Coupling homogeneous catalysts to dendrimers with rigid nuclei is one possible strategy to recycle these compounds in an industrial environment. During this study attempts were made to attach the well-defined ruthenium carbene complex 2 to the alicyclic compound 1A. To achieve this goal attempts were made to functionalise 1A with anime groups to facilitate the attachment of phosphine groups. The catalyst 2 would then be attached through a phosphine exchange reaction. Oximes were used as precursors in attempts to prepare cage amines from 1A. For this purpose, the dioxime 28 was prepared from 1A. Reduction of 28 was unsuccessful. Molecular modelling showed that the lobes of the LUMOs of the oxime carbon atoms of 28 do not protrude from the total electron density of this molecule. This observation indicates that 28 would probably not react with nucleophiles, such as the hydride ion. Molecular modelling was used to probe the unreactive nature of oxime 28. The probe revealed that the imide ring deactivates the oxime groups in this compound. Based on these results, attempts were made to change the carbon framework of 1A to eliminate unwanted interaction between the carbonyl groups. Clemmensen reduction of 1A did not yield the expected ketol 40, but gave a mixture of 62 and 63. Extended reaction times yielded 63 only. Reduction of 1A with zinc and acetic acid produced a mixture of 62 and 40 that could not be separated. Consequently, the applicability of 62 as a possible dendrimer nucleus was investigated. Compound 62 was obtained by oxidisation of the diol 63 with sodium periodate. Attempts to synthesise the dioxime 69 from 62 failed and only the mono oxime 71 was obtained. Reduction of 71 with lithium aluminium hydride was unsuccessful. Molecular modelling revealed that the oxime carbon atom does not have a LUMO and that the carbonyl carbon atom would probably be unreactive towards nucleophiles. Several other attempts were made at reducing the oxime 71 to an amine. None of these attempts met with any success. The reason for the unreactive nature of 71 is less clear than in the case of 28. Failure to produce a cage amine from 1A or derivatives of 1A meant failure in functionalising the cage system with phosphine groups and coupling the Grubbs-I catalyst. It seems that cage compounds based on 1A are generally not suitable as starting materials for amine-functionalised dendrimer nuclei. / Thesis (M.Sc. (Chemistry))--North-West University, Potchefstroom Campus, 2011.

In the frame of this thesis different calix[4]resorcin- and calix[4]pyrogallolarene derivatives were used as platform for the synthesis of novel star polymers and dendritic structures. The objectives of this work can be portrayed under the following points: First: Synthesis and modification of calix[4]resorcin- and calix[4]pyrogallolarenes with a varying number and varying type of functional sites and their precise characterization by modern NMR techniques and single crystal X-ray diffraction. Second: Synthesis of well-defined star polymers and dendrimers with different number of arms and accordingly dendrons, based on calix[4]resorcin- and calix[4]pyrogallolarenes, via convenient polymerization and generation growth reactions and analysis of the obtained products by different methods (MALDI-TOF-MS, SEC-RI and SEC-MALLS, NMR).

