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Yan, Linglong. « Self-assembly of sulfonated amphiphiles for channel-like synthetic membranes ». [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=984365605.
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Parg, Roland Peter. « Synthesis of novel bis- and tris- tetrathiafulvalene amphiphiles for use in Langmuir-Blodgett film deposition ». Thesis, University of Southampton, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259972.
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Guha, Pritam. « Physicochemical studies on liposome mimetic systems and their complexes with biologically relevant polymers ». Thesis, University of North Bengal, 2018. http://ir.nbu.ac.in/handle/123456789/2799.
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Satyal, Uttam. « Efficient Drug and Nucleic Acid Delivery Systems based on Synthetic Amphiphiles with Tuned Oil/Water Interfaces ». Diss., Temple University Libraries, 2018. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/531985.
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Pharmaceutical SciencesPh.D.
Today, drugs are an integral part of healthy human life, with new drug entities being introduced every year in clinic. The advancement of drug development brings complexity and variation, in terms of both physical and chemical properties. Some of these physicochemical characteristics are many times suboptimal, eventually requiring robust delivery systems that can precisely deliver the drugs to the desired tissues. Although many materials have been studied for the generation of drug delivery systems, there is always a need for biomaterials with better properties that can translate into superior delivery systems. In this context, new drug delivery systems that are interface-engineered at materials level for better stability and delivery efficiency in vitro and in vivo are introduced in this dissertation. In the first part of the dissertation, novel oil/water interface-engineered amphiphilic block copolymer micelles that were previously introduced by our lab were assessed for their stability in the presence of various esterase enzymes present in serum and on blood vessel walls, normally encountered by drug delivery systems on route to the targeted tissues. I also assessed the vulnerability of the polymeric micelles in presence of enzymes typically present either inside the tumor cells or secreted in the tumor microenvironment. I revealed the selective stability of empty- and docetaxel-loaded polymeric micelles to enzymatic degradation en route/in tumors and I have correlated this selective stability with polymer structure and interfacial engineering mentioned above. The unique delivery capabilities of interfacial-engineered polymeric micelles were tested in vivo using a mouse model of triple negative breast cancer. We proved that our novel engineered triblock copolymer-based drug delivery systems are superior to similar delivery systems made out of standard diblock copolymer micelles and also to the clinically used Taxotere® formulation towards cancer cell killing and tumor treatment, without displaying any significant toxicity in experimental animals. The second part of the dissertation focuses on the development and assessment of a pyridinium-based pseudo-gemini surfactant that combined the high nucleic acid packaging capacity of pyridinium lipids with the high transfection efficiency of gemini surfactants while displaying a reduced associated cytotoxic effect. I have analyzed the temperature treatment on compaction of nucleic acids into lipoplexes and I have established a high temperature annealing method for this purpose. This novel formulation technique allowed a substantial reduction of the amount of amphiphiles required to compact a specific amount of nucleic acids. This in turn also reduced the cytotoxic effect associated with the use of pyridinium amphiphiles. The effect of inclusion of colipids to lipoplex compaction, the robustness and the transfection efficiency of the lipid/nucleic acid lipoplex systems were assessed in detail, and correlations between formulation composition and biological activity were established. I was also able to show for the first time that pyridinium pseudo-gemini surfactants were able to compact different types of nucleic acids, including pDNA, mRNA and siRNA at lower charge ratios than standard, state-of-the art formulations used for this purposes. I also showed that irrespective to the nucleic acid compacted within the lipoplexes, the novel amphiphiles can efficiently deliver the cargo into the targeted cells even in the presence of very high concentration of serum, a premise for future use of these amphiphiles and formulations in vivo.
Temple University--Theses
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Sharma, Vishnu Dutt. « INTERFACIAL ENGINEERING OF SYNTHETIC AMPHIPHILES AND ITS IMPACT IN THE DESIGN OF EFFICIENT GENE AND DRUG DELIVERY SYSTEMS ». Diss., Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/280244.
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Pharmaceutical SciencesPh.D.
Cancer is currently the second most common cause of death in the world. Despite tremendous progress in the treatment of different forms of cancer, the five year survival rates for lung, colorectal, breast, prostate, pancreatic and ovarian cancers remain quite low. New therapies are urgently needed for the better management of these diseases. In this context, both therapeutic gene and drug delivery constitute promising approaches for cancer treatment and are addressed in this thesis. Focusing on gene delivery, we are proposing the use new pyridinium amphiphiles for obtaining gene delivery systems with improved stability and efficiency and low toxicity (Chapters 2 and 3). The main focus was on pyridinium gemini surfactants (GSs), which possess a soft charge, a high charge/mass ratio and a high molecular flexibility - all key parameters that recommend their use in synthetic gene delivery systems with in vitro and in vivo efficiency. In Chapter 2, we optimized a novel DNA delivery systems through interfacial engineering of pyridinium GS at the level of linker, hydrophobic chains and counterions. In Chapter 3, we tested the effects of blending pyridinium cationic GS into pyridinium cationic lipid bilayers and we have evaluated these blends towards plasmid DNA compaction and delivery process. We have also correlated the cationic bilayer composition with the dynamics of the DNA compaction process, and with transfection efficiency, cytotoxicity and internalization mechanism of resulted nucleic acid complexes. Toward improved drug delivery systems, we introduced new amphiphilic block copolymers synthesized from biocompatible and biodegradable segments. Although their capabilites for loading, transport and release of lipophilic substances stored in their hydrophobic cores are widely known, their stability in vivo is limited due to rapid degradation by esterases present in the body. In Chapter 4, we examined the possibility to increase the enzymatic stability of PEG-PCL macromolecular amphiphiles through interfacial engineering, in a process which separates the hydrophilic/hydrophobic interface from the degradable/non-degradable block interface. We evaluated the stability, toxicity, drug loading and release properties of these new polymers using docetaxel as a model chemotherapeutic drug. The results revealed how hydrophilic/ hydrophobic interface tuning can be used to adjust key properties of polymeric drug delivery systems of this type.
Temple University--Theses
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Silioc, Christelle. « Synthèse et étude des propriétés d’auto-association de molécules amphiphiles dérivées de D-glucose ». Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10083/document.
