Yes / In this paper we investigate the optical and structural properties of a zwitterionic poly[3-(N-(4-sulfonato-1-butyl)-N,N-diethylammonium)hexyl-2,5-thiophene] (P3SBDEAHT) conjugated polyelectrolyte (CPE) and its interaction in water with surfactants, using absorption, photoluminescence (PL), electrical conductivity, molecular dynamics simulations (MDS) and small-angle X-ray scattering (SAXS). Different surfactants were studied to evaluate the effect of the head group and chain length on the self-assembly. PL data emphasize the importance of polymer–surfactant electrostatic interactions in the formation of complexes. Nevertheless, conductivity and MDS data have shown that nonspecific interactions also play an important role. These seem to be responsible for the spatial position of the surfactant tail in the complex and, eventually, for breaking-up P3SBDEAHT aggregates. SAXS measurements on P3SBDEAHT-zwitterionic cocamidopropyl betaine (CAPB) surfactant complexes showed a specific structural organization of the system. The CAPB surfactant promotes a structural transition from pure P3SBDEAHT 3-dimensional aggregates (radius of gyration ∼85 Å) to thick cylindrical aggregates (∼20 Å) where all CAPB molecules are associated with the polymer. For molar ratios (in terms of the polymer repeat unit) >1 the SAXS interference maximum of the complexes resembles that of pure CAPB thus suggesting ongoing phase segregation in the formation of a “pure” CAPB phase. / The Coimbra Chemistry Centre is supported by the Fundação para a Ciência e a Tecnologia (FCT), Portuguese Agency for Scientific Research, through the project PEst-OE/QUI/UI0313/2014. TC and BS thank FCT, which has supported this work through Postdoctoral Grants (SFRH/BPD/47181/2008 and SFRH/BPD/82396/2011, respectively). DA acknowledges CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil, for financial support through the Grant “Bolsista do CNPq – Brasil”. The research leading to the SAXS data has received funding from the European Community's Seventh Framework Programme (FP7/2007–2013) CALIPSO under grant agreement no. 312284.

No description available.

Synthetic strategies for polysaccharide-protein conjugates, pH-responsive hydrogels, and amorphous solid dispersion (ASD) polymers were developed. Conjugating a polysaccharide to a protein drug via a covalent bond may improve its medical properties including solubility, stability, immunogenicity, circulation time, and targeting ability. Regioselectivity of conjugation is still challenging. We developed a strategy for regioselective conjugation of amino acid esters to polysaccharides, by employing 6-Br-polysaccharides in SN2 substitution reactions with amino acid esters. This work provides a good starting point for the regioselective conjugation of polysaccharides to proteins. Polysaccharides can also serve as hydrogel drug carriers. Most hydrogels employed in drug delivery work by incorporating the drug physically. We synthesized sustained and pH-responsive hydrogels using oxidized hydroxypropyl cellulose (Ox-HPC)/carboxymethyl chitosan (CMCS) crosslinked by imine bond. Phenylalanine as a model amine-containing drug was chemically bonded to the Ox-HPC hydrogel component and was observed to release faster at the pH of a tumor microenvironment. These hydrogels show promise as targeting cancer drug carriers. ASDs are polymeric systems to disperse poorly soluble drugs amorphously and enhance permeation from the gastrointestinal tract (GI tract) to the bloodstream. We synthesized potentially zwitterionic cellulose derivatives by reductive amination of Ox-HPC with ω-aminoalkanoic acids and obtained products with the degree of substitution (cation and anion) up to 1.6, which is difficult to attain using previous methods. The products showed manipulated amphiphilicity and excellent thermostability, exhibiting potential application in ASDs. We anticipate that these strategies will benefit future polysaccharide chemistry research and permit synthesis of a broad variety of more functional biomedical materials. / Doctor of Philosophy / Polysaccharides are long chains of individual sugars ("polymers"). Many natural-sourced polysaccharides are sustainable, biodegradable, and have low toxicity. Polysaccharide-based materials may improve the properties of current drugs, resulting in decreased cost, enhanced absorption efficiency, and continuous and/or targeted delivery. Protein drugs such as human insulin have a significant role in medicine. However, the residence time of a protein drug in the human body is short. To overcome this challenge, we designed a method to link polysaccharides to proteins at controlled reaction sites, and reported herein the first step of this route. The final polysaccharide-protein products will even have the ability to recognize and access target cells, like those of tumors. Tumor tissues are more acidic than normal tissue and can trigger faster release of drug from drug carriers. We developed polysaccharide-based hydrogels, which are gels that bind a great deal of water but won't dissolve in it, as acid-sensitive carriers. In addition, our hydrogels are also injectable, and can spontaneously repair themselves. These properties make our hydrogels promising as cancer targeting drug carriers. Most new drug candidates have poor water solubility and permeation through the gastrointestinal tract to reach the blood stream. Dispersing the insoluble drug into a properly designed polymer network can enhance dissolution, permeation, and absorption. We developed a new family of polymers designed for this purpose using two cheap starting materials. These polymers can interact with the drug, preventing it from forming crystals and simultaneously promoting slow drug release. Overall, we explored ways to modify polysaccharides to create harmless, effective medical materials. We aim to promote science and benefit human health via our research.

