Biodegradation of pentafluorosulfanyl-substituted aminophenol in Pseudomonas spp.

Abstract

The pentafluorosulfanyl (SF-) substituent conveys properties that are beneficial to drugs and agrochemicals. As synthetic methodologies improve the number of compounds containing this group will expand and these chemicals may be viewed as emerging pollutants. As many microorganisms can degrade aromatic xenobiotics, we investigated the catabolism of SF-substituted aminophenols by bacteria and found that some Pseudomonas spp. can utilise these compounds as sole carbon and energy sources. GC-MS analysis of the culture supernatants from cultures grown in 5-(pentafluorosulfanyl) 2-aminophenol demonstrated the presence of the N-acetylated derivative of the starting substrate and 4-(pentafluorosulfanyl)catechol. Biotransformation experiments with re-suspended cells were also conducted and fluorine-19 NMR analyses of the organic extract and aqueous fraction from suspended cell experiments revealed new resonances of SF-substituted intermediates. Supplementation of suspended cell cultures with yeast extract dramatically improved the degradation of the substrate as well as the release of fluoride ion. 4-(Pentafluorosulfanyl)catechol was shown to be a shunt metabolite and toxic to some of the bacteria. This is the first study to demonstrate that microorganisms can biodegrade SF-substituted aromatic compounds releasing fluoride ion, and biotransform them generating a toxic metabolite.

19F NMR as a tool in chemical biology

“…The spectra are from culture supernatants of different bacteria incubated with SF 5 -aminophenol. Figure 16 was reprinted from [110].…”

“…Intuitively, investigating the biodegradation of these compounds in the absence of any reference compounds is complicated. Saccomanno et al [110] investigated the bacterial degradation of pentafluorosulfanyl (SF 5 )-substituted aminophenols and via 19 F NMR analysis of culture extracts was able to determine the production of new fluorinated metabolites (Figure 16). Subsequent analysis by GC-MS was required to further characterize the products, but only one could be detected (SF 5 -catechol) despite the 19 F NMR analysis showing the presence of multiple fluorometabolites.…”

Photochemical Activation of Sulfur Hexafluoride: A Tool for Fluorination and Pentafluorosulfanylation Reactions

“…41 For instance, trifluoralin has a 5-fold enhanced activity against quackgrass and crabgrass if the CF3 group is replaced by SF5, fenfluramine (an appetite suppressant) shows 10-fold strong binding to the receptor. 42,43 Moreover, the SF5 group is both thermally and widely chemically stable and not prone to hydrolysis under physiological conditions. After initial metabolic processing it has recently been shown for some compounds that the SF5 substituent finally can be metabolized under formation of fluoride anions.…”

“…After initial metabolic processing, it has recently been shown for some compounds that the SF 5 substituent can finally be metabolized with formation of fluoride anions. 42,44 The SF 5 substituent on phenyl rings shows a group electronegativity of 3.65 in contrast to 3.35 for CF 3 , as well as a Hammett parameter of  p = 0.68, between CF 3 ( p = 0.54) and NO 2 ( p = 0.78) (Figure 1), and is highly lipophilic (Hansch parameter  = 1.23, between SCF 3 :  = 1.44 and OCF 3 :  = 1.04). 45 The SF 5 group has been discussed as a bioisosteric replacement not only for the CF 3 group but also for tBu, NO 2 and halogen substituents.…”

Recent Advances in the Chemistry and Application of SF5-Compounds

“…Moreover, preliminary biological studies proved that SF5-compounds could be biodegradated by bacteria, offering a potential alternative to the perfluoro-and polyfluoroalkyl substances so called PFAS such as the CF3. 2 The history began in 1950 with the preparation of trifluoromethylsulfurpentafluoride CF3SF5 by Cady. 3a A decade later was uncovered the preparation of SF5Cl, the most powerful pentafluorosulfanylation reagent until now.…”