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

Ye-Guang Fang,Antonio Carlos Borin,Leticia González,Sylvio Canuto,Sebastian Mai,Danillo Valverde,Ganglong Cui

doi:10.1021/acs.jpcb.0c10855

Abstract

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.

Highlights

In the prebiotic age, the protection of the ozone layer was not efficient and the flux of UV radiation on Earth was much higher than it is nowadays, resulting in an hostile atmosphere capable of causing severe damage to DNA.[1]
Photostability originates from an efficient excited-state decay that releases the excess of energy via ultrafast and efficient radiationless deactivation processes.[2−5] Today, it is well established that low-energy conical intersections that allow the system to return to the electronic ground state in a short time scale are responsible for the excited-state decay efficiency.[6−11]
Particular attention has been devoted to thiobases analogues in which oxygen atoms are replaced by sulfur because, unlike their canonical counterparts, intersystem crossing results in high quantum yields of triplet states.[13−20] For instance, 6-thioguanine (6tG) has an intersystem crossing quantum yield of ca. 60%

Summary

INTRODUCTION

The protection of the ozone layer was not efficient and the flux of UV radiation on Earth was much higher than it is nowadays, resulting in an hostile atmosphere capable of causing severe damage to DNA.[1]. Theoretical theory is well suited to unravel the photophysical mechanisms responsible for the efficient electronic population of excited states.[35] all previous studies in sulfur- and selenium-substituted nucleobases[36−43] have systematically excluded the effect of the DNA environment due to the complexity involved, despite it could strongly influence the photophysical properties of its chromophores.[44]. According to previous theoretical studies in gas phase,[47] in 6SeG the S2 1(ππ*) state transfers its population to the S1 1(nπ*) state via a conical intersection, from which the triplet states are formed. Three selenium-substituted uracils (2SeU, 4SeU, and 2,4SeU) have been investigated in gas phase and similar excited-state relaxation pathways to triplet states are reported.[48,49] The primary goal of this contribution is to examine whether the main photophysical events of 6SeG are affected by the presence of water and/or biological media

COMPUTATIONAL DETAILS

RESULTS AND DISCUSSION

CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES