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Lateral flow assays (LFAs), such as pregnancy tests or antigen tests, are probably the most widespread point-of-care testing. They combine all their advantages: rapid, low cost, ease of use and straightforward signal. However, LFAs, in biomedical diagnostics, are sometimes considered as not sufficiently reliable due to their poor sensitivity. Indeed, the analyte in extremely low amounts is not detected, increasing the false negative rate. Many strategies were recently developed to enhance the sensitivity of LFAs. In this thesis, investigations were focused on the colorimetric reporters involved in the assay. Indeed, the red-colored signal observed in most of the LFAs is due to the binding of gold nanoparticles (AuNPs), used as colorimetric reporters, at the test line. AuNPs belong to the plasmonic nanomaterials class, which are able to strongly absorb light. However, silver nanoparticles are known to have higher extinction coefficient compared to their gold counterpart, but suffer from a low stability against external stress, limiting their applications. Recently, calix[4]arene-based coating emerged as promising strategy to drastically enhance stability of plasmonic nanoparticles. First, the calix[4]arene-coated AgNPs, with a 20 nm average diameter, were synthesized and used for the detection of Anti-SARS-CoV-2 IgG in clinical samples. Calix[4]arene coating conferred remarkable stability to the resulting AgNPs, as no degradation was observed over several months. In comparison with lateral-flow immunoassays (LFIAs) based on classical gold nanoparticles, the limit of detection for Anti-SARS-CoV-2 IgG was reduced by 1 order of magnitude and similar signals were observed with 10 times fewer particles with our AgNPs-based assay. These results represent one of the first examples of the use of AgNP-based LFA in the case of real clinical samples.Secondly, silver nanoplates (AgNPls) synthesis was developed. In contrast to AgNPs, the absorption spectrum of this anisotropic na, Doctorat en Sciences de l'ingénieur et technologie, info:eu-repo/semantics/nonPublished

In recent decades, the study of anion transport across model lipid bilayer membranes has evolved rapidly. Initially focused on chloride transport using simple synthetic transporters, the field has expanded to encompass the investigation of different anions, the development of new monitoring methods for the understanding of the process, and the creation of new transporters. This thesis touches on all these aspects and can be divided in three parts, each dealing with the transport of a different anion.After a general introduction of the concepts of anion transmembrane transport and the use of synthetic transporters, the second chapter of the thesis addresses the transport of phosphate through the lipid membranes of liposomes, a process never reported previously. The work focuses primarily on the development of two methods for monitoring the transport process: the [Eu.pBOH2]+ assay and the 31P NMR assay. The former relies on emission spectroscopy, while the latter utilizes NMR spectroscopy.Each assay came with its own distinct set of challenges. These include the research of a suitable phosphate-sensitive probe and the acquisition of consistent and clear results, in an emission-based assay. Meanwhile, for the NMR-based assay, the primary aim was to enhance sensitivity and optimize the signal-to-noise ratio. We discuss these challenges and the successful implementation of both methods, along with their application in studying phosphate transport mediated by synthetic carriers. Our results conclusively demonstrate the feasibility of phosphate transport and highlight the influence of pH on the process, given by the prevalence of different forms of the anion, namely H2PO4– (the transported form) and HPO42–. Additionally, our exploration of various efficient chloride transporters, found to be poor phosphate transporters, underscores the difficulty of transporting phosphate.Successively, in the third chapter, we focus on fluoride transport, with a primary emphasis on mechani, Doctorat en Sciences de l'ingénieur et technologie, info:eu-repo/semantics/nonPublished

The increasing CO2 levels and associated climate change are drivers to move towards a circular chemical industry. Therefore, there is besides recyclable carbon an urgent need for means to access renewable carbon. Two main strategies have been put forward: (i) carbon capture and utilization (CCU) and (ii) use of biomass as feedstock. One particularly interesting biorenewable resource is lignin, part of lignocellulose biomass, giving access to phenolics, i.e. guaiacols, syringols, catechols and pyrogallols. These substrates are often referred to as platform molecules with the potential to serve as renewable feedstock for the production of commodity chemicals as an alternative to oil. However, lignin derived aromatics have a high oxygen content, which is in sharp contrast to benzene, toluene, xylene (BTX) obtained from current petroleum refining. Therefore, instead of an oxidative approach to introduce functional groups required for oil, a reductive approach is needed for bioaromatics. One way to allow a controlled decrease in oxygen content of lignin derived aromatics while maintaining aromaticity is chemoselective hydrodeoxygenation. A particular interesting subclass of HDO reactions is selective hydrodehydroxylation allowing removal of hydroxy groups in presence of methoxy groups. However, this transformation requires pre-activation of the hydroxy group by installment of a leaving group. Acetate is introduced as a renewable leaving group for selective hydrodeacetoxylation of aryl acetates using a homogeneous Ni0-NHC catalyst and pinacolborane reductant in green dimethyl carbonate solvent. Proof-of-concept for oil derived substrates was demonstrated using renewable 4-propylguaiacol obtained from pine wood via reductive catalytic fractionation (RCF). Furthermore, overcoming the limitations of air- and water-sensitive Ni0 catalysts, a heterogeneous Ni-catalyzed hydrodeoxygenation method was developed for methyl aryl carbonates and catechol carbonates. This methodology, Doctorat en Sciences, info:eu-repo/semantics/nonPublished

