De nouveaux complexes allyl-borohydrure de terres rares trivalents, RE(BH4)2(C3H5)(THF)x (RE = Sc, x = 2; Y, La, Nd, Sm, x = 3) ont été synthétisés. Les complexes ont été caractérisés, y compris par diffraction des rayons X, et leur réactivité vis-à-vis de l’insertion de petites molécules organiques est décrite, qui met en jeu de façon comparative les liaisons métal-borohydrure et métal-allyle. Dans ce travail de thèse, il a été montré que le complexe de néodyme est capable d’amorcer la polymérisation de l’isoprène, seul ou combiné avec un co-catalyseur de type magnésium, conduisant à du trans-1,4-polyisoprène avec une bonne activité. Cette famille de complexes est également très active en polymérisation par ouverture de cycle des esters cycliques tels que l’ɛ-caprolactone et le L-lactide, avec amorçage de la réaction via le ligand borohydrure plutôt que l'allyle. La copolymérisation statistique L-lactide/ɛ-caprolactone a été réalisée, conduisant à la formation de copolymères avec une large gamme de microstructures, de statistique à alternée. Une autre approche organométallique a été abordée avec la synthèse de nouveaux complexes borohydrures de terres rares (Sc, Y, Nd) à base de ligands Phosphasalen. Certains de ces complexes ont été isolés et caractérisés. / A series of new trivalent rare earth allyl-borohydride complexes with the formula RE(BH4)2(C3H5)(THF)x (RE = Sc, x = 2; Y, La, Nd, Sm, x = 3) was synthesized. The complexes were fully characterized including by X-ray and their reactivity toward small organic molecules insertion is described, which involves comparatively metal-borohydride and metal-allyl bonds. In this dissertation, It was shown that the neodymium congener could initiate isoprene polymerisation, as single component or combined with a magnesium co-catalyst, to afford trans-1,4-polyisoprene with good activity. All the complexes were also found extremely active toward the Ring-Opening Polymerisation of ɛ-caprolactone and L-lactide with initiation through the borohydride rather than the allyl moiety. The statistical copolymerisation of L-lactide and ɛ-caprolactone was successfully performed with all complexes affording copolymers with a wide range of microstructure, from random to fairly alternating. Another organometallic approach has been studied with the synthesis of novel rare earth (Sc, Y, Nd) borohydride complexes based on Phosphasalen ligands. Some of these complexes have been isolated and characterized.