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Cette thèse s’inscrit dans une thématique de recherche visant à synthétiser des moléculesamphiphiles présentant des propriétés bioactives, pouvant être mises à profit dans diversesapplications biomédicales ou encore dans le domaine de l’agrochimie. Les molécules amphiphilessont alors les propres actrices de leur formulation de par leurs propriétés d’auto-association et debioactivité (concept dit « d’économie moléculaire »). Dans ce contexte, la première partie de cetravail a été consacrée à la synthèse de molécules amphiphiles modèles dérivées de D-glucose etde N-acétyl-D-glucosamine. La voie de synthèse choisie pour les obtenir a été une aminationréductrice régiosélective à partir de chaînes alkylamine de différentes longueurs (6, 12 et 16atomes de carbone). Leur caractérisation a été réalisée par RMN et spectrométrie de masse. Ladeuxième partie de ce travail a été orientée vers l’étude du comportement auto-associatif desmolécules à base de D-glucose en solution aqueuse, seules, ou en mélange avec un phospholipidemodèle. Une organisation à différentes échelles de taille a été mise en évidence par les techniquesde diffusion de la lumière, microscopie électronique en transmission et grâce à la modélisation dedonnées expérimentales obtenues en diffusion des rayons X aux petits anglesThis work is part of a research program on the synthesis of amphiphilic molecules havingbioactive properties, which could be used in biomedical applications or in agrochemistry.Amphiphilic molecules could be the own actor of their formulation because of the dual propertyof bioactivity and self-assembly. In this context, the first part of this work concerns the synthesisof model amphiphilic molecules derived from D-glucose and N-acetyl-D-glucosamine. The chosenway to synthesize these molecules was a regioselective reductive amination from alkylaminechains of different lengths (6, 12 and 16 carbon atoms). Compounds were characterized by NMRand Mass Spectrometry. The second part of this work was oriented towards the study of the selfassemblyproperties of molecules derived from D-glucose in an aqueous solution, alone, or mixedwith a model phospholipid. An organization with different sizes was shown with severaltechniques: light diffusion, transmission electronic microscopy, and thanks to the establishment ofa model from experimental small-angle X-ray scattering data. When the amphiphilic moleculewith 12 atoms of carbon on this hydrocarbonated chain is studied alone in a solution, ellipsoidalmicelles seem to be present, mixed with bigger aggregates (~100 nm). However, when this sameamphiphilic molecule is used in a mix with a model phospholipid, a size diminution of theassembly was observed with the increase of amphiphilic molecules in the formulations
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Redmond, Adrian Patrick. « Synthesis of steroidal facial amphiphiles ». Thesis, University of Bristol, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396678.
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Coumes, Fanny. « Synthèse et caractérisation de copolymères amphiphiles à base de poly(acide lactique) et de poly(éthylène glycol) pour la délivrance de principes actifs ». Thesis, Montpellier 1, 2014. http://www.theses.fr/2014MON13522/document.
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Ce travail avait pour but de synthétiser et caractériser des copolymères amphiphiles à base de poly(éthylène glycol) (PEG) et de poly(acide lactique) (PLA) pour la confection de systèmes de délivrance de principes actifs (PA). Les polymères ont été choisis pour leur biocompatibilité et de leur biorésorbabilité. Plusieurs architectures de copolymères amphiphiles ont été créées et leur comportement auto-associatif en milieu aqueux ainsi que leur capacité à encapsuler des principes actifs ont été étudiés. Tout d'abord, un copolymère greffé a été synthétisé par copolymérisation d'un monomère fonctionnel, le glycolide monopropargylé, avec du L-lactide pour obtenir un squelette polyester fonctionnel sur lequel des branches hydrophiles de PEG ont été greffés avec plusieurs degrés de substitution. Ensuite, un copolymère peigne tribloc a été synthétisé à partir d'un bloc central PLA dont les extrémités de chaînes ont été modifiées pour permettre l'amorçage de la polymérisation de méthacrylate d'oligo(éthylène glycol) avec des taux de substitution variables. L'étude de l'auto-assemblage et de la capacité à encapsuler des PA a révélé que l'architecture et la balance hydrophile/hydrophobe sont des facteurs déterminants pour la nature des objets formés et leur potentiel d'encapsulation. Enfin, des stratégies de fonctionnalisation ont été mises en place afin d'augmenter et de moduler l'efficacité des PA encapsulés. Ceci est illustré par le couplage d'une molécule fluorescente modèle et, dans le cadre d'une collaboration, par la conjugaison d'un peptide immunostimulateur sur un système dibloc amphiphile. La comparaison à d'autres formulations a montré que le conjugué permettait de moduler et renforcer l'efficacité du PA utiliséThe objective of this work was to synthesize and characterize amphiphilic copolymers based on poly(ethylene glycol) (PEG) and poly(lactic acid) (PLA) intended for drug delivery applications. The polymers were chosen regarding to their biocompatibility and bioresorbability. Different architectures of amphiphilic copolymers were prepared, and their behavior in aqueous media, as well as their abilities to encapsulate drugs were studied. First, a graft copolymer was synthesized through copolymerization of a functional monomer, monopropargylated glycolide, with L-lactide to yield a functionalized polyester backbone. The latter was then grafted with different densities of hydrophilic branches of PEG. Then, a brush-like triblock copolymer was synthesized through ROP and ATRP. To this end, chain ends of a telechelic block of PLA were modified to yield a macroinitiator able to initiate oligo(ethylene glycol) methacrylate polymerization with variable substitution degrees. Self-assembly and drug loading studies revealed that architecture and hydrophobic/hydrophilic balance played a major role on the nature of the formed objects and on their encapsulation potential. Finally, to modulate and increase the efficacy of encapsulated drugs, functionalization strategies were realized. This is illustrated by the linking of a fluorescent model molecule on a triblock brush-like copolymer and, in a collaboration project, the linking of an immunostimulant peptide on an amphiphilic diblock system. Comparison with other formulations revealed that the conjugate allowed modulating and reinforcing the drug's efficacy
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Jose, Robin. « Synthesis and characterization of novel amphiphiles ». Laramie, Wyo. : University of Wyoming, 2006. http://proquest.umi.com/pqdweb?did=1296090121&sid=1&Fmt=2&clientId=18949&RQT=309&VName=PQD.
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Findlay, Brandon. « Design and synthesis of cationic amphiphiles ». American Society for Microbiology, 2010. http://hdl.handle.net/1993/21708.
