Search for: All records

Abstract The (6–4) photolesion is a key photodamage that occurs when two adjacent pyrimidine bases in a DNA strand bond together. To better understand how the absorption of UVB and UVA radiation by the 2‐pyrimidinone moiety in a (6–4) lesion can damage DNA, it is important to study the electronic deactivation mechanism of its 2‐pyrimidinone chromophore. This study employs theoretical (MS‐CASPT2/cc‐pVDZ level) and experimental (steady state and femtosecond broadband spectroscopic) methods to elucidate the photochemical relaxation mechanisms of 2‐(1H)‐pyrimidinone and 1‐methyl‐2‐(1H)‐pyrimidinone in aqueous solution (pH 7.4). In short, excitation at 320 nm leads to the population of the S₁¹(ππ*) state with excess vibrational energy, which relaxes to the S₁¹(ππ*) minimum in one picosecond or less. A trifurcation event in the S₁¹(ππ*) minimum ensued, leading to radiative and nonradiative decay of the population to the ground state or the population of the long‐lived and reactive T₁³(ππ*) state in hundreds of picoseconds. Collectively, the theoretical and experimental results support the idea that in DNA and RNA, the T₁³(ππ*) state of the 2‐pyrimidinone moiety in the (6–4) lesion can further participate in photosensitized chemical reactions increasing DNA and RNA damage. 

Abstract N₁‐Methylation of pseudouridine (m¹ψ) replaces uridine (Urd) in several therapeutics, including the Moderna and BioNTech‐Pfizer COVID‐19 vaccines. Importantly, however, it is currently unknown if exposure to electromagnetic radiation can affect the chemical integrity and intrinsic stability of m¹ψ. In this study, the photochemistry of m¹ψ is compared to that of uridine by using photoirradiation at 267 nm, steady‐state spectroscopy, and quantum‐chemical calculations. Furthermore, femtosecond transient absorption measurements are collected to delineate the electronic relaxation mechanisms for both nucleosides under physiologically relevant conditions. It is shown that m¹ψ exhibits a 12‐fold longer¹ππ* decay lifetime than uridine and a 5‐fold higher fluorescence yield. Notably, however, the experimental results also demonstrate that most of the excited state population in both molecules decays back to the ground state in an ultrafast time scale and that m¹ψ is 6.7‐fold more photostable than Urd following irradiation at 267 nm.