough vibrational energy to surmount a small barrier of 0.2 eV to reach (S1/S0)CI, making the overall process to proceed at a slower relative rate as compared to other compounds such as thymine, which is not susceptible of forming so stable excimers.

The higher formation yields measured in the ultrafast photoinduced formation of cyclobutane thymine dimers (T<>T) with respect to those of cytosine (C<>C) are explained, on the basis of ab initio CASPT2 results, by the existence in thymine of more reactive orientations and a less efficient photoreversibility, whereas in cytosine the funnel toward the photolesion becomes competitive with that mediating the internal conversion of the excited-cytosine monomer.

The photoinduced formation of cyclobutane pyrimidine dimers in the triplet excited state of the DNA/RNA pyrimidine nucleobases pairs has been studied at the CASPT2 level of theory. A stepwise mechanism through the triplet state of the homodimer is proposed for the pairs of nucleobases cytosine, thymine, and uracil involving a singlet-triplet crossing intermediary structure of biradical character representing the most favorable triplet state conformation of the nucleobases as found in the DNA environment. The efficiency of the mechanism will be modulated by two factors: the effectiveness of the triplet-triplet energy transfer process from a donor photosensitizer molecule, which relates to the relative position of the intermediate in the three acceptor systems, determined here to be lower in energy in the thymine and uracil dimers than in the cytosine pairs, and that of the intersystem crossing process toward the ground state of the photoproduct. SECTION Dynamics, Clusters, Excited StatesO ne of the most notorious examples of evidence of the photosensitivity of the genetic material to the action of ultraviolet (UV) light is the photoinduced formation of cyclobutane pyrimidine dimers (CBPyr or Pyr<>Pyr, see Figure 1) by pairs of DNA/RNA intrastrand adjacent pyrimidine nucleobases. 1 Those adducts constitute a major source of photoinduced DNA/RNA lesions, leading even to photomutagenesis and photocarcinogenesis, particularly in cellular DNA. 2 The process takes place in biological environments, solvents, and in the solid phase. 1 Femtosecond spectroscopy has proved that thymine (T) dimerization is an ultrafast photoreaction in which cyclobutane thymine dimers (CBT) are fully formed ∼1 ps after UV illumination. 3 Theoretical determinations have confirmed in thymine and cytosine (C) dimers a mechanism for a corresponding ultrafast nonadiabatic photoreaction mediated by the presence of a conical intersection (CI), an energy-degenerate structure between the low-lying singlet excited (S 1 ) and the ground state (S 0 ). 4-7 In those quantum-chemical CASPT2 studies, the [2 þ 2] photocycloaddition reaction leading to the formation of CBT and cyclobutane cytosine (CBC) dimers was characterized in the singlet manifold. 4-7 Barrierless relaxation paths from favorable conformations of the nucleobases were shown to lead from an initially irradiated singlet state to a shearing-type CI structure, in which the nucleobases ethylenic C 5 -C 6 and C 5 0 -C 6 0 bonds laid parallel (parallelogram-type) and elongated, connecting the S 1 and S 0 states and allowing an efficient internal conversion process. Intrastrand nucleobase sequence and relative orientations were also proven to be essential for an efficient photoreaction to take place. This is particularly true for those conformations maximizing the overlap between the π structures of stacked nucleobases, which formed favorable excimer arrangements. 4-7 They were shown to yield the most stable structures leading to the photoreactive arrangements, in agreement with the higher yields ob...

The present study provides new insight into the intrinsic mechanisms for the population of the triplet manifold in DNA nucleobases by determining, at the multiconfigurational CASSCF/CASPT2 level, the singlet-triplet states crossing regions and the main decay paths for their lowest singlet and triplet states after near-UV irradiation. The studied singlet-triplet interacting regions are accessible along the minimum energy path of the initially populated singlet bright (1)ππ* state. In particular, all five natural DNA/RNA nucleobases have, at the end of the main minimum energy path and near a conical intersection of the ground and (1)ππ* states, a low-energy, easily accessible, singlet-triplet crossing region directly connecting the lowest singlet and triplet ππ* excited states. Adenine, thymine, and uracil display additional higher-energy crossing regions related to the presence of low-lying singlet and a triplet nπ* state. These funnels are absent in guanine and cytosine, which have the bright (1)ππ* state lower in energy and less accessible nπ* states. Knowledge of the location and accessibility of these regions, in which the singlet-triplet interaction is related to large spin-orbit coupling elements, may help to understand experimental evidence such as the wavelength dependence measured for the triplet formation quantum yield in nucleobases and the prevalence of adenine and thymine components in the phosphorescence spectra of DNA.

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