L’objectif de ce travail est la synthèse de complexes contenant des ligands NHC protiques fonctionnalisés avec un groupement imine dans le but de développer des méthodologies de synthèse donnant accès à des ligands pNHC ainsi que la synthèse des groupes imidazolide anioniques liés par le C et leurs complexes homo et hétéro-dinucléaires. Dans le cas des imidazoles sans groupe fonctionnel, la déprotonation à l’aide de n-butyl lithium a permis l’obtention de (1-aryl-1H-imidazol-2-yl)lithium avec de bons rendements. La réaction de (1-aryl-1H-imidazol-2-yl)lithium avec [Ir(cod)(μ-Cl)]2 ou [Rh(cod)(μ-Cl)]2 a conduit à des complexes dinucléaires bipontés en C2,N3. Dans le cas de l’imidazole possédant une fonctionnalité imine, le complexe de l’Ir(I) lié au N de l’imidazole peut se tautomériser en complexe de l’Ir(I) imine avec un ligand pNHC suite à la réaction d’abstraction du chlorure à température ambiante, alors que la tautomérisation de l’analogue du Rh(I) nécessite une température de 110°C. La déprotonation des complexes de l’Ir(I) et Rh(I) liés par le N de l’imidazole avec addition de [Ir(cod)(μ-Cl)]2 ou de [Rh(cod)(μ-Cl)]2 in situ permet l’obtention de complexes homo et hétéro-dinucléaires. La métallation des sels d’imidazolium fonctionnalisés avec un groupement imine s’est avére être une méthode efficace pour la synthèse de complexes métallés ayant un ligand pNHC et a été étendue des complexes bidentes aux complexes chélatants pNHC. / The purpose of this work is the synthesis of complexes containing imine-functionalized protic NHC ligands in order to further develop synthetic methodologies giving access to pNHC, C-bound ‘anionic’ imidazolide, and homo- and heterodinuclear complexes. In the case of imidazoles without functional group, deprotonation with n-butyl lithium afforded (1-aryl-1H-imidazol-2-yl)lithium in good yield. Reaction of (1-aryl-1H-imidazol-2-yl)lithium with [Ir(cod)(μ-Cl)]2 or [Rh(cod)(μ-Cl)]2 yielded a doubly C2,N3-bridged dinuclear complex. In the case of imine-functionalized imidazole, the Ir(I) N-bound imidazole complex can tautomerize to Ir(I) imine-functionalized pNHC complex chloride abstraction at room temperature, while in the Rh(I) analog the tautomerization can be achieved at 110 °C. In situ deprotonation of the N-bound imidazole Ir(I) or Rh(I) complexes, followed by addition of [Ir(cod)(μ-Cl)]2 or [Rh(cod)(μ-Cl)]2 led to the isolation of homo- and heterodinuclear complexes. The metalation of imine-functionalized imidazolium salts is also an effective procedure for synthesis of pNHC metal complexes, and it was extended from bidentate to pincer-type pNHC complexes.

Ce projet consiste à fabriquer et à étudier des micelles à la fois biocompatibles et capables de relarguer des molécules volatiles bioactives à partir d’une solution aqueuse sous l’influence de stimuli extérieurs tel que le pH, la température ou la concentration. Pour atteindre ce but, nous avons étudiés un nouveau type d’objets micellaires qui sont formés par l’auto-assemblage d’amphiphiles covalents dynamiques (DCAs), des surfactants peu onéreux formés de l’association moléculaire réversible d’un bloc hydrophile et d’un bloc hydrophobe. Ces systèmes peuvent relarger une large gamme de fragrances à partir d’une solution, que cela soit à partir du coeur hydrophobe de la micelle ou alors à partir de l’amphiphile (profragrance). Ils ont aussi été capables de stabiliser en solution des aldéhydes sensibles à l’hydrolyse. / This project relies on the simple design and the study of biocompatible responsive micelles, capable of releasing a hydrophobic bioactive volatile from an aqueous solution and that, depending on the modulation of external factors such as pH, temperature, and concentration. To reach this goal, we have taken advantages of a new kind of micellar objects that are formed by the efficient self-assembly of biodegradable Dynamic Covalent Amphiphiles (DCAs), low cost surfactants that are made by the reversible molecular association of one hydrophilic and one hydrophobic block. These systems can release a broad variety of fragrances from solution, both from the hydrophobic micellar core or directly from the amphiphile (profragrance). It also proved able to stabilise some sensitive aldehydes in solution.

