Synthetic molecular receptors find applications in the selective extraction, transport and detection of neutral or charged species and the study of these systems is an important facet of supramolecular chemistry. In this thesis, we focused our attention on a specific family of molecular receptors called calix[6]arenes. These receptors possess a hydrophobic cavity formed by 6 aromatic rings that can accommodate small organic molecules. They can furthermore be easily functionalized and give rise to for example ditopic receptors or sensing systems. We worked with two families of calix[6]arenes but also looked at the complexation properties of some related compounds: a homooxacalix[3]arene and a resorcin[4]arene derivatives. The first part of this thesis is devoted to the study of the complexation properties of a fluorescent calix[6]tris-pyrenylurea. The binding of anions, ion pairs, ion triads and phospholipids was monitored by 1H Nuclear Magnetic Resonance (NMR) and Emission Spectroscopy. Our results showed that the receptor exhibits a remarkable selectivity for the sulfate anion in DMSO for which a binding constant of the order of 103 M-1 was found. In chloroform the affinity for sulfate is of the order of 105 M-1 and the selective recognition of ammonium-TBASO4 triads was observed (TBA = tetra-n-butylammonium; ammonium = PrNH3+, HexNH3+ or DodNH3+). This work has been reported in the paper “Fluorescent Chemosensors for Anions and Contact Ion Pairs with a Cavity-Based Selectivity” Emilio Brunetti, Jean-François Picron, Karolina Flidrova, Gilles Bruylants, Kristin Bartik and Ivan Jabin J. Org. Chem. 2014, 79, 6179–6188. We also showed that calix[6]tris-pyrenylurea displays a remarkable selectivity in chloroform for phospholipids bearing a phosphatidylcholine head (PCs) over those bearing a phosphoethanolamine head (PEs). We were able to show that this fluorescent receptor is able to extract PCs from a water solution enabling their quantification. This work has been reported in the paper “A Selective Calix[6]arene-based Fluorescent Chemosensor for Phosphatidylcholine Type Lipids” Emilio Brunetti, Steven Moerkerke, Johan Wouters, Kristin Bartik and Ivan Jabin Org. Biomol. Chem. 2016. Accepted Manuscript. DOI: 10.1039/C6OB01880G.The second part of this thesis is devoted to the evaluation of the binding properties of different receptors incorporated into dodecylphosphocholine (DPC) micelles. This strategy was used to make the hydrophobic molecular receptors “water-compatible” without having to undertake synthetic modifications. Our results showed that a calix[6]azacryptand-based receptor can be incorporated into DPC micelles, either as a zinc complex or as a polyammonium at low pH. We observed that the zinc complex incorporated in the micelles is able to bind small and long linear primary amines in its cavity and we were able to highlight that complexation is driven by the hydrophobic effect. This work has been reported in the paper “Primary Amine Recognition in Water by a Calix[6]aza-cryptand Incorporated in Dodecylphosphocholine Micelles” Emilio Brunetti, Alex Inthasot, Flore Keymeulen, Olivia Reinaud, Ivan Jabin and Kristin Bartik Org. Biomol. Chem. 2015, 13, 2931-2938.We also validated the micellar incorporation strategy with a homooxacalix[3]tris-acid and with a resorcin[4]arene zinc complex bearing four methyl-imidazole moieties. Once incorporated into DPC micelles, we showed that the two receptors can bind small organic guests: the homooxacalix[3]arene derivative can bind tert-butylammonium or adamantylammonium, albeit with low affinity and the resorcin[4]arene-based zinc complex can bind acetate and acetylacetone.The final part of this thesis is devoted to the work undertaken in order to try and elucidate the guest exchange mechanism of calix[6]arene-zinc complexes where the zinc is tri-coordinated to the calixarene-based ligand and coordinates a guest molecule inside the calixarene cavity. The hypothesis that we put forward is that when the zinc is only tri-coordinated to the calixarene ligand, the guest exchange mechanism involves a zinc penta-coordinated intermediate where the zinc atom is simultaneous coordinated to an endo-complexed guest (inside the cavity) and an exo-complexed molecule (outside the cavity). 1D EXchange SpectroscopY experiments (EXSY) were undertaken with two calix[6]arene-zinc complexes where the zinc is tri-coordinated to the calixarene ligand and with a calix[6]arene-zinc complex where the zinc is tetra-coordinated to the calixarene ligand. The exchange of different guests (ethanol, dimethylformamide and acetonitrile) was monitored in deuterated dichloromethane. We observed that in all cases water accelerates guest exchange but that the guest residence times are highly dependent on the acidity of the metal center and on the nature of the guest buried inside the cavity. / Doctorat en Sciences de l'ingénieur et technologie / info:eu-repo/semantics/nonPublished

The development of synthetic molecular receptors that can selectively bind anions, translocate them through a lipidic bilayer membrane and release them on the other side is a very topical and emerging field of supramolecular chemistry, warranted by the biological importance of transmembrane anion transport.The first part of this thesis is devoted to the study of the transmembrane transport of chloride and of the organic ion pair propylammonium chloride with calix[6]arene receptors functionalized with three (thio)urea arms on their small rim. The transport of chloride across the lipid bilayer of liposomes was monitored by fluorescence spectroscopy using the lucigenin assay. We report the first example of calix[6]arenes able to act as mobile carrier for the transport of chloride via a Cl-/NO3- antiport. We furthermore show that our calixarene systems are able to perform the cotransport of propylammonium chloride, with the chloride bound at the level of the (thio)urea groups and the ammonium included in the calixarene cavity. To provide direct proof of cotransport, we developed a 1H NMR methodology involving a thulium- complex shift reagent with which we were able to distinguish the signals of the ammonium transported inside the liposomes from those of the external ammonium. We also highlight the role of the complexing calixarene cavity for the cotransport by comparing the calixarenes to known transporters deprived of a cavity. The transmembrane transport organic ion pairs could find applications in the transport of biologically relevant ammonium compounds such as catecholamines and amino acids. Our results are reported in the publication “Repositioning Chloride Transmembrane Transporters: Transport of Organic Ion Pairs” Grauwels, G. Valkenier, H. Davis, A. P. Jabin, I. Bartik, K. Angew. Chemie - Int. Ed. 2019, 58, 6921–6925.The second part of this thesis is devoted to the study of binding of chloride to receptors embedded in a lipid membrane, the first step of the transmembrane transport process. Both 1H and 31P NMR spectroscopy proved to be inadequate to study the binding using liposomes or micelles as model membranes. With liposomes, the NMR signals are too broad to be exploited and in the case of micelles, the competition between the lipid headgroups and chloride made it impossible to obtain a NMR signature which unambiguously characterizes chloride binding. The 35Cl NMR signal is on the other hand strongly affected by the presence of anion receptors, both in organic solvents and when incorporated lipid bilayers. We developed a methodology to evaluate the binding of chloride, based on the monitoring of the chloride linewidth during titration experiments. A linear relationship between the linewidth and the concentration of receptors is observed and the slopes can be exploited to compare the binding strengths of different structurally related receptors. We show that 35/37Cl NMR is a versatile tool which can help in the understanding and development of new transporters by providing new insights of the physicochemical understanding of the transport process. / Doctorat en Sciences de l'ingénieur et technologie / info:eu-repo/semantics/nonPublished