Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 338-365).

Thesis (Ph. D.)--University of Texas at Austin, 2006. / Vita. Includes bibliographical references.

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Dendrimers are characterized as synthetic, spherical macromolecules with tree- like branched structures. Their well-controlled sizes (3 - 10 nm), ease of functionalization, high water solubility, well-defined chemical structure, and biocompatibility make these nanomaterials attractive for a wide spectrum of promising biomedical applications. Peptide dendrimers and polyamidoamine (PAMAM) dendrimers have been used to date as effective transdermal or topical drug delivery systems, with the latest in a much greater extent. The structural characteristics of the aforementioned molecules guided us to design a novel repeating unit for dendrimers (monomer) possessing amino branching point and able to afford generation expanding through repeating amide bonds. The novel monomer, after appropriate modifications, was used to develop lower generations of polyamidoamino dendritic structures having amide groups and amino-branching points in their interior. The new dendrimers were isolated and fully characterized by typical spectroscopic technics. The final molecules will be used in human skin permeation experiments and will be evaluated for their effect on skin permeability.

Carbosilane dendrimers have been prepared via iterative hydrosilylation/alkenylation reactions using a variety of chlorosilanes (HSiMe₃₋nC1n)and alkenyl nucleophiles (CH₂=CHCH₂MgBr and CH₂=CHMgBr). Characterization by multinuclear NMR spectroscopy of the stepwise trifurctate dendrimers RED₃ (E=Si; R=Ph; D=Dendritic carbosilane fragment) assists end-group counting (NMR, R vs D) and can be related to analogous spheroidal ED₄ and hexafunctional E₂D₆ systems (E=Si or Ge). Typical D units contain (prnSiMe₃₋n)N Nb linkers; where pr=(CH₂)₃, N=generation number, Nb=branch multiplicity at silicon. For higher symmetry ED₄ and E₂D₆ systems (and also trifurcate) the Nb=1 (1B series) or Nb=2 (2B series) also allows for end-group counting by proton NMR spectroscopy (Ph:D:Me). ²⁹Si NMR chemical shifts have been developed for topographical mapping of dendritic structure. Peripheral and core substitution reactions have been examined for a series of trifurcate and related Ge₂D₆ ‘masked trifurcate' dendrimers. Replacement of end groups with a range of substrates is facilitated by the reactivity of the intermediate silicon chlorine bonds formed by hydrosilylation reactions. Selective removal of the core phenyl group (via triflic acid), or alternatively oxidative Ge-Ge cleavage, allows for unprecedented ‘bifunctionalization’; offering routes into dendrimer periphery:core electron transfer (‘photon-harvesting’) processes. Methodology for a ‘rapid-synthesis’ of hyperbranched structures has been developed and examined on a range of initial core molecules. Use of multinuclear NMR spectroscopy via comparison with step-wise products, as well as GPC chromatography, gives some insight into the overall architectures produced. Alteration of Si branch point from Nb=2 to Nb=3, using presynthesised ‘hypercores’ facilitates an alternate method of end group counting for higher symmetry cores. This methodology allows for population counting at large N in dendrimer generation G(N) (D interior vs D periphery). / Graduate

Effect of the concentration of amino-decorated polyamidoamine dendrimers with ethylenediamine core at the (trans)dermal delivery of 5-Fluorouracil Pavlína Chladová Dendrimers are synthetic, symmetrically tree-like branched molecules. They are composed of repeating units (monomers). They have high density of surface functional groups and spherical shape in solution. Since their molecular weight is highly controllable, they are characterized by monodispersity and this is their main difference from classical polymers. Dendrimers have a wide spectrum of applications in biomedicine. Due to the empty space between the branches of the molecule, they can encapsulate drugs, and by conjugation and complexation to the surface groups, they are able to carry even larger drug molecules. Thus, dendrimers can be used as drug delivery systems. In addition, they have been used for skin application of several active molecules, either as topical or transdermal delivery. Suitable properties for (trans)dermal application have been demonstrated for dendrimers which consist of monomers with amine groups and are connected with amide bonds. The goal of this thesis was the preparation of dendrimers with these characteristics and the evaluation of their concentration influence to the permeability of 5-Fluorouracil (5-FU) to human...

Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: Dr. Georgios Paraskevopoulos, Ph.D. Consultant: Mgr. Anna Nová ková Author: Denisa Houšková Title of thesis: Effect of the generation of amino-decorated polyamidoamine dendrimers with ethylenediamine core at the (trans)dermal delivery of 5-fluorouracil. Dendrimers can be defined like highly branched, star-shaped macromolecules with nanometer-scale dimensions and unlimited applications in both biological and materials sciences. Polyamidoamine (PAMAM) dendrimers have been used to effectively enhance the (trans)dermal drug delivery of several active substances. Inspired by the structure of PAMAM dendrimers, a new class of dendrimers was designed having amino-functionalized periphery and ethylenediamine core. A repeating motif of bis(2-aminoethyl)glycine was used for generation growth up to the third generation. The new dendritic molecules of zero, first, second and third generation were tested for their ability to enhance the deposition of 5-fluorouracil in the different layers of human skin ex vivo by using Franz diffusion cells. The results suggest that the new dendrimers, at a concentration of 20 mg/mL in 60 % propylene glycol in water as vehicle, are able to deliver 5-fluorouracil at the...

This thesis hypothesizes that the introduction of facile functional handles on the periphery and cores of dendrimers can lead to novel highly functional dendrimers useful for modular surface modifications of dendrimers with biological units of choice for tunable delivery devices and for high-end imaging applications respectively. The first functional handles introduced were on the periphery of poly(amide)-based dendrimers. The dendrimers were built by convergent strategies and were equipped with one and/or two selective, robust, and orthogonal functional handles for modular attachment to and transformation of dendrimer surface. By using azides, alkynes and aldehydes as robust functional handles and investigating their orthogonality and activity by high yielding couplings with small organic and biologically significant molecules a strategy and methodology for development of tunable dendrimer surfaces for numerous future applications was facilitated. Our second functional handles were introduced in the core of poly(amidoamine) based dendrimers. Raman labels such as triple bonds and carbon-deuterium bonds with vibrational frequencies in the background free vibrational zone of 2100-2500 cm-1 were introduced in the core of dendrimers for scaffold specific labeling. By encapsulationg Ag nanodots within these dendrimers, high fluorescence and scaffold specific Raman labeling could be achieved. This strategy lays the foundation for the creation of ultrabright, scaffold specific information containing biological labels for studying single cell dynamics. Finally, the use of dendritic frameworks in heterogeneous solid supported catalysis for enhanced cooperativity in reactions involving bimetallic transition states is explored and applied. Prior to this thesis work, heterogeneous resin supported catalysts for HKR reactions suffered from high catalyst loadings and low enantioselectivities induced by the solid support. With the use of flexible linker and dendron framework supporting the catalysts, both of these problems were addressed. This method opens up new routes for creation of highly active heterogeneous solid catalysts involving a bimetallic intermediate. In the end, the current status of dendritic frameworks is reviewed and methodological extensions to this work are suggested. Conceptions of how our functional dendritic architectures would be useful for future biological and catalytic applications are explored and detailed.

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