Cette thèse porte sur l’analyse du processus d’adoption par le client d’une innovation commerciale. Plus particulièrement, elle étudie le rôle de la Socialisation Organisationnelle du Client sur le lien entre la Satisfaction Relationnelle et la Fidélité client à une nouvelle forme de vente. Dans cette optique, nous avons réalisé une étude exploratoire dans le but d’identifier les variables favorisant le succès d’une innovation commerciale ainsi que le processus d’adoption et d’apprentissage d’une innovation commerciale. La particularité de notre démarche réside dans le fait d’avoir interrogé différents segments de clients (et de non clients) mais aussi d’avoir observé les collaborateurs d’un DRIVE (Click&Carry). La première partie aboutit ainsi à une modélisation de l’adoption d’une innovation commerciale que nous testons dans la deuxième partie auprès de clients et d’employés. De plus, nous mettons en relation l’extraction des données de consommation des clients interrogés avec les données déclaratives issues des clients et des employés de contact.Les résultats de la recherche corroborent le rôle modérateur de la Socialisation Organisationnelle du Client (SOC) et de la Perception de la Socialisation Organisationnelle de l’Employé (PSOE), leur rôle variant en fonction du type d’innovation commerciale observée. Il en va de même au sujet du lien entre la Socialisation Organisationnelle de l’Employé (SOE) et, la Socialisation Organisationnelle du Client (SOC) d’une part, et, d’autre part, la Perception de la Socialisation Organisationnelle de l’Employé (PSOE), bien qu’il ne s’agisse que d’une démarche exploratoire / This thesis focuses on the analysis of a retailing innovation adoption process by customers. More in particular it examines the effect of Customer Organizational Socialization on the relationship between Relational Satisfaction and Customer Loyalty to a new form of selling.Towards this end, we conducted an exploratory study to identify variables promoting the success of a retailing innovation as well as the adoption and learning processes of a new form of selling. The advantage of our approach lies not only on having surveyed various customers and non-customers groups but also on having observed employees of a "Click and Collect". The first part led to a model of the adoption of a retailing innovation. In the second part, we tested this model on the basis of a customer and employee database. In addition, we related the extraction of our surveyed customers consumption data with declarative data from customers and contact employees.The research findings support the moderating effect of Customer Organizational Socialization (COS) and the Perception of Employee Organizational Socialization (PEOS), their role varying depending on the type of the retailing innovation. The same results are obtained about the relationship between Employee Organizational Socialization (EOS) and Customer Organizational Socialization (COS) on one part, and the Perception of Employee Organizational Socialization (PEOS) on the other part, although it is only an exploratory approach

This paper is divided into 3 parts. First part defines the interactive media and describes particular types of internet and mobile media. The second part is focused on interesting projects in the Czech Republic, which offer new possibilities of internet and mobile advertising. The last part describes the project www.golfeurope.cz and its starting campaign with using the interactive media.

Pas de résumé / Recently targeted therapies appeared as attractive alternatives to classical antitumoral treatments. The approach, developed on the concept of targeting drug to cancer cells, aims to spear normal tissues and decrease the side effects. This doctoral dissertation focuses on developing new anticancer targeted treatments in the field of chemotherapy and cancer immunotherapy by exploiting an original targeting moiety, the B subunit of Shiga toxin (STxB). Its specific properties, such as, recognition with its receptor Gb3 overexpressed in cancer cells or in antigen-presenting cells, its unconventional intracellular trafficking, guided the choice of this protein as targeting carrier. This project is based in the use of copper-free Huisgen [3+2] cycloaddition as a coupling method, which led to successful preparation of various conjugates for their respective applications. The concept was first validated by STxB-biotin conjugate. The high yield of the reaction and the compatibility between the targeting carrier and the chemical ligation promoted the design of conjugates for chemotherapy and immunotherapy. Two therapeutical optimizations of previously developed strategy in STxB drug targeting delivery were investigated: synthesis of multivalent drug-conjugates and synthesis of conjugates containing a highly potent anticancer agent. Both approaches exploited three anticancer agents: SN38, Doxorubicin and Monomethyl auristatin F. The disulfide spacer, combined with various self-immolative systems, insured drug release. Two cytotoxic conjugates STxB–doxorubicin (STxB-Doxo) and STxB-monomethyl auristatin F (STxB-MMAF) were obtained in very high yield and demonstrated strong tumor inhibition activity in the nanomolar range on Gb3-positive cells. Based on the results the STxB-MMAF conjugate was investigated on a mouse model. The project aimed also to develop STxB bioconjugates for vaccine applications. Previous studies used B subunit as a targeting carrier coupled to an antigenic protein in order to induce a more potent immune response against cancer. The conjugates were prepared using a commercial linker, requiring modifying the antigen at first place, or by oxime ligation, where slightly acidic conditions promoted the coupling. Thus, the work presented herein proposed an alternative ligation via copper-free click chemistry especially for more sensitive antigenic proteins. Various types of conjugates were synthesised and investigated for their immune stimulation properties. The STxB targeting strategy was also applied to the development of a new vaccine based on coupling the targeting carrier to alpha-GalCer, one of the most potent immune stimulating agents known. The work focused on the synthesis of functionalised alpha-Galcer with an azide handle.