Dans cette thèse sont développées les synthèses et caractérisations de nouveaux polymères conjugués pour des applications dans l’électronique organique. Ces polymères ont été synthétisés via des réactions de polymérisation sans utilisation de métaux de transition. Des polyazomethines à base de carbazole ont ainsi été synthétisés par polycondensation entre des carbazole portant des fonctions amine et aldéhyde en positions 2,7 et 3,6. Leurs propriétés optiques et électroniques ont été étudiées en fonction de la position des fonctions imines ainsi formées. Un comonomère de type EDOT a ensuite été intégré dans le polymère et l’impact de ce comonomère sur les propriétés du copolymère ainsi formé a été étudié.Des polymères à base d’acide squarique et croconique ont ensuite été synthétisés. En faisant varierles conditions de synthèse, les propriétés optoélectroniques ont pu être contrôlées, permettant d’obtenir des composés présentant une émission blanche, qui ont ensuite été intégrés en tant que couche active dans des dispositifs de type OLED.Enfin, des polymères plus originaux ont été étudiés, utilisant des réactions de polymérisation originale, permettant par exemple la formation de benzobisthiazole in situ. D’autres polymères ont été synthétisés en intégrant dans leur chaine des monomères originaux, comme la tetrazine ou la divanilline. Les propriétés optoélectroniques de ces composés ont ensuite été étudiées en vue deleur éventuelle intégration dans des dispositifs. / In this work, synthesis and characterizations of new conjugated polymers are described.These polymers, developed for their integration into devices, have been synthesized via transitionmetalfree polymerizations. Carbazole based polyazomethines have been synthesized via polycondensation reactions between di-substituted carbazoles, bearing amino and formyl functionsin positions 3,6 or 2,7. Optical and electronical properties of such polymers have been studieddepending of the linkage position. A comonomer EDOT has then been integrated into the polymer chain, and impact of such insertion has been studied. Squaric and croconic acid base polymers have also been synthesized. By varying polymerization conditions, optoelectronic properties have been tuned, leading to the formation of polymers exhibiting a white emission. These polymers have then been integrated into OLED, as the active layer. Finally, more original polymers have been synthesized, using more original reactions or monomers such as by forming in situ benzobisthiazole. Other polymers integrating more originals monomers, such a tetrazine or divanillin, have been synthesized. Optoelectronic properties of such materials have been studied for the purpose of their integration into devices.