Over recent years significant progress has been made in the design and development of late transition metal cationic catalysts for olefin polymerisation. Never-the-less, the activation of catalyst precursors and generation of active species still remains a challenge. In this respect, zwitterionic catalysts could offer a range of advantages over the traditional two component catalytic systems. For example, stable zwitterions are well-defined, single component catalysts which do not require Lewis acid co-catalysts for activation. Therefore, this eliminates the possibility of anions coordinating to the active site and could provide highly active catalysts. Moreover, this could reduce the production costs. In this thesis the 6-aminofulvene-2-aldiminate (AFA) ligand system has been employed to develop zwitterionic, charge-neutral complexes, analogues of Brookhart-type cationic alkene polymerisation catalyst containing 1,2-diimine ligand. Chapter 1 of the thesis provides a comprehensive literature review of the late transition metal (Group 10) α-diimine catalytic systems and the zwitterionic early and late transition metal alkene polymerisation catalysts. Chapter 2 describes the synthesis and characterisation of some novel zwitterionic complexes [(Ph2AFA)Pd(Me)(DMAP)], [(Ph2AFA)(N,N-dimethylbenzylamine-2-C,N)- Pd(II)] and [(Ph2AFA)Ni(η 3-C3H5)] and their possible application as catalyst precursors in alkene polymerisation. In principle, upon activation these complexes should exhibit higher catalytic activity. The ideal catalyst precursor for a highly active palladium based system would be a halide-bridged dimer of the form [(Ph2AFA)Pd(μ-X)]2. Chapter 2 describes several efforts towards the synthesis of such complexes using a range of R2AFA ligands. Even with the introduction of bulky N-substituents such as cyclohexyl or tert-butyl, the halidebridged dimers could not be synthesised. Instead, the reaction between the deprotonated ligand and [PdCl2(NCPh)2] provides bis-chelated complexes [(R2AFA)2Pd]. In order to introduce more steric bulk into the AFAH ligand which might lead to a halide-bridged dimer, two more ligands N,N’-bis(2,6-diisopropyl)phenyl-6-aminofulvene-2-aldimine and N,N’-di-(2,4,6-trimethyl)phenyl-6-aminofulvene-2-aldimine have been synthesised and characterised. It has been found that the presence of the 2,6-diisopropylphenyl substituents in N,N'-bis(2,6-diisopropyl)phenyl-6-aminofulvene-2-aldimine not only prevents the coordination of two ligands to the same metal, but precludes complexation all together. Chapter 2 also describes several efforts to develop a hemi-labile complex for alkene polymerisation. Chapter 3 describes the synthesis of metalloligands of aminofulvene-aldimine (AFA) and corresponding bimetallic complexes. The AFA ligand affords transition metal complexes via both η 5- as well as κ 2-coordination modes. A new synthetic methodology has been developed to synthesise metalloligands [Cp*RuII(Ph2AFA)H][BF4], [Cp*RhIII(Cy2AFA)H][BF4]2 and [Cp*RhIII(Cy2AFA)]- [BF4]. The basicity of the monocationic Rh metalloligand is found to be significantly lower than that of its Ru analogues. This is significant as it opens a potentially easy synthetic route to bimetallic complexes. The bimetallic complex [Cp*RhIII(Cy2AFAPdCl2)][BF4] has been developed for alkene polymerisation in an attempt to investigate the charge effect in alkene polymerisation catalysis. Upon activation this monocationic Rh/Pd bimetallic complex would provide a dicationic active species which would in principle be a more highly active catalyst than the Brookhart mono cationic diimine catalysts. Chapter 4 describes all the experimental procedure and polymerisation tests in this thesis.