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Inspired by nature, artificial hydrogen bond‐based anion receptors have been developed to achieve high anion selectivity; however, their binding affinity is usually low. The potency of these receptors is usually increased by the introduction of aryl substituents, which withdraw electrons from their binding site through the resonance effect. Here, we show that the polarization of the C(sp 3 )‐H binding site of bambusuril receptors, and thus their potency to bind anions, can be modulated by the inductive effect. The presence of electron‐withdrawing groups on benzyl substituents of bambusurils significantly increases their binding affinities to halides, resulting in the strongest iodide receptor reported to date with an association constant greater than 10 13 M −1 in acetonitrile. A Hammett plot showed that while the bambusuril affinity toward halides linearly increases with the electron‐withdrawing power of their substituents, their binding selectivity remains essentially unchanged., SCOPUS: ar.j, info:eu-repo/semantics/published

It is widely acknowledged within the scientific community that studying the physical properties of cells can serve as a valuable tool in gaining insight into various diseases and their progression. Across different pathological conditions, researchers have observed distinct variations in these properties. For instance, it has been well-documented that cancer cells are typically less rigid than their healthy counterparts. As such, the potential value of isolating, recovering and studying cells or extracellular vesicles that have undergone such changes for diagnostic and prognostic purposes is incredibly significant.This dissertation presents an exploration into the utilization of an acoustofluidic chip to analyse the density and compressibility of diverse biomimetic particles, and into the capability of the chip in manipulating and sorting the particles solely based on their compressibility. To achieve the research objectives, a rigorous methodology was developed that entailed validating a numerical model to forecast the particles' and cells' behaviour under different resonator designs. The numerical model was used to design a device that could produce half-wavelength resonance or an integer multiple of that, and apply an acoustophoretic field to manipulate and sort solutions of particles. Moreover, three types of biomimetic microparticle solutions with varying compressibility conditions were created, thus simulating diverse experimental scenarios.\In this thesis, it was conducted an analysis on the behaviour of biomimetic microparticles when subjected to acoustophoretic conditions. Specifically, the research involved the use of polyethylene microbeads and biomimetic microparticles, which included Alginate, Polydimethylsiloxane (PDMS), and Giant unilamellar vesicles. To carry out the experiments, the microparticles were exposed to acoustic radiation force within a specially designed acoustofluidic chip. The study relied on the known physical properties of polyethylen, Doctorat en Sciences de l'ingénieur et technologie, info:eu-repo/semantics/nonPublished

Le travail présenté dans ce manuscrit repose sur l’étude et le développement de nouvelles méthodes de synthèse de nanodiamants dans des conditions contrôlées et modérées de pression et de température. Le but de ces études est de pouvoir exercer un contrôle accru sur les propriétés des nanodiamants formés en modérant les conditions drastiques de synthèse. Ainsi, il serait possible d’obtenir des NDs de manière contrôlée du point de vue de leurs propriétés et de franchir leurs barrières actuelles de production. Contrairement aux méthodes usuelles de synthèse qui reposent généralement sur la conversion de dérivés carbonés simples (e.g. méthane, graphite, carbone amorphe), l’approche réalisée dans le cadre de ce manuscrit consiste en l’utilisation de dérivés fonctionnalisés de l’adamantane comme précurseurs moléculaires plus élaborés de nanodiamants. L’hypothèse sous-jacente de cette approche repose sur le principe qu’un précurseur structurellement similaire au diamant (tel que l’adamantane) permettrait d’abaisser les barrières synthétiques. Le présent manuscrit est réparti en chapitres qui exposeront dans un premier temps des notions introductives sur l’adamantane (Chapitre I), les nanodiamants (Chapitre II) et la chimie à haute pression (Chapitre III). Après avoir présenté les objectifs (Chapitre IV) et la stratégie mise en place (Chapitre V), les chapitres suivants seront dédiés à la présentation et la discussion des résultats obtenus. Dans un premier temps, la synthèse des précurseurs dérivés de l’adamantane et de diamantoïdes sera présentée (Chapitre VI). Le chapitre suivant présentera et discutera la conversion des précurseurs en nanodiamants (Chapitre VII). Finalement, des conclusions générales et perspectives (Chapitre VIII), la section expérimentale (Chapitre IX), et les références bibliographiques (Chapitre X) concluront ce manuscrit. En ce qui concerne les résultats présentés dans le Chapitre VI, les synthèses sont divisées en plusieurs sous-chapitres dédiés à, Doctorat en Sciences, info:eu-repo/semantics/nonPublished

