Photochemistry of 5‐Fluorouracil Dideoxyribonucleoside Monophosphate

Abstract

5-Fluorouracil is an artificial nucleobase analog of thymine and uracil, with a substituent in the 5-position that has a mass similar to the methyl group in thymine, but very different electronic, steric and vibrational coupling properties. UVC irradiation of 5-fluorouracil dideoxyribonucleoside monophosphate (dXpdX) is examined here with mass spectrometry and UV-Vis absorption spectroscopy and is compared to the UV photochemistry of other pyrimidine dideoxyribonucleoside monophosphates. The results show that the photochemical products and kinetics of dXpdX are similar to those of uracil dideoxyribonucleoside monophosphate and similar to those of the isolated 5-fluorouracil nucleobase. The photochemistry of dXpdX is compared to the photochemistry of thymine and uracil dideoxyribonucleoside monophosphates.

Photoaddition of 5-Bromouracil to Uracil in Oligonucleotides Leading to 5,5′-Bipyrimidine-Type Adducts: Mechanism of the Photoreaction

“…The latter undergoes further thermal dehydration to form a thermally stable 5,5′-diuridynyl adduct. Furthermore, on the basis of the above observations and previous reports, − the formation of cyclobutane-type adducts can now be assigned as a general feature of the photochemistry of 5-halogenouracil ( F U, Cl U and Br U) compounds.…”

“…It has been demonstrated that the adduct is thermally unstable, undergoing cyclobutane ring cleavage with concomitant hydrolysis to form the 5-hydroxyuracil analogue of the starting dinucleotide model . Furthermore, the formation of cyclobutane-type adducts was also observed for other 5-halogenouracil compounds, namely, in the case of thymidylyl-(3′-5′)-2′-deoxy-5-fluorouridine monophosphate and 5-chlorouracil containing dinucleotide model compounds and 5-bromo-2′-deoxyuridine in frozen aqueous solution …”

Initial Excited-State Structural Dynamics of 9-Methyladenine from UV Resonance Raman Spectroscopy

“…The value for the photochemical component of the reorganization energy for 9-MeA (66%) is lower than for 5-fluorouracil (81%) and thymine (73%), , but it is more than that reported for cytosine and uracil . Therefore, less of cytosine’s and uracil’s reorganization energy are directed along the photochemical coordinate, compared to 9-MeA, 5-fluorouracil and thymine.…”

“…The resonance Raman spectra obtained for the related analogue of these two, 5-FU, shows intensity that are more similar to thymine than uracil, thereby supporting the mass barrier hypothesis. 23 The value for the photochemical component of the reorganization energy for 9-MeA (66%) is lower than for 5-fluorouracil (81%) and thymine (73%), 23,56 but it is more than that reported for cytosine and uracil. 22 Therefore, less of cytosine's and uracil's reorganization energy are directed along the photochemical coordinate, compared to 9-MeA, 5-fluorouracil and thymine.…”

“…Therefore, less of cytosine’s and uracil’s reorganization energy are directed along the photochemical coordinate, compared to 9-MeA, 5-fluorouracil and thymine. The quantum yield of dimerization for these nucleobases are in the order cytosine (0.04) > thymine (0.013) > 5-FU = U (0.007) > 9-MeA (0.003). − ,,, By scaling the reorganization energy in the photochemically active modes by the percentage of the modes which is localized along a photochemically relevant coordinate, a lower limit for the percentage of the reorganization energy along the photochemically active coordinate of 36% is obtained. This compares with 38% for thymine and 46% for 5-fluorouracil, but it is significantly different from 7% reported for cytosine …”