This thesis considers methods which can be employed to increase the mass of copper transferred into and out of the organic phase during the load and strip stages of commercial solvent extraction processes. Conventional 5-alkylsalicylaldoxime reagents transfer 1 mol of divalent copper per 2 mol of ligand in a neutral complex of the type [Cu(L-H)2] via a pH-swing process. New triacidic ligands have been designed which triple the molar transport of copper to form [Cu3(L-3H)2]. Until recently copper recovery by solvent extraction has been confined to oxidic ores which are leached with sulfuric acid. New leaching technologies generate high tenor copper sulfate feed streams from sulfidic ores. The conventional 5- alkylsalicylaldoxime reagents do not work effectively in conjunction with these leach processes as they do not consume the acid which is generated on loading the oxime. To address this problem ditopic zwitterionic ligands have been designed which can transfer both metal cation and attendant anion. These new metal salt reagents are diacidic, therefore not only transfer metal salts but also increase the molar transport relative to the conventional reagents. Equilibrium-modifiers are often added to improve the mass transport efficiency of conventional solvent extraction processes. The nature of their interaction with the species in solution is poorly understood. This thesis investigates their interaction with the free ligands and copper complexes to gain an understanding of their mode of action in order to rationalise the design of future modifiers to optimise recovery efficiencies. Increased molar transport is addressed in Chapter 2. The diacidic ligand 5- methylsalicylaldehyde-pivaloylhydrazide (L2) and its dinuclear copper complex [Cu2(L2-2H)2] were synthesised and characterised to gain an understanding of their speciation in solution. X-ray structural analysis of [Cu2(L2-2H)2] confirmed that the phenolate oxygen atoms bridge the copper centres rather than the amidato oxygen atoms of the hydrazone. Variable temperature magnetic susceptibility data confirm that the copper centres are antiferromagnetically coupled as expected for the Cu-OCu angle (99.6(2)°). An understanding of the coordination geometry of the dinuclear systems lead to design of triacidic ligands. A series of 3-hydrazono- and 3- hydroxyanil- 5-alkylsalicylic acids were synthesised. The prototype ligand 5-methyl 3-octanoylhydrazonosalicylic acid (L6) was demonstrated to triple molar transport and increase mass transport by 2.5 fold. Solvent extraction results indicate that copper is sequentially loaded as pH is increased. The plateaux observed in loading curves suggest formation of stable mono-, di-, and tri-nuclear copper complexes within the pH-ranges 1.75 - 2.75, 3.25 - 4.0 and > 4.25 respectively. The triacidic ligands were also demonstrated to double the molar transport of the conventional salicylaldoximes when used in 1:1 blends by formation of a ternary complex. Chapter 3 describes the incorporation of two tertiary amine groups into diacidic salicylaldehydehydrazone ligands to form dinucleating metal salt extractants. Piperidinomethyl, piperazinomethyl and dihexylamino groups were incorporated into various positions of the ligand including 3- and/or 5- positions of the salicylaldehyde or incorporated into the hydrazone. Solvent extraction results obtained for 3,5- bis((dihexylamino)methyl)salicylaldehyde-octanoic hydrazone (L20) are consistent with transfer of 1 mol of copper sulfate per mol of ligand in the organic phase between pH 2.0 and 2.5. This result is indicative of the formation of [Cu2(L20)2(SO4)2]. Conventional salicylaldoximes are “strong” copper extractants which require concentrated acid electrolyte to efficiently strip the copper from the organic phase. However, as the use of concentrated acid affects the quality of the copper cathodes, oxygen-containing equilibrium modifiers are often added. These facilitate copper stripping without adversely affecting the loading. The affect of 2-ethylhexanol (2- EH) and trioctylphosphine oxide (TOPO) on the extractive ability of 5-toctylsalicylaldoxime (19) in n-heptane is reported. Both are found to decrease copper extraction more under stripping conditions than loading conditions. 2-EH shows little affect at pH greater than 2.5. TOPO does not significantly affect copper loading at pH greater than 3.0. Evidence for the formation of the adduct [Cu(19-H)2)(TOPO)] was obtained from UV/Vis, IR, EPR and sonic spray mass spectrometry.