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Synthetic anion receptors are increasingly being explored for the transport of anions across lipid membranes because of their potential therapeutic applications. A considerable amount of research focuses on the transport of chloride, whereas the transmembrane transport of inorganic phosphate has not been reported to date, despite the biological relevance of this anion. Here we present a calix[4]pyrrole with a bisurea strap that functions as a receptor and transporter for H2PO4–, relying on the formation of eight hydrogen bonds and efficient encapsulation of the anion. Using a phosphate-sensitive lanthanide probe and 31P NMR spectroscopy, we demonstrate that this receptor can transport phosphate into vesicles by H2PO4–/Cl– antiport, H2PO4– uniport, and Cs+/H2PO4– symport mechanisms. This first example of inorganic phosphate transport by a neutral receptor opens perspectives for the future development of transporters for various biological phosphates., SCOPUS: ar.j, info:eu-repo/semantics/published

Synthetic anion transporters are developed to transport anions across lipid membranes with the long-term perspective of biological applications. The lucigenin assay is a popular tool to study their transport of chloride and other anions in liposomes. It relies on the quenching of the fluorescence of encapsulated lucigenin by anions, which can be monitored by fluorescence spectroscopy. This article provides a tutorial introduction to the practical use and understanding of the lucigenin assay. It describes in detail how to use this assay to monitor chloride/nitrate antiport in liposomes, process and interpret the data, and solve common issues. Variations of the assay enabling the investigation of the transport of other anions and transport mechanisms are discussed. Furthermore, a zwitterionic analogue of lucigenin is demonstrated to have advantages for use in experiments over longer time scales, as it does not leak out of the liposomes, or when studying chloride uniport, as it avoids interference from antiport with nitrate that is present in commercial lucigenin., SCOPUS: ar.j, info:eu-repo/semantics/published

Development of synthetic anion receptors capable of facilitating transmembrane transport across lipid bilayers have been an active area of research since the late 1990s. However, despite the great biological relevance of phosphates, their transmembrane transport by synthetic anion receptors remains an area in which only a few examples can be found.This thesis details the work carried out towards the development of receptors capable of facilitating the transport of organic phosphates, using dynamic covalent chemistry as an approach to the development and synthesis of these receptors. The work is divided into three overall parts describing the three approaches used in the development process. The first part of the thesis deals with the dynamic approach using acylhydrazones as the dynamic covalent functional group, detailing the design concept of the dynamic combinatorial libraries, the synthesis of the building blocks, as well as the initial attempts at carrying out exchange with the obtained building blocks. This chapter also describes the challenges involved in using acylhydrazones in transmembrane transport through a range of acylhydrazone based receptors which have been synthesized and evaluated for Cl-/NO3- antiport in liposomes using the lucigenin assay. The results of these investigations, in combination with the lessons learned from the initial dynamic combinatorial chemistry exchange experiments, led to the conclusion that acylhydrazones turned out to be a moiety with too many drawbacks when used in the design of receptors capable of facilitation of transmembrane transport.The second part of the thesis deals with alternative azomethine based moieties as replacements for acylhydrazones as the dynamic bond. Herein we show that, while imines have some precedent as transmembrane transporters and dynamic combinatorial libraries using imines can facilitate amplification in the presence of TBAH2PO4, outside of edge cases imines are too unstable within a lipidic invi, Doctorat en Sciences de l'ingénieur et technologie, info:eu-repo/semantics/nonPublished