Dendrimers are synthetic macromolecules with branches-upon-branches structures, nanoscale dimensions and a high density of surface groups. Presence of multiple cationic sites in dendrimers permits their efficient nucleic acid complexation and cellular internalization through endocytic pathways. PETIM dendrimers of are characterized by tertiary amine branch points, and ether linkages. A third generation PETIM dendrimer, G3(NH2)24, with nitrogen at the core and twenty four peripheral primary amines was synthesized through alternate Michael addition and reduction reactions. The ability of G3(NH2)24 to interact with DNA was ascertained by spectroscopic and bio-physical techniques. These studies established the formation of dendrimer-DNA, and complex formation was also shown to protect the plasmid DNA from nucleases. Toxicity studies in cell culture, as well as, in female Balb/c mice established the non-toxic properties of the dendrimer. G3(NH2)24 was able to mediate efficient transfection in mammalian cells and in vivo. Targeted delivery of small interfering RNA (siRNA) to hepatocytes, in order to combat hepatitis C virus (HCV) infection was undertaken to expand the scope of PETIM dendrimer based gene delivery. Functionalization of the dendrimer periphery with galactose units ensured preferential delivery to the liver through multivalent interactions with the asialoglycoprotein receptors on the liver cell surface. The delivery of siRNA to the perinuclear region, in close proximity to the HCV RNA replication site resulted in ~75% decrease in viral RNA levels in replicon containing cells, as well as, JFH-1 infectious virus systems. The dendrimer-siRNA complexes were preferentially delivered to mice liver and were active in vivo. Physico-chemical studies of the protonation pattern of PETIM dendrimer indicated that the protonation of the dendrimer amines proceeded in a shell-wise pattern from the periphery to the core. The primary amines of the dendrimer as well as the outer shell tertiary amines with pKa values ~7-10 were protonated at physiological pH and were cationic sites for nucleic acid condensation. The inner shell tertiary amines with a pKa of ~4-6 were protonated at endosomal pH and aided ‘endosomal escape’ due to the high buffering capacity of 3.5. Work described in the Thesis establish a new synthetic dendrimer vector, namely, the series of PETIM dendrimers, as a high value gene delivery vector, making in-roads towards pre-clinical and possible clinical trials in future studies.

Le cancer est une cause majeure de décès dans le monde, 7,6 millions de décès en 2008. Bien que de nombreux progrès ont été réalisés dans le traitement du cancer, de nouvelles approches sont nécessaires afin de minimiser les effets secondaires délétères et d'augmenter le taux de survie. Par conséquent, l'avenir de la nanomédecine réside dans le développement de nano-plateformes multifonctionnelles. Il ne fait aucun doute que les hybrides organique / inorganique à base de dendrons représentent des outils très avancés, capables de cibler spécifiquement et d'être suivis par imagerie en même temps. Dans ce contexte, les objectifs de cette thèse sont non seulement la conception de nano-objets magnétiques dendronisés biocompatibles permettant à la fois le diagnostic par imagerie à résonance magnétique (IRM) ainsi que par imagerie optique (IO) mais également la validation in vitro et in vivo des propriétés de ces nano-objets et la démonstration de leur efficacité pour le ciblage spécifique de tumeurs. / Cancer is a worldwide leading cause of death, 7.6 million deaths in 2008 with 13% mortality. Although much progress has been made in early cancer diagnosis and treatment, new approaches are needed to minimize the deleterious side effects while increasing survival rate. Therefore, the future of Nanomedicine relies in the development of multifunctional nano-platforms that combine therapeutic components, multimodal imaging and active targeting. Organic/inorganic dendrimer-based hybrids are very advanced tools, especially for targeting a specific cell type or a particular organ and for being followed by imaging techniques at the same time.In this context, the objective of this thesis is not only the design of multifunctional magnetic dendronized nano-objects, but also their in vitro and in vivo validation and assessment of their active targeting effectiveness.