Particles that deposit in the respiratory airways can come from many sources, such as environmental pollution, particles created in the workplace, and inhalers that are designed to deliver medicines to the lungs. Once these particles deposit in the respiratory airways, they can interact in a variety of ways. Some particles are toxic and can cause damage to lung tissues, others may have little to no effect on health, and some may provide some benefit or therapy. Once particles land in the respiratory airways, the interactions they have with proteins can impact where they go and how they behave. This thesis explores how particles that are inhaled may impact health through toxicity to lung cells. Aerosols produced from photooxidation of decamethylcyclopenta-siloxane, an ingredient common in personal care products, were exposed to lung cells using an air-liquid interface exposure system to assess if these aerosols impact lung cell health. No significant impacts on lung cell health were observed. Copper oxide, a component of cigarette smoke, urban particulate matter, and e-cigarette vapor, was assessed for its role in lung disease. Copper oxide nanoparticles were exposed to lung cells, and their viability, expression of a platelet activating factor receptor (PAFR), and susceptibility to infection with a pneumonia-causing bacterium (S. pneumoniae) were measured. Copper oxide nanoparticles were found to be toxic to lung cells. At some doses, increases in PAFR were observed, but no clear differences in susceptibility to bacterial infection were observed. This research improves knowledge of how inhaled materials can impact health, providing insight into how particles from human-derived sources affect the lungs. This thesis further explores how particles behave in the thin layer of fluid that covers the respiratory epithelium. This fluid contains a complex mixture of proteins, and this work aims to identify some of the ways these proteins interact with particles and influence behavior. This was accomplished by first investigating how individual proteins from this fluid interact with particles. Particle behavior was studied after exposure to these proteins, as well as the lung cell responses to the particles before and after interaction with individual proteins. These lung proteins were found to induce aggregation, significantly alter surface charge, and reduce cell uptake of particles. After studying how individual proteins might specifically affect particle behavior, particles were exposed to bronchoalveolar lavage fluid (BALF), a diluted lung fluid collected by rinsing lungs with saline. Particle responses to proteins in this fluid were compared to those in serum, a protein-rich blood extract. These studies identified differences in how various surface-functionalized polystyrene particles aggregated in BALF compared to serum. When particles were exposed to serum or BALF, they tended to be less likely to associate with lung cells. With some particle types studied, there were significant differences in how much BALF or serum reduced cell attachment and uptake. In addition to demonstrating that lung fluids impact particle behavior in a manner that differs from serum, a method was developed to increase the concentration of the proteins in BALF to partially undo the dilution that occurs during collection. After studying how protein adsorption can cause aggregation, cover up particle surfaces, and reduce attachment and uptake by lung cells, a polymer coating was synthesized to reduce particle interactions with these proteins and assist in stabilizing particles in lung fluids. This coating was tested in both BALF and serum to demonstrate its general utility at reducing undesired interactions with proteins in biological fluids and was found to enhance particle stability in lung fluids as well as saline. This research enhances understanding of how particles behave in the respiratory airways, providing tools to further study how particles behave in lung fluids and demonstrating a polymer coating that is useful in this environment.

