Fluorinated Pharmaceutical
and Pesticide Photolysis:
Investigating Reactivity and Identifying Fluorinated Products by Combining
Computational Chemistry,19F NMR, and Mass Spectrometry
posted on 2024-02-10, 14:10authored byAkash
P. Bhat, William C. K. Pomerantz, William A. Arnold
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.