Abstract
Reactive carbonyl compounds are common pollutants and endogenous metabolites that are often toxic at high concentrations. Removal/detoxification of carbonyl compounds requires selective small molecule scavengers; however, few molecules suitable for this task have been fully characterised. Here, we report NMR-based kinetic and selectivity studies on representative 1-amino-but-3-enes, which are reported to be selective formaldehyde scavengers. Our experiments reveal that 1-amino-but-3-enes containing phenyl groups at position 1 react with formaldehyde via a 2-aza-Cope rearrangement. However, they also react with other carbonyl compounds, including the biologically relevant 1,2-dicarbonyl compound glyoxylic acid. The most efficient and promiscuous scavenging compound promoted the growth of Escherichia coli cells, while studies on cell lysate revealed potential for aldehyde sequestration. Overall, our analyses suggest that 1-amino-but-3-enes can be used to scavenge a variety of toxic carbonyl compounds and may be used in imaging and quantification studies, as well as for biomedical applications.
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Acknowledgements
This work was funded by the Engineering and Physical Sciences Research Council (EP/T033460/1), the Wellcome Trust (215293/Z/19/Z), and Cancer Research UK (DDPMA-May22\100086). We thank Matthew Hopkinson and Paul Cullis for helpful discussions, Vanessa Timmermann, Rebecca Hawker, Fred Muskett and Phil Young for help with NMR analyses, and Sharad Mistry for help with MS studies. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to the Author Accepted Manuscript version arising from this submission.
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R.J.H. conceived the study, conducted the studies with E. coli and wrote the paper. N.F.A.B. conducted synthesis and NMR-based kinetic and selectivity studies. V.L.E., L.A.T., and L.B. conducted the synthesis. All authors assisted with the preparation of the paper.
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Bulman, N.F.A., Emms, V.L., Thomas, L.A. et al. 1-Amino-but-3-enes scavenge formaldehyde and glyoxylic acid. Commun Chem (2026). https://doi.org/10.1038/s42004-025-01873-9
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DOI: https://doi.org/10.1038/s42004-025-01873-9
