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

Systems chemistry is an emerging field of chemistry that studies complex mixtures of molecules that give rise to emergent properties that are not always predictable when studying the components of the mixtures in isolation. A systems chemistry approach has been adopted in fields such as self-assembly and self-sorting, where the dynamic recognition of complementary binding motifs to organize molecules is the central focus. Supramolecular systems are assembled through reversible, non-covalent interactions. The reversibility of supramolecular systems makes them dynamic. Understanding the dynamic nature of complex systems will allow for a bottom-up approach to the rational design of complex mixtures, such as kinetically trapped self-sorting systems. The first objective of this work was to understand the effects the identity and concentration of biologically relevant metal cations have on a the mechanism of binding and rate of kinetics of a cucurbit[7]uril (CB[7])-guest complex. Metal cations are frequently added to cucurbit[n]uril (CB[n]) systems. While metal cations are known to decrease the overall equilibrium constant of a CB[n]-guest complex, there has not been much consideration about how different metal cations can affect the CB[n]-guest binding mechanism beyond introducing competitive equilibria. Kinetic studies of the interactions between CB[7] and 1-(2-naphthyl)-ethylammonium (NpH+) in the presence of Ca2+ and Na+ were investigated. It was found that the binding mechanism between NpH+ and CB[7] was the formation of an exclusion complex and an inclusion complex. An exclusion complex is the formation of a complex where the cationic ammonium group of the guest associates to the carbonyl lined portals of CB[7], while the aromatic group remains exposed to the surrounding; while an inclusion complex is formed when the aromatic group of the guest enters the hydrophobic cavity of CB[7]. By increasing the metal cation concentrations, the exclusion complex was seen to disappear from the overall kinetics. When Ca2+ cations were used instead of Na+ cations, a Ca2+ cation capped inclusion complex was formed. The Ca2+ cation capped inclusion complex was found to have a lower dissociation rate constant than the uncapped complex between NpH+ and CB[7]. The second objective of this work was to understand how the structure of guest molecules effected the kinetic time scale of reaction with CB[7]. The kinetics between CB[7] and three different aromatic dications were measured to understand the structural features that influence the change in kinetic time scales: methyl viologen (MV2+), benzidine (Bn2+) and 2,7’-dimethyl-diazapyrenium (MDAP2+). It was found that moving the cationic charges further apart slowed down the kinetics from the sub millisecond time scale (MV2+) to the millisecond time scale (Bn2+); further, it was found that adding rigidity and width to the molecule (MDAP2+) slowed down the kinetics onto the minute time scale. The final objective of this work was to use the understanding of complexity gained in the metal cation project and the guest design for kinetic time scales project to rationally design a kinetically-trapped self-sorting system. The equilibrium constants and time scale of kinetics between a ditopic guest molecule and three host molecules (CB[6], CB[7] and β-CD) were determined to investigate the feasibility of the kinetically-trapped self-sorting system. Due to the complexity introduced by metal cations discovered earlier, β-cyclodextrin (β-CD) was used to modulate the concentration of guest that could be bound by CB[n]s. As a concentration modulator the requirements of β-CD were that the kinetics must be faster than the millisecond time scale and the equilibrium constant with the guest must be much lower than the equilibrium constants between the guest and CB[n]s. CB[6] was proposed as a thermodynamic sink due to its slow kinetics for complex formation with benzyl ammonium. The requirements for the guest complexation with CB[6] were that the kinetics had to be on the minute to hour time scale and the equilibrium constant with the guest had to be the highest of the three host molecules. CB[7] was chosen as the kinetic trap of the self-sorting system. The requirements for the CB[7] complex were that the kinetics had to be on the millisecond to second time scale and the equilibrium constant needed to be lower than the equilibrium constant of the guest@CB[6] complex, but higher than the guest@β-CD complex. The kinetic and thermodynamic requirements between the guest molecule and CB[7], and between the guest molecule and β-CD were met. The kinetics between CB[6] and the guest molecule were on the hour time scale, meaning the kinetic requirement was met, however, the equilibrium constant was found to be lower than the equilibrium constant between the guest molecule and CB[7]. The results in this work showed that the rational design of kinetically-trapping self-sorting systems is possible, but some modifications to the structure of the guest molecule is required to make this self-sorting system work. / Graduate / 2021-06-05

