Les travaux rapportés dans cette thèse consistent à synthétiser et à caractériser de nouveaux composés à clusters d'éléments de transition par assemblages de briques moléculaires à clusters octaédriques de molybdène. Ils s'inscrivent dans le cadre des activités du Laboratoire International Associé (LIA} CLUSPOM et ont conduit à de nombreuses collaborations notamment avec le Nikolaev Institute of Inorganic Chemistry de Novossibirsk en Russie. Les composés obtenus ont été caractérisés par diffraction des rayons X par la poudre et le monocristal, par spectroscopie infrarouge et de luminescence et par magnétométrie à SQUID. Le premier volet de cette recherche consiste à faire réagir des briques moléculaires hexacyanées [ Moc.B~s(CN}'•Jl" et [Mo.Br'.Q;,(CN}'•]'• (Q = S, Se) avec des métaux de transition pour obtenir des composés dont la stnrcture dérive de celle du Bleu de Prusse. Cette stratégie a permis de synthétiser douze nouveaux composés dont neuf polymères de coordination à structure 1-, 2- et 3-D. Une série de composés basés sur les motifs (MOoBr'8(CN)'6]'- et (Mo6Br;6Q;2(CN)'6f'"• (Q = S, Se} a mis en évidence l'existence de types architecturaux stables et une modulation possible des propriétés optiques et magnétiques par contrôle de la charge du motif. Les complexes de coordination ((Ni(NHJ)o},(Ni,(NHJ}s})IMOoBr6Q2( CN}6).1 2H20 présentent une structure cristalline basée sur des dimères de nickel stabilisés par des liaisons hydrogène. Les mesures d'aimantation magnétique en fonction de la température montrent q 'entre 270 et 13 K, l'ensemble des ions Ni" présente un comportement paramagnétique. Entre 13 et 2 K, seule la contribution paramagnétique des complexes octaédriques de nickel [Ni(NH3)6]" est mesurée. Il y a donc couplage magnétique, à faible température, entre les complexes de nickel des dimères. Des calculs théoriques sur ces phases ont mis en évidence que ce couplage est de type antiferromagnétique. Le second volet de recherche consiste à synthétiser, par hydrolyse contrôlée et auto-assemblage des motifs à clusters, des composés basés sur un réseau de liaisons hydrogène fortes et présentant des propriétés de luminescence et de conductivité protonique. Le composé (H)2[MOoCis(OH}G)l2H20 (X = Cl, Br} présente une conductivité de 1,4. 10"" S.cm••. / Results reported in this PhD thesis consist in synthesizing and characterizing new transition element clusters based compounds by assembling molybdenum octahedral clusters building blocks. They are part of the activities of the CLUSPOM International Associated Laboratory and have led to numerous collaborations especially with the Nikolaev Institute of Inorganic Chemistry of Novosibirsk in Russia. Compounds were characterized by X-ray powder and single crystal diffraction, infrared and luminescence spectroscopies and by SQU ID magnetometry. The first part of this research consists in reacting hexacyano molecular building blocks (Mo.Br's(CN)'6Jl" and (M o. B~6Q'2(CN)'6] '• (Q = S, Se) with transition metals to obtain compounds of which the structure derives from that of the Prussian Blue. This strategy made it possible to synthesize twelve new compounds including nine coordination polymers with structure 1-, 2- and 3-D. A series of compounds based on (Mo.Br's(CN )'6f and (Mo6Br'6Q'2(CN)'6]J.I4• (Q = S, Se) cluster units demonstrated the existence of stable architectural types and possible modulation of optical and magnetic properties by charge switching. The coordination complexes ({ Ni(NHJ}6 )4{Ni2(NHJ)s }]-[Mo.Br6Q2(CN)6].12H20 have a crystal structure which is based on nickel dimers stabilized by hydrogen bonds. Magnetic magnetization measurements as a function of temperature show that between 270 and 13 K, all Ni2+ cations exhibit a paramagnetic behavior. Between 13 and 2 K, only the paramagnetic contribution of nickel octahedral complexes (Ni(NHJ}t;]H is measured. There is therefore magnetic coupling, at low temperature, between the nickel complexes of the dimers. Theoretical calculations on these phases have shown that this coupling is of the antiferromagnetic type. The second part of the research consists in synthesizing, by controlled hydrolysis and self-assembly of cluster units, compounds based on a strong hydrogen bonding network and exhibiting luminescence and proton conductivity properties. The compounds (H)l[Mo.X8(0H)6]-12H20 (X= Cl, Br) and (H),[Mo6Br6Sl(OH)6] have conductivities of up to 1.4 x 10-o S.cm-1