The primary objective of this research was to develop a new and efficient pathway for well-defined multicomponent homo/co/terpolymers of cyclic esters/ethers using an organocatalytic approach with an emphasis on the macromolecular engineering aspects of the overall synthesis. Macromolecular engineering (as discussed in the first chapter) of homo/copolymers refers to the specific tailoring of these materials for achieving an easy and reproducible synthesis that results in precise molecular characteristics, i.e. molecular weight and polydispersity, as well as specific structure and end?group choices. Precise control of these molecular characteristics will provide access to new materials that can be used for pre-targeted purposes such as biomedical applications. Among the most commonly used engineering materials are polyesters (biocompatible and biodegradable) and polyethers (biocompatible), either as homopolymers or when or copolymers with linear structures. The ability to create non-linear structures, for example stars, will open new horizons in the applications of these important polymeric materials. The second part of this thesis describes the synthesis of aliphatic polyesters, particularly polycaprolactone and polylactide, using a metal-free initiator/catalyst system. A phosphazene base (t?BuP2) was used as the catalyst for the ring-opening copolymerization of ?-aprolactone (??CL) and L,Lactide (LLA) at room temperature with a variety of protic initiators in different solvents. These studies provided important information for the design of a metal-free route toward the synthesis of polyester?based (bio) materials. The third part of the thesis describes a novel route for the one?pot synthesis of polyether-b polyester block copolymers with either a linear or a specific macromolecular architecture. Poly (styrene oxide)?b?poly(caprolactone)?b?poly(L,lactide) was prepared using this method with the goal of synthesizing poly(styrene oxide)-based materials since this styrene oxide (SO) monomer has been less investigated than other well-known epoxide monomers. The new one?pot synthesis of polyether?b?polyester block copolymers allowed a high degree of control with respect to the molecular weight and molecular weight distribution. It also eliminates the need for a multi-step process in which the first block must be isolated and purified prior to its subsequent use as a macroinitiator for the second block. It is also worth noting that this approach is based primarily on the use of organocatalyst because this class of block copolymers has greater potential in biomedical and pharmaceutical applications and because organocatalysts are believed to be less toxic than their metallic counterparts. The fourth part of the thesis describes the extension of the scope of the newly developed catalyst?switching approach in the synthesis of different macromolecular architectures, with a special focus on styrene oxide as a monomer, which had not previously been explored either as a linear copolymer with other monomers (except with EO) or with a macromolecular architecture such as block star or mikto arm star. The results detailed in Chapter 4 demonstrate the validity of extending the newly developed strategy to the synthesis of a variety of polymers with different macromolecular architectures. Since organic catalysts (phoshazene bases) have been utilized in this work for the synthesis of polyethers and polyesters with the aim of alleviating the toxic properties associated with metal-based catalysts, it was necessary to investigate the toxicity of this class of organocatalyst since, until now, no evidence has appeared of any attempt to address this issue. The objective of the work presented in the fifth part of this thesis was therefore to assess whether this class of organocatalysts are safe with respect to human health and whether their structure and concentration are dependent on an evaluation of the level of cytotoxicity or on other parameters. Both the pure catalyst and the polymers synthesized using this class of catalysts were tested using a CKK?8 assay, which is a very well?known protocol for measuring cytotoxicity.

Une grande partie des matériaux plastiques produits chaque année dans le monde est encore enfouie après leur utilisation, constituant une source sérieuse de pollution pour la planète. Depuis plusieurs décennies, la synthèse de polyesters biodégradables par polymérisation par ouverture de cycle d'esters cycliques issus de la biomasse comme le lactide connait un intérêt croissant tant de la part du milieu industriel que de la communauté scientifique. Malgré de très nombreux systèmes catalytiques décrits, certains métaux restent relativement peu étudiés à ce jour. Le but de cette thèse a été de synthétiser et d'étudier les propriétés de polymérisation d'amorceurs basés sur du cobalt et fer (II) présentant potentiellement une géométrie bipyramidale trigonale, peu étudiée pour des métaux divalents. Les différents systèmes obtenus se sont révélés actifs à température ambiante et ont permis d'obtenir des polymères présentant des tacticités très diverses en fonction de l'encombrement du pro-ligand ainsi que du métal utilisé avec de très bonnes activités et de manière contrôlée. Les complexes de fer ont ainsi permis d'obtenir de manière inédite des PLA fortement isoenrichis (Pm = 0,86-0,91). En outre, les complexes de cobalt (II) ont permis d'obtenir également de manière inédite des polymères iso- ou hétéroenrichis (constituant donc deux nouveaux cas modestes d'inversion de sélectivité, en fonction du centre métallique ou du ligand utilisé). Ces amorceurs constituent un bon point de départ pour le développement de systèmes productifs pour la polymérisation stéréosélective du rac-lactide basés sur un métal non toxique et abondant ainsi que des ligands facilement accessibles. / A large part of the plastic materials produced every year in the world are disposed in landfill, representing a serious menace for the environment. Since several decades, industrial and academic scientists are interested in the synthesis of biodegradable polyesters via the ring opening polymerization of biobased cyclic esters like lactide. Despite a large number of initiators described in the literature, several metals remains not well studied. The goals of this thesis were to synthetize and study the polymerization properties of new iron and cobalt (II) initiators with a trigonal bipyramidal geometry. The different initiators were active at room temperature and polymers with a large variety of tacticity were obtained depending on the steric hindrance of the pro-ligand and the metallic center used, with very good activity and in a controlled manner. Highly isotactic-rich PLA (Pm = 0,86-0,91) were obtained with iron (II) based initiators for the first time. Moreover, cobalt (II) initiators gave isotactic and heterotactic-rich PLA with moderate selectivity, constituting two new cases of stereoselectivity switch. These initiators constitute a good starting point for the development of new productive initiators for the stereoselective polymerization of rac-lactide based on non-toxic and abundant metals and easily accessible pro-ligands.