No description available.

The present work describes a selection of strategies for the synthesis of functional aliphatic polycarbonates. Using an end-group functionalization strategy, a series of DNA-binding cationic poly(trimethylene carbonate)s was synthesized for application as vectors for non-viral gene delivery. As the end-group functionality was identical in all polymers, the differences observed in DNA binding and in vitro transfection studies were directly related to the length of the hydrophobic poly(trimethylene carbonate) backbone and the number of functional end-groups. This enabled the use of this polymer system to explore the effects of structural elements on the gene delivery ability of cationic polymers, revealing striking differences between different materials, related to functionality and cationic charge density. In an effort to achieve more flexibility in the synthesis of functional polymers, polycarbonates were synthesized in which the functionalities were distributed along the polymer backbone. Through polymerization of a series of alkyl halide-functional six-membered cyclic carbonates, semicrystalline chloro- and bromo-functional homopolycarbonates were obtained. The tendency of the materials to form crystallites was related to the presence of alkyl as well as halide functionalities and ranged from polymers that crystallized from the melt to materials that only crystallized on precipitation from a solution. Semicrystallinity was also observed for random 1:1 copolymers of some of the monomers with trimethylene carbonate, suggesting a remarkable ability of repeating units originating from these monomers to form crystallites. For the further synthesis of functional monomers and polymers, azide-functional cyclic carbonates were synthesized from the bromo-functional monomers. These were used as starting materials for the click synthesis of triazole-functional cyclic carbonate monomers through Cu(I)-catalyzed azide–alkyne cycloaddition. The click chemistry strategy proved to be a viable route to obtain structurally diverse monomers starting from a few azide-functional precursors. This paves the way for facile synthesis of a wide range of novel functional cyclic carbonate monomers and polycarbonates, limited only by the availability of suitable functional alkynes.

Förfrågan efter nya och mer avancerade applikationer är en pågående process vilket leder till en konstant utveckling av nya material. För att förstå relationen mellan en applikations egenskaper och dess sammansättning krävs full förståelse och kontroll över materialets uppbyggnad. En sådan kontroll över uppbyggnaden hos material hittas i en undergrupp till dendritiska polymerer som kallas dendrimerer. I den här doktorsavhandlingen belyses nya metoder för att framställa dendrimer med hjälp av selektiva kemiska reaktioner. Sådana selektiva reaktioner kan hittas inom konceptet klickkemi och har i detta arbete kombinerats med traditionell anhydrid- och karbodiimidmedierad kemi. Denna avhandling diskuterar en accelererad tillväxtmetod, dendrimerer med inre och yttre reaktiva grupper, simultana reaktioner och applikationer baserade på dessa dendritiska material. En accelererad tillväxtmetod har utvecklats baserad på AB2- och CD2-monomerer. Dessa monomerer tillåter tillväxt av dendrimerer utan att använda sig av skyddsgruppkemi eller aktivering av ändgrupper. Detta gjordes genom att kombinera kemoselektiviteten hos klickkemi tillsammans med traditionell syraklorid kopplingar. Dendrimerer med inre alkyn- eller azidfunktionalitet syntetiserades genom att använda AB2C-monomerer. Den dendritiska tillväxten skedde med hjälp av karbodiimidmedierad kemi. Monomererna som användes bär på en C-funktionalitet, alkyn eller azid, och på så sätt byggs får interiören i de syntetiserade dendrimeren en inneburen aktiv funktionell grupp. Ortogonaliteten hos klickkemi användes för att sammanfoga monomerer till en dendritisk struktur. Traditionell anhydridkemi- och klickemireaktioner utfördes samtidigt och på så sätt kunde dendritiska strukturer erhållas med färre antal uppreningssteg. En ljusemitterande dendrimer syntetiserades genom att koppla azidfunktionella dendroner till en alkynfunktionell cyclenkärna. Europiumjoner inkorporerades i kärnan varpå dendrimerens fotofysiska egenskaper analyserades. Mätningarna visade att den bildade triazolen hade en sensibiliserande effekt på europiumjonen. Termiska studier på några av de syntetiserade dendrimerer utfördes för att se om några av dem kunde fungera som templat vid framställning av isoporösa filmer. / The need for new improved materials in cutting edge applications is constantly inspiring researchers to developing novel advanced macromolecular structures. A research area within advanced and complex macromolecular structures is dendrimers and their synthesis. Dendrimers consist of highly dense and branched structures that have promising properties suitable for biomedical and electrical applications and as templating materials. Dendrimers provide full control over the structure and property relationship since they are synthesized with unprecedented control over each reaction step. In this doctoral thesis, new methodologies for dendrimer synthesis are based on the concept of click chemistry in combination with traditional chemical reactions for dendrimer synthesis. This thesis discusses an accelerated growth approach, dendrimers with internal functionality, concurrent reactions and their applications. An accelerated growth approach for dendrimers was developed based on AB2- and CD2-monomers. These allow dendritic growth without the use of activation or deprotection of the peripheral end-groups. This was achieved by combining the chemoselective nature of click chemistry and traditional acid chloride reactions. Dendrimers with internal azide/alkyne functionality were prepared by adding AB2C monomers to a multifunctional core. Dendritic growth was obtained by employing carbodiimide mediated chemistry. The monomers carry a pendant C-functionality (alkyne or azide) that remains available in the dendritic interior resulting in dendrimers with internal and peripheral functionalities. The orthogonal nature of click chemistry was utilized for the simultaneous assembly of monomers into dendritic structures. Traditional anhydride chemistry and click chemistry were carried out concurrently to obtain dendritic structures. This procedure allows synthesis of dendritic structures using fewer purification steps. Thermal analyses on selected dendrimers were carried out to verify their use as templates for the formation of honeycomb membranes. Additionally, a light emitting dendrimer was prepared by coupling of azide functional dendrons to an alkyne functional cyclen core. A Europium ion was incorporated into the dendrimer core, and photophysical measurements on the metal containing dendrimer revealed that the formed triazole linkage possesses a sensitizing effect. / QC 20100629