Ever since traditional medicine developed thousands of years ago, humans have looked to natural substances as remedies for maladies. Today, many isolation and natural product chemists have begun revisiting ancient folk medicines in an attempt to isolate the compound(s) responsible for effective treatment. In addition to the examination of traditional remedies, the secondary metabolites of many newly discovered species, especially bacteria, get tested against a wide array of pathogenic cells. Isolated from the myxobacterium Sorangium cellulosum, the secondary metabolite carolacton was discovered to be lethal to Streptococcus mutans cells transitioning to the biofilm state. This was a significant finding since S. mutans is the main causative agent of dental caries, the most prevalent chronic childhood and adolescent disease worldwide. Herein, our efforts to design, synthesize, and biologically evaluate a 16-member library of carolacton-inspired analogs is described. In addition to natural product inspired research, two projects borne from a target-oriented templated approach are also described. The first, the synthesis of the antitumor compound FRAX-1036, was completed as part of a collaboration with the Chernoff group at Fox Chase Cancer Center to provide them with more material for murine testing. The second, the synthesis of macrocycles for the formation of atomically precise membranes, was conducted using spiroligomer building blocks and unnatural amino acids to furnish a triangle-shaped macrocycle via solution and solid phase techniques. This dissertation highlights the usefulness of the techniques of diverted total synthesis and building block synthesis in organic chemistry. / Chemistry

5 Title: Methylene-bis(phosphonate) Derivatives for Modification of Biomolecules Author: Tomáš David Department: Department of Inorganic Chemistry, Faculty of Science Supervisor: RNDr. Vojtěch Kubíček, Ph.D. Supervisor's e-mail address: vvvojta@seznam.cz Abstract The aim of this work was to prepare derivatives of methylen-bis(phosphonic) acid. Thirty compounds (from which 29 are new) were prepared with moderate or good yields. All compounds were fully characterized by NMR and MS. Four new crystal structures were obtained by RTG monocrystal analysis. Derivative containing 4-nitrobenzyl group in the side chain was used for study of bis(phosphonates) adsorption parametres to hydroxyapatite (with quantification by UV-Vis spectroscopy). Several derivatives containing characteristic functi- onal groups (-NH2, -COOH, -NCS) were prepared. These compound are suitable for further derivatization, mainly for conjugation with more complex structures through amide bond or thiourea bridge. Conjugates of building blocks with fluorescent probe (fluorescein and dansyl) were prepared for potencial optical imaging. Further modification of one of the dansyl derivative afforded trifunctional molecule - contating bis(phosphonate) as a vector for a bone tissue, a fluorescent probe for a possible fluorescent imaging and a free...

Over the past few decades, vast majority of industrial and academic research throughout the world has witnessed the emergence of materials that can serve as ideal candidates for potential utility in desired applications, and these materials are known as Metal Organic Framework (MOFs). This exceptional new family of porous materials is fabricated by linkage of metal ions or clusters and organic linkers via strong bonds. MOFs have been awarded with remarkable interest and widely studied due to their inherent structural methodology (e.g. use of various metals, expanded library of organic building blocks with different geometry and functionality particularly frameworks designed from carboxylate organic linkers) and unquestionably unique structural and chemical features for many practical applications. (i.e. gas storage/separation, catalysis, drug delivery etc). Simply, metal organic frameworks epitomize the beauty of porous chemical structures. From a design perspective, the introduction of the Molecular Building Block (MBB) approach is actively being pursued pathway by researchers toward the construction of MOFs by employing inorganic building blocks and organic linkers and taking advantage of not only their multiple coordination modes and geometries but also the way in which they are reticulated to generate final framework. In this thesis, research studies will be directed toward (i) the investigation of the relationship between experimental parameters and synthesis of well-known fcu –MOF, (ii) rational design and synthesis of new rare earth (RE) based MOFs, (ii) isoreticular materials based on particular MBB ([M3O(RCO2)6]), M= p-and d-block metals, and (iv) zeolite- like metal organic framework assembled from single-metal ion based MBB ([MN2(CO2)4]) via 2-, 3-,and 4-connected organic linkers. Consequently, the porosity, chemical and thermal stability, and gas sorption properties will be evaluated and detailed.

