Excited-State Properties and Relaxation Pathways of Selenium-Substituted Guanine Nucleobase in Aqueous Solution and DNA Duplex

The excited-state properties and relaxation mechanisms after light irradiation of 6-selenoguanine (6SeG) in water and in DNA have been investigated using a quantum mechanics/molecular mechanics (QM/MM) approach with the multistate complete active space second-order perturbation theory (MS-CASPT2) method. In both environments, the S11(nSeπ5*) and S21(πSeπ5*) states are predicted to be the spectroscopically dark and bright states, respectively. Two triplet states, T13(πSeπ5*) and T23(nSeπ5*), are found energetically below the S2 state. Extending the QM region to include the 6SeG-Cyt base pair slightly stabilizes the S2 state and destabilizes the S1, due to hydrogen-bonding interactions, but it does not affect the order of the states. The optimized minima, conical intersections, and singlet–triplet crossings are very similar in water and in DNA, so that the same general mechanism is found. Additionally, for each excited state geometry optimization in DNA, three kind of structures (“up”, “down”, and “central”) are optimized which differ from each other by the orientation of the C=Se group with respect to the surrounding guanine and thymine nucleobases. After irradiation to the S2 state, 6SeG evolves to the S2 minimum, near to a S2/S1 conical intersection that allows for internal conversion to the S1 state. Linear interpolation in internal coordinates indicate that the “central” orientation is less favorable since extra energy is needed to surmount the high barrier in order to reach the S2/S1 conical intersection. From the S1 state, 6SeG can further decay to the T13(πSeπ5*) state via intersystem crossing, where it will be trapped due to the existence of a sizable energy barrier between the T1 minimum and the T1/S0 crossing point. Although this general S2 → T1 mechanism takes place in both media, the presence of DNA induces a steeper S2 potential energy surface, that it is expected to accelerate the S2 → S1 internal conversion.


Table of Contents
I. Active Spaces Figure S1. Orbitals included in the active space of 6SeG used in the QM1/MM calculations in the DNA environment. Orbitals in the red frame are excluded in the geometry optimizations. Note that these two orbitals do not correspond to the  and * orbitals located on the C-Se bond (as in Fig. 2 of the main text) but to  orbitals, which were more favourable for the optimization in DNA. Figure S2. Orbitals included in the active space of the 6SeG-C base pair used for the QM2/MM calculations in the DNA environment. Orbitals in the red frame are excluded in the geometry optimizations.

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II. Superposition of the selected snapshots in water Figure S3. Superposition of the ten selected snapshot in water considering the closest solvent molecules in three viewing angle.

III. Electronic Absorption Spectrum of 6SeG in Water
The electronic absorption spectrum of 6SeG in water solution is based on an ensemble of 500 snapshots taken from a previous classical molecular dynamics simulation, where a Gaussian function (FWHM=0.3 eV) centered on the calculated vertical excitation is superposed, see Figure S3. The spectrum exhibits two well-defined absorption bands with maxima at 3.25 eV (381 nm) and 5.58 eV (222 nm), respectively, in good agreement with the experiment S4 (357 and 209 nm, respectively). Although the predicted intensity of the bands is at variance with experiment, since the simulated first absorption band is more intense than that reported experimentally, the experimental spectrum is fairly reproduced by our simulations.
Regarding the individual contributions of the electronic states to the absorption spectrum: the first absorption band is best represented by the adiabatic S2 state, while the adiabatic S3 state appears with a broad contribution in the range of 250-400 nm.
Therefore, we conclude that the S3 is responsible for the shoulder around 300 nm.
IV. Excited State Minima of 6SeG and 6SeG-C in DNA Figure S5. QM(CASSCF)/MM optimized excited-state structures of 6SeG in DNA of "D type", i.e. with the selenium atom in a down position compared to the molecular plane (see also Figure S8). Figure S6. QM(CASSCF)/MM optimized excited-state structures of 6SeG in DNA of "C type", i.e. with the selenium atom lying in the molecular plane, (see also Figure S8).    , from the ground-state optimized geometry, computed at QM(CASSCF(12,9))/MM level. Each point generated was followed by a vertical excitation energy calculation at the QM(MS-CASPT2(14,12))/level of theory.

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VIII. Tables   Table S1. QM(MS-CASPT2//CASSCF)/MM calculated vertical excitation energies (in eV) of 6SeG in water to the two lowest singlet excited states. Ten snapshots that are randomly sampled from the 1 ns MD simulation are chosen as the starting QM/MM calculations. The calculated root mean square deviations (RMSD) are also given.