Taking advantage of ATRP and using functionalized initiators, different functionalities were introduced in both α and ω chain-ends of synthetic polymers. These functionalized polymers could then go through modular synthetic pathways such as click cycloaddition (copper-catalyzed or copper-free) or amidation to couple synthetic polymers to other synthetic polymers, biomolecules or silica monoliths. Using this general strategy and designing these co/polymers so that they are thermoresponsive, yet bioinert and biocompatible with adjustable cloud point values (as it is the case in the present thesis), the whole generated system becomes "smart" and potentially applicable in different branches. The applications which were considered in the present thesis were in polymer post-functionalization (in situ functionalization of micellar aggregates with low and high molecular weight molecules), hydrophilic/hydrophobic tuning, chromatography and bioconjugation (enzyme thermoprecipitation and recovery, improvement of enzyme activity). Different α-functionalized co/polymers containing cholesterol moiety, aldehyde, t-Boc protected amine, TMS-protected alkyne and NHS-activated ester were designed and synthesized in this work. / In dieser Arbeit wurden mittels der ATRP Methode sowie durch Benutzung funktioneller Initiatoren verschiedene Funktionalitäten an der α- und ω-Position der synthetischen Polymere (Kettenenden) eingeführt. Diese funktionalisierten Polymere können durch modulare synthetische Methoden wie z.B. die “Klick-Zykloaddition” (kupferkatalysiert oder auch kupferfreie Methoden möglich), Amidierung mit anderen synthetischen Polymeren oder Biomolekülen, oder auch mit Silikatmonolithen gekuppelt werden. Den beschriebenen Strategien folgend und unter Benutzung von thermoresponsiven, bioinerten und biokompartiblen (Co-) Polymeren mit einstellbaren Trübungspunkten können mittels Temperaturänderungen leicht steuerbare, „smarte“ Polymersysteme für verschiedene Anwendungen hergestellt werden. Im Rahmen dieser Arbeit wurden speziell Anwendungen wie die Postfunktionalisierung (in situ Funktionalisierung mizellarer Aggregate mit Molekülen, die sowohl niedrige als auch höhere Molekulargewichte aufweisen), hydrophiles/hydrophobes Tuning von Polymeren, Chromatographie an Polymeren sowie Biokonjugation von Polymeren (Enzymthermoprezipitation und -Gewinnung, Enzymaktivitätsmodifizierung) genauer untersucht. Es wurden verschiedene α-funktionalisierte (Co-)Polymere, die Cholesterol, Aldehyde, t-Boc geschützte Amine, TMS-geschützte Alkine und NHS-aktivierte Ester entwickelt und hergestellt und mittels passender ATRP Initiatoren eingeführt.