Cette thèse est dédiée à la conception de synthons entrelacés pour la préparation efficace de machines moléculaires pH-sensible de type rotaxane et de rotaxanes dénués de site de reconnaissance. Bien que la stratégie dirigée par l’effet « template » ait été employée très fréquemment et avec succès à ce jour, elle ne mène dans la plupart des cas qu’à des composés entrelacés qui contiennent les sites d’interactions nécessaires à la reconnaissance préalable des éléments moléculaires à assembler. Pour remédier à cette limitation, une nouvelle voie d’accès directe utilisant des synthons entrelacées pour la préparation de machines moléculaires de type rotaxanes et de rotaxanes dénués de site d’interaction fort a été étudié. Dans un premier temps, des « briques moléculaires » [2]rotaxanes isolables, bien qu’activées, ont été obtenus par une stratégie de glissement. Dans le but de les convertir aisément en machines moléculaires, les paramètres cinétiques et thermodynamiques relatifs au processus d’entrelacement ont été déterminés et ont permis de juger de l’importance de la nature et de l’orientation des pseudo-bouchons sur la cinétique d’entrelacement, ainsi que du rôle primordial du degré de liberté conformationnel de l’axe moléculaire sur la vitesse de formation des rotaxanes. Par la suite, les synthons entrelacées activés sous forme d’ester actif (ester de NHS isolable) sont utilisées dans la préparation de différentes machines moléculaires possédant une station moléculaire principale ammonium et une station moléculaire secondaire triazolium ou amide (secondaire ou tertiaire). D’autres synthons entrelacés qui différent par l’orientation du motif NHS sont utilisé comme transporteurs d’éther couronne pour permettre la préparation de rotaxanes dénués de site d’interaction fort. Enfin, dans la continuité des travaux réalisés au laboratoire sur le contrôle de la conformation chaise d’un mannosyl par une machinerie moléculaire, de nouvelles navettes pH-sensible de type glyco[2]rotaxanes contenant toutes une station moléculaire principale anilinium, et qui différent des machines précédentes par la deuxième station pyridinium, ont été obtenus et étudiés. / This thesis is dedicated to the synthesis of interlocked synthons for the efficient preparation of pH-sensitive rotaxane molecular machines and rotaxanes devoid of recognition site. Although the strategy directed by the "template" effect has been used very frequently and successfully so far, in most cases it only leads to interlocked compounds that contain the interaction sites necessary for prior recognition molecular elements to assemble. To overcome this limitation, a new direct access using interlocked synthons for the preparation of molecular machines of the rotaxane and rotaxane type devoid of strong interaction sites has been studied. Firstly, isolable [2]rotaxane "building block", although activated, were obtained by a slipping strategy. In order to easily convert them into molecular machines, the kinetic and thermodynamic parameters relating to the slipping process were determined and made it possible to judge the importance of the nature and orientation of the pseudo-stopper on the kinetics of slipping, as well as the primordial role of the degree of conformational freedom of the molecular axis on the speed of formation of rotaxanes. Subsequently, the activated ester (NHS isolatable ester) interlocked synthon are used in the preparation of different molecular machines having a main ammonium molecular station and a secondary molecular triazolium or amide station (secondary or tertiary). Other interlocked synthons that differ in the orientation of the NHS motif are used as crown ether transporters to enable the preparation of rotaxanes devoid strong interaction sites. Finally, in the continuity of the work carried out in the laboratory on the control of the chair conformation of a mannosyl by a molecular machinery, new pH-sensitive shuttles of glyco[2]rotaxane containing a main molecular station anilinium, and which different previous machines by the second station pyridinium, were obtained and studied.

Supramolecular chemistry is an emerging field of chemistry which has attracted much attention in recent years as a result of its broad applicability in many areas. Thus, the design of functional supramolecular systems is strongly in demand in this field. For this purpose, we have developed novel phenylethynyl-BODIPY oligomer series which have absorption and emission maxima at the red part of the visible region of electromagnetic spectrum. Careful design to assemble the decyl groups to the system allowed us to dissolve the molecules in organic solvents easily. That`s why, not only we could characterize the molecules, but also spectroscopic and photopysical properties of them were investigated. As expected, as the number of repeating units &ldquo / n&rdquo / increase, peak absorption and emission wavelengths are shifted to the red end of the visible spectrum, with smaller increments as &ldquo / n&rdquo / increases. Consequently, these rigid rod like overall arrangement of oligomers could lead to applications as functional building blocks.