<p>Liquid chromatography is an important separation technique for a vast number of analytes. This thesis mainly focuses on the development of stationary phases for liquid chromatography based on zwitterionic sulfobetaine polymers.</p><p>In the thesis, various ways to prepare zwitterionic polymers in an aqueous environment using reversible addition fragmentation chain transfer (RAFT) polymerization are described. Both telomers, i.e. short soluble polymer chains containing a functional terminal group, as well as graft polymers on various supports have been synthesized. The RAFT polymerization technique provides an increased degree of control of the final polymers, which may aid in the preparation of more specifically tailored separation materials.</p><p>Sulfobetaine polymers carry both a positive and a negative charge within a single entity, which results in interesting solution properties as well as highly biocompatible features. These unique features make them especially suited for separation of highly polar and/or charged compounds. An example of the successful separation of short peptides using a stationary phase synthesized with the RAFT technique is given.</p><p>The unusual properties of sulfobetaine-type polymers are believed to be associated with the structure of water close to the polymer. A study of water structure in some silica based stationary phase grafted with zwitterionic sulfobetaine polymers was conducted. The impact of water structure on retention characteristics was investigated.</p>

This study used jatropha oil, waste cooing oil, and soybean oil as the raw materials for investigating effects of catalyst concentration, reaction time, reaction temperature, methanol-to-oil ratio, and catalyst types on biodiesel yield. The authors also heated up the oil to speed up the transesterification and to make the reaction more complete. Jatropha oil, waste cooing oil, and soybean oil were used as the raw materials, and three types of ionic liquid or zwitterionic liquid, [PyrMe][HSO4], [PyrMeBuS][HSO4], and [MorMeA][Br], were added as catalysts for co-catalysis while heating the oil raw materials to create the best operational condition for biodiesel production. For soybean oil used as the raw material, the best catalyzing effect (a 99.4% yield) was achieved by adding [MorMeA][Br] while the reaction time was 6min, reaction temperature was 70 ¢J, and the methanol-to-oil ratio was 9:1. Under the best reaction condition, catalyzing effect was compared between the addition of sulfate-containing ionic liquid and sulfate-containing zwitterionic liquid. The yield of the addition of sulfate-containing ionic liquid and sulfate-containing zwitterionic liquid were 97.2% and 98.7% respectively. It can be found from this study that for increasing biodiesel yield, the addition of zwitterionic liquid for co-catalysis is more effective than the addition of homogeneous ionic liquid. Comparing the best operational condition between jatropha oil and soybean oil, the best yield of jatropha oil and soybean oil was 98.5% and 99.4% respectively, while the concentration of sodium hydroxide was 0.75 wt%, [MorMeA][Br] of 1.00 wt% was added, the methanol-to-oil ratio was 9:1, the reaction time was 6 min, and the reaction temperature was 70¢J. As for disposed cooking oil, the best operational condition rendered a yield of 98.1% when the concentration of sodium hydroxide was 0.75 wt%, [MorMeA][Br] of 1.00 wt% was added, the methanol-to-oil ratio was 9:1, the reaction time was 7 min, and the reaction temperature was 70¢J. For waste cooking oil, because of the containing of impurities from frying, the yield was slightly lower and the reaction time was longer.

Liquid chromatography is an important separation technique for a vast number of analytes. This thesis mainly focuses on the development of stationary phases for liquid chromatography based on zwitterionic sulfobetaine polymers. In the thesis, various ways to prepare zwitterionic polymers in an aqueous environment using reversible addition fragmentation chain transfer (RAFT) polymerization are described. Both telomers, i.e. short soluble polymer chains containing a functional terminal group, as well as graft polymers on various supports have been synthesized. The RAFT polymerization technique provides an increased degree of control of the final polymers, which may aid in the preparation of more specifically tailored separation materials. Sulfobetaine polymers carry both a positive and a negative charge within a single entity, which results in interesting solution properties as well as highly biocompatible features. These unique features make them especially suited for separation of highly polar and/or charged compounds. An example of the successful separation of short peptides using a stationary phase synthesized with the RAFT technique is given. The unusual properties of sulfobetaine-type polymers are believed to be associated with the structure of water close to the polymer. A study of water structure in some silica based stationary phase grafted with zwitterionic sulfobetaine polymers was conducted. The impact of water structure on retention characteristics was investigated.