The work presented herein focus upon crystal engineering of nutraceutical cocrystals. Cocrystals are considered unique solid dosage form which has many advantages over other traditionally known solid forms. Furthermore, cocrystals have proven to improve stability, solubility and bioavailability of Active Pharmaceutical Ingredient (API) as shown in the case of carbamazepine and other APIs in previous studies. Crystal engineering is commonly used to design new solid forms based on the bases of supramolecular chemistry. In this study, crystal engineering based on intensive Cambridge Structural Database (CSD) analysis used to predict and design new cocrystals of targeted nutraceuticals. Two nutraceuticals were selected for this study; resveratrol and citric acid. The rationale behind selecting resveratrol was to improve its solubility and, accordingly, bioavailability. On the other hand, citric acid is known as a highly soluble and safe nutraceutical, and thus it can be used as a coformer. Five new cocrystals were prepared and characterized using a variety of techniques that include single crystal X-ray diffraction (XRD), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), FT-IR, and thermo-gravimetric analysis (TGA). Most of the reported cocrystals were obtained using different techniques; solvent slow evaporation, mechanichemical approach, slurry, and from melt. Moreover, dissolution test has been performed on resveratrol and two of its cocrystals, using UV-vis spectrophotometer, where the data demonstrate that through cocrystallization with different cocrystal formers, solubility of resveratrol could be greatly modified, and further controlled. The polymorphism phenomenon is encountered, and accordingly addressed, herein where four novel polymorphs were obtained during cocrystallization attempts. Polymorphism has a significant importance in industry, in general, and in pharmaceutical industry, in particular, due to the vast differences in physical properties of polymorphs. Furthermore, the study of polymorphism provides valuable information essential to understand how different crystal forms are attained.

This dissertation investigates the chemical ingenuity into the development of various photoactive supramolecular donor – acceptor systems to produce clean and carbon free energy for the next generation. The process is inspired by the principles learned from nature’s approach where the solar energy is converted into the chemical energy through the natural photosynthesis process. Owing to the importance and complexity of natural photosynthesis process, we have designed ideal donor-acceptor systems to investigate their light energy harvesting properties. This process involves two major steps: the first step is the absorption of light energy by antenna or donor systems to promote them to an excited electronic state. The second step involves, the transfer of excitation energy to the reaction center, which triggers an electron transfer process within the system. Based on this principle, the research is focused into the development of artificial photosynthesis systems to investigate dynamics of photo induced energy and electron transfer events. The derivatives of Porphyrins, Phthalocyanines, BODIPY, and SubPhthalocyanines etc have been widely used as the primary building blocks for designing photoactive and electroactive ensembles in this area because of their excellent and unique photophysical and photochemical properties. Meanwhile, the fullerene, mainly its readily available version C60 is typicaly used as an electron acceptor component because of its unique redox potential, symmetrical shape and low reorganization energy appropriate for improved charge separation behavior. The primary research motivation of the study is to achieve fast charge separation and slow charge recombination of the system by stabilizing the radical ion pairs which are formed from photo excitation, for maximum utility of solar energy. Besides Fullerene C60, this dissertation has also investigated the potential application of carbon nanomaterials (Carbon nanotubes and graphene) as primary building blocks for the study of the artificial photosynthesis process.

