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In this research a range of salen ligands have been synthesised with a variety of diamine backbones.;Derivatives of these ligands (M = Ni(II), Zn(II), Cu(II)) have subsequently been prepared and used as catalysts in the synthesis of enaminodiones, the enantioselective alkylation of carbonyls and imines, the enantioselective trifuoromethylation and the enantioselective Reformatsky reaction.;Yields better than 90% were achieved for the enaminodiones reaction for [Zn(salen)] derivatives in 24 hours and a range of substrates was studied. Once the best catalysts and conditions were determined, experiments were carried out in order to determine the recyclability of the catalyst by supporting it on Silica gel or FRPSG (Fluorous Reverse Phase Silica Gel). Unfortunately, only one catalyst could be recovered four times without loosing activity. ICP/MS showed large amounts of Zn in the organic phase.;In the enantioselective addition of ZnEt2 to benzaldehyde, the conversion was calculated by 1H NMR spectroscopy and the enantioselectivity was calculated using chiral GC. Non fluorous [Zn(Salen)] demonstrated to enhance enatioselectivity better than fluorous ones. However, results for one fluorous salen ligand were good enough to perform recycling experiments using FPSE (Fluorous Solid Phase Extraction).;In the enantioselective trifluoromethylation of benzaldehyde the conversions were calculated by 1H NMR spectroscopy and enantioselectivities were studied by chiral GC. Poor enantioselectivities were obtained and [M(salen)] complexes demonstrated not to be catalysts for this reaction. In the enantioselective Reformatsky reaction the conversion were calculated by 1H NMR spectroscopy and the enantioselectivity was calculated by using a chiral solvent. However, no enantioselectivity was induced in any case. In the enantioselective addition of ZnEt2 to benzaldehyde the conversion was calculated by 1H NMR spectroscopy and the enantioselectivity was calculated by HPLC. No enantioselectivity was induced using these catalysts.

Mammalian cells contain a pool of iron not strongly bound to proteins. The cellular ligands of this biologically important 'chelatable', 'labile' or 'transit' iron are not known. Such ligands are expected to prevent iron from undergoing redox cycles that catalyse hydroxyl radical formation. Amongst small cellular molecules, myo-inositol phosphates containing the equatorial-axial-equatorial 1,2,3-trisphosphate grouping, are very effective at complexing Fe3+ in such a 'safe' manner ill vitro. myo-Inositol hexakisphosphate (InsP6, phytic acid), the most abundant inositol phosphate, was consequently recognised as a potential candidate for an intracellular Fe3+ ligand. However, thermodynamic data has recently excluded InsP6 as a potential intracellular Fe3+ complexing agent due to competition with the more abundant Mg2+ cations. It is not clear however, whether this same limitation also applies to myo-inositol 1,2,3- trisphosphate [Ins(l,2,3)P3], the simplest member of this group. Ins(1,2,3)P3 is a cellular constituent of unknown function, present in a variety of mammalian cells at concentrations of 1-10 JIM. The aim here was to synthesise Ins(I,2,3)P3 and study for the first time, its metal complexation behaviour under simulated cellular conditions. The stability constants of the comf-Iexes formed by Ins(I,2,3)P3 with biologically relevant metal cations (Na+, K+, Mg +, Ca2+, Cu2+, Fe2+ and Fe3+) are reported. These data indicate that Ins(1,2,3)P3 can be expected to complex to all available Fe3+, both in the cytosol/nucleus and acidic cellular compartments. The capability of Ins(1,2,3)P3 to inhibit iron redox cycling and associated production of free radicals is crucial, as redox-active iron should have been minimised by evolution. The binding conformation of Ins(1,2,3)P3 is predicted to be key to the ability of the 1,2,3-trisphosphate motif to bind iron in a 'safe' manner. Ironcoordinated Ins(1,2,3)P3 has been proposed to adopt the less stable penta-axial conformation, orientating the phosphate groups axial-equatorial-axiaL Structural examination of the Ins(I,2,3)P3-Fe3+ complex however, is severely restricted due to the paramagnetic properties of Fe3+ cations. In this work, the structure of the Ins(1,2,3)P-Fe3+ complex has been studied using a combination of approaches. The synthesis of 4,6-carbonate-myo-inositol 1,2,3,5-tetrakisphosphate as a model for the penta-axial conformation of the 1,2,3-trisphosphate motif is described. Subsequent iron binding studies with this molecule were comparable to that of Ins(1,2,3)P3. In contrast, the simple straight-chain analogue, trisphosphoglycerol, was unable to completely inhibit Fe3+-catalysed free radical formation. Furthermore, it was possible to monitor the conformation using a synthetic pyrene-based fluorescent probe, 4,6- bispyrenoyl-myo-inositol 1,2,3,5-tetrakisphosphate. Conformational ring-flip of the cyclohexane chair upon association with Fe3+ is accompanied by a dramatic change in fluorescence emission, due to 1C-1C stacking of the pyrene groups, promoting the formation of excimer fluorescence. High level quantum chemical calculations on the Ins(1,2,3)P3-Fe3+ complex revealed detailed structural information on the complex, predicting the involvement of inositol p/wsp/wester oxygens as well as terminal oxygens in the coordination of Fe3+. The findings here suggest Ins(1,2,3)P3 is the first viable proposal for an iron transit ligand. In addition, structural studies support the general principle that Fe3+ binds to the penta-axial conformation ofIns(l,2,3)P3.