Biodegradable polyesters represent a class of extremely useful polymeric materials for many applications. Among these polyesters, the biodegradable and biocompatible, polylactide is very promising for many applications in both medical and industrial areas. Other biodegradable polymers such as polytrimethylene carbonate, polybutyrolactone, polyvalerolactone, and polycaprolactone can be blended or copolymerized with polylactide to fine tune the properties to fit the needs for their applications. The properties of these polymers and copolymers depend upon the tacticity of the polymers which can be directly controlled by the catalysts used for polymer production. Therefore, it has been of great interest to develop new selective catalytic systems for the ring-opening polymerization of lactide and other cyclic monomers. This dissertation focuses on developing new zinc and aluminum complexes and studying their selectivity and reactivity of these complexes for the ring-opening polymerization of lactide and other cyclic monomers, i.e. trimethylene carbonate, beta-butyrolactone, delta-valerolactone, and epsilon-caprolactone. Herein, aspects of the ring-opening polymerization of lactide and other cyclic monomers utilizing novel zinc and aluminum complexes will be discussed in detail. In the process for the ring-opening polymerization of lactide, chiral zinc half-salen complexes derived from natural amino acids have shown to be very active catalysts for producing polymers with high molecular weight and narrow polydispersities at ambient temperature. The chiral zinc complexes were found to catalyze rac-lactide to heterotactic polylactides with Pr values ranging from 0.68-0.89, depending on the catalyst and reaction temperature employed during the polymerization process. The reactivities of the various catalysts were greatly affected by substituents on the Schiff base ligands, with sterically bulky substituents being rate-enhancing. Furthermore, a series of both chiral and achiral aluminium half-salen complexes have been synthesized and characterized. These aluminum complexes all showed moderate selectivity to the ring-opening polymerization of rac-lactide to produce isotactic polylactide with Pm value up to 0.82 in toluene at 70 degrees C. Moreover, some of the studied aluminum complexes displayed epimerization of rac-lactide to meso-lactide during the polymerization process. Kinetic studies for the ring-opening polymerization of lactide utilizing these zinc and aluminum complexes are included in this dissertation. Along with these studies, the copolymerization of lactide with epsilon-caprolactone and delta-valerolactone will also be presented.

No description available.

The racemic (±)-2,4-di-tert-butyl-6-(((2-(dimethylamino)cyclohexyl)(methyl) amino)methyl)phenol ((±)-(NNMeOtBu)H), (±)-2,4-di-tert-butyl-6-((2-(dimethylamino) cyclohexylamino)methyl)phenol ((±)-(NNHOtBu)H), and (±)-2-(((2-(dimethylamino) cyclohexyl)(methyl)amino) methyl)phenol ((±)-(NNMeOH)H) are chiral ancillary NNO proligands, which synthesis was adapted from a published procedure. Reaction of (±)-(NNMeOtBu)H ((±)-2), (±)-(NNMeOH)H ((±)-3) and (±)-(NNHOtBu)H ((±)-1) with ZnEt2 successfully yielded the corresponding zinc ethyl complexes (±)-5, (±)-6 and (±)-7 respectively; the enantiomerically pure (R,R)-5 was synthesized from (R,R)-2. NMR spectroscopy experiments and X-ray crystallography allowed identification of two stereoisomers for (±)-5, which were observed in solution and in the solid state. The two stereoisomers, 5-α and 5-β, are in equilibrium in solution, with 5-β being thermodynamically favored. The zinc ethyl complexes were found to be unreactive towards weakly acidic alcohols (methanol, ethanol, isopropanol). However, the zinc chloride complex (±)-(NNMeOtBu)ZnCl ((±)-8) and the zinc phenoxide (NNMeOtBu)ZnOPh ((±)-9 and (R,R)-9) could be isolated and characterized. Comparison of the reactivity of both (±)-5 and the reported L₁ZnEt (L₁ = 2,4-di-tert-butyl-6- {[(2'-dimethylaminoethyl) methylamino]methyl}phenolate) in presence of pyridine led to the proposal of a dissociative mechanism explaining the fundamental difference between the two zinc ethyl species. Polymerization of rac-lactide catalyzed by 9 showed that the complex, in its racemic or enantiomerically pure version, has a slow activity and is not stereoselective.

