Observation of Enhanced Dissociative Photochemistry in the Non-Native Nucleobase 2-Thiouracil

Abstract

<jats:p>We present the first study to measure the dissociative photochemistry of 2-thiouracil (2-TU), an important nucleobase analogue with applications in molecular biology and pharmacology. Laser photodissociation spectroscopy is applied to the deprotonated and protonated forms of 2-TU, which are produced in the gas-phase using electrospray ionization mass spectrometry. Our results show that the deprotonated form of 2-thiouracil ([2-TU-H]−) decays predominantly by electron ejection and hence concomitant production of the [2-TU-H]· free-radical species, following photoexcitation across the UVA-UVC region. Thiocyanate (SCN−) and a m/z 93 fragment ion are also observed as photodecay products of [2-TU-H]− but at very low intensities. Photoexcitation of protonated 2-thiouracil ([2-TU·H]+) across the same UVA-UVC spectral region produces the m/z 96 cationic fragment as the major photofragment. This ion corresponds to ejection of an HS· radical from the precursor ion and is determined to be a product of direct excited state decay. Fragment ions associated with decay of the hot ground state (i.e., the ions we would expect to observe if 2-thiouracil was behaving like UV-dissipating uracil) are observed as much more minor products. This behaviour is consistent with enhanced intersystem crossing to triplet excited states compared to internal conversion back to the ground state. These are the first experiments to probe the effect of protonation/deprotonation on thionucleobase photochemistry, and hence explore the effect of pH at a molecular level on their photophysical properties.</jats:p>

Linking Electronic Relaxation Dynamics and Ionic Photofragmentation Patterns for the Deprotonated UV Filter Benzophenone-4

“…This is clear evidence of statistical decay, driven by fragmentation on a hot ground state surface, which in turn demonstrates that deprotonated BP4 is behaving like an efficient UV filter. However, the results presented here are of broader importance, as they provide a theoretical basis to support the widely adopted argument linking ionic photofragmentation patterns and decay dynamics that has been used for interpreting the behavior of key gaseous ionic systems including nucleobases and nucleotides. ,− ,, …”

“…Very recently, laser-interfaced mass spectrometry (LIMS) has been used to probe the photophysics of several ionic sunscreen systems in detail. − These studies reveal that protonation and deprotonation can dramatically affect the sunscreen’s UV absorption profile. Information on decay dynamics (and hence the intrinsic sunscreen efficiency), however, has only been inferred indirectly in these experiments, through attempting to match the photofragmentation products against the corresponding thermal fragmentation products to elucidate whether excited-state decay is statistical or nonstatistical. , This is a general problem for gaseous studies of ionic systems that extends well beyond the specific field of sunscreens, ,− since there are currently few experiments where direct time-resolved measurement of ionic photofragments is possible. , …”

“…However, the results presented here are of broader importance, as they provide a theoretical basis to support the widely adopted argument linking ionic photofragmentation patterns and decay dynamics that has been used for interpreting the behavior of key gaseous ionic systems including nucleobases and nucleotides. 17,[19][20][21][22][23]35,36 ■ ASSOCIATED CONTENT * sı Supporting Information…”

Illuminating the Effect of the Local Environment on the Performance of Organic Sunscreens: Insights From Laser Spectroscopy of Isolated Molecules and Complexes

“…Laser-interfaced mass spectrometry (LIMS) is an excellent experimental method for exploring the spectroscopy and photochemistry of protonated and deprotonated forms of the same molecular system ( Matthews and Dessent, 2018 ; Matthews et al, 2018 ; Uleanya et al, 2020 ). Since experiments are conducted on isolated, mass-selected ions, the charged system under investigation is unambiguous, and any complications of the bulk environment are removed.…”

Photoproducts of the Photodynamic Therapy Agent Verteporfin Identified via Laser Interfaced Mass Spectrometry

“…Any resulting photoproducts are then directly associated with the photodecay of the isolated molecule and can be identified using mass spectrometry. This general approach to using gas phase measurements to probe the intrinsic photodegradation pathways of photopharmaceutical molecules has been applied previously in our group to better understand the photochemistry of systems including photoCORMs and non-natural nucleobases [ 14 , 15 , 16 , 17 ]. In the current work, we also present preliminary results obtained by photolyzing a MeCN solution of Verteporfin, using mass spectrometric analysis to identify photoproducts.…”