par Lahboubi, Mounsef 
Président du jury Jabin, Ivan
Promoteur Vaeck, Nathalie
Co-Promoteur Bartik, Kristin
Publication Non publié, 2025-04-11
Président du jury Jabin, Ivan
Promoteur Vaeck, Nathalie
Co-Promoteur Bartik, Kristin
Publication Non publié, 2025-04-11
Thèse de doctorat
| Résumé : | The use of halogen bonds (XB) has been attracting more and more attention over the past twenty years. The unique characteristics of this non-covalent interaction (directionality, strength, and tunability) offer new opportunities in the design of molecular receptors, particularly for the selective recognition of anions. While this interaction has been intensively studied in the solid phase, a more limited number receptors containing halogen bond donor units have been studied in solution. Among these units, 2-iodoperfluoroarene, 2-iodotriazole and 2-iodotriazolium are mostly used for the binding of anionic species. This thesis is devoted to the exploration of halogen bonding systems through a combined experimental and computational approach. The first part focuses on the development and experimental study of halogen bond-based receptors. Systems with one, two and three XB binding motifs based on two types of platforms were studied, namely 1,3,5-trisubstituted triethylbenzene and calix[6]arene. While bidentate systems and the tridentate calixarene-based receptor were already available, docking experiments using molecular modelling suggested that two triethylbenzene-based receptors with three iodotriazole binding motifs would be of interest. One receptor was easily obtained while the other remains inaccessible due to synthetic challenges. The binding affinity of the systems towards different anions were evaluated by 1H and 19F NMR in different solvents and in micellar media. In acetone, halides were bound selectivity over oxoanions with a pronounced preference for chloride ions (Cl-) over bromide (Br-) and iodide (I-). Association constants increased with the number of binding units going from 102 M-1 to larger than 105 M-1, highlighting the efficiency of multidentate platform-based receptors. The addition of water to the medium induced a drastic drop in affinity, a consequence of the efficient hydration of the anions which also lead to an enhanced selectivity for more polarizable iodide. The transfer of the different systems into water was tested through their micellar incorporation. Only the calixarene-based XB receptor could be efficiently incorporated into Triton-X-100 micelles. Association constants of up to 104 M-1 were measured for the binding of halides in water. This is a remarkably high value considering that the binding of anions in aqueous environment remains very challenging due to the highly competitive nature of water molecules. Interestingly, 19F NMR experiments suggest that a bidentate binding mode could occur.The second part of this thesis is devoted to a computational study of the halogen bonding interaction. Key characteristics such as electrostatic potential map, HOMO-LUMO orbitals, natural bond order and Mulliken population analysis were evaluated in order to find a correlation between their evolution and the halogen bond strength of the receptors in solution. The objective was not only to understand the binding ability experimentally observed but also to predict the behaviour of other XB-based receptors in solution. The calculations were performed using several quantum chemical methods, including Density Functional Theory (DFT) and Perturbative Methods (MPX). Additional tools such as Conformer-Rotamer Sampling Tool (CREST) were used to explore the conformation adopted by our series of receptors in order to evaluate the geometric effect on the halogen bond strength. Additionally, both implicit and explicit solvent models are employed to unravel the impact of solvation on receptor-anion interactions, offering predictive insights into receptor performance under varying environmental conditions. |