Biological systems have the incredible ability to accomplish uncommon chemical transformations with supreme delicacy. Many of those chemical transformations take place within the pocket of enzymes, which provide unique micro environment. From the quest of better understanding and to mimic such complex biological systems chemists have developed their own prototypes having well-defined cavity. To this end, in last few years many aesthetically elegant 3D discrete architectures have been devised by employing noncovalent interactions especially metal-ligand co-ordination and hydrogen bonding. Conversely, architectures based on purely covalent interactions are relatively limited in number, owing to the laborious traditional covalent synthesis, which involves multi-step synthetic protocols and irreversible covalent bond formations. Nevertheless, in recent times by utilizing dynamic covalent chemistry (DCC) several such organic 3D discrete ensembles have been developed with ease and efficiency from simple and easily accessible building blocks. Interestingly in most of such cases imine condensation reaction has been utilized due to easy formation and cleavage of the imine bonds in an efficient and reversible manner. However, it is quite surprising that even though the dynamic nature of imine bonds has been well established; self-sorting/self-selection process has been overlooked in organic cage systems. Self-sorting in biological realm is a well-established synthetic protocol. DNA double helix formation via hydrogen bonding between the complimentary base pairs is probably the best known example of biological self-sorting. Self-sorting process has the ability to discriminate self from non-self to achieve highly ordered architectures from within a random reaction mixture. The credit of self-sorting/self-selection process goes to the hidden ‘molecular instructions’ encrypted within the complimentary building blocks. The foremost objective of the present thesis work is to implement the self-sorting/self-selection protocol in organic cage formation by harnessing the dynamic imine chemistry. During the course of the investigation it has been observed that non-covalent interaction especially hydrogen bonding could manipulate the outcome of such a process. Besides that, selective formation of a single isomer of an organic cage from a reaction mixture of an unsymmetrical aldehyde and a flexible amine has been successfully achieved by simply fine tuning the geometric features (shape and size) of the reacting aldehyde. Such three-dimensional cages are well appreciated by the scientific community owing to their potential applications in anion sensing, catalysis and gas storage/separation. However, they have not been explored as sensors for nitroaromatic explosives. Therefore, at this juncture several fluorescent organic cages have been synthesized and their potential application as chemosensor for the nitroaromatics has been tested. Moreover, a new synthetic protocol has been introduced for the post-synthetic modification of organic cages. Chapter 1 covers a brief introduction about dynamic covalent chemistry with main emphasis on dynamic imine chemistry and its use in covalent cage synthesis. Moreover, this chapter accounts the very recent applications of such cage compounds in various fields such as a pours material for gas storage/separation, a molecular host for the stabilization of reactive species and for the recognition of ions or molecules. Chapter 2 describes first time ever achieved self-sorting process in three-dimensional purely organic cages. First of all, four different [3+2] cages were synthesized by treating two different triamines with two different dialdehydes separately, by employing dynamic imine chemistry. The formation of desired cages was ascertained by various spectroscopic techniques. When a mixture of all the four components (two aldehydes and two amines) was subjected to reaction, only two cages were found to form (Scheme 1) out of several equally probable possibilities, which suggest a high-fidelity self-recognition. The issue of partner preferences was further verified by transforming a non-self-sorted cage into a self-sorted cage by treating the former with appropriate triamine or dialdehyde. For an in-depth understanding on this subject, theoretical calculations (gas phase DFT) were carried out, which suggested that observed self-sorting is a thermodynamically governed process. Scheme 1. Self-sorting in organic imine cages through partner preferences. Chapter 3 focuses that supramolecular interaction especially hydrogen-boding could be a possible way to direct a self-sorting process operating in imine based organic cage systems. It is a well-accepted fact that in most of the cases self-sorting process operates owing to the difference in geometric features (shape and size) of the competing building blocks. Thus increasing similarity in geometric features would create the situation more complex. It is anticipated that in such circumstances H-bonding could have a decisive role in partner selection. In order to investigate this, four different dialdehydes (A, B, C and D) having similar geometric background were synthesized. These aldehydes upon treatment with flexible amine X were found to form three nanosocpic [3+2] organic cages (aldehyde C gave insoluble uncharacterized material). When a one-pot reaction of triamine X with mixture