Ce travail s'articule autour de deux grands axes : les ligands électroactifs et la chiralité hélicoïdale dans les tétrathiafulvalènes, avec l'élaboration de TTF-triazoles, TTF-bis(bis-oxazolines) et de TTF-hélicènes. La synthèse de TTF-triazoles via deux stratégies de click chemistry, CuAAC et RuAAC, a permis d'obtenir une bibliothèque de ligands électroactifs mono- et polydentates dont les structures cristallines sont reportées ainsi que l'étude théorique des TTF-mono-triazoles. La capacité de ces ligands à coordiner a été testée avec la synthèse et la caractérisation structurale de complexes de métaux de transition. Aussi, nous avons développé la synthèse d'un TTF-bis(bis-oxazoline) chiral et étudié sa coordination ainsi que son activité dans des réactions de catalyse homogène énantiosélective. Dans une seconde partie, nous présentons la synthèse de nouveaux précurseurs hélicoïdaux : les TTF-hélicènes, incluant les études théoriques et expérimentales de leurs propriétés chiroptiques. Plus particulièrement, une étude du dichroïsme circulaire en fonction de l'état redox du TTF a permis de mettre en évidence un phénomène de switch chiroptique pour ces composés. Enfin, une ouverture sur les complexes dithiolènes a été faite avec la synthèse et caractérisation de deux complexes de platine (II) (bipyridine) (hélicènedithiolate), les premiers complexes dithiolènes hélicoïdaux.

Cette thèse a pour objectif l'élaboration de nanoparticules hybrides à base de silice par microémulsion inverse. Les nanoparticules de silice constituent une matrice de base permettant de confiner et de protéger des molécules organiques et/ou des nanoparticules métalliques. L'incorporation combinée de différentes entités dans la silice ouvre ainsi de larges perspectives de par l'introduction de nouvelles propriétés liées à la structure hybride. Afin d'élaborer de tels objets, nous avons utilisé des micelles inverses à base d'eau, de Triton X-100, d'hexanol et de cyclohexane comme milieu réactionnel. L'influence des conditions opératoires sur le contrôle de la taille des micelles inverses a d'abord été étudiée. Ces micelles inverses ont ensuite été mises à profit comme nanoréacteurs pour la synthèse de nanoparticules de silice par procédé sol-gel en utilisant les précurseurs alkoxysilanes adéquats. Nous avons regardé dans quelle mesure il était possible de contrôler la taille des nanoparticules de silice en fonction du pourcentage d'eau par rapport au tensioactif. Il a ainsi été possible d'accéder de façon reproductible à des nanoparticules avec de tailles variables, de 30 nm à 200 nm. Nous avons ensuite regardé qu'il était possible d'encapsuler au sein de cette matrice nanométrique des fluorophores et des nanoparticules d'or et d'argent de façon contrôlée. En vue d'assurer une bonne stabilisation colloïdale en solution, ces nanoparticules hybrides ont été fonctionnalisées d'une part par ajout d'un silane fonctionnel et d'autre part par click chemistry. Nous avons ainsi pu montrer qu'il est possible d'effectuer dans un même milieu micellaire l'ensemble des processus de fabrication de la nanoparticule hybride, de la matrice de silice à sa fonctionnalisation en passant par l'incorporation d'entités fonctionnelles. Cette méthode de synthèse séquentielle nous a ainsi permis de supprimer les étapes de purification et de redispersion qui peuvent s'avérer problématiques dans les procédés classiques. L'ensemble de ce travail a été mis à profit pour la conception d'un agent antibactérien à base de nanoparticules argent/silice capables d'empêcher la prolifération bactérienne grâce au relargage progressif des ions argent. Les tests effectués en solution comme sur le coton et le polyéthylène téréphtalate imprégnés montrent effectivement un caractère antibactérien certain de ces systèmes.

Chemical biology encompasses the study and manipulation of biological system using chemistry, often by virtue of small molecules or unnatural amino acids. Much insight has been gained into the mechanisms of biological processes with regards to protein structure and function, metabolic processes and changes between healthy and diseased states. As an ever expanding field, developing new tools to interact with and impact biological systems is an extremely valuable goal. Herein, work is described towards the synthesis of a small library of heterocyclic-containing small molecules and the mechanistic details regarding the interesting and unexpected chemical compounds that arose; an alternative set of non-toxic copper catalyzed azide-alkyne click conditions for in vivo metabolic labelling; and the synthesis of an unnatural amino acid for further chemical modification via [3+2] cycloadditions with nitrones upon incorporation into a peptide of interest. Altogether, these projects strive to supplement pre-existing methodology for the synthesis of small molecule libraries and tools for metabolic labelling, and thus provide further small molecules for understanding biological systems.