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Cationic antimicrobial peptides (CAMPs) are produced by plants, animals and bacteria to protect their host against antagonistic microbes. The antitheses of selective antibiotics, these peptides are drawn by electrostatic and hydrophobic interactions to targets as diverse as the bacterial membrane, nucleic acids and serum proteins. This lack of specificity is their greatest strength, as mutations to single genes rarely lead to bacterial resistance. Resistance may be conferred by large scale alterations in cell envelope composition, which generally reduces bacterial fitness in the absence of peptide.
Clinical applications of natural CAMPs are limited, as the peptides are toxic to mammalian cells and rapidly inactivated in vivo by serum albumin and proteases. Faced with these challenges we have prepared a number of CAMP analogues, with the goal of creating lead compounds for further development of antibacterial therapeutics. Much of our work has focused on ultrashort lipopeptides and lipopeptoids, which have properties similar to natural CAMPs and extremely abbreviated sequences. The simple structure of these scaffolds allows rapid creation of CAMP analogues in a brief period of time, allowing us to rapidly explore the structural requirements for CAMP activity. The balance of this work focuses on imparting CAMP-like behaviour to known antibiotics, in order to expand their spectrum of susceptible bacteria and combat the development of drug-resistant bacteria. In particular, the aminoglycosides neomycin and tobramycin have been fused to phenolic disinfectants such as triclosan and biclotymol, in order to improve their diffusion across the bacterial envelope and activity against Gram-negative bacteria.
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Cottenye, Nicolas. « Antimicrobial surfaces based on self-assembled nanoreactors : from block copolymer synthesis to bacterial adhesion studies ». Phd thesis, Université de Haute Alsace - Mulhouse, 2010. http://tel.archives-ouvertes.fr/tel-00598560.
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The aim of this work is to develop a new strategy for the prevention of biofilm growth. For this purpose, we prepared bioactive surfaces resulting from the surface-immobilization of nanoreactors self-assembled from amphiphilic poly(isobutylene)-block-oligonucleotide copolymers. The block copolymer was synthesized and characterized via appropriate complementary techniques. Self-assembly into vesicles allowed the functional encapsulation of enzymes, as assayed through enzyme activity monitoring, leading to a prodrug-drug system. The self-assembled structures were specifically immobilized on surfaces via base pairing between the oligonucleotide block of the copolymer and the surface tethered complementary nucleotide sequence. Using E.coli strains, we first observed an influence of the two density of oligonucleotides immobilized on the surface on the number of adherent bacteria. This influence may be due to an effect of surface charge density. We then confirmed the well-known role of curli in biofilm cohesion, and we showed gene over-expression associated with curli production on oligonucleotide-modified surfaces. We demonstrated that gene over-expression does not depend on the topographical features of the surface or on the composition of the nucleotide sequences used in this study. Finally, we demonstrated tha the presence of the vesicular structure is able to produce strong anti-adhesive properties of the surface. We assume, from observations of bacterial response in dynamic conditions, that this effect is due to increased bacterial motility on the surface, leading to a high detachment rate. Which is further confirms by a comparable bacterial response observed on agar hydrogel of different hardnesses. This result provides a preliminary outcome, paving the way to new approaches to antimicrobial strategies.
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Macri, Richard Vincent. « Synthesis, Characterization, and Micellar Properties of Dendritic Amphiphiles ». Diss., Virginia Tech, 2009. http://hdl.handle.net/10919/27831.
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Two new homologous series of amphiphiles–five long-chain, three-headed amphiphiles [3CCb14, 3CCb16, 3CCb18, 3CCb20, 3CCb22; CH3(CH2)n-1OCONHC(CH2CH2COOH)3, n = 14, 16, 18, 20, 22], and six branched-chain, three-headed amphiphiles [3CCb1(7,7), 3CCb1(8,8), 3CCb1(9,9), 3CCb1(10,10), 3CCb1(11,11), 3CCb1(12,12); (CH3(CH2)n-1)2CHOCONHC(CH2CH2COOH)3, n = 7, 8, 9, 10, 11, 12]–were synthesized. The synthesis of the 3CCbn series was accomplished in two steps from Weisocyanate™ and the long chain alcohol in good yields of chromatographed products (65–81%). The 3CCb1(n,n) series was similarly synthesized from Weisocyanate™ and the two-tailed symmetric alcohol (produced from a reaction of alkyl magnesium bromide and ethyl formate) in good yields of chromatographed products (71–84%). CMC data were collected by pendent-drop technique for the 3CAmn, 3CCbn, 3CUrn, and 3CCb1(n,n) series of amphiphiles to establish the concentration required for detergency. The triethanolammonium salt provided better solubility and higher CMCs of these amphiphiles than the potassium salt. All amphiphilic series tested lowered the solution surface tension from ~ 72 mN/m to ~ 50–55 mN/m, indicating that these amphiphiles are less surface active than typical surfactants such as sodium dodecyl sulfate. The CMCs for the 3CAmn series were found to decrease in value from 2 × 10⁻² M (3CAm15) to 2 × 10⁻³ M (3CAm21) in a linear fashion. The CMCs for the 3CCbn series were found to decrease in value from 7 × 10⁻³ M (3CCb16) to 0.4 × 10⁻³ M (3CCb22) in a linear fashion. The CMCs for the 3CUrn series were found to decrease in value from 2 × 10⁻³ M (3CUr18) to 1 × 10⁻³ M (3CUr22) in a linear fashion.
Due to discrepancies in several of the IFT vs. log concentration plots for the previous homologous series of amphiphiles, the CMC data was collected using a pyrene fluorescence measurement technique. The data from the pyrene fluorescence technique seems likely to be more accurate, indicating that surface tension may not be the most reliable method for determining the CMC of these amphiphiles. The CMCs (as determined by pyrene fluorescence) for the 3CAmn series were found to decrease in value from 2 × 10⁻² M (3CAm15) to 2 × 10⁻³ M (3CAm21) in a linear fashion. The CMCs for the 3CCbn series were found to decrease in value from 7 × 10⁻³ M (3CCb16) to 0.3 × 10⁻³ M (3CCb22) in a linear fashion. The CMCs for the 3CUrn series were found to decrease in value from 7 × 10⁻³ M (3CUr16) to 0.2 × 10⁻³ M (3CUr22) in a linear fashion. In both the surface tension and the pyrene fluorescence techniques, the shortest chain length homologues (3CAm13, 3CCb14, and 3CUr14) did not show a break up to the limits of solubility.