of all the four aldehydes was carried out, selective formation of cage B3X2 was observed (Scheme 2). Conversely, the same reaction in absence of aldehyde B resulted in the formation of mixture of products. Theoretical and experimental studies fully support the fact that the presence of hydroxyl moiety adjacent to the formyl group in aldehyde B has the key role in selective formation of cage B3X2 from a complex reaction mixture, in which there are numerous equally probable possibilities. Such remarkable selection was further examined by converting a non-hydroxy (non-preferred) cage into hydroxy cage B3X2 (preferred) by treating the former with aldehyde B. The role of the H-bond in self-sorting process of two dialdehydes and two triamines has been established. Furthermore, the possibility of cage–to- cage transformation through imine bond metathesis has also been addressed. Scheme 2. H-bond directed 15-fold (2+3) incomplete self-sorting in organic imine cages. Chapter 4 presents the investigation on the formation of single isomeric species of a [3+2] oligoimine cage from a reaction mixture of an unsymmetrical dialdehyde and a flexible triamine. So far, most of the reported organic cages are derived by symmetric building units. Asymmetric building blocks for the construction of such organic architectures are not the desirable choices, as they could lead to form mixture of isomeric cages. However, the asymmetric building blocks might form selectively one isomer only under the thermodynamic bias, which prefers the formation of one isomer over the other (s). In order to understand the factors that can direct such a process, three asymmetric dialdehydes (A, B and C) were synthesized and their reaction with a flexible amine X was carried out. Experimental outcomes suggested a striking difference in the abilities of isomer selection between aldehydes A/B and C. In case of aldehyde A/B selective formation of one oligoimine cage was observed, whereas aldehyde C led to form two isomeric oligoimine cages (Scheme 3). Experimental and theoretical findings have pointed out that the geometric features (shape and size) of the aldehyde play a decisive role in such isomer selection process. Scheme 3. Shape and size directed self-selection in organic imine cages. Part A of Chapter 5 describes the synthesis and characterization of a fluorescent organic cage compound and its application as a sensor for the detection of explosive picric acid (PA). Picric acid is known to be as explosive as trinitrotoluene (TNT) and one of the principle constituents of many unexplored landmines. Though there are several fluorescent polymers, metal-organic frameworks and small molecule based sensors have been devised in last few years but very little attention has been given towards selective and sensitive detection of picric acid. In this context desired organic cage compound 4 was synthesized by employing imine condensation between 4,4-diformyltriphenylamine (1) with 1,3,5-tris(aminomethyl)-2,4,6-trimethylbenzene (2) followed by reduction of the imine bonds (Scheme 4). This fluorescent nature of the cage in both the solid and solution has been utilized for the detection of nitroaromatic compounds (NACs). Among the various NACs tested it has been found that PA induces highest quenching of the initial fluorescence intensity of the cage solution. Furthermore, this cage has the ability to discriminate PA from other nitrophenolic compounds, such as 2,4-dinitrophenol (DNP) and 4-nitrophenol. In addition to solution phase detection cage 4 has also been successfully utilized for the solid phase detection of PA. The experimental results demonstrates that high sensitivity of the cage towards PA is attributed to the stronger ground state complex formation between the cage and PA as well as excitation v energy transfer (EET) process from protonated cage to the picrate. This represents the first report of a cage compound as a sensor for nitroaromatic compounds. Scheme 4. Synthesis of a fluorescent organic cage for the selective detection of picric acid. Part B of Chapter 5 reports a new synthetic methodology to decorate covalent organic cages post-synthetically, based on one-pot copper(I) catalyzed A3 coupling. A3-coupling is a three-component reaction between formaldehyde, secondary amine and terminal alkyne. In the present study selected organic cage 4 is furnished with six secondary amine moieties and thus it was allowed to react with 6 equiv. of formaldehyde and 6 equiv. of terminal alkyne in presence of CuI as a catalyst (Scheme 5). By employing this synthetic strategy parent cage 4 has been modified to cages 5a-c with appendages phenyl-, xylyl- and napthyl-actylenes. The resulting decorated cages were characterized by multinuclear NMR (1H and 13C), MALDI-TOF and FTIR spectroscopy. All the post-synthetically decorated cages were found to be fluorescent in nature and thus in v order to explore their potential use as a chemosensor for nitroaromatic compounds, cage 5a was tested. Experimental findings have suggested high selectivity of the cage towards nitroaromatic compounds. Interestingly, among the various nitroaromatics tested it has been observed that the cage is more sensitivity towards nitrophenolic compounds, whereas among the various nitrophenols tested, picric acid induced highest quenching. Scheme 5. Post-synthetic modification of an organic cage via cu+ catalyzed A3 coupling.

