Tracking Fluorine during Aqueous Photolysis and Advanced UV Treatment of Fluorinated Phenols and Pharmaceuticals Using a Combined ¹⁹F-NMR, Chromatography, and Mass Spectrometry Approach

Abstract

Fluorine incorporation into organic molecules has increased due to desirable changes in the molecular physiochemical properties. Common fluorine motifs include: aliphatic fluorines and −CF 3 , or −F containing groups bonded directly onto an aromatic (Ar−CF 3 and Ar−F) or heteroaromatic ring. Photolysis of these compounds, either in natural or engineered systems, is a potential source of new fluorinated byproducts. Given the potential persistence and toxicity of fluorinated byproducts, monitoring of product formation during photolysis of various fluorinated motifs is needed. 19 F-NMR is a means to detect and quantify these species. Ar−CF 3 and Ar−F model compounds (2-, 3-, and 4-(trifluoromethyl)phenol, 2-, 3-, 4-fluorophenol, and 2,6-, 3,5difluorophenol) were photolyzed under a variety of aqueous conditions: pH 5, pH 7, pH 10, 1 mM H 2 O 2 at pH 7 to form •OH, and 0.5 mM SO 3 2− at pH 10 to form e aq − . Pharmaceuticals with the Ar−CF 3 (fluoxetine) and Ar−F plus pyrazole-CF 3 (sitagliptin) motifs were treated similarly. Parent molecule concentrations were monitored with high pressure liquid chromatography with a UV detector. Fluorine in the parent and product molecules was quantified with 19 F-NMR and complete fluorine mass balances were obtained. High resolution mass spectrometry was used to further explore product identities. The major product for Ar−F compounds was fluoride. The Ar−CF 3 model compounds led to fluoride and organofluorine products dependent on motif placement and reaction conditions. Trifluoroacetic acid was a product of 4-(trifluoromethyl)phenol and fluoxetine. Additional detected fluoxetine products identified using mass spectrometry resulted from addition of −OH to the aromatic ring, but a dealkylation product could not be distinguished from fluoxetine by 19 F-NMR. Sitagliptin formed multiple products that all retained the pyrazole-CF 3 motif while the Ar−F motif produced fluoride. 19 F-NMR, mass spectrometry, and chromatography methods provide complementary information on the formation of fluorinated molecules by modification or fragmentation of the parent structure during photolysis, allowing screening for fluorinated photoproducts and development of fluorine mass balances.

Finding Fluorine: Photoproduct Formation during the Photolysis of Fluorinated Pesticides

“…For the current compounds that have p K a values of <6 (p K a ( penoxsulam ) = 5.2, p K a ( florasulam ) = 4.54, and p K a ( fluroxypyr ) = 2.94), the rates observed at pH values greater than or equal to 7 are similar. The effect of acidic pH was not studied because of slow degradation rates and low relevance to natural environmental conditions. ,, At pH values lower than 5, the prevalence of protonated forms of pesticides decreases the rate of photolysis. ,− …”

“…A 600 MHz Avance Neo NMR equipped with a 5 mm three-channel TCI inverse cryoprobe for 19 F NMR spectral acquisition without 1 H decoupling was used to analyze and quantify the fluorinated parent compound along with all the fluorinated products from the photolysis experiments. The experimentally determined parameters to give a sufficient signal-to-noise ratio and complete longitudinal relaxation for accurate and reproducible quantitative measurements for the NMR were 1024 scans, 10 s delay time (D1), and a 0.9 s acquisition time (AQ) . For a more detailed explanation of NMR conditions and parameters, see the SI.…”

“…Fluorine nuclear magnetic resonance ( 19 F-NMR) detects fluorine in structures and offers an advantage due to the 100% abundance of 19 F in fluorinated compounds, higher sensitivity, and lack of background signals . Changes in 19 F-NMR spectra over time provide information about structural modification, changes to functional groups, formation of new fluorinated structures, and fluoride formation . There have been several studies that have established 19 F-NMR to quantify and detect fluorinated structures. ,− Quantitative 19 F-NMR has been used to track trifluralin fate in soil and organic matter and fluorinated acids in rainwater along with trifluoroacetic acid .…”

“…LC–MS/MS methods were not able to identify several structures that were determined by noise-reduced NMR methods. Our previous study established a robust and reliable quantitative NMR method for tracking fluorine during the photolysis of some model fluorinated compounds and provided accurate mass balances for fluorine . Even though quantifiable NMR methods have been developed, products from photolysis and advanced oxidation and reduction-based processes for widely used fluorinated pesticides have not been quantified or tracked under conditions relevant to natural and engineered water systems.…”

Fluoro‐recognition: New in vivo fluorescent assay for toluene dioxygenase probing induction by and metabolism of polyfluorinated compounds

“…In the period of 1998–2020, greater than 50% of newly introduced agrichemicals are fluorinated, and most of those are aromatic compounds (Ogawa et al, 2020 ). Major blockbuster drugs are ingested by millions of people and much of the fluorinated benzene moieties are passed and enter wastewater treatment plants (Bhat et al, 2022 ; Britton et al, 2021 ; Murphy, 2016 ). For example, sitagliptin, a diabetes drug currently enjoying greater than $5.5 billion in sales, contains a 1,2,4‐trifluorobenzene moiety (Han et al, 2021 ).…”