<p>  </p> <p>A staggering number of problems in materials chemistry relate to controlling the assembly of matter at <10 nm scales, including those with applications in nanoelectronics, energy harvesting, and biomedical device design. It is difficult to achieve precise chemical patterning at the short length scales required for such applications using traditional top-down fabrication methods (<em>e.g., </em>lithographic techniques). On the other hand, biological systems create high-resolution chemical patterns with remarkable efficiency, by assembling simple molecular building blocks with nm-scale features (<em>e.g.,</em> nucleotides, amino acids, lipids) into structurally complex motifs capable of carrying out the diverse functions required for life. </p> <p>Drawing inspiration from the diverse structures and functions of lipids in biological membranes, this work uses lipids to create high-resolution chemical patterns at interfaces, control the growth and self-assembly of nanocrystals, and to facilitate interactions that precisely template nanocrystals at chemically patterned surfaces.</p> <p>Functional alkanes assemble into striped phase monolayers on highly oriented pyrolytic graphite (HOPG), in which the alkyl chains are oriented parallel to the substrate, expressing both the polar and nonpolar regions of the amphiphile at the environmental interface. The same is true for diyne phosphoethanolamine (dPE), a phospholipid with a zwitterionic headgroup. When assembled into striped phases on HOPG, the headgroup zwitterions of dPE are confined in 1-nm-wide rows of functional groups with a pitch of ~7 nm, resulting in ordered arrays of orientable dipoles at the HOPG surface. The chemistry of dimensionally confined functional groups is distinct from bulk solution phase chemistry, and in this case enables powerful directing effects which can be used to template the adsorption of ultranarrow gold nanowires (AuNWs) in precise alignment with the template stripes. </p> <p>Technical grade oleylamine (<em>cis</em>-9-octadecen-1-amine, OLAm, 70% purity) serves as the capping ligand for the AuNWs used in this work, and additionally plays an important role in the assembly of AuNWs at dPE/HOPG surfaces. While technical-grade reagents enable cost-effective and scalable production of materials, variation in the composition of impurities between different batches have significant impacts on nanocrystal morphology and assembly. We show that thermal transitions of alkyl chain impurities (<em>trans</em> and saturated chains) in AuNW ligand shells can be used to regulate AuNW assembly at chemically patterned interfaces. </p> <p>Characterization of OLAm reagents by 1H NMR and mass spectrometry reveals significant and highly variable fractions elaidylamine (ELAm, <em>trans</em>-9-octadecen-1-amine) and octadecylamine (ODAm) between different batches of OLAm. To understand the phase behavior of mixtures of the C18 alkylamines commonly found in technical grade OLAm, we synthesize isomerically pure OLAm and its <em>trans</em> isomer, elaidylamine (ELAm), to generate binary and ternary mixtures with (ODAm), which is commercially available in high purity. Differential scanning calorimetry reveals limited miscibility of the C18 chains, and demonstrates the significant impact of chain composition on the physical properties of mixtures of alkyl chains (<em>e.g.,</em> tech. grade OLAm). Finally, we examine the impacts of <em>trans</em> and saturated alkyl chains on AuNW synthesis. We find that inclusion of ODAm and ELAm in the ligand blend used for AuNW synthesis each result in shorter AuNWs than those synthesized with pure OLAm. We also observe enhanced stability of surface adsorbed AuNWs conferred by <em>trans </em>and saturated chains. </p>

Pillar[n]arenes are a class of macrocycles with outstanding properties given by its electron rich and symmetric cavity, and facile functionalization that allows to tune its solubility and host-guest properties. In this work, the versatility of pillar[n]arenes for the design of porous materials is studied. Pillar[n]arenes are stable to guest removal, giving solvent-free phases and thus resulting in permanent porous structures. From simple ethyl pillar[5,6]arenes, nonporous adaptive crystals are obtained and studied for the recognition and separation of butanol isomers. The cavity size of the pillar[n]arene hosts and the linear or branched characteristic of the butanol isomers influences the assembly of the pillararene to selectively adsorb an isomer. Then, an A1/A2 benzaldehyde-functionalized pillar[5]arene is used as a building block for the synthesis of an imine porous organic cage, which would result in material with intrinsic and extrinsic porosity. Finally, a lipoic acid modified pillar[5]arene is implemented as ligand for nanoclusters, improving their stability. Taking advantage of the cavity of the pillar[5]arene, a host-guest complex is formed, enhancing the optical properties of nanoclusters.

L'objectif de cette thèse est la mise en place et l'étude d'un transfert d'énergie électronique réversible (REET), à la suite d’une excitation lumineuse, entre des sous-composants moléculaires au sein d’architectures nanométriques de type rotaxane. Dans un système bichromophorique, lorsque les états excités du chromophore les plus bas sont quasi-isoénergétiques et que la cinétique du transfert interchromophore est rapide, le REET peut être instillé en modifiant les propriétés de l'état excité. Des dérivés du pyrène et du tris(bipyridine)ruthénium(II) ont été choisis comme chromophores appariés. La formation de rotaxane a été catalysée par du cuivre (réactions de Huisgen et Cadiot-Chodkiewicz) au sein d’un macrocycle doté de pyrène, couplant des demi-fils moléculaires comprenant des groupements terminaux volumineux - dont Ru(bpy)32+. Des durées de vie de luminescence prolongée (jusqu'à 14 μs), comparées au parent Ru(bpy)32+, indiquent que des processus de transfert d'énergie électroniques réversibles ont été établis dans une série de rotaxanes de structure variable, sont étudiés par spectroscopies stationnaire et résolue dans le temps. / The focus of this thesis is the establishment and study of reversible electronic energy transfer (REET), following light excitation, between molecular subcomponents within ring-on-thread rotaxane nanometric architectures. When the lowest-lying chromophore excited states are quasi-isoenergetic and kinetics of interchromophore transfer are rapid, REET can be instilled - changing excited-state properties. Pyrene and ruthenium(II) tris(bipyridine) derivatives were chosen as matched chromophores. Rotaxane formation was based on active template copper catalysis (Huisgen and Cadiot-Chodkiewicz reactions) within a pyrene-decorated macrocycle, coupling half threads comprising bulky stopper groups - one of which being Ru(bpy)32+. Prolonged luminescence lifetimes (up to 14 μs), compared to parent Ru(bpy)32+, indicated that reversible electronic energy transfer processes were instilled in a series of rotaxanes of varying structure, which were studied by state-state and time-resolved spectroscopies.