The racemic (±)-2,4-di-tert-butyl-6-(((2-(dimethylamino)cyclohexyl)(methyl) amino)methyl)phenol ((±)-(NNMeOtBu)H), (±)-2,4-di-tert-butyl-6-((2-(dimethylamino) cyclohexylamino)methyl)phenol ((±)-(NNHOtBu)H), and (±)-2-(((2-(dimethylamino) cyclohexyl)(methyl)amino) methyl)phenol ((±)-(NNMeOH)H) are chiral ancillary NNO proligands, which synthesis was adapted from a published procedure. Reaction of (±)-(NNMeOtBu)H ((±)-2), (±)-(NNMeOH)H ((±)-3) and (±)-(NNHOtBu)H ((±)-1) with ZnEt2 successfully yielded the corresponding zinc ethyl complexes (±)-5, (±)-6 and (±)-7 respectively; the enantiomerically pure (R,R)-5 was synthesized from (R,R)-2. NMR spectroscopy experiments and X-ray crystallography allowed identification of two stereoisomers for (±)-5, which were observed in solution and in the solid state. The two stereoisomers, 5-α and 5-β, are in equilibrium in solution, with 5-β being thermodynamically favored. The zinc ethyl complexes were found to be unreactive towards weakly acidic alcohols (methanol, ethanol, isopropanol). However, the zinc chloride complex (±)-(NNMeOtBu)ZnCl ((±)-8) and the zinc phenoxide (NNMeOtBu)ZnOPh ((±)-9 and (R,R)-9) could be isolated and characterized. Comparison of the reactivity of both (±)-5 and the reported L₁ZnEt (L₁ = 2,4-di-tert-butyl-6- {[(2'-dimethylaminoethyl) methylamino]methyl}phenolate) in presence of pyridine led to the proposal of a dissociative mechanism explaining the fundamental difference between the two zinc ethyl species. Polymerization of rac-lactide catalyzed by 9 showed that the complex, in its racemic or enantiomerically pure version, has a slow activity and is not stereoselective.