The CMCs as determined by surface tension for the 3CCb1(n,n) series were found to decrease in value from 0.5 × 10⁻³ M (3CCb1(9,9)) to 0.02 × 10⁻³ M (3CCb1(12,12)) in a linear fashion. The 3CCb1(8,8) and 3CCb1(7,7) amphiphiles did not show a CMC break up to the limits of solubility. The 3CCb1(12,12) showed an unusually steep decrease in surface tension over a very narrow range of concentration. There is considerable doubt as to the accuracy of the 3CCb1(11,11) data, and the CMCs for these two-tailed amphiphiles needs to be measured by a second method as was done for the single-tail series to verify the CMCs of all the two-tail homologues. Activity (minimal inhibitory concentrations, MICs) for the 3CAmn, 3CCbn, 3CUrn, 3CCb1(n,n), 2CAmn, and 2CCbn series was measured against several different bacteria, mycobacteria, yeast, and fungi. Additionally, anti-HIV and cytotoxicity data was collected for the 3CAmn, 3CCbn, and 3CUrn series. Greatest inhibition was typically seen from the 18–20 carbon tail length homologues of each series (3CAm19–3CAm21, 3CCb18–3CCb20, 3CUr18–3CUr20, 2CAm19–2CAm21, and 2CCb18–2CCb20).
Inoculum density affected the activity of our earlier studies, and selected organisms were retested to obtain the intrinsic activity. 3CUr18 and 3CAm19 proved most effective against Mycobacterium smegmatis, with MIC99 = 6.3 μM @ 10⁵ CFU/mL inoculum density. 3CCb20 was most effective against Mycobacterium marinum with MIC99 = 16 μM @ 10⁵ CFU/mL inoculum density. 3CAm19, 3CCb18, and 3CUr18 all showed equivalent activity against Mycobacterium chelonae with MIC99 = 17 μM @ 10⁵ CFU/mL inoculum density. Against Staphylococcus aureus, the 2CAm21 was most effective, with MIC90 = 2.0 μM @ 10⁵ CFU/mL inoculum density. 3CCb20 was most effective against MRSA with MIC90 = 2.9 μM @ 10⁵ CFU/mL inoculum density. The two-tailed analogs (3CCb1(n,n), 3CUr(n,n), and 3CUr1(n,n)) typically showed little to no activity against the tested microorganisms. Comparison of MIC to CMC is a relative measure of safety of a drug candidate. All single-tail amphiphiles showed ratios of MIC/CMC of 16–126, with a ratio of 100 or better being optimal. The ratios for the two-tail amphiphiles ranged from 0.39 to 2.9.Ph. D.
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Abid, S. K. « Synthesis and phase behaviour of some novel quaternary ammonium ion derivatives of cholesterol ». Thesis, University of Strathclyde, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.382288.
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Percival, Darryl. « The Synthesis of Simplified Peptide Amphiphiles for Cell Adhesion ». Thesis, University of Aberdeen, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.521348.
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Currently peptide amphiphiles incorporate a large number of amino acids into their structure which has the drawback of limiting production to the gram scale rather than kilogram scale required by the pharmaceutical industry. Therefore simplified peptide amphiphiles containing significantly fewer amino acids were synthesised. The simple peptide amphiphiles contained the RGD (Arginine-Glycine-Aspartic Acid) and IKVAV (Isoleucine-Lysine-Valine-Alanine-Valine) cell adhesion ligands. The RGD cell adhesion ligand is non-specific and interacts with most cell types whereas the IKVAV ligand interacts specifically with nerve cells. The inclusion of the IKVAV peptide sequence in a peptide amphiphile may permit the resultant hydrogel to be used as a scaffold for nerve regeneration. The main target compound investigated was Alky-CCRGD (Palmitic Acid-Cysteine-Cysteine-Arginine-Glycine-Aspartic Acid). This was synthesised using solid phase peptide synthesis and a solution phase strategy which enabled the advantages and disadvantages of each synthetic method to be determined. A variety of peptide amphiphiles containing the RGD sequence were also successfully synthesised. These compounds were tested for gelation by exposing their solutions to acid vapours and adding different metal cation solutions. IKVAV-containing peptide amphiphiles were also successfully synthesised. The gel structure of Alkyl-CCRGD was investigated using cryo-SEM and preliminary cell adhesion studies were carried out on RGD-containing simple peptide amphiphiles that formed gels upon the addition of metal cations in order to test the biocompatibility of the resultant hydrogels formed.
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Roebuck, Deborah Anne. « Investigation into synthetic amphiphilic polymers for intracellular delivery ». Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/32273.
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Delivery of siRNA therapeutics to their target site within the cell interior is a challenge that hinders their effective use in disease treatment. PP-75, a pH-responsive polymer, demonstrates potential to enhance intracellular siRNA-delivery by overcoming endosomal entrapment. PP-75 also provides a promising platform for development of targeted delivery, following conjugation of DARPin targeting ligands. Novel PP-75 cross-linker derivatives, PP-75-aminofluorescein, PP-75-siRNA and PP-75-DARPin conjugates have been developed and characterised for in vitro application. PP-75 delivery to SK-BR-3 (Her2+) and MDA-MB-231 (Her2-) breast cancer cells has been demonstrated for the first time. The membrane-lytic activity of PP-75 was limited at physiological pH but effective within the pH range typical of early endosomes. PP-75 did not demonstrate cytoxicity, with cells tolerating treatments up to 2.5 mg/mL over 72 h. Cellular internalisation and endosomal escape of PP-75 aminofluorescein (AFC) was confirmed via confocal microscopy, demonstrated by diffuse cytoplasmic delivery. Flow cytometry confirmed cellular internalisation of PP-75 AFC was via endocytosis. As reporter cells expressing firefly and Renilla luciferases, the breast cancer lines offered a robust assay read out capable of distinguishing between target specific and non-specific gene knockdown. The functionality of novel siRNA payloads that targeted firefly luciferase was confirmed by mRNA and protein knockdown and provided the foundation for delivery of PP-75 siRNA conjugates. Target specific DARPin affinity was confirmed for the SK-BR-3 (Her2+) cells and not MDA-MD-231 (Her2-) cells, demonstrating selective binding to the extracellular Her2 protein. The expression of a novel but structurally comparable negative control DARPin (5K D1) demonstrated no affinity for either cell line. The introduction of a free cysteine residue to the DARPin sequences facilitated attachment onto PP-75. PP-75 therefore has the potential to demonstrate intracellular delivery of siRNA payloads, capable of delivery to specific cell populations via DARPin targeting.
