The design and study of structurally modified nucleobases have attracted considerable interest due to their potential applications as fluorescent or phosphorescent probes, or as photosensitizers in photodynamic therapy. In this work, we employ high-level XMS-CASPT2 calculations to investigate the excited state relaxation mechanisms of tzSeA, a selenium-substituted isothiazolo-adenosine analogue. Our results show that upon photoexcitation to the lowest bright \({^1}(\pi \pi ^{*})\) state, the system relaxes to a minimum energy region on its potential energy surface, from which fluorescence emission is possible, as the conical intersection with the ground state lies high in energy. Alternatively, population transfer from the \({^1}(\pi \pi ^{*})\) to the dark \({^1}(n\pi ^{*})\) state may occur around the Franck–Condon region, followed by relaxation to the \({^1}(n\pi ^{*})\) min region, where radiative decay can also take place due to the inaccessibility of the conical intersection with the ground state. While intersystem crossing to the triplet manifold is not expected to be efficient, it is worth describing a possible pathway in which the T2 \({^3}(n\pi ^{*})\) min state serves as a doorway, allowing relaxation to the T1 \({^3}(\pi \pi ^{*})\) state through a conical intersection. Once on the T1 \({^3}(\pi \pi ^{*})\) potential energy surface, the excess energy can be released through phosphorescence, as the T1/GS crossing is not energetically accessible. These findings provide mechanistic insights into the photophysical behavior of tzSeA and support its potential mainly as a fluorescent probe.
