5-fluorouracil - complete insight into its neutral and ionised forms

Justyna Wielińska , Andrzej Nowacki , Beata Liberek


5-fluorouracil (5FU), a common anti-cancer drug, occurs in four tautomeric forms and possesses two potential sites of both protonation and deprotonation. Tautomeric and resonance structures of the ionized forms of 5FU create the systems of connected equilibriums. Since there are contradictory reports on the ionized forms of 5FU in the literature, complex theoretical studies on neutral, protonated and deprotonated forms of 5FU, based on the broad spectrum of DFT methods, are presented. These indicate that the O4 oxygen is more willingly protonated than the O2 oxygen and the N1 nitrogen is more willingly deprotonated than the N3 nitrogen in a gas phase. Such preferences are due to advantageous charge delocalization of the respective ions, which is demonstrated by the NBO and ESP analyses. In an aqueous phase, stability differences between respective protonated and deprotonated forms of 5FU are significantly diminished due to the competition between the mesomeric effect and solvation. The calculated pKa values of the protonated, neutral and singly deprotonated 5FU indicate that 5FU does not exist in the protonated and double-deprotonated forms in the pH range of 0–14. The neutral form dominates below pH 8 and the N1 deprotonated form dominates above pH 8.
Author Justyna Wielińska (FCh / DOCh / LG)
Justyna Wielińska,,
- Laboratory of Glycochemistry
, Andrzej Nowacki (FCh / DOCh / LG)
Andrzej Nowacki,,
- Laboratory of Glycochemistry
, Beata Liberek (FCh / DOCh / LG)
Beata Liberek,,
- Laboratory of Glycochemistry
Journal seriesMolecules, ISSN 1420-3049, (N/A 100 pkt)
Issue year2019
Publication size in sheets0.9
Article number3683
Keywords in English5-fluorouracil, protonation, deprotonation, charge delocalisation, pKa value, DFT methods
ASJC Classification1605 Organic Chemistry
URL https://doi.org/10.3390/molecules24203683
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)100
Score sourcejournalList
ScoreMinisterial score = 100.0, 28-01-2020, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2017 = 1.146; WoS Impact Factor: 2018 = 3.06 (2) - 2018=3.38 (5)
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