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Collette, Elisabeth Anne. « Synthesis and Characterization of Amphiphilic Polymers ». University of Akron / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=akron1386959114.
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Zanirati, Stefano. « Synthesis and nanostructuring modulations of self-assembled dynamic covalent amphiphiles ». Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAF039.
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Contrôler les forces supramoléculaires et chirales a toujours été un défi pour la communauté scientifique. Dynablocks sont amphiphile basés sur des liaisons covalentes réversibles (imine) qui, dans l’eau, s’auto–assemblent en mésophases. Avec un nouveaux aldéhydes chargés et avec divers types d'amines (pKa et chaînes de PEG variables) dynablocks chargées ont été utilisés pour ajuster les surfaces micellaires (inversion noyau/coquille). Nous avons également étudié les propriétésd'auto-réplication (autopoiesis) et leur intérêt pour les premiers réplicateurs de la Terre prébiotique. Dynablocks non chargés ont plutôt été utilisés pour l'étude des structures à haute concentration et pour l’amplification chirale. Dans ce dernier,peptides amphiphiles dynablocks agissaient comme gelators avec une matrice formée d’un réseau 3D entrelacé. Une torsion supramoléculaire a été observée et une amplification chirale au niveau de la morphologie des structures a pu être détectée par AFM et TEMTaking the control over supramolecular and chiral forces has always been a challenge for the scientific community. Dynablocks are amphiphiles based on reversible imine covalent bond that, in water, self-assemble in mesophases. With a new charged aldehyde, charged dynablocks were used to tune the surface of the assemblies directing the charged heads inward or outward, changing the PEG units and the pKa of the amines. Moreover, we continued the study on focusing the interest on self-replicating properties (autopoiesis), topic that provides insights for the first replicators that could have appeared in the prebiotic Earth. Non-charged dynablocks were instead employed for the study of structures in high concentration and for chiral amplification. In this latter, peptide amphiphilic dynablocks acted as gelators with a typical 3D intertwined network matrix. A supramolecular twist was observed and a chiral amplification in the structures morphologies was detected in AFM and TEM pictures
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Liu, Yang. « Synthesis and Characterization of Polyhedral Oligomeric Silsesquioxane (POSS) Based Amphiphiles ». Diss., Virginia Tech, 2011. http://hdl.handle.net/10919/77182.
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Polyhedral oligomeric silsesquioxanes (POSS) have attracted substantial academic interest for many years as hybrid materials and nanofillers for controlling thermal and mechanical properties, and providing thermal and chemical resistance while retaining ease of processing. A natural extension of these studies has been POSS-based amphiphiles and thin film coatings. Studies at the air/water (A/W) interface have shown that trisilanol-POSS derivatives are amphiphilic and form uniform Langmuir films, whereas closed-cage POSS derivatives are hydrophobic and aggregate.
In previous work, a triester (POSS-triester) and a triacid (POSS-triacid) were synthesized from PSS-(3-hydroxypropyl)-heptaisobutyl (POSS-OH) and Weisocyanate and fully characterized by surface pressure – area per molecule (Π-A) isotherm and Brewster angle microscopy (BAM) studies at the A/W interface. The results indicated that POSS-triester is surface active forming a liquid expanded (LE) monolayer, whereas POSS-triacid forms a liquid condensed (LC) monolayer that is only weakly affected by pH. A face-on conformation was proposed and examined to understand the packing of POSS-based amphiphilic molecules at the A/W interface. The face-on/vertex-on comparison is rarely discussed for Langmuir monolayers at the A/W interface.
In this thesis, three other POSS-based esters were synthesized from POSS-OH and aminopropylisobutyl-POSS (POSS-NH₂) using Weisocyanate and a similar isocyanate containing two tert-butyl protected carboxylic acids. The synthesized materials are characterized by Π-A isotherm and BAM. For POSS-OH based diester (PAlDE) and POSS-NH2 based diester (PAmDE), LE/LC phase transitions were observed in Π-A isotherms over part of the experimentally accessible temperature range and were attributed to a change from a vertex-on to face-on conformation. Apparent BAM images confirmed LC islands coexisted with the LE phase. The experimentally observed dynamic estimates of the critical temperatures (Tc) were estimated from a two-dimensional Clausius-Clapeyron analysis and were consistent with the temperature dependence of the Π-A isotherms. These LE/LC phase transitions are the first observed for POSS amphiphiles.Ph. D.
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Liu, Yang. « Synthesis and Characterization of Polyhedral Oligomeric Silsesquioxane (POSS) Based Amphiphiles ». Thesis, Virginia Tech, 2010. http://hdl.handle.net/10919/76922.
Texte intégralRésumé :
Polyhedral oligomeric silsesquioxanes (POSS) have attracted substantial academic interest for many years as hybrid materials and nanofillers for controlling thermal and mechanical properties, and for providing thermal and chemical resistance while retaining ease of processing. A natural extension of these studies has been working on POSS-based amphiphiles and thin film coatings. Studies at the air/water (A/W) interface have shown that trisilanol-POSS derivatives are amphiphilic and form uniform Langmuir films, whereas closed-cage POSS derivatives are hydrophobic and aggregate.
In this study, two novel POSS derivatives were synthesized from PSS-(3-hydroxypropyl)-heptaisobutyl substituted (POSS-OH) and completely characterized. Weisocyanate reacted with POSS-OH, and a POSS-based triester (POSS-triester) was obtained. Trifluoroacidolysis of the POSS-triester at room temperature afforded the corresponding triacid (POSS-triacid). Purified POSS-OH, POSS-triester, and POSS-triacid were studied by using surface pressure - area per molecule (? -A) isotherms as well as Brewster angle microscopy (BAM) at the air/water (A/W) interface. Compared with previous work on trisilanol-POSS derivatives, the results indicated that POSS-triester was surface active and formed a liquid-expanded (LE) monolayer. In contrast, POSS-triacid monolayers were more condensed (LC) and were not dramatically affected by changes in pH. Results for the lift-off areas (Alift-off), limiting areas (A0), collapse areas (Ac), and collapse pressures (? c) of POSS-OH, POSS-triester, and POSS-triacid were compared to trisilanolisobutyl-POSS (TiBP) and were interpreted in terms of possible molecular conformations. Whereas, TiBP has been hypothesized to exist in a vertex-on conformation, POSS-OH and POSS-triacid packing at the A/W interface was consistent with face-on conformations. For POSS-triester, the isotherm was consistent with a vertex-on conformation at low ? , but a face-on conformation at high ? .Master of Science
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Dong, Xuehui. « Giant Molecular Shape Amphiphiles : Click Synthesis, Supramolecular Assembly, and Beyond ». University of Akron / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=akron1384774671.
