Issue 27, 2024

Key structural features to favour imines over hydrates in water: pyridoxal phosphate as a muse

Abstract

Imination reactions in water represent a challenge not only because of the high propensity of imines to be hydrolysed but also as a result of the competing hydrate formation through H2O addition to the aldehyde. In the present work we report a successful approach that allows for favouring imitation reactions while silencing hydrate formation. Such remarkable reactivity and selectivity can be attained by fine-tuning the electronic and steric structural features of the ortho-substituents of the carbonyl groups. It resulted from studying the structure–reactivity relationships in a series of condensation reactions between different amines and aldehydes, comparing the results to the ones obtained in the presence of the biologically-relevant pyridoxal phosphate (PLP). The key role of negatively-charged and sterically-crowding units (i.e., sulfonate groups) in disfavouring hydrate formation was corroborated by DFT and steric-hindrance calculations. Furthermore, the best-performing aldehyde leads to higher imine yields, selectivity and stability than those of PLP itself, allowing for the inhibition of a PLP-dependent enzyme (transaminase) through dynamic aldimine exchange. These results will increase the applicability of imine-based dynamic covalent chemistry (DCvC) under physiological conditions and will pave the way for the design of new carbonyl derivatives that might be used in the dynamic modification of biomolecules.

Graphical abstract: Key structural features to favour imines over hydrates in water: pyridoxal phosphate as a muse

Supplementary files

Article information

Article type
Edge Article
Submitted
03 avr. 2024
Accepted
10 juin 2024
First published
11 juin 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2024,15, 10408-10415

Key structural features to favour imines over hydrates in water: pyridoxal phosphate as a muse

F. Esteve, T. Rieu and J. Lehn, Chem. Sci., 2024, 15, 10408 DOI: 10.1039/D4SC02206H

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