Photochemical Reactivity of dTPT3: A Crucial Nucleobase Derivative in the Development of Semisynthetic Organisms

In 2017, the Romesberg group successfully developed the dTPT3·dNaM unnatural base pair to create a semisynthetic organism with enhanced genetic fidelity and the ability to store additional genetic information indefinitely. It is also desirable that the newly developed genetic material remains stable upon exposure to radiation. However, the photochemical properties of dTPT3 are presently unknown. In this contribution, excitation of dTPT3 with near-visible radiation is shown to efficiently populate a reactive triplet state in high yield and on a sub-1 ps time scale; a state that is able to survive for up to a few microseconds in aqueous solution. The triplet state can also generate singlet oxygen in ca. 30% yield, suggesting that dTPT3 can act as a pervasive photosensitizer to accelerate oxidatively generated damage within DNA and to other biological molecules within cells.