Parmi les systèmes biologiques, on trouve des protéines contenant des centres métalliques dans des architectures bien définies. Celles-ci sont appelées métalloprotéines et font partie des systèmes les plus efficaces pour la détection de petites molécules, le transfert d’électrons ou encore la catalyse. La majorité des métaux impliqués dans ces processus sont des métaux de transition Certaines de ces métalloprotéines sont redox-actives et peuvent associer un cofacteur organique redox directement lié à la chaîne protéique de manière covalente qui joue alors un rôle essentiel dans la catalyse en elle-même ou dans la régénération du catalyseur (ie l’état d’oxydation du centre métallique). On retrouve plusieurs types de cofacteurs organiques redox comme les groupements phénols (résidu tyrosine) ou les groupements quinones. Ces systèmes sont particulièrement adaptés dans la catalyse de petites molécules et le transfert de multiples protons et électrons. Par exemple la cytochrome c oxidase permet la transformation extrêmement efficace de O2 en H2O via le transfert très sélectif de 4 électrons et 4 protons. L’une des transformations de petite molécule qui concentre le plus d’efforts de la recherche scientifique est la catalyse du CO2 en raison de clairs enjeux climatiques associés à son émission excessive par l’homme et sa contribution au réchauffement climatique. L’objectif de cette thèse est d’associer les différents éléments caractéristiques de ces métalloenzymes en un seul système synthétique basé sur les calixarènes. En effet un calixarène chapeauté par un ligand polyazoté permet de reproduire 1) une cavité adaptée à de petites molécules, 2) des cofacteurs organiques situé à distance idéale d’un 3) centre métallique enfoui dans la cavité. La stratégie de cette thèse a donc été de synthétiser les ligands calixaréniques ciblés ainsi que leurs complexes de ZnII d’une part et d’autre part les complexes de CoII correspondant puisque ce dernier est un des métaux les plus pro, Doctorat en Sciences, info:eu-repo/semantics/nonPublished

Here we present a new method to monitor fluoride transmembrane transport into liposomes using a europium(III) complex. We take advantage of the long emission lifetime of this probe to measure the transport activity of a fluorescent transporter. The high sensitivity, selectivity, and versatility of the assay allowed us to study different types of fluoride transporters and unravel their mechanisms of action., info:eu-repo/semantics/published

The development of synthetic molecules able to transport ions through lipid bilayer membranes is of growing interest in the field of supramolecular chemistry. The balance of anions and cations has an important role in the biology of all living organisms. This thesis will focus on the development of copper(I) transporters, the methodologies developed to study them, and their biological applications. The first part of this thesis is focused on the development of copper(I) transmembrane transporters and the methodology required for their study. These transporters were developed for a potential therapeutic application, with the idea that synthetic copper(I) transporters could replace dysfunctional copper(I) transport proteins, which are responsible for distributing copper(I) within cells. Dysfunction of these proteins is the cause of Wilson and Menkes diseases.Calix4arene functionalised with two imidazole groups can strongly bind copper(I) through a linear coordination motif. This ability and their high lipophilicity made them good candidates to transport copper(I) through bilayer membranes. For that, a new assay was developed using liposomes as model systems for membranes, in which a phenanthroline based copper(I) sensitive dye is encapsulated. The changes in fluorescence as monitored by spectroscopy allowed for the observation of copper(I) transport. Most of these results are reported in the publication: “Transmembrane transport of copper(I) by imidazole-functionalised calix[4]arenes” N. Renier, O. Reinaud, I. Jabin, and H. Valkenier. Chem. Commun. 2020, 56, 8206-8209. The improvement and limitations of the transport assay are also described. In the second part, the development of a deliverable copper(I) transporter is described along with the biological effects of the compound on various biological systems. A new transporter was synthesised and shown to be able to reach liposomes membrane when added from an organic solution or from other liposomes, which was not th, Doctorat en Sciences de l'ingénieur et technologie, info:eu-repo/semantics/nonPublished

Mechanistic studies on bicarbonate transport by simple di(thio)amidocarbazoles reveal two distinct transport mechanisms as well as potent antimicrobial properties., info:eu-repo/semantics/published

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The development of synthetic anion transporters is motivated by their potential application as treatment for diseases that originate from deficient anion transport by natural proteins. Transport of bicarbonate is important for crucial biological functions such as respiration and digestion. Despite this biological relevance, bicarbonate transport has not been as widely studied as chloride transport. Herein we present an overview of the synthetic receptors that have been studied as bicarbonate transporters, together with the different assays used to perform transport studies in large unilamellar vesicles. We highlight the most active transporters and comment on the nature of the functional groups present in active and inactive compounds. We also address recent mechanistic studies that have revealed different processes that can lead to net transport of bicarbonate, as well as studies reported in cells and tissues, and comment on the key challenges for the further development of bicarbonate transporters., info:eu-repo/semantics/published