Figure shows the changes in absorption spectra for 5mCyd and Cyd upon low intensity laser irradiation. The absorbance of the solutions was matched at the irradiation wavelength of 267 nm and the experiments were performed under back-to-back conditions in ultrapure water at pH 5.6. At this pH, 5mCyd exists as an equilibrium of the protonated (4.8%) and neutral keto (95.2%) forms, while Cyd exists as an equilibrium of the protonated (3.8%) and neutral keto (96.2%) forms, given the pKa values of 4.3 and 4.2 for 5mCyd and Cyd, respectively. We used ultrapure water at pH 5.6 for these experiments because the separation of the photoproducts using high-performance liquid chromatography (Figure ) shown below required the use of ultrapure water at pH 5.6 as a mobile phase for optimal separation. As reported in Figure in phosphate buffer solutions at pH 7.4, irradiation of both molecules at pH 5.6 results in a decrease in absorbance of the lowest energy band and of 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 233 and 256 nm for 5mCyd and at 234 and 250 nm for Cyd. These changes in the absorption spectra with an increased irradiation time evidence the formation of photoproducts for both 5mCyd and Cyd (as reported in Figure but at pH 7.4). 5mCyd was found to photodegrade with a rate that is three-fold smaller than Cyd in ultrapure water at pH 5.6. The increased photostability of 5mCyd compared to Cyd is consistent within the error to the experimental observations reported in the main text using phosphate buffer at pH 7.4. For Cyd, the increase in absorbance near 240 nm has previously been suggested to be due to the formation of 5,6saturated cytosine monomers, where 6-hydroxy-5,6-dihydrocytosine and 𝛽-D-ribocytidine-2', 3'-cyclic phosphate have been proposed as plausible photoproducts. Figure shows the separation of the photoproducts of 5mCyd and Cyd after 10 minutes of lowintensity laser irradiation at 267 nm in ultrapure water at pH 5.6. The absorption spectra of the primary photoproducts are also shown, while those of other minor photoproducts are not shown. Using ultrapure water at pH 5.6 as the mobile phase, the parent nucleoside elutes at ca. 23 minutes for 5mCyd and at ca. 10 minutes for Cyd, well separated from the primary photoproducts. Note that the elution time of Cyd slightly changes before and after irradiation. We suggest this is due to a small change in the pH of the irradiated solution given that the irradiation experiments were performed in unbuffered, ultrapure water. The longer elution time of Cyd after irradiation (compared to before irradiation) was reproducibly observed in multiple independent irradiation experiments.