Sequential redox strategies for enhanced defluorination and degradation of a Trifluoromethylated Pharmaceutical using a single bimetallic catalyst.

In this study, we explored for the first time the degradation of trifluoromethylated pharmaceutical through catalytic reduction, oxidation, sequential reduction and oxidation, and sequential oxidation and reduction processes, employing a single bimetallic catalyst which can activate both H and peroxymonosulfate for reduction and oxidation reactions, respectively. Sitagliptin contains both trifluorophenyl and trifluoromethyl moieties, exhibiting different reactivities. While the trifluorophenyl moiety underwent successful defluorination through both reduction and oxidation processes, the trifluoromethyl moiety remained intact and persisted in the majority of transformation products (TPs) as confirmed by high-resolution mass spectrometry, resulting in limited defluorination up to 50 %. Computational chemistry based on density functional theory (DFT) confirmed that the attack of SO on the trifluoromethyl site was thermodynamically unfavorable, necessitating high activation energy. Nevertheless, the sequential reduction and oxidation process overcame these limitations, achieving approximately 84 % defluorination. This was facilitated by the preliminary removal of 3 F atoms from the phenyl site during the pre-reduction step, enabling oxidative defluorination of the trifluoromethyl site in the subsequent oxidation step, as supported by DFT results. In contrast, the sequential oxidation and reduction process did not favor the defluorination of the trifluoromethyl site. Therefore, this study highlights that alternating the sequences of catalytic reduction and oxidation can lead to significant alterations in defluorination, reaction pathways and associated formation of TPs, and overall degradation of fluorinated pharmaceuticals. Such insights will contribute to the development of more sustainable and efficient water treatment technologies tailored to effectively degrade fluorinated pharmaceuticals.