A kinetic study of the reactions of Group VI-B hexacarbonyls with primary amine and halide ligands was undertaken in order to determine the possible mechanisms of these reactions. As well as the expected dissociative pathway, the reactions with the primary amines were seen to proceed by a concurrent pathway which was dependent upon the ligand concentration. Since nitrogen donor ligands are expected to be poor donor ligands, the mechanism proposed was a "dissociative interchange" mechanism which should not be too dependent upon the nucleophilicity of the ligand. Comparison of the rate constants for the amines studied as well as those of the previously investigated Lewis base ligands indicated all such reactions may proceed through the same mechanism. The similarity in rate constants for the ligand-independent and ligand-dependent pathways supports this mechanism. The rate of formation of the final product was seen to be dependent upon the square of the mercuric halide concentration. Therefore, the conversion of Fe(CO)4(HgX)2 to the final product was proposed to proceed by the successive abstraction by each HgX group of two molecules of mercuric halide. These oxidative elimination reactions are related to a chemical model for the intermediate step in the reduction of dinitrogen to ammonia and their similarities and differences are discussed.

In recent studies it was reported that the D-amino acid containing peptide HYD1 was used in the treatment of necrotic cell death in multiple myeloma cell lines and showed promising biological activity and in vivo activity. It was meaningful to explore strategies for increasing the therapeutic efficacy of HYD1, a linear peptide. These efforts led to the development of MT1-101 (cyclized peptidomimetics), a lead compound that showed increased in vitro activity and in vivo activity. MTI-101 was found to bind the cell adhesion molecule CD44 and induce programmed necrosis in myeloma cell lines. It was important to improve on the binding efficiency of the MTI-101 to this target and explore more cost effective ways to synthesize this peptide. This lead to developing Cyclic beta-hairpin-like peptoid scaffolds, which introduced diverse families of random peptoid-body libraries that will be screened to find small stable scaffolds that compete with and can replace antibodies as cell-surface targeting reagents. The synthesis of peptoids on solid-support can be more cost effective and a large library can be developed using a diverse library of primary amines. This initiated this thesis project to develop a generalized scheme for the synthesis of TRP-like primary amine peptoid side chains used in the cyclic beta-hairpin - Like scaffolds.

Submitted by (lucia.rodrigues@ufrpe.br) on 2017-02-15T12:46:59Z No. of bitstreams: 1 Jose Torres Litivack Junior.pdf: 1021307 bytes, checksum: 23166bc9966fb074f01ede1fa2f5f5bd (MD5) / Made available in DSpace on 2017-02-15T12:46:59Z (GMT). No. of bitstreams: 1 Jose Torres Litivack Junior.pdf: 1021307 bytes, checksum: 23166bc9966fb074f01ede1fa2f5f5bd (MD5) Previous issue date: 2009-08-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / In this work a series of novel lapachol adducts with aliphatic primary amines were synthesized. These amines included 2-aminoethanol, 3-amino-1-propanol, 2- methoxy-ethylamine, 3-methoxy-propylamine, n-butylamine and glycine. All reactions were performed under ambient temperature and without solvents. The newly products with unique structures were characterized by IR and UV spectroscopy and 1H and 13C NMR with bi-dimensional techniques. A possible mechanism was proposed based on the ability of the quinones to react as radical species, where a initially formed imine act as a nucleophile with a second molecule of lapachol, and this primary adduct results in observed products under the oxidant conditions used in reaction. To test this hypothesis the reaction was conducted in inert atmosphere or in the presence of an antioxidant (BHT), and the reaction mixture behaves differently, as expected. / Neste trabalho foi sintetizada uma série de novos adutos do lapachol com aminas alifáticas primárias. Entre as aminas estão o 2-amino etanol, o 3-amino-1- propanol, a 2-metoxi-etilamina, o 3-metoxi-propilamina, a n-butilamina e a glicina. Todas as reações foram realizadas sob temperatura ambiente e sem solvente. Os novos produtos de estrutura inédita foram caracterizados por infravermelho, espectroscopia UV, RMN 1H e 13C, incluindo técnicas bidimensionais. Um possível mecanismo foi proposto baseado na capacidade das quinonas reagirem como espécies radicalares, onde a imina inicialmente formada atua como nucleófilo com uma segunda molécula de lapachol, resultando em um aduto primário que se converte nos produtos observados nas condições oxidantes utilizadas na reação. Para testar essa hipótese, a reação foi conduzida em atmosfera inerte ou na presença de um antioxidante (BHT), onde a mistura reagente se comportou de forma diferente, como esperado.

