Glycosylium Ions in Superacid Mimic the Transition State of Enzyme Reactions
The hydrolysis of glycosides is a biochemical transformation that occurs in all living organisms, catalyzed by a broad group of enzymes, including glycoside hydrolases. These enzymes cleave the glycosidic bond via a transition state with substantial oxocarbenium ion character, resulting in short-lived oxocarbenium ion-like species. While such transient species have been inferred through theoretical studies and kinetic isotope effect measurements, their direct spectroscopic characterization remains challenging. In this study, we exploit a superacid environment to generate, accumulate, and fully characterize nonprotected 2-deoxy glycosyl cations in the d-glucopyranose, d-galactopyranose, and l-arabinofuranose series using low-temperature NMR spectroscopy, supported by DFT calculations. Additionally, QM/MM MD simulations reveal that the properties of these glycosyl cations in superacid closely resemble those within the active sites of glycosidase enzymes, particularly in terms of conformation and anomeric charge distribution. These findings highlight a parallel between the stabilizing effect of counterions in superacid media and the network of multidentate noncovalent interactions within glycosidase active sites, which stabilize transition states with pronounced oxocarbenium ion character.
Authors
- Emanuela Berrino (ORCID: https://orcid.org/0000-0002-4258-0678)
- Ana Ardá (ORCID: https://orcid.org/0000-0003-3027-7417)
- Yves Blériot (ORCID: https://orcid.org/0000-0002-3209-9282)
- Jesús Jiménez‐Barbero (ORCID: https://orcid.org/0000-0001-5421-8513)
- Bastien Michelet (ORCID: https://orcid.org/0000-0002-3248-5781)
- Sébastien Thibaudeau (ORCID: https://orcid.org/0000-0002-6246-5829)
- Martine Armand (ORCID: https://orcid.org/0000-0002-8712-6620)
- Agnès Martin‐Mingot (ORCID: https://orcid.org/0000-0002-2633-3714)
- Carme Rovira (ORCID: https://orcid.org/0000-0003-1477-5010)
- Alba Nin‐Hill (ORCID: https://orcid.org/0000-0002-8670-9031)
- Jérôme Désiré (ORCID: https://orcid.org/0000-0003-1076-3610)
Institutions
- Ikerbasque (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Centre National de la Recherche Scientifique (FR)
- University of the Basque Country (ES)
- Université de Poitiers (FR)
- Institut de Chimie des Milieux et des Matériaux de Poitiers (FR)
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (ES)
- CIC bioGUNE (ES)
- Instituto de Química Orgánica General (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2024-11-13
- DOI
- https://doi.org/10.1021/jacs.4c11677
- Citations
- 4
- Primary Topic
- Carbohydrate Chemistry and Synthesis
- Type
- article
- Field-Weighted Citation Impact
- 1.00
Funders
- Ministerio de Ciencia, Innovación y Universidades
- Fundación Carmen y Severo Ochoa
- Agence Nationale de la Recherche
- Université de Poitiers
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- European Regional Development Fund
- Institut de chimie
- H2020 Marie Skłodowska-Curie Actions