Abstract
Elucidating the photophysical mechanisms in sulfur-substituted nucleobases (thiobases) is essential for designing prospective drugs for photo- and chemotherapeutic applications. Although it has long been established that the phototherapeutic activity of thiobases is intimately linked to efficient intersystem crossing into reactive triplet states, the molecular factors underlying this efficiency are poorly understood. Herein we combine femtosecond transient absorption experiments with quantum chemistry and nonadiabatic dynamics simulations to investigate 2-thiocytosine as a necessary step to unravel the electronic and structural elements that lead to ultrafast and near-unity triplet-state population in thiobases in general. We show that different parts of the potential energy surfaces are stabilized to different extents via thionation, quenching the intrinsic photostability of canonical DNA and RNA nucleobases. These findings satisfactorily explain why thiobases exhibit the fastest intersystem crossing lifetimes measured to date among bio-organic molecules and have near-unity triplet yields, whereas the triplet yields of canonical nucleobases are nearly zero.
Highlights
Elucidating the photophysical mechanisms in sulfur-substituted nucleobases is essential for designing prospective drugs for photo- and chemotherapeutic applications
We use 2-thiocytosine (2tC) as a testbed to understand how thionation leads to a strong stabilization of different parts of the excited-state potential energy surfaces (PESs), which favours intersystem crossing (ISC) to the triplet manifold over internal conversion to the electronic ground state
Femtosecond transient absorption spectra were recorded exciting with UV-B (308 nm) and UV-A (321 nm) wavelengths, which correspond to the low-energy tail of the steady-state absorption spectrum
Summary
Elucidating the photophysical mechanisms in sulfur-substituted nucleobases (thiobases) is essential for designing prospective drugs for photo- and chemotherapeutic applications. We show that different parts of the potential energy surfaces are stabilized to different extents via thionation, quenching the intrinsic photostability of canonical DNA and RNA nucleobases These findings satisfactorily explain why thiobases exhibit the fastest intersystem crossing lifetimes measured to date among bio-organic molecules and have near-unity triplet yields, whereas the triplet yields of canonical nucleobases are nearly zero. Is 2tC relevant for many medicinal applications—due to its anti-cancer[33], anti-viral[34], anti-bacterial[35], anti-microbial[36] and cytotoxic activities37—but it is the only pyrimidine thiobase derivative that has not yet been investigated using time-resolved techniques[15] By filling this gap we are able to deliver a comprehensive explanation of the remarkable photophysics of thiobases, providing design criteria for the synthesis of prospective drugs
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