We report an IgG (=immunoglobulin) electrochemical immunosensor using a newly synthesized redox-active ferrocenyl dendrimer of generation 2 (G2Fc) as a voltammetric transducer. The ferrocenyl dendrimer N(CH2CH2C(O)NHCH2CH2NHC(O)Fe(η5-C5H4)(η5-C5H5))(CH2CH2N(CH2CH2C(O)NHCH2CH2NHC(O)Fe(η5-C5H4)(η5-C5H5))2)2 (G2Fc) was used as a functional moiety to immobilize the antibody on the surface of the electrode. A sandwich immunosensor of the type IgG/Bovine serum albumin (BSA)/anti-IgG/G2Fc/glassy carbon electrode (GCE) was fabricated. The electrochemical properties of G2Fc were thoroughly studied in aqueous and non-aqueous electrolytes with varying scan rates. The incubation time was optimized for better analytical performance of the immunosensor. It is found that the developed amperometric immunosensor is sensitive to a concentration of IgG as low as 2 ng mL−1. / Dieser Beitrag ist aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Arbetet har utförts i samarbete med Naturskyddsföreningen för att undersöka vilka vattenavvisande behandlingar som görs på ytterplagg för barn och hur tillverkarna förhåller sig till perfluorerade ämnen. I arbetet har vattenavvisande ytterplagg för barn i förskoleåldern studerats, med syfte att se i vilken mån perfluorerade ämnen används i plaggen. Barnen som har studerats är utomhus varje dag i alla väder. Vid kraftigt regn eller när det är mycket blött ute används vattentäta regnställ, vid lättare väta bär de ytterplagg med vattenavvisande funktion. En egen oljedropptestmetod har utvecklats. Testet har utförts på de plagg som hänger på förskolorna. Det finns flera typer av vattenavvisande behandlingar. De vanligaste är perfluorerade ämnen, silikoner, dendrimerer och vaxer. De har olika egenskaper och funktioner sinsemellan. De perfluorerade ämnena har den bästa vattenavvisande förmågan och de är också de enda som är oljeavvisande. Perfluorerade ämnen är persistenta, bioackumulerande, hormonstörande och toxiska. Hormonstörande ämnen kan bidra till fetma, cancer, neurologiska störningar, fortplantningsstörningar och missbildningar. Silikoner har goda vattenavvisande egenskaper. Råvaran till silikoner är persistent, bioackumulerande och toxisk. Även dendrimerer har goda vattenavvisande egenskaper. Lite är känt om miljö- och hälsopåverkan men partiklar i nanostorlek kan potentiellt ta sig in cellerna och orsaka cancer. Inga allvarligare miljö- och hälsokonsekvenser av vaxer/paraffiner har hittats. De har sämre vattenavvisande egenskaper, påverkar greppet och tål tvätt och nötning dåligt. De kläder som används på förskolorna håller generellt barnen torra, men en försämring kan märkas på gamla eller dåligt konstruerade plagg. Ytterplagg som behandlats med perfluorerade ämnen är vanliga. Företagen har fasat ut perfluorerade ämnen under de senaste åren, planerar att byta ut dem eller har vidtagit åtgärder enligt Reach. Dendrimerer är det vanligaste alternativet till perfluorerade ämnen. Inga krav förekommer från vare sig företag eller användare på att plaggen ska vara smuts- och oljeavvisande. / Program: Textilingenjörsutbildningen

Les polyoxométallates (POMs) dendritiques constituent une catégorie de catalyseursrelativement nouvelle. L’association d’un dendrimère avec un polyoxométallate permet debénéficier des propriétés catalytiques intéressantes des POMs et de pouvoir modifier cespropriétés en variant la structure du dendrimère. Une variété de composés hybrides POMsdendritiques a été préparée par formation de liaisons ioniques entre une unité POM anioniqueachirale et des cations dendritiques énantiopurs. Ces composés se sont montrés très efficacespour la catalyse d’oxydation asymétrique, avec une stéréosélectivité significative. Cesrésultats ont démontré pour la première fois un transfert de chiralité d’une structure organiqueénantiopure vers une unité POM achirale. Ces composés sont stables et recyclables dans desconditions douces, sans perte significative de réactivité et de stéréosélectivité. / Polyoxometalates (POMs) represent a new generation of catalysts. Association of dendrimersand POMs allows modification of POM catalytic properties by modifying the dendrimerstructure. Several dendritic POM hybrid compounds have been prepared by ionic bondformation between an anionic POM unit and enantiopure dendritic cations. These compoundsare efficient for asymmetric oxidation catalysis with significant stereoselectivity. Theseresults have shown, for the first time, a chirality transfer from an enantiopure organicstructure to an achiral POM unit. These compounds are stable and recoverable under mildconditions without any significant loss of reactivity and stereoselectivity.

