Department of Chemistry, Case Western Reserve University, 44106, Cleveland, Ohio, United States.
Chemistry. 2022 Jan 27;28(6):e202103667. doi: 10.1002/chem.202103667. Epub 2021 Dec 21.
N -Methylation of pseudouridine (m ψ) 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 m ψ. In this study, the photochemistry of m ψ 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 m ψ exhibits a 12-fold longer ππ* 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 m ψ is 6.7-fold more photostable than Urd following irradiation at 267 nm.
N-甲基化假尿嘧啶（mψ）取代了几种治疗药物中的尿嘧啶（Urd），包括 Moderna 和 BioNTech-Pfizer 的 COVID-19 疫苗。然而，重要的是，目前尚不清楚电磁辐射的照射是否会影响 mψ 的化学完整性和固有稳定性。在这项研究中，通过使用 267nm 的光辐照、稳态光谱和量子化学计算，比较了 mψ 和尿嘧啶的光化学性质。此外，还收集了飞秒瞬态吸收测量结果，以描绘两种核苷在生理相关条件下的电子弛豫机制。结果表明，mψ 的ππ*衰减寿命比尿嘧啶长 12 倍，荧光产率高 5 倍。然而，实验结果还表明，在两种分子中，大部分激发态种群都以超快时间尺度回到基态，并且在 267nm 辐照后，mψ 的光稳定性比 Urd 高 6.7 倍。