The work presented in this Thesis describes the design, synthesis and reactivity of a symmetric and various asymmetric Schiff-base macrocycles that are capable of forming a wedge-shaped “Pacman” conformation upon metal binding. Chapter One introduces catalysts for small molecule transformation as well as transition metal complexes of pyrrole-containing macrocycles. Further to this, Pacman systems, including previous work from Love and co-workers, and complexes capable of secondary coordination-sphere control will be discussed. Chapter Two details the design and synthesis of two asymmetric macrocycles that both contain one neutral and one N₄-donor imine-pyrrole binding pocket, H₂LP and H₂LNMe. The synthesis and characterisation of the series of complexes [M(LP)] and [M(LNMe)] (M = Pd, K₂, Co, VCl, TiCl, Mg, Fe and Mn) and their characteristics highlighted, including the formation of a supramolecular cyclic hexamer. Chapter Three presents the modification of the above ligands at the meso-group, the N-substituent and the non-pyrrolic binding pocket to give H2LFP and H₂LFNMe, H₂LNMes and H₂L(NH)NMe respectively. Palladium and cobalt complexes of these macrocycles were prepared and characterised. Chapter Four describes the design and synthesis of the ligand H₄LEt as well as the synthesis and characterisation of tin-alkyl and mononuclear calcium complexes of LEt, as well as the heterobimetallic complexes [SnMe₂(M)(THF)(LEt)] (M = Zn or Fe). The homobimetallic complexes [M₂(LEt)] (M = Co, Mg and NbCl) are also presented along with a magnesium-cubane structure of LEt in which the cubane is encapsulated by two, bowl-shaped macrocycles. Chapter Five provides a summary of the work presented in this thesis. Chapter Six describes the full experimental details and analytical data for all compounds synthesised in this work.

Thesis (MSc (Chemistry and Polymer Science))--Stellenbosch University, 2008. / In this study the coordination of ligands with several coordination sites, 2-aminoazoles (2- amino-4-methylthiazole), 2-aminobenzothiazole, 2-aminobenzoimidazole and 2- aminothiazoline and a biguanidine (N-(2-methylphenyl)imidodicarbonimidic diamide) to soft metal centres [gold(I) (group 11), chromium(0) (group 6) and tungsten (0) (group 6)] was investigated. The aminoazoles have three coordination sites, an exocyclic amine nitrogen, an endocyclic imine nitrogen and an endocyclic thioether sulphur. The biguanidine ligand has three sites for deprotonation, one central amine and two imine nitrogens, and at least five sites available for nitrogen coordination.

