Activation of fluoride anion as nucleophile in water with data-guided surfactant selection

Krishna Sharma, Alison McCorry, Samuel Boobier, James Mottram, Rachel Napier, Ian W. Ashworth, A. John Blacker, Nikil Kapur, Stuart L. Warriner, Megan H. Wright, Bao N. Nguyen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


A principal component surfactant_map was developed for 91 commonly accessible surfactants for use in surfactant-enabled organic reactions in water, an important approach for sustainable chemical processes. This map was built using 22 experimental and theoretical descriptors relevant to the physicochemical nature of these surfactant-enabled reactions, and advanced principal component analysis algorithms. It is comprised of all classes of surfactants, i.e. cationic, anionic, zwitterionic and neutral surfactants, including designer surfactants. The value of this surfactant_map was demonstrated in activating simple inorganic fluoride salts as effective nucleophiles in water, with the right surfactant. This led to the rapid development (screening 13-15 surfactants) of two fluorination reactions for β-bromosulfides and sulfonyl chlorides in water. The latter was demonstrated in generating a sulfonyl fluoride with sufficient purity for direct use in labelling of chymotrypsin, under physiological conditions.

Original languageEnglish
Pages (from-to)5764-5774
Number of pages11
JournalChemical Science
Issue number15
Publication statusPublished - 19 Mar 2024

Bibliographical note

Funding Information:
The authors thank the EPSRC for grant support (EP/S013768/1). AMC thanks the EPSRC and AstraZeneca for a CASE studentship. We thank Dr Nicole Hondow (Univer-sity of Leeds) for her help with TEM and SEM measurements. We thank Dr Christopher Pask and Ms Jennie Dickinson for their help with DOSY experiments. Special thanks go to Prof. Brent Murray and Prof. Steven Abbott (University of Leeds) for their insightful discussions and comments into the nature of the emulsions during reaction. We also thank Croda for their generous donation of surfactants.

Publisher Copyright:
© 2024 The Royal Society of Chemistry

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