The racemic (±)-2,4-di-tert-butyl-6-(((2-(dimethylamino)cyclohexyl)(methyl) amino)methyl)phenol ((±)-(NNMeOtBu)H), (±)-2,4-di-tert-butyl-6-((2-(dimethylamino) cyclohexylamino)methyl)phenol ((±)-(NNHOtBu)H), and (±)-2-(((2-(dimethylamino) cyclohexyl)(methyl)amino) methyl)phenol ((±)-(NNMeOH)H) are chiral ancillary NNO proligands, which synthesis was adapted from a published procedure. Reaction of (±)-(NNMeOtBu)H ((±)-2), (±)-(NNMeOH)H ((±)-3) and (±)-(NNHOtBu)H ((±)-1) with ZnEt2 successfully yielded the corresponding zinc ethyl complexes (±)-5, (±)-6 and (±)-7 respectively; the enantiomerically pure (R,R)-5 was synthesized from (R,R)-2. NMR spectroscopy experiments and X-ray crystallography allowed identification of two stereoisomers for (±)-5, which were observed in solution and in the solid state. The two stereoisomers, 5-α and 5-β, are in equilibrium in solution, with 5-β being thermodynamically favored. The zinc ethyl complexes were found to be unreactive towards weakly acidic alcohols (methanol, ethanol, isopropanol). However, the zinc chloride complex (±)-(NNMeOtBu)ZnCl ((±)-8) and the zinc phenoxide (NNMeOtBu)ZnOPh ((±)-9 and (R,R)-9) could be isolated and characterized. Comparison of the reactivity of both (±)-5 and the reported L₁ZnEt (L₁ = 2,4-di-tert-butyl-6- {[(2'-dimethylaminoethyl) methylamino]methyl}phenolate) in presence of pyridine led to the proposal of a dissociative mechanism explaining the fundamental difference between the two zinc ethyl species. Polymerization of rac-lactide catalyzed by 9 showed that the complex, in its racemic or enantiomerically pure version, has a slow activity and is not stereoselective. / Science, Faculty of / Chemistry, Department of / Graduate

No description available.

The biocompatibility and biodegradability of poly(lactic acid) (PLA) facilitate its use in a variety of biomedical applications, ranging from sutures to drug delivery. However, uncontrolled interactions with cells and insufficient mechanical properties have prevented PLA from reaching its full potential as a scaffold for use in tissue engineering. Methods to improve the mechanical, chemical and biological properties of PLA are limited by the lack of functional groups along the backbone of the polymer. One possible approach towards overcoming these limitations involves the incorporation of functional groups into the backbone of the polymer through the copolymerization of monomers bearing protected functional groups. Deprotection and modification of these functional groups could provide the opportunity to direct the attachment of cells, and enhance to the physical properties of the polymer. We have developed a general methodology for the synthesis of lactide monomers substituted with protected functional groups (alcohols protected as benzyl ethers, amines protected as benzyl carbamates and carboxylic acids protected as benzyl esters). The monomers were homopolymerized, and copolymerized with lactide, and deprotected to give functional PLA copolymers with pendant hydroxyl, amine, and carboxyl groups. A thorough investigation of the chemical modification of PLA copolymers bearing functional groups along the polymer backbone was performed on a copolymer prepared by copolymerizarion of a dibenzyloxy-substituted lactide monomer with lactide followed by reductive debenzylation. Reaction of the resulting hydroxyl-substited PLA with succinic anhydride resulted in an acid-substituted PLA that is amenable to standard EDC/NHS coupling. The utility of this copolymer was illustrated by coupling with an amine derivative of biotin, and an RGD-containing peptide sequence. The preparation of the biodegradable polyester substituted with RGD, a ubiquitous adhesion peptide, provided us with control over cellular attachment to the hybrid material. We also explored approaches to make use of the pendant functional groups on PLA to enhance the physical properties of polymer foams. Copolymers with pendant photocrosslinkable cinnamate groups were prepared by reaction of the hydroxyl-substited PLA copolymers with cinnamoyl chloride. The copolymer was foamed using thermally-induced phase separation (TIPS), and photocrosslinked upon irradiation at 300 nm. Irradiation resulted in an increase in the compressive modulus of the foams. Crosslinking also led to a decrease in the rate of hydrolytic degradation of the foams, thereby demonstrating the potential for use of these strategies in the development of porous scaffolds for bioengineering. Another potential approach towards the preparation of robust polymer foams is the incorporation of a rigid polymer block which can phase separate during foam formation to provide additional structural integrity. Several poly(norbornene)-PLA diblock copolymer compositions were prepared by the ring-opening of lactide by a hydroxyl-terminated poly(norbornene) macroinitiator. The ability of the diblock copolymer to phase separate at elevated temperature was verified using small-angle x-ray scattering and wide-angle x-ray scattering.