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Yang, Da. « Synthesis and polymerization of bicontinuous cubic nanoparticles from reactive amphiphiles ». Diss., The University of Arizona, 2003. http://hdl.handle.net/10150/280459.
Texte intégralRésumé :
Amphiphiles are composed of a polar, hydrophilic headgroup and one or more non-polar, hydrophobic tail(s). Hydrated amphiphiles self-organize to form various liquid crystal phases as a function of molecular structure, temperature, concentration, and pressure. Self-supported arrays of self-organized, hydrated amphiphile assemblies include lamellar/vesicles, various normal (Q I) and inverted (QII) cubic phases, and normal (HI) and inverted (HII) hexagonal phases. A bicontinuous cubic liquid crystalline lipid-water phase is one in which the lipid bilayers are arranged in periodic three-dimensional cubic lattice structures. Cubic liquid crystalline nanoparticles prepared from aqueous dispersions of cubic lipid-water phases are kinetically stable in the presence of certain dispersing agents. The ability to incorporate and deliver lipophilic, amphiphilic, and water-soluble molecules in a controlled manner and great biocompatibility of cubic nanoparticles make them excellent candidates for drug delivery applications. Stabilization of the cubic nanoparticles has been achieved through polymerization of the reactive lipids in cubic lipid assemblies. Several QII-forming amphiphiles have been designed and synthesized. Certain compositions of these amphiphiles and water plus cross-linking monomers yield bicontinuous cubic phases, which can be dispersed into cubic nanoparticles in water using Poloxamer 407. These cubic nanoparticles were studied by 2H NMR, Transmission Electron Microscopy, and Scanning Electron Microscopy. The polymerization of the hydrated amphiphiles in the lipid region successfully stabilized the cubic nanoparticles. Selective and simultaneous polymerizations of the reactive groups in regions of different polarity within an inverted bicontinuous cubic phase were achieved via appropriate choice of initiation chemistry. The ability to form stable biocompatible nanoparticles with interpenetrating water channels of high internal surface area provides opportunities for the sequestration and release of relatively large molecules from these novel nanoparticles. Organic light-emitting diodes (LEDs) have attracted much attention because of their academic interests and potential utility of this technology in a wide variety of applications. A more efficient electroluminescent (EL) device requires balanced charge injection and transport of both electrons and holes. Discotic liquid crystalline LEDs are very effective as charge transport and energy transfer conduits, due to the high degree of electron communication between mesogen cores within the columnar packing. Phthalocyanines are well known to form columnar discotic liquid-crystalline mesophases. A novel oxadiazole substituted liquid crystalline phthalocyanine containing hole-transport phthalocyanine moiety as the core and electron-transport oxadiazole moieties on the periphery was designed and synthesized.
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Morkel, C. E. « Synthesis and characterisation of amphiphilic block copolymers / ». Link to the online version, 2005. http://hdl.handle.net/10019/1119.
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Morkel, Charl Ernst. « Synthesis and characterisation of amphiphilic block copolymers ». Thesis, Stellenbosch : University of Stellenbosch, 2005. http://hdl.handle.net/10019.1/1213.
Texte intégralRésumé :
Thesis (PhD (Chemistry and Polymer Science)--University of Stellenbosch, 2005.This study involves the synthesis and characterisation of PEG-based amphiphilic block copolymers for the hydrophilization of polysulphone ultrafiltration membranes. PEG based macro RAFT agents were synthesized and characterised. PEG-b-PS block copolymers were synthesized via the RAFT assisted controlled free radical polymerisation utilizing the synthesized PEG macro RAFT agents. The resulting polymerisation products were then analyzed by two-dimensional chromatography at the “critical conditions” for PS. In the second phase of this study PEG-b-PSU block copolymers were synthesized via the polycondensation of bis (4-chlorophenyl) sulphone, Bisphenol A, and PEG. The resulting products were characterised by NMR spectrometry. PEG-b-PS films and modified PSU membranes (modified by the addition of PEG-b-PSU block copolymer to the membrane casting solution) were prepared and analyzed. Surface analyses included static contact angle, AFM force-distance analysis, and FTIR-PAS analysis. Results showed the successful synthesis of both PEG-b-PS and PEG-b-PSU amphiphilic block copolymers. Surface analysis proved the successful hydrophilization of the surface of the modified PSU membranes.
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Sugandhi, Eko Winny. « Synthesis, Characterization, and Antimicrobial Activity of Water-soluble, Tri-carboxylato Amphiphiles ». Diss., Virginia Tech, 2007. http://hdl.handle.net/10919/26106.
Texte intégralRésumé :
Many previous studies of biological activity in a homologous series of amphiphiles have shown a cut-off effect, where the biological activity increases with an increase in chain length, after which the activity plateaus or weakens. One factor suspected to cause this problem is solubility issues. We have designed several series of very hydrophobic, water-soluble amphiphiles to overcome this problem. Three homologous series containing mobile hydrophobic moieties and two series of epimers containing rigid cholestane moieties have been synthesized; the hydrophobic moiety is connected to the first-generation, Newkome-type dendron via a ureido linker. We have demonstrated that as tris(triethanolammonium) salts, these amphiphiles show excellent solubility in water. The solubilities in aqueous triethanolamine solution of the three series containing mobile hydrophobic moieties are 19,500 to 25,700 μM depending on the formula weight of the homolog, while those containing rigid cholestane moieties are 18,900 and 17,400 μM.
Having eliminated the solubility issue, the antimicrobial activity against a broad spectrum of microorganisms has been screened. We have demonstrated that the antimicrobial activity depends on the amphiphile-series, species, chain-length, or epimer specificities, as well as hydrophobicity. The one-tailed, tri-carboxylato amphiphiles are generally better than the other series, with two exceptions. First, the two-tailed tri-carboxylato amphiphiles, 3CUr1(11)2 and 3CUr1(12)2, are more active against Cryptococcus neoformans; in fact, both amphiphiles (MICs are 6.9 and 7.2 μM, respectively) are considered to display good antifungal activity. Second, amphiphile 3CUr-β-cholestane, whose MIC is 27 μM, is more active against Staphylococcus aureus. Overall, these new tri-carboxylato amphiphiles only exhibit moderate activity with two promising leads.
