Ozonation of the 5-fluorouracil anticancer drug and its prodrug capecitabine: Reaction kinetics, oxidation mechanisms, a
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RESEARCH ARTICLE
Ozonation of the 5-fluorouracil anticancer drug and its prodrug capecitabine: Reaction kinetics, oxidation mechanisms, and residual toxicity Siyu Chen1, Lee Blaney1,2, Ping Chen1, Shanshan Deng1, Mamatha Hopanna2, Yixiang Bao1, Gang Yu (✉)1 1 School of Environment, State Key Joint Laboratory of Environmental Simulation and Pollution Control (SKLESPC), Beijing Key Laboratory for Emerging Organic Contaminants Control, Tsinghua University, Beijing 100084, China 2 Department of Chemical, Biochemical, and Environmental Engineering, University of Maryland Baltimore County, Baltimore, MD 21250, USA
HIGHLIGHTS
GRAPHIC ABSTRACT
• Specific second-order rate constants were determined for 5-FU and CAP with ozone. • Reaction sites were confirmed by kinetics, Fukui analysis, and products. • The olefin moiety was the main ozone reaction site for 5-FU and CAP. • Carboxylic acids comprised most of the residual TOC for 5-FU. • Ozonation removed the toxicity associated with 5-FU and products but not CAP.
ARTICLE INFO Article history:
Received 3 April 2019 Revised 1 May 2019 Accepted 15 May 2019 Available online 24 June 2019 Keywords: Ozone 5-fluorouracil Capecitabine Hydroxyl radicals Chemotherapy agents Toxicity
ABSTRACT Anticancer drugs (ADs) have been detected in the environment and represent a risk to aquatic organisms, necessitating AD removal in drinking water and wastewater treatment. In this study, ozonation of the most commonly used antimetabolite ADs, namely 5-fluorouracil (5-FU) and its prodrug capecitabine (CAP), was investigated to determine reaction kinetics, oxidation mechanisms, and residual toxicity. The specific second-order rate constants between aqueous ozone and 5-FU, 5-FU–, 5-FU2–, CAP, and CAP– were determined to be 7.07(0.11)104 M–1$s–1, 1.36(0.06) 10 6 M –1 $s–1 , 2.62(0.17)10 7 M–1$s–1 , 9.69(0.08)103 M –1 $s –1 , and 4.28(0.07) 105 M–1$s–1, respectively; furthermore, the second-order rate constants for OH reaction with 5-FU 9 –1 –1 9 –1 –1 and CAP at pH 7 were determined to be 1.85(0.20)10 M $s and 9.95(0.26)10 M $s , respectively. Density functional theory was used to predict the main ozone reaction sites of 5-FU (olefin) and CAP (olefin and deprotonated secondary amine), and these mechanisms were supported by the identified transformation products. Carboxylic acids constituted a majority of the residual organic matter for 5-FU ozonation; however, carboxylic acids and aldehydes were important components of the residual organic matter generated by CAP. Ozone removed the toxicity of 5-FU to Vibrio fischeri, but the residual toxicity of ozonated CAP solutions exhibited an initial increase before subsequent removal. Ultimately, these results suggest that ozone is a suitable technology for treatment of 5-FU and CAP, although the residual toxicity of transformation products must be carefully considered. © Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019
✉ Corresponding author E-mail: [email protected]
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Front. Environ. Sci. Eng. 20
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