The addition of isocyanates to C=N double bonds of imines gives triazindione heterocycle structures; their thermal properties are reported. Mono-isocyanates were used to form 2:1 adducts with the imine bases 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and 2-tert-butyl-1,1,3,3-tetramethylguanidine (tBuTMG). A 2:1 stoichiometry of the adducts was proven by NMR and IR spectroscopy, and single crystal X-Ray diffraction; certain cleavage temperatures (70 and 160 °C) were measured. Thermal analysis (TG-MS) of adducts indicates the release of free isocyanate during adduct cleavage. Furthermore, a new class of step-growth oligomers (MN = 750–7,000 g∙mol–1) composed of multi-functional isocyanates and these imine bases was introduced. Their systematic spectroscopic and thermal analysis is shown revealing the similarity in their chemical properties to the 2:1 adducts. Radical homo- and copolymerization of acrylates is initiated by the meta-stable adducts and oligomers of this work; the generation of novel telomeric block-copolymer architectures composed of polyacrylate and oligourea building blocks is demonstrated. / Dieser Beitrag ist aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

A terapia de quelação tem sido descrita na literatura como uma ferramenta importante no combate de processos neurodegenerativos como a doença de Alzheimer (AD). Esta doença é caracterizada pela agregação de peptídeos β-amiloides, formando fibrilas, que parece ser induzida ou facilitada em presença de íons metálicos como Cu2+, Zn2+ ou Fe3+. Vários compostos já foram testados e descritos como ligantes competitivos para coordenar e retirar estes íons dos agregados proteicos em condições patológicas, na chamada hipótese da cascata amiloide. O presente projeto visou investigar a reatividade de ligantes imínicos, derivados de oxindóis, na quelação de cobre(II) e zinco(II), numa tentativa de inibir ou evitar a formação de agregados relacionados à AD. Foram sintetizados seis compostos imínicos, sendo duas hidrazonas inéditas: isahim e isahpy e quatro bases de Schiff: isapn, misapn, isaen e misaen, as três últimas também inéditas. Os compostos foram caracterizados por espectroscopia FTIR, RMN, UV/VIS e por análise elementar CHN e espectrometria de massas ESI-MS/MS. Os valores das constantes de estabilidade (log β 2,7 - 5,1) para a formação dos complexos [ML]2+ e do aduto [(Aβ1-16)2•isahim] em solução aquosa foram determinadas por espectroscopia UV/VIS. As formas de interação dos compostos isapn, misapn e isahim com o peptídeo Aβ1-16 foram analisadas por espectroscopia 1H RMN, observando-se uma forte interação com as histidinas His6, His13 e His14 e com os carboxilatos do peptídeo. A eficácia dos ligantes foi testada frente ao processo de inibição da agregação do peptídeo Aβ1-40 na presença e ausência de íons Cu2+ ou Zn2+ por turbidimetria. Estudos de docking e dinâmica molecular suportam que a interação dos ligantes imínicos com o peptídeo Aβ1-16 ocorre nos mesmos sítios de coordenação dos íons metálicos. Os resultados indicam que os compostos aqui estudados podem atuar como eficientes inibidores de agregação dos peptídeos amiloides implicados na AD. / Chelation therapy has been considered in the literature an important tool in neurodegenerative processes like Alzheimer disease (AD). This disease is characterized by aggregation of β-amyloid peptides that seems to be improved in the presence of metal ions, particularly copper, zinc and iron. Several compounds have been tested and reported as competitive ligands to withdrawal these metal ions from protein aggregates in pathologic conditions, in the \"amyloid cascade hypothesis\". The present project aims to investigate the reactivity of imine ligands, particularly those derived from oxindoles, in the chelation of copper(II) and zinc(II) ions trying to inhibit or avoid aggregate formation related to AD. Six iminic compounds were synthesized, being two of them hydrazones: isahim and isahpy and four Schiff bases: isapn, misapn, isaen, and misaen. The compounds were characterized by spectroscopic analysis (FTIR, NMR, UV/VIS), elemental analysis CHN and mass spectrometry ESI-MS/MS. The corresponding stability constants (log β 2,7-5,1) for each complex formation [ML]2+ as well as for the adduct [(Aβ1-16)2•isahim] in aqueous solution were determined by UV/VIS spectroscopy. Interactions of compounds isapn, misapn and isahim with the Aβ1-16 peptide were detected and analyzed by 1H NMR spectroscopy, indicating a strong interaction among the compounds and the histidines His6, His13 e His14 as well as the carboxylate residues in the peptides. The ligands efficiency toward the inhibition aggregation process for the Aβ1-40 peptide were evaluated in the presence, and in absence of Cu2+ or Zn2+ ions by turbidimetry. Computational calculations (docking and molecular dynamics) indicated that the interaction of the imine ligand with the Aβ1-16 peptide occurs in the metal coordination sites. The results indicate that these imine compounds studied may act as efficient inhibitors of amyloid peptides implicated in AD.

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