With a few exceptions, all organisms are restricted to the 20 canonical amino acids for ribosomal protein biosynthesis. Addition of new amino acids to the genetic code can introduce novel functionalities to proteins, broadening the diversity of biochemical as well as chemical reactions and providing new tools to study protein structure, reactivity, dynamics and protein-protein-interactions. The site directed in vivo incorporation developed by P. G. SCHULTZ and coworkers, using an archeal orthogonal tRNA/aaRS (aminoacyl-tRNA synthase) pair, allows site-specifically insertion of a synthetic unnatural amino acid (UAA) by reprogramming the amber TAG stop codon. A variety of over 80 different UAAs can be introduced by this technique. However by now a very limited number can form kinetically stable bonds to late transition metals. This thesis aims to develop new catalytically active unnatural amino acids or strategies for a posttranslational modification of site-specific amino acids in order to achieve highly enantioselective metallorganic enzyme hybrids (MOEH). As a requirement a stable protein host has to be established, surviving the conditions for incorporation, posttranslational modification and the final catalytic reactions. mTFP* a fluorescent protein was genetically modified by excluding any exposed Cys, His and Met forming a variant mTFP*, which fulfills the required specifications. Posttranslational chemical modification of mTFP* allow the introduction of single site metal chelating moieties. For modification on exposed cysteines different maleiimid containing ligand structures were synthesized. In order to perform copper catalyzed click reactions, suitable unnatural amino acids (para-azido-(L)-phenylalanine, para-ethynyl-(L)-phenylalanine) were synthesized and a non-cytotoxic protocol was established. The triazole ring formed during this reaction may contribute as a moderate σ-donor/π-acceptor ligand to the metal binding site. Since the cell limits the incorporation of boronic acids, an aqueous protocol for Miyaura borylation using a highly active palladacycle catalyst was established and can be transferred to a selective borylation of proteins. It allows subsequent Suzuki cross coupling and therefore broadens the possibilities for chemical modifications and the establishment of new metalloenzymes. Different metal chelating amino acids were investigated, such as Hydrochinolin-Alanine, Bipyridyl-Alanine, Dipyridine-Lysines and phosphorous containing amino acids.

5 Abstract The formerly reported hydroxyamide Ph2PfcC(O)NHCH2CH2OH 1 and its respective novel congeneric analogues Ph2PfcC(O)NHCH3−n(CH2OH)n (3: n = 2; 4: n = 3) were used to prepare a series of arene-ruthenium(II) complexes [(η6 -arene)RuCl2(L-κP)] 6-8 (arene = C6H6, p-cymene, C6Me6; L = 1, 3 or 4). These complexes were studied as pre-catalysts in redox isomerization of allylic alcohols to carbonyl compounds. Among the compounds prepared, complex 6b [(η6 -p-cymene)RuCl2(1-κP)] showed best results. The solid state structure of the product of photolytic decomposition of complex [(η6 - C6Me6)RuCl2(2-κP)] (2 = Ph2PfcC(O)N(CH2CH2OH)2), viz, [(µ-Cl)3{Ru(η6 -C6Me6)}2] [FeCl4] 9, was determined by single-crystal X-ray diffraction analysis. The bis-phosphane complexes [MII Cl2(1-κP)2] (M = trans-Pd (10), cis-Pt (11) and trans- Pt (12)) together with chalcogenide derivatives Ph2P(O)fcC(O)NH(CH2)2OH (13) and Ph2P(S)fcC(O)NH(CH2)2OH (14) derived from hydroxyamide 1 were tested in vitro for their cytotoxicity against human ovarian A2780 cancer cell line. Complexes tested showed moderate cytotoxicity. Triol-amide FcC(O)NHC(CH2OH)3 15 (Fc = ferrocenyl) reacted with decavanadate (Bu4N)2[H3V10O28] at elevated temperature and prolonged reaction time yielding the hybrid hexavanadate (Bu4N)2[{FcC(O)NHC(CH2O)3}2V6O13] 16...

Ce travail de thèse a consisté en la synthèse et en la valorisation d’une nouvelle famille de cyclodextrines amphiphiles en catalyse aqueuse : les OléoSodioSuccinyl-Cyclodextrines (OSS-CDs). Ces OSS-CDs ont été obtenues en trois étapes principales. La première étape a consisté en la maléinisation thermique ou rhodiocatalysée de l’acide oléique ou de son ester méthylique. Les anhydrides succiniques substitués obtenus peuvent ensuite optionnellement subir une réaction d’hydrogénation de leur double liaison carbone-carbone par catalyse au rhodium sur charbon. Mis en réaction avec diverses cyclodextrines natives ou modifiées, ces anhydrides ont conduit à des esters de cyclodextrines présentant des fonctions acides carboxyliques. Les OSS-CDs, obtenues par neutralisation à la soude de ces fonctions, possèdent une solubilité aqueuse élevée (50-500 g.L-1 à 20°C), sont tensioactives (concentration d’agrégation critique : 4-360 g.L-1 à 20°C) et forment des agrégats en phase aqueuse. Les chaines grasses de ces OSS-CDs possèdent une forte tendance à s’inclure dans la cavité de la cyclodextrine sur laquelle elles sont greffées. Les OSS-CDs ont montré une très bonne capacité à promouvoir le transfert de matière en hydroformylation biphasique aqueuse et rhodiocatalysée d’alpha-oléfines grasses, avec des vitesses de réaction plus importantes obtenues lors de l’utilisation d’OSS-CDs issues de l’oléate de méthyle. Certaines OSS-CDs issues de l’acide oléique se sont avérées quant à elles de très bons stabilisants de nanoparticules de ruthénium. Les suspensions colloïdales auxquelles elles ont conduit présentent une forte stabilité, sont actives dans l’hydrogénation de nombreux substrats et peuvent être recyclées sans perte d’activité. / This thesis work consisted of the synthesis and valorisation of a new family of amphiphilic cyclodextrins in aqueous catalysis: OleoSodioSuccinyl-Cyclodextrins (OSS-CDs). These OSS-CDs were obtained in three main steps. The first step consisted of the thermal or rhodiocatalysed maleinisation of oleic acid or its methyl ester. The carbon-carbon double bond of the obtained substituted succinic anhydrides can then possibly be hydrogenated by rhodium on carbon catalysis. By reacting with native or modified cyclodextrins, these anhydrides led to cyclodextrin esters having carboxylic groups. The OSS-CDs, obtained by neutralisation with sodium hydroxide of these functions, have high aqueous solubilities ( 50-500 g.L-1 at 20° C), are surfactant (aggregation concentration: 4-360 g.L-1 at 20°C) and form aggregates in water. The fatty chains of these OSS-CDs have a strong tendency to include in the cavity of the cyclodextrin on which they are grafted. The OSS-CDs showed a very good mass transfer capacity in aqueous biphasic rhodiocatalysed hydroformylation of alpha-olefins, with higher reaction rates when using the OSS-CDs obtained from methyl oleate. Some OSS-CDs coming from oleic acid have been found to be very good stabilizers for ruthenium nanoparticles. The colloidal suspensions obtained with them were very stable, active in the hydrogenation of many substrates and can be recycled without loss of activity.