Fluorinated Pharmaceutical and Pesticide Photolysis: Investigating Reactivity and Identifying Fluorinated Products by Combining Computational Chemistry,¹⁹F NMR, and Mass Spectrometry

Fluorinated breakdown products from photolysis of pharmaceuticals and pesticides are of environmental concern due to their potential persistence and toxicity. While mass spectrometry workflows have been shown to be useful in identifying products, they fall short for fluorinated products and may miss up to 90% of products. Studies have shown that ¹⁹F NMR measurements assist in identifying and quantifying reaction products, but this protocol can be further developed by incorporating computations. Density functional theory was used to compute ¹⁹F NMR shifts for parent and product structures in photolysis reactions. Computations predicted NMR spectra of compounds with an R² of 0.98. Computed shifts for several isolated product structures from LC-HRMS matched the experimental shifts with <0.7 ppm error. Multiple products including products that share the same shift that were not previously reported were identified and quantified using computational shifts, including aliphatic products in the range of −80 to −88 ppm. Thus, photolysis of fluorinated pharmaceuticals and pesticides can result in compounds that are polyfluorinated alkyl substances (PFAS), including aliphatic-CF₃ or vinyl-CF₂ products derived from heteroaromatic-CF₃ groups. C-F bond-breaking enthalpies and electron densities around the fluorine motifs agreed well with the experimentally observed defluorination of CF₃ groups. Combining experimental-computational ¹⁹F NMR allows quantification of products identified via LC-HRMS without the need for authentic standards. These results have applications for studies of environmental fate and analysis of fluorinated pharmaceuticals and pesticides in development.