Ion transport across lipid bilayers

Since 2015, the EMNS Lab also studies ion transport across lipid membranes using supramolecular carriers.
Hennie Valkenier recently presented an overview of recent results from different transport projects at the CHAINS conference and her talk can be watched on You Tube

Channel-forming membrane proteins are responsible for the transport of charged species through cell membranes. Dysfunction in ion transport is the cause of numerous diseases, of which cystic fibrosis is probably the most well-known. It is possible to compensate for the defect or under-expressed membrane protein channel activity by using synthetic molecules which can carry anions through the lipid bilayer. Our goal is to study the thermodynamics, kinetics, and structural parameters of anion carriers inside lipid bilayer membranes in order to highlight the key parameters governing the efficiency of organic receptors as transporters. We use both state-of-the-art physical organic chemistry and biophysical methods, such as advanced NMR techniques, microcalorimetry and fluorescence spectroscopy, to obtain an extensive understanding of the transport phenomenon and propose new rules for the design of the next generation of anion transporters.

Heads: Dr Hennie Valkenier & Prof. Kristin Bartik
Co-workers/researchers: Mr Alessio Cataldo, Mr Matúš Chvojka, Dr Nathan Renier, Dr Glenn Grauwels
Collaborations: Prof. Tony Davis (University of Bristol), Prof. Ivan Jabin (ULB), Prof. Vladimir Sindelar (Masaryk University, Brno)
Funding: FNRS (Post-doctoral and PhD fellowships)

Publications:
Repositioning Chloride Transmembrane Transporters: Transport of Organic Ion Pairs
Grauwels G., Valkenier H., Davis A. P., Jabin I., & Bartik K., Angewandte Chemie International Ed. 58, 6921-6925 (2019).

Fluorinated Bambusurils as Highly Effective and Selective Transmembrane Cl−/HCO3− Antiporters
Valkenier H., Akrawi O., Jurček P., Sleziaková K., Lízal T., Bartik K. and Šindelář V., Chem 5(2), 429-444 (2019) - Download post-print.

Membranes function as impermeable barriers for ionic and hydrophilic species which can only cross the membrane with the aid of dedicated membrane proteins. For biotechnological and biophysical applications, the development of anion carriers that can bind an anion and transport it across the lipid bilayer could be of great relevance.

In this project, synthetic anion receptors will be developed to bind biologically relevant organic phosphorylated compounds, like nucleotides. Dynamic combinatorial chemistry will be used to synthesise and identify efficient receptors. These will then be used to transport the organophosphates across membranes. Liposomes will be used as model systems to study the transport process.

Head: Dr Hennie Valkenier
Co-workers/researchers: Mr Anurag Singh, Mr Alessio Cataldo, Dr Aaron Torres Huerta, Dr Karolis Norvaisa, Dr Marcin Konopka, Dr Lau Halgreeen, Dr Anca Dascalu, Dr Luis Martinez Crespo
Funding: This project has received funding from the FNRS (H.V. is a Chercheuse Qualifiée of the Fonds de la Recherche Scientifique–FNRS) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 802727).

Publications:
Transmembrane Transport of Phosphate by a Strapped Calix[4]pyrrole
Cataldo A., Norvaisa K., Halgreen L., Bodman S. E., Bartik K., Butler S. J. & Valkenier H., JACS (2023).

Dynamic covalent chemistry with azines
Dascalu A-E., Halgreen L., Torres-Huerta A. & Valkenier H., Chem. Commun. 58, 11103-11106 (2022). OA

Calix[6]arenes with halogen bond donor groups as selective and efficient anion transporters
Singh A., Torres Huerta A., Vanderlinden T., Renier N., Martínez-Crespo L., Tumanov N., Wouters J., Bartik K., Jabin I. & Valkenier H., Chem. Commun. 58, 6255-6258 (2022). OA

Hydrazones in anion transporters: The detrimental effect of a second binding site
Martínez-Crespo L., Halgreen L., Soares M., Marques I., Félix V. and Valkenier H., Organic & Biomolecular Chemistry 9, 8324-8337 (2021).

Transmembrane Transport of Bicarbonate Unravelled
Martínez-Crespo L., Hewitt S.H., Alessandro de Simone N., Šindelář V., Davis A.P., Butler S. and Valkenier H., Chem. Eur. J. 27, 26, 7367-7375 (2021). Cover Picture

This project addresses transmembrane transport of copper(I) cations. Different proteins transport copper(I) ions across the membranes of organelles and cells, while problems with these proteins is the cause of various diseases.

The aim of this project is to develop and study synthetic molecules which are able to selectively bind and transport copper(I) ions through lipid bilayer membranes. These molecules are integrated in the membrane and behave as mobile carriers by diffusing across the bilayer.

Head: Dr Hennie Valkenier
Co-worker/researcher: Dr Nathan Renier
Collaboration: Prof. Ivan Jabin (ULB, Laboratory of Organic Chemistry)
Funding: FNRS (FRIA PhD fellowship)

Publication:
Transmembrane transport of copper(I) by imidazole-functionalised calix[4]arenes
Renier N., Reinaud O., Jabin I. & Valkenier H., Chem. Commun. 56, 8206-8209 (2020). Download pre-print.

Based on the publication of Nathan's article in Chemical Communication , the RSC has published an interview with Hennie: https://blogs.rsc.org/cc/2020/12/09/chemcomm-milestones-hennie-valkenier/