Since their first observation in 1991, carbon nanotubes (CNTs) have attracted a lot of attention owing to their exceptional properties. Their excellent electrical and thermal conducting performances combined with their high toughness and transverse flexibility allow their use in a large range of varied applications. Offering at the same time a high aspect ratio (length-to-diameter) and a low density, carbon nanotubes show strong application potential in reinforced composite materials. Unfortunately, CNTs have the strong tendency to form bundles very difficult to dissociate and disperse in a majority of polymer matrices. Without efficient CNTs dispersion, nanocomposites can not present optimal mechanical, thermal and electrical properties. To overcome this drawback, one solution consists to graft polymer chains on the carbon nanotubes surface in order to disaggregate bundles and, in few cases, to improve interaction between the polymer matrix and nanotubes. The thesis work can be divided into three parts. The first is the one-step amination of multi-walled carbon nanotubes (MWNTs) via an original microwave plasma process. The MWNTs, placed in the post-discharge chamber in presence of H2, are subjected to a reactive flow of atomic nitrogen produced by the plasma. The results give evidence for efficient covalent grafting of primary amine groups along the sidewalls of MWNTs, avoiding any structural damage and alteration of properties. The so-grafted amine groups have been further consider as initiation sites for promoting the ring opening polymerization of lactone monomers yielding polyester-grafted MWNT nanohybrids. Finally, these nanohybrids have been used as highly filled masterbatches to be dispersed in the molten state within several polymer matrices, such as polycaprolactone (PCL) and high density polyethylene (HDPE), to obtain nanocomposites with largely improved properties. For instance, electrical measurements and morphological characterizations showed that the polyester surface-grafting allows for improving the dispersion state of the nanotubes in the different polymer matrices leading to enhanced electrical properties as well as thermal and mechanical performances.

Primary amine-based plasma polymer films (PPF) attract an increasing interest due to their potential applications as platforms to support cell growth and biomacromolecule immobilization. It has been demonstrated that the biological response of these films is correlated to their primary amine content (%NH2). Control and optimization of the process are thus very important requirements. However, despite the abundant literature related to this attractive technology, plasma polymerization remains very complex so that strong efforts are still needed to understand the relationship between the plasma chemistry and the PPF characteristics. The main part of this work describes the pulsed plasma polymerization of two isomeric precursors, namely allylamine and cyclopropylamine, with the aim to study the influence of the precursor on the plasma and the PPF physico-chemistries. The systems have been compared in similar conditions of mean power injected in the discharge (Pmean). Both experimental and theoretical approaches have been used to shed light on the process. Taking into account the electron energy in the plasma, differences between allylamine and cyclopropylamine plasma chemistries have been rationalized with the help of Density Functional Theory calculations. It is demonstrated that %NH2 can be increased by an appropriate choice of the precursor and the experimental conditions. Indeed, the use of cyclopropylamine can yield to PPF with a larger %NH2 compared to allylamine due to a preferential opening of the ring structure in the plasma. A method is also proposed to discriminate the PPF according to their cross-linking density (÷). While it appears to be independent of the chemical structure of the precursor, ÷ is observed to significantly vary with Pmean. The PPF have further been investigated with the aim to better understand the phenomena taking place when immersed in liquid medium, an essential step for biological applications. The results show that the decrease in the PPF thickness (Äd), conventionally observed upon immersion, directly depends on Pmean; the higher Pmean, the lower Äd. For the first time to our knowledge, the present work allows to unambiguously attribute this phenomenon to an increase of ÷ with Pmean. Furthermore, thanks to the analysis of the resulting solutions, the data give a new insight into the PPF behavior in liquid medium, suggesting that Äd is mostly related to a reorganization of the PPF network and not to material dissolution as usually claimed. Finally, some preliminary experiments indicate that the PPF can be used to support muscle cell culture; the performances of the PPF-coated materials reveal to be at least similar to those of the standard surfaces.

