reported in this Letter, and by Ma et al., are consistent with those reported by Wang et al. To investigate the photoreactivity of 5mCyd relative to Cyd, low intensity laser irradiation experiments were performed back-to-back exciting at 267 nm with a matched absorbance at the excitation wavelength (Figure ), as has been reported recently for N1-methylpseudouridine and uridine. Irradiation of both molecules results in a decrease in absorbance at the lowest energy band and at the higher energy absorption band near 200 nm. A simultaneous increase in absorbance and red shift is observed for the absorption band originally at 239 and 232 nm for 5mCyd and Cyd, respectively. In addition, isosbestic points are observed at 228 and 252 nm for Cyd. These changes in the absorption spectra with an increased irradiation time evidence the formation of photoproducts for both 5mCyd and Cyd. We note that similar absorption trends were detected by Todd et al. and Burr et al. for Cyd. Importantly, however, we demonstrate that 5mCyd photodegrades with a rate that is three-fold smaller than Cyd under identical experimental conditions at pH of 7.4. The increased photostability of 5mCyd compared to Cyd is also consistent with the population of an excited state in Cyd that is six-fold longer-lived than the longest excited state in 5mCyd (Figure and Table ). Before closing, we present high-performance liquid chromatography (HPLC) and computational results, and photodegradation experiments in acetonitrile, in the SI to partially characterize the primary photoproducts formed in both 5mCyd and Cyd under the experimental conditions used in this work (see Figures S8 to ). We remark that the complete characterization and identification of the Cyd photoproducts have proven challenging because of the formation of photohydrates is reversible and the possibility of deamination at the C4 position. The report of a longer-lived n* state in this Letter, and in previous works, which is not detected in 5mCyd (Figure ), lend important support to the idea that a 1 n* excited state of Cyd participates in the formation of one or more of these photoproducts. This seems to be particularly the case for the 6hydroxycytidine photohydrate (see Figure and discussion in the SI).