Cette thèse concerne l’élaboration par réaction “click” CuAAC denouveaux nanomatériaux présentant diverses applications, en particulier en catalyse.Ces macromolécules (dendrimères, dendrimères supportés sur oxide et polymères)comprenant des cycles 1,2,3-triazoles ont été utilisés pour stabiliser desnanoparticules essentiellement de palladium actives en catalyse de couplage C-C,réduction du 4-nitrophenol et oxydation des alcools dans des solvants aqueux.L’utilisation de ces nanoparticules à l’échelle du ppm traduit leur efficacité et l’aspectécologique visé avec ce projet. L’intégration d’unités triazolylbiferrocéniques au seinde ces polymères a permis d’étendre la gamme d’applications de ces matériaux auxsondes électrochimiques, réduction d’ions métalliques en nanoparticules, composéspoly-électrolytes, poly-électrochromes, à valence mixte. L’imprégnation denanoparticules de palladium stabilisées par des dendrimères sur support magnétiquea permis d’augmenter la robustesse des catalyseurs ainsi que leur recyclablité paraimantation. / This thesis concerns the synthesis by “click” CuAAC reactions of newnanomaterials that have various applications, in particular in catalysis. Thesemacromolecules are dendrimers, supported dendrimers and polymers that contain1,2,3-triazole rings and were used in the stabilization of essentially palladiumnanoparticles (PdNPs). These PdNPs are extremely active in the catalysis in greensolvents of C-C coupling, reduction of 4-nitrophenol and selective oxidation ofalcohols. The use of these nanoparticle catalysts at the ppm level shows theirefficiency and their ecological aspect. The integration of biferrocene units in thepolymers allowed expanding their applications to electrochemical sensors, reductantsof metallic ions to nanoparticles, polyelectrolytes, polyelectrochromic, and mixedvalentcomplexes. The impregnation of PdNPs stabilized by dendrimers on magneticsupport led to the increase of the catalyst robustness and recyclability using amagnet.

<p>In this thesis, I present the electrochemical studies of three dendrimeric polypropylene imine (PPI) nanomaterials and their applications as a platform in the development of a novel label free DNA nanobiosensor based on electrochemical impedance spectroscopy. Cyclic voltammetry (CV), differentia pulse voltammetry (DPV), square wave voltammetry (SWV) and electrochemical impedance spectroscopy (EIS) techniques were used to study and model the electrochemical reactivities of the nanomaterials on glassy carbon electrode (GCE) as the working electrode.</p>

Over the past few decades there has been great interest in exploring alternatives to conventional separation methods due to their high cost and energy requirements. Membranes offer a potentially attractive alternative as they potentially address both of these points. The overarching theme of this dissertation is to design nanocomposite membranes for processes where existing separation schemes are inadequate. This dissertation focuses on three challenges: 1) designing organic-inorganic hybrid membranes for reverse-selective removal of alkanes from light gases, 2) defect-free inorganic nanocomposite membranes that have uniform pores, and 3) nanocomposite membranes for minimizing protein fouling in microfiltration applications. Reverse-selective gas separations that preferentially permeate larger/heavier molecular species based on their greater solubility have attracted considerable recent attention due to both economic and environmental concerns. In this study, dendrimer-ceramic hybrid membranes showed exceptionally high propane/nitrogen selectivities. This result was ascribed to the presence of stable residual solvent that affects the solubility of hydrocarbon species. Mesoporous silica-ceramic nanocomposite membranes have been fabricated to provide defectless mesoporous membranes. As mesoporous silica is iteratively synthesized in the ceramic macropores, the coating method and the surfactant removal step significantly affected permeance and selectivity. It was also shown that support layers can cause a lower selectivity than Knudsen limit. Membrane fouling which results from deposition and nonspecific adsorption of proteins on the membrane surface is irreversible in nature, and results in a significant decrease in the membrane performance. To address this problem, two approaches were explored: 1) control of the surface chemistry tethering alumina membranes with organic components and 2) development of a novel photocatalytic membrane that exhibits hydrophilicity and can be easily regenerated. Both approaches can offer a viable route to the synthesis of attractive membranes, in that 1) the density of protein-resistant organic groups such as PEG is controllable by changing scaffolds or synthesis conditions and 2) the photocatalytic nanocomposite membranes can open the way for a new regeneration method that is environmentally benign.