Furthermore, we have demonstrated the intrinsic activity (MIC0) of the one-tailed, tri-carboxylato amphiphile series (3CUrn) against Mycobacterium smegmatis. All the MIC0s observed are at least 8-fold lower than the corresponding CMCs. Amphiphile 3CUr16 is the most active; the MIC0 is 100-fold smaller than the CMC. With this consideration, we have suggested that the mechanism of action of the antimycobacterial activity in amphiphile 3CUr16 is not related to detergency.Ph. D.
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LaManna, Caroline Marie. « Synthesis, characterization, and evaluation of photo-active amphiphiles for gene delivery applications ». Thesis, Boston University, 2013. https://hdl.handle.net/2144/12803.
Texte intégralRésumé :
Thesis (Ph.D.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.Gene therapy has the potential to alter the landscape of medical therapeutic techniques by offering a means of introducing or knocking out genes to treat a number of diseases. Both viral and nonviral vectors are currently being utilized in gene therapy clinical trials. To overcome the obstacles in the cellular uptake and transfection pathways which impede nonviral gene delivery, novel lipids, polymers, and dendrimers are being engineered. Cationic lipid vectors have been widely characterized as gene delivery tools as they electrostatically interact with the anionic nucleic acid backbone to form a supramolecular structure (lipoplex). This complex allows the nucleic acid to be protected from enzymatic degradation during transport and interacts with the cell membrane to facilitate internalization by endocytosis. A limitation of current systems is a lack of mechanism for release of the nucleic acid, which is an integral step toward transcription and translation. The use of a charge-reversal or charge-switching amphiphile has been previously described by which the amphiphile initially has a net positive charge and is rendered negatively charged upon enzymatic removal of a terminal ester group. In order to further improve the transfection efficacy of cationic lipids and to impart an externally controlled release mechanism, we have developed a library of novel photo-active chargereversal lipids which can be triggered by ultraviolet (UV) light. In this work, we describe the synthesis and characterization of photo-active lipids for binding and releasing deoxyribonucleic acid (DNA) and evaluate the cellular uptake kinetics and transfection efficiency in vitro. The binding, release, and cellular uptake behaviors of lipoplexes were found to be dependent on lipid composition and resulting supramolecular structures. The transfection efficiency of the photo-active lipoplexes was further affected by variables associated with cellular incubation and UV exposure. Continued development of controlled release gene delivery vectors, including photoactive lipids, will enhance the understanding and utility of gene therapy by providing spatiotemporal control of the process.
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Maisuria, Bhadreshkumar B. « Synthesis, Characterization, Critical Micelle Concentration and Antimicrobial Activity of Two-headed Amphiphiles ». Thesis, Virginia Tech, 2009. http://hdl.handle.net/10919/34607.
Texte intégralRésumé :
This project is about the synthesis of homologous series of two-headed, long-chain amphiphiles (the 2CCbn series, where n = 16, 18, 20, 22, 30, 5α-cholestan-3à -ol). The 2CCbn series was synthesized in five steps. The first step involves a reaction of nitroethane and two equivalents of tert-butyl acrylate to form nitrodiester by successive Michael addition reaction. The second step is the reduction of nitrodiester with Raney nickel to form aminodiester. The third step involves a reaction of aminodiester with di-tert-butyl dicarbonate [(Boc)2O] to form isocyanatediester. The fourth step is addition of iscocyanatediester with aliphatic alcohol to give alkyl carbamate diester (2ECbn) series. The fifth step is the removal of the tert-butyl protecting group to give the 2CCbn series.
The critical micelle concentrations (CMC) were measured by the pyrene-based fluorescent probe method. The pyrene excited at 345 nm and fluoresces with maxima at 374 nm (I1) and 385 nm (I3). The stock solution and the dilution series for each amphiphiles were made in 0.9% triethanolamine solution. The CMCs were measured at two pH ~9.2 and 7.4. The CMCs were determined by plotting I1/I3 vs. concentrations. The CMCs were decreasing with increasing chain length. The CMCs for the 2CCbn series are lower than the 3CCbn series but higher than the fatty acids.
The minimal inhibitory concentrations were measured against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. These strains were grown on BHIB+S with 5% triethanolamine. The MICs of the 2CCbn series amphiphiles were measured by using microtiter plate reader and by looking turbidity. The cutoff effect was found for the 2CCbn series. The MIC decreased up to C20 chain length and started rising for C22. The 2CCb18 (MICâ 2.2 µg/mL) of the 2CCbn series was the most effective amphiphile against S. aureus and MRSA.
The CMC/MIC ratio was used to determine the safety of an amphiphile as a drug use. The amphiphile 2CCb18 has given the largest safety ratio (CMC/MIC = 273) against S. aureus and MRSA. It suggests that micelle formation is not a mechanism of action for anti-Staphylococcal activity.Master of Science
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Actis, Marcelo. « Synthesis, Characterization, Critical Micelle Concentration and Biological Activity of two-Headed Amphiphiles ». Thesis, Virginia Tech, 2008. http://hdl.handle.net/10919/35774.
Texte intégralRésumé :
In this project, we synthesized a new homologous series of five long-chain, two-headed amphiphiles [2CAm13, 2CAm15, 2CAm17, 2CAm19, 2CAm21; CH3(CH2)n-1CONHC(CH3)(CH2CH2COOH)2, n = 13, 15, 17, 19, 21]. The synthesis of the 2CAmn series was accomplished in four steps. The first step involves a reaction of nitroethane and two equivalents of tert-butyl acrylate to create the nitrodiester synthon [O2NC(CH3)(CH2CH2COOtBu)2] by successive Michael additions. The second step in the synthesis consists of a reduction of nitrodiester with H2 and Raney nickel to give the diesteramine [H2NC(CH3)(CH2CH2COOtBu)2]. The third step is the condensation of an acid chloride with diesteramine to give an alkanamido diester [2EAmn; CH3(CH2)n-1CONHC(CH3)(CH2CH2COOtBu)2, n = 13, 15, 17, 19, 21]. The final step is the removal of the tert-butyl protecting groups to give 2CAmn.