Orientador: Watson Loh / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-19T04:42:09Z (GMT). No. of bitstreams: 1 Brinatti_Cesar_M.pdf: 6269984 bytes, checksum: 65e7cdbf89a7e16102822d62f57e20e9 (MD5) Previous issue date: 2011 / Resumo: As sulfobetaínas (SB) são uma classe de surfatantes zwitteriônicos. A presença de grupos carregados tanto positiva quanto negativamente na mesma molécula concede à sua cabeça polar uma hidrofilicidade intermediária entre surfatantes iônicos e não-iônicos. O estudo termodinâmico de associação da série homóloga de sulfobetaínas, bem como sua interação com polímeros iônicos e não-iônicos, foi feito utilizando a técnica de titulação calorimétrica isotérmica (ITC), em diferentes temperaturas. O aumento da temperatura leva a um valor mais negativo de energia livre de Gibbs de micelização DmicG, o que favorece a micelização. O termo entrópico TDmicS, embora sempre positivo, é o responsável pela micelização em baixas temperaturas. No entanto, com o aumento da temperatura este termo perde sua intensidade, enquanto o termo entálpico DmicHinverte seu sinal, de positivo para negativo, superando em intensidade o termo entrópico, sendo então o responsável pela micelização em temperaturas elevadas. No estudo de interação com polímeros não-iônicos, o poli (ácido acrílico), PAA, induziu a formação de agregados de unímeros de surfatantes em concentrações abaixo de sua cmc, enquanto o poli (óxido de propileno), PPO, foi incorporado às micelas. Em relação aos polímeros iônicos, o polímero catiônico cloreto de poli (dialildimetilamônio), PDADMAC, e o polímero aniônico poli (acrilato de sódio), PAA, não apresentaram interação alguma com a sulfobetaína. Apenas o polímero aniônico poli (4-estireno sulfonato de sódio), PSS, induziu a formação de agregados de unímeros de surfatante em concentrações muito abaixo da cmc. Esta indução deve-se à interação eletrostática entre o grupo sulfonato (-SO3) do PSS e o grupo amônio ( RNMe2X ) da SB, auxiliada pela presença do grupo hidrofóbico estireno do polímero, que é incorporado às micelas / Abstract: Sulfobetaines (SB) are a class of zwitterionic surfactants. The presence of groups both positively and negatively charged in the same molecule renders an intermediate hydrophilicity between ionic and nonionic surfactants. The self-assembly thermodynamic study of a homologous series of sulfobetaines, as well as its interaction with ionic and nonionic polymers, was performed by isothermal titration calorimetry (ITC), in different temperatures. The increase in temperature leads to a more negative value of the Gibbs free energy of micellization DmicG, which favors micellization. The entropic term TDmicS, although always positive, is the responsible for the micellization in lower temperatures. However, with the increase in temperature this term loses its intensity, while the enthalpic term DmicH changes its sign, from positive to negative, overcoming the entropic term in intensity, and therefore being the responsible for the micellization in higer temperatures. In the study of interaction with nonionic polymers, poly (acrylic acid), PAA, induced the formation of aggregates of surfactant monomers in concentrations below its cmc, while poly (propylene oxide), PPO, was incorporated to the micelles. Regarding ionic polymers, the cationic poly(diallyldimethylammonium chloride), PDADMAC, and the anionic polymer poly (sodium acrylate), PAA, didn't show any interaction with the sulfobetaine. Only the anionic polymer poly(sodium 4-styrenesulfonate), PSS, induced the formation of aggregates of surfactant monomers in concentrations well below its cmc. This induction is due to the electrostatic interaction between the sulfonate group (-SO3) from the PSS and the ammonium group (RNMe2X) from the SB, aided by the presence of the hydrophobic group styrene in the polymer, which is incorporated into the micelles / Mestrado / Físico-Química / Mestre em Química