Functionalized poly(para-xylylene) (PPX) coatings can be useful for biomaterials applications due to their biocompatibility and useful chemistry for the immobilization of biomolecules. However, their application is not widespread due to the difficulty in synthesizing the corresponding precursors. Here, a two-step method for amine functionalization of [2.2]paracyclophane (PCP) via direct nitration and reduction is developed. Nitration at super acidic conditions and temperatures as low as -78 °C, improved the stability of PCP toward strong acids and successfully minimized side reactions such as oxidation and polymerization. This procedure resulted in quantitative yields of 4-nitro-PCP, which was successively reduced by Raney nickel catalysis with sodium borohydride. Compared to the many other reduction systems, this method is simple, inexpensive and applicable in large scales. Additionally, carboxylation of PCP using the Freidel-Crafts acylation was attempted and so far, we have been able to show the synthesis of intermediate acylated products. Then, through the chemical vapour deposition polymerization of amino-PCP amine-functionalized poly(para-xylylene) (PPX-A) thin films were coated on Si wafer substrates. The substrates coated with PPX-A showed a higher surface energy compared with those of coated with un-substituted or chlorine substituted PPX films. Furthermore, results of the surface characterization demonstrated that the CVD process was able to transfer the functionalities of the precursors to deposited polymer films without alteration. However, the stability of primary amine groups in air and aqueous solutions is a matter of concern. Aging of amino-PCP and corresponding PPX-A films showed a decrease in the amount of primary amines which was accompanied by the appearance and increase of oxygen, indicating that the decrease of available amine groups is associated with oxidation. Nevertheless, both aminated precursor and polymer films remained intact under argon. The method presented here has great potential for widespread application of PPX-A as a convenient biomaterial for microarrays and cell culture. / Thesis / Master of Science (MSc)

Functionalized reactive polymer coatings can be used in various biomaterials applications such as immunoassays and biomolecule immobilization. Poly(para-xylelene) is a relatively new biomaterial that has attracted attention over the past few decades in these areas due to its unique properties and biocompatibility. The introduction of functionalized, particularly aminated, poly(para-xylylene) will extend the application of these polymer coatings to a wide variety of biological studies. However, their application is not widespread due to the difficulty in synthesizing the corresponding precursors. Here, a two-step method for amine functionalization of [2.2]paracyclophane via direct nitration and reduction is developed. Nitration at super acidic conditions and temperatures as low as -78 °C, improved the stability of [2.2]paracyclophane toward strong acids and successfully minimized side reactions such as oxidation and polymerization. This procedure resulted in quantitative yields of 4-nitro[2.2]para-cyclophane, which was successively reduced by Raney nickel catalysis with sodium borohydride. Compared to the many other reduction systems, this method is simple, inexpensive and applicable in large scales. It does not require harsh reaction conditions and within short reaction times, delivers quantitative amounts of the reduced product. At the end, 4-amino[2.2]paracyclophane was collected in 77% overall yield. Additionally, carboxylation of [2.2]paracyclophane using the Freidel-Crafts acylation was attempted and so far, we have been able to show the synthesis of intermediate acylated products. The successful syntheses of products were verified by FT-IR, NMR and MS, and comparison of their solubility and physical properties showed significant changes upon substitution of the pristine [2.2]paracyclophane. Then, through the chemical vapour deposition polymerization of 4-amino[2.2]paracyclophane amine-functionalized thin films were coated on Si wafer substrates and their properties were compared with Parylene N and C, two well-known poly(para-xylylene) films. The substrates coated with amino-poly(para-xylylene) showed a higher surface energy compared with those of coated with un-substituted or chlorine substituted poly(para-xylylene) films. Furthermore, results of the surface characterization conducted by grazing angle reflectance IR spectroscopy and XPS, demonstrated that the CVD process was able to transfer the functionalities of the precursors to deposited polymer films without alteration. However, with the applied process parameters we obtained a higher functional density of amine groups on the surface. These polymer films can be deposited on a variety of substrates and be used as functional surfaces for a variety of applications. However, the stability of primary amine groups in air and aqueous solutions is a matter of concern. Aging of 4-amino-[2.2]paracyclophane and corresponding poly(para-xylylene) films in air and mili-Q water was studied via XPS and NMR spectroscopies. The results showed a decrease in the amount of primary amines with storage time in air or water for both aminated precursor and polymer. The kinetics for these changes, however, were not equal for the precursors and polymer films. The decay of amine groups was accompanied by the appearance and increase of oxygen, indicating that the decrease of available amine groups is associated with oxidation which can transform them to more stable amide and nitro compounds. In total, practical challenges involved in manufacture, durability and applications of amine-functionalized Parylene coatings are discussed and a reliable scheme for fabricating such films with high tunabiliy of the surface functional density is demonstrated. The highly practical method presented here provides great potential for widespread application of amine-functionalized poly(para-xylylene) as an outstanding biomaterial for microarrays, tissue engineering and cell culture studies. / Thesis / Master of Science (MSc)