La chiralité inhérente, provenant d’une structure concave associée à une substitution dissymétrique, est la forme de chiralité la plus répandue et est une des bases fondamentales de la reconnaissance enzymatique : outre le fait que les briques constitutives des protéines présentent un carbone asymétrique, leur repliement définit la chiralité inhérente de la poche du site actif, et est responsable de l’étonnante sélectivité des réactions enzymatiques. De façon générale, les calixarènes ont été notamment utilisés afin de modéliser les processus enzymatiques complexes. Ils sont ainsi à la base de la construction de nombreux récepteurs moléculaires artificiels, capables de reconnaître des cations, des anions ou des molécules neutres par des interactions spécifiques. L’objectif de cette thèse est la synthèse de calix[6]arènes présentant une chiralité inhérente, en leur introduisant différentes fonctionnalités différentes en l’absence de carbone asymétrique, ainsi que l’étude de leurs propriétés de reconnaissance de molécules chirales. Cet objectif est indissociable du challenge classique de la chimie organique qu’est la monofonctionnalisation de molécules possédant plusieurs fonctions réactives équivalentes. Dans un premier temps, nous avons utilisé une stratégie biomimétique et supramoléculaire pour monofonctionnaliser très sélectivement un complexe zincique de calix[6]arène portant trois bras imidazole ou un chapeau Tris(2-aminoÉthyl)AmiNe. En tirant profit de la nature réceptrice de ces complexes, différents substrats ont pu être greffés à la structure sur un seul des trois sites équivalents du grand col. Les limites de cette réaction « monoclick » biomimétique ont été quantifiées. Les complexes monofonctionnalisés sont de nouveaux objets aux propriétés réceptrices considérablement différentes des « complexes entonnoirs » décrits par notre équipe. Le contrôle de l’accès de la cavité des complexes de Zn(II), Cu(I) et Cu(II) pour des ligands exogènes a été étudiés en présence de différents ligands compétiteurs. Par ailleurs, nous avons montré que dans le cas des complexes de cuivre, l’accès à la cavité pouvait être contrôlé par un switch électrochimique. Nous avons également développé deux stratégies de synthèse de calix[6]arènes chiraux de façon inhérente à partir de précurseurs monofonctionnalisés, et nous avons synthétisé le premier »complexe entonnoir » présentant cette propriété. Sa chiralité a été mise en évidence par l’inclusion de ligands achiraux et achiraux. Nous avons également prouvé que ces phénomènes complexes pouvaient être étudiés simplement grâce à la technique RMN 19F. / Inherent chiralty, which arises from a concave structure associated with asymetric substitution, is the most common form of chiralty and is fundamental in enzymatic recognition : although aminoacids have an asymetric center, the folding of proteins creates the inherently chiral active site of enzymes and is responsible for the extraordinary selectivity of enzymatic reactions. Calix[6]arenes have been used as a tool to study complex enzymatic processes. They have also been used to build artificial molecular receptors for cations, anions or neutral molecules through very specific interactions. The goal of this thesis is the synthesis of inherently chiral calix[6]arenes by introducing different functionalities devoid of asymetric centers, and the study of the recognition of chiral molecules. First, we developped a biomimetic and supramolecular strategy to monofunctionalize a zinc calix[6]arene complex bearin three imidazole arms or a tris(2-aminoethyl)amine cap, with high selectivity. By using the recognition abilities of theses substrates, several molecules were liked only one of the three equivalent sites of the big rim of the calixarene. The limits of the biomimetic « monoclick » reaction were also quantified. The monofunctionalized complexes are new objects whose abilities as molecular receptors greatly differ from the previous « funnel complexes » described by our team. The control of the access of the cavity of Zn(II), Cu(II) and Cu(I) complexes to exogenous ligands was thoroughly studied with different competitive ligands. Also, we proved that the access to the cavity could be controled with an electrochemical switch. We also developed strategies to synthesize inherently chiral calix[6]arenes from monofunctionalized complexes and we synthesized the first inherently chiral funnel complex. Its chirality was evidenced by the inclusion of chiral and achiral guests. We also provided the proof of concept that these particular phenomena could be simply studied with 19F NMR spectroscopy.