Porous solids are a class of materials of high scientific and technological significance. Indeed, they have the ability to interact with atoms, ions or molecules not only at their surface but also throughout the bulk of the solid. This ability places these materials as a major class involved in many applications such as gas storage and separation, catalysis, drug delivery and sensor technology. Metal-Organic Materials (MOMs) or coordination polymers (CPs) are crystalline compounds constructed from metal ions or clusters and organic components that are linked via coordination bonds to form zero-, one-, two or three-periodic structures. Porous Metal-Organic Materials (MOMs) or Metal-Organic Frameworks (MOFs) are a relatively new class of nanoporous materials that typically possess regular micropores stable upon removal of guests. An extraordinary academic and industrial interests was witnessed over the past two decades and is evidenced by a fantastic grow of these new materials. Indeed, due to a self-assembly process and readily available metals and organic linkers, an almost infinite number of materials can, in principle, be synthesized. However, a rational design is very challenging but not impossible. In theory, MOMs could be designed and synthesized with tuned functionalities toward specific properties that will determine their potential applications. The present research involves the design and synthesis of functional porous Metal-Organic Materials that can be used as platforms for specific studies related to many applications such as for example gas storage and particularly hydrogen storage. In this manuscript, I will discuss the studies performed on existing major Metal-Organic Frameworks, namely Zeolite-like Metal-Organic Frameworks (ZMOFs) that were designed and synthesized in my research group. My research was also focused on the design and the synthesis of new highly porous isoreticular materials based on Metal-Organic Polyhedra (MOP) where desirable functionality and unique features can be introduced in the final material prior and/or after the assembly process. The use of hetero-functional ligands for a rational design toward binary or ternary net will also be discussed in this dissertation.

No description available.

The design of functional materials for specific applications has been an ongoing challenge for scientists aiming to resolve present and future societal needs. A burgeoning interest was awarded to developing methods for the design and synthesis of hybrid materials, which encompass superior functionality via their multi-component system. In this context, Metal-Organic Materials (MOMs) are nominated as a new generation of crystalline solid-state materials, proven to provide attractive features in terms of tunability and versatility in the synthesis process. In strong correlation with their structure, their functions are related to numerous attractive features, with emphasis on gas storage related applications. Throughout the past decade, several design approaches have been systematically developed for the synthesis of MOMs. Their construction from building blocks has facilitated the process of rational design and has set necessary conditions for the assembly of intended networks. Herein, the focus is on utilizing the single-metal-ion based Molecular Building Block (MBB) approach to construct frameworks assembled from predetermined MBBs of the type MNx(CO2)y. These MBBs are derived from multifunctional organic ligands that have at least one N- and O- heterochelate function and which possess the capability to fully saturate the coordination sphere of a single-metal-ion (of 6- or higher coordination number), ensuring rigidity and directionality in the resulting MBBs. Ultimately, the target is on deriving rigid and directional MBBs that can be regarded as Tetrahedral Building Units (TBUs), which in conjunction with appropriate heterofunctional angular ligands are capable to facilitate the construction of Zeolite-like Metal-Organic Frameworks (ZMOFs). ZMOFs represent a unique subset of MOMs, particularly attractive due to their potential for numerous applications, arising from their fully exploitable large and extra-large cavities. The research studies highlighted in this dissertation will probe the validity and versatility of the single-metal-ion-based MBB approach to generate a repertoire of intended MOMs, ZMOFs, as well as novel functional materials constructed from heterochelating bridging ligands. Emphasis will be put on investigating the structure-function relationship in MOMs synthesized via this approach; hydrogen and CO2 sorption studies, ion exchange, guest sensing, encapsulation of molecules, and magnetic measurements will be evaluated.

Le premier chapitre traite d’une réaction de cycloaddition (4+1) sur des énones et des énals à l’aide du diméthoxycarbène. Cette méthode permettrait d’obtenir des hétérocycles à cinq membres à partir de substrats linéaires simples et faciles à fabriquer. On retrouve dans ce chapitre l’optimisation de cette étape réactionnelle, ainsi que son utilisation pour préparer une gamme de substrats. Le second chapitre traite de la transformation des hétérocycles obtenus, et décrits au chapitre précédent, en furannes ainsi qu’en furanones. Cette méthode permet la transformation d’énones et d’énals en hétérocycles oxygénés à cinq membres en seulement deux étapes. On retrouve dans ce chapitre la description de plusieurs méthodes développées pour parvenir aux substrats, ainsi que les échecs rencontrés pour l’obtention de benzofuranne.