In this thesis, different cycloaddition reactions, such as the enantioselective 1,3-dipolar-cycloaddition, which takes place between in situ generated stabilized azomethine ylides, and electrophilic alkenes, and the diastereoselective multicomponent reactions Amine-Aldehyde-Dienophile (AAD) or Phosphoramidate-Aldehyde-Dienophile (PAD) are described. In Chapter 1, an asymmetric 1,3-dipolar cycloaddition reaction involving an imino ester with tert-butyl acrylate was carried out using a silver(I) complex with double chirality, formed from a chiral phosphoramidite and chiral silver binolphosphate(I). The goal of this reaction is to synthesize key enantiomerically enriched structures to access the GSK-third generation of HCV inhibitors. In Chapter 2, the synthesis of polysubstituted cyclohex-2-enylamines using the multicomponent Amine-Aldehyde-Dienophile reaction involving benzyl or 4-methoxybenzylamine, is described. The study the diastereoselective version, employing commercially available chiral benzylic amines, or even a maleimide with the chiral information at the nitrogen atom, are also reported. In Chapter 3, the synthesis of polysubstituted cyclohex-2-enylamines derivatives using the multicomponent Phosphoramidate-Aldehyde-Dienophile (PAD), is described. Several series of N-substituted phosphoramidates reacted with α,β-unsaturated aldehydes, bearing hydrogen atoms at the γ-position, in good yields.

<p dir="ltr">Water molecules present an obstacle between most synthetic adhesives and surfaces, limiting molecular contact between the glue and substrates. Water can also hydrolyze or swell bulk adhesives, weakening cohesive strength. Nature has solved these challenges for millennia. Marine mussels’ ability to adhere well to wet surfaces stems from an uncommon amino acid, 3,4-dihydroxyphenylalanine (Dopa). The amino acid Dopa contains a catechol moiety that contributes to adhesion and cohesion through hydrogen bonding, metal coordination, and oxidative cross-linking. Hence, biomimetic systems often incorporate catechol groups to provide strong adhesion in both dry and wet environments. In addition to Dopa, mussel adhesive proteins are rich in cationic amino acids lysine and arginine. Previous studies have suggested that cations could displace surface-bound ions, enhancing surface adhesion. However, adhesion performance varied between systems, with no agreement on whether cations are advantageous or disadvantageous. A clear picture of how cations influence underwater adhesion has yet to emerge; therefore, this thesis aims to systematically study these effects.</p><p dir="ltr">In Chapter 2, the synthesis of catechol-containing biomimetic polymers with varying amounts of quaternary ammoniums is presented. Quaternary ammoniums, unlike protonated primary amines, contain non-reactive cations and were used to isolate effects from only charges on adhesion. In Chapter 3, differences between reactive primary amines and quaternary ammoniums were investigated. Structure-function studies have shown how cations influence bulk cohesion versus surface adhesion in dry, under deionized water, and under salt water. The roles of cations in adhesion were complex, with both cohesive and surface bonding relevant in different ways, sometimes even working in opposite directions.</p><p dir="ltr">Furthermore, a styrene-based catechol-containing polymer with excellent underwater adhesion performance is ready to enter the market, but several barriers hinder its industrial implementation. In Chapter 4, new synthetic strategies were developed to scale up and reduce the cost of producing p[vinylcatechol-<i>co-</i>styrene], which are essential for commercialization. This was achieved by selecting cheaper starting materials, switching from anionic to suspension polymerization, and optimizing deprotection reaction conditions. This change also improved adhesion in both dry and underwater conditions. This work is presented as part of our effort to advance the design of adhesives that function in challenging environments.</p>