Dans ce travail, nous présentons dans la première partie la substitution du molybdène par du tungstène dans les anions de type Keplerates, [{Mo6}12Mo30O312E60(AcO)30]42- (E = O or S). L'introduction du tungstène dans le milieu de synthèse a entraîné l'isolement d'une série de composés, [{WxMo6- x}12Mo30O312E60(AcO)30]42-, avec une teneur en métal variable dans leurs unités pentagonales {M6}. Une observation remarquable a révélé l'occupation sélective de la position centrale dans l'unité pentagonale par les atomes W. Cette observation a été étendue à d'autres structures telles que les roues du bleu du molybdène [Mo154O462H14(H2O)70]14- et l’anion Krebs [Mo36O112(H2O)16]8- qui ont également montré la même occupation préférentielle des atomes W pour le site héptavalent, au centre du pentagone. Dans la deuxième partie, nous nous concentrons sur l’élaboration d'un matériau hybride à trois composantes à base de polyoxométallates (POM), de clusters métalliques et de - cyclodextrine ( -CD). La conception de ce matériau suivant une approche synthétique basée sur la propagation à l’infini des interactions spécifiques entre la CD et les deux types d'unités inorganiques. Dans la dernière partie, nous étendons l’étude des interactions CD-POM aux structures POMs géantes telle que l’anneau du bleu du molybdène. Une complexation non conventionnelle résulte de l'encapsulation du macrocycle organique dans la cavité centrale du l’anneau inorganique anionique. Accroître la complexité du système en introduisant une troisième espèce, conduit à la formation d'un assemblage supramoleculaire hybride par agencement hiérarchique des molécules organiques et inorganiques / In this work, we report in the first part the substitution of molybdenum by tungsten within Keplerate-type anions [{Mo6}12Mo30O312E60(AcO)30]42- (E = O or S). Introducing tungsten to the synthesis medium resulted in the isolation of a series of compounds, [{WxMo6- x}12Mo30O312E60(AcO)30]42, with variable metal content within their pentagonal units {M6}. An outstanding observation revealed the selective occupation of the central position in the pentagonal unit by the W atoms. This revelation was stretched to reach other historical structures as Mo-blue wheel [Mo154O462H14(H2O)70]14- and Krebs [Mo36O112(H2O)16]8- anions that also showed the same preferential occupation of W atoms for the heptacoordinated site. In the second part, we focus on the fabrication of a three-component hybrid material based on polyoxometalates (POMs), metallic clusters and -cyclodextrin ( -CD). Investigation of such material has been conducted using bottom-up approach by investigating the specific interactions between CD and both types ofinorganic units. Finally, the three componentsassociate together to give a well orderedpolymer-like hybrid chain that is derived ashydrogel and single crystals. In the last part, we extend the CD-POMinvestigation to reach giant POM structures asthe Mo-blue ring. A non-conventional complexation results from this interaction explained by the encapsulation of the organic macrocycle within the inorganic torus. Increasing the complexity of the system by introducing a third species provoked the formation of a hierarchical hybrid assembly.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第20201号 / 理博第4286号 / 新制||理||1616(附属図書館) / 京都大学大学院理学研究科化学専攻 / (主査)教授 北川 宏, 教授 竹腰 清乃理, 教授 島川 祐一 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

付記する学位プログラム名: 充実した健康長寿社会を築く総合医療開発リーダー育成プログラム / 京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第21798号 / 工博第4615号 / 新制||工||1719(附属図書館) / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 松田 建児, 教授 杉野目 道紀, 教授 浜地 格 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM