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Pregled bibliografske jedinice broj: 1125623

Chlorination of 5-Fluorouracil: Reaction Mechanism and Ecotoxicity Assessment of Chlorinated Products


Hok, Lucija; Ulm, Lea; Tandarić, Tana; Krivohlavek, Adela; Šakić, Davor; Vrček, Valerije
Chlorination of 5-Fluorouracil: Reaction Mechanism and Ecotoxicity Assessment of Chlorinated Products // Computational Chemistry Day : Book of Abstracts
Zagreb: University of Zagreb Faculty of Science, 2018. str. 24-24 (poster, domaća recenzija, sažetak, znanstveni)


CROSBI ID: 1125623 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Chlorination of 5-Fluorouracil: Reaction Mechanism and Ecotoxicity Assessment of Chlorinated Products

Autori
Hok, Lucija ; Ulm, Lea ; Tandarić, Tana ; Krivohlavek, Adela ; Šakić, Davor ; Vrček, Valerije

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Computational Chemistry Day : Book of Abstracts / - Zagreb : University of Zagreb Faculty of Science, 2018, 24-24

ISBN
978-953-6076-45-1

Skup
Computational Chemistry Day 2018

Mjesto i datum
Zagreb, Hrvatska, 12.05.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
5-fluorouracil ; chlorination ; quantum-chemical methods ; ecotoxicological analysis

Sažetak
5-Fluorouracil (5-FU) is a pyrimidine antimetabolite introduced in the clinic as an anticancer drug. The reaction between 5-FU and hypochlorous acid (HOCl) is the fundamental process which can occur in activated neutrophils in cancer patients [1] or during chemical treatment of wastewaters [2]. This study combines synthesis, NMR and MS spectroscopy, quantum chemical calculations, and toxicity experiments on Daphnia magna to investigate chemical fate of 5-FU in chlorinated environment. All structures were fully optimized with the B3LYP functional. The standard 6-31+G(d) basis set was used for geometry optimizations and frequency calculations. Improved energetics have been calculated using B2K-PLYP functional and 6- 311+G(3df, 2p) basis set. Gibbs energies of solvation were determined using the SMD continuum solvation model at the B3LYP/6- 31+G(d) level (ε = 78.4). Two explicit water molecules were found as „the ideal number of solvent molecules” for a reliable description of the corresponding potential energy surfaces. The first chlorinated product chlorohydrin 3a was less toxic than the parent 5-FU, suggesting the beneficial effect of chlorination (Figure 1). Further chlorination leads to N1- chlorinated intermediate 6, that undergoes pyrimidine ring opening reaction. The final product 11 was obtained after the loss of the chlorinated urea fragment. This is the most potent compound in the reaction sequence, with toxicity parameter EC50 more than twice lower compared to the parent 5-FU. Interplay between experimental and theoretical procedures, to properly describe reaction pathways and provide more information on toxicity profiles, is a way forward in environmental science research. [1] C. C. Winterbourn, A. J. Kettle and M. B. Hampton, Ann. Rev. Biochem. 85 (2016) 765- 792. [2] J. L. Acero, F. J. Benitez, F. J. Real and G. Roldan, Water Res. 44 (2010) 4158-4170.

Izvorni jezik
Engleski

Znanstvena područja
Interdisciplinarne prirodne znanosti, Farmacija



POVEZANOST RADA


Ustanove:
Farmaceutsko-biokemijski fakultet, Zagreb,
Institut "Ruđer Bošković", Zagreb,
Nastavni zavod za javno zdravstvo "Dr. Andrija Štampar"

Profili:

Avatar Url Lea Ulm (autor)

Avatar Url Lucija Hok (autor)

Avatar Url Valerije Vrček (autor)

Avatar Url Adela Krivohlavek (autor)

Avatar Url Davor Šakić (autor)

Avatar Url Tana Tandarić (autor)

Poveznice na cjeloviti tekst rada:

Pristup cjelovitom tekstu rada www.pmf.unizg.hr

Citiraj ovu publikaciju:

Hok, Lucija; Ulm, Lea; Tandarić, Tana; Krivohlavek, Adela; Šakić, Davor; Vrček, Valerije
Chlorination of 5-Fluorouracil: Reaction Mechanism and Ecotoxicity Assessment of Chlorinated Products // Computational Chemistry Day : Book of Abstracts
Zagreb: University of Zagreb Faculty of Science, 2018. str. 24-24 (poster, domaća recenzija, sažetak, znanstveni)
Hok, L., Ulm, L., Tandarić, T., Krivohlavek, A., Šakić, D. & Vrček, V. (2018) Chlorination of 5-Fluorouracil: Reaction Mechanism and Ecotoxicity Assessment of Chlorinated Products. U: Computational Chemistry Day : Book of Abstracts.
@article{article, author = {Hok, Lucija and Ulm, Lea and Tandari\'{c}, Tana and Krivohlavek, Adela and \v{S}aki\'{c}, Davor and Vr\v{c}ek, Valerije}, year = {2018}, pages = {24-24}, keywords = {5-fluorouracil, chlorination, quantum-chemical methods, ecotoxicological analysis}, isbn = {978-953-6076-45-1}, title = {Chlorination of 5-Fluorouracil: Reaction Mechanism and Ecotoxicity Assessment of Chlorinated Products}, keyword = {5-fluorouracil, chlorination, quantum-chemical methods, ecotoxicological analysis}, publisher = {University of Zagreb Faculty of Science}, publisherplace = {Zagreb, Hrvatska} }
@article{article, author = {Hok, Lucija and Ulm, Lea and Tandari\'{c}, Tana and Krivohlavek, Adela and \v{S}aki\'{c}, Davor and Vr\v{c}ek, Valerije}, year = {2018}, pages = {24-24}, keywords = {5-fluorouracil, chlorination, quantum-chemical methods, ecotoxicological analysis}, isbn = {978-953-6076-45-1}, title = {Chlorination of 5-Fluorouracil: Reaction Mechanism and Ecotoxicity Assessment of Chlorinated Products}, keyword = {5-fluorouracil, chlorination, quantum-chemical methods, ecotoxicological analysis}, publisher = {University of Zagreb Faculty of Science}, publisherplace = {Zagreb, Hrvatska} }




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