Critical micelle concentration measurements were collected by the pendant drop method for measuring surface tension for a series of triethanolamine/2CAmn solutions to establish the concentration required for detergency. The CMCs for the 2CAmn series were found to decrease in value from 3.0 à 10â 2 M (2CAm13) to 1.7 à 10â 4 M (2CAm21) in a linear fashion [log CMC = (â 0.28 ± 0.01)n + (2.2 ± 0.1)]. The CMCs for the 2CAmn series falls in between the CMCs for three series of homologues three-headed amphiphiles (3CAmn, 3CCbn, 3CUrn) and the CMCs for fatty acids, with fatty acids having the lowest CMCs.
Antibacterial activity (minimal inhibitory concentrations, MICs) for a series of homologous dendritic two-headed amphiphiles and three series of homologous, three-headed amphiphiles against Staphylococcus aureus and methicillin-resistent S. aureus (MRSA) were measured by broth microdilution to compare the effect of chain length and, hence, hydrophobicity. Inoculum density affected antibacterial activity of the 2CAmn series against both S. aureus and MRSA. MIC measurements at different cell densities showed that activity decreased with higher cell densities. For all four series, the MICs were relatively flat at low inoculum densities. This flat region defines the intrinsic activity, MIC0. The MIC0 results revealed that inoculum density, chain-length, and hydrophobicity all influenced antibacterial activity and that activity correlates strongly with clogp, an established measure of hydrophobicity. The most hydrophobic members from each homologous series exhibited antibacterial activity. The most active homologue of the 2CAmn series was 2CAm21 with MIC0 of 2.0 ± 1.0 and 3.2 ± 1.0 μM against S. aureus and MRSA, respectively.
The CMCs and MIC0s of the two- and three-headed amphiphiles were compared for both S. aureus and MRSA to gauge the effect that micelles may have on activity. Amphiphile 2CAm19 has the largest ratio between CMC and MIC0 (CMC/MIC0 = 205) against S. aureus and 3CUr20 has the largest ratio (CMC/MIC0 = 339) against MRSA. These ratios suggest that micelle formation is not a mechanism of action for anti-Staphylococcal activity.
Master of Science
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Grey-Stewart, Danielle(Danielle N. ). « Synthesis of guanidinium-functionalized amphiphiles for the exploration of chaotropic supramolecular nanoribbons ». Thesis, Massachusetts Institute of Technology, 2021. https://hdl.handle.net/1721.1/131010.
Texte intégralRésumé :
Thesis: S.B., Massachusetts Institute of Technology, Department of Materials Science and Engineering, February, 2021Cataloged from the official PDF version of thesis.
Includes bibliographical references (pages 28-30).
Nanoscale self-assembly driven by the hydrophobic effect is of intense research interest due to the ability to synthesize complex, chemically diverse structures with molecular length scales. Supramolecular self-assemblies comprised of amphiphilic molecules have been engineered to achieve diverse applications, from drug delivery to 3D printing. The design of the component molecules in engineered assemblies are often bio-inspired, where structures are highly dynamic to respond to changes in their environment. Molecules within dynamic assemblies move rapidly due to molecular exchange and rearrangement, and the supramolecular structure is often only retained for a limited amount of time before breaking down. Aromatic amide (aramid) amphiphiles, which can form strong hydrogen bonding and pi-pi stacking between them, self-assemble into stable, mechanically strong nanofibers, in stark contrast to the assemblies that precede them. This study seeks to functionalize the aramid amphiphile nanofibers surface for the study of water dynamics by attaching a chaotropic guanidinium head group. This head group will disturb the hydrogen bonding network of surrounding water, causing a measurable change in water dynamics when analyzed using Overhauser Dynamic Nuclear Polarization. Guanidinylation was achieved, but future work must be done to create a kosmotropic analog. These two structures will be used to run parallel experiments to study the water dynamics in the local environment.
by Danielle Grey-Stewart.
S.B.
S.B. Massachusetts Institute of Technology, Department of Materials Science and Engineering
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Bell, Owen Alexander. « Synthesis, self-assembly and applications of functional amphiphiles based on oligo(aniline) ». Thesis, University of Bristol, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.702109.
Texte intégralRésumé :
Self-assembly is a promising route to provide functional nanomaterials that meet technological challenges in organic electronics, energy storage and biomaterials. Oligomers of aniline are switchable, conductive organic materials that can self-assemble, mimicking the properties of the well-known conducting polymer poly(aniline) but with improved solubility and versatility for applications. In this thesis, the preparation of a family of amphiphiles based on oligo(aniline) is described. The structure of these species, bearing a cationic headgroup common to surfactants, was designed to endow water-solubility and thus provide a strong driving force for the hydrophilic oligo(aniline) section to self-assemble. The headgroup structure was varied to include several different quaternary amines, and the self-assembly of a trimethylammonium-bearing oligo(aniline) amphiphile in water was investigated in detail. Investigations by electron microscopy, UV-Vis spectroscopy and X-ray diffraction showed isodesmic self-assembly into one-dimensional anisotropic nanowires of single-molecule thickness occurred in a manner typical of chromonic liquid crystals, and the arrangement of oligo(aniline)s within self-assemblies was elucidated. Self-assembled helical conductive nanowires were produced in water by ionic complexation of single-enantiomer camphorsulfonic acid with oligo(aniline) amphiphiles, as observed by circular dichroism, four-point probe resistance and UV-Vis spectroscopy measurements. A variety of other · strong organic acids were found to promote self-assembly into fibrous or spherical structures; proof of principle that oligo(aniline) is a versatile platform for construction of supramolecular functional materials. Oligo(aniline) amphiphiles were used to address an important technological challenge by dispersing carbon nanotubes in water. Dispersion conditions were investigated and optimised by UV-Vis and electron microscopy, and the resulting oligo(aniline)-carbon nanotube dispersions were used to fabricate flexible all-organic electrochemical capacitors for energy storage. Oligo(aniline) amphiphiles are found to be promising for highly ordered, tunable, functional supramolecular materials. This work provides understanding and a basis for their further development.
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Yu, Xinfei. « Synthesis and Self-Assembly of Molecular Shape Amphiphiles : Polystyrene-Tethered Hydrophilic POSS/C60 ». University of Akron / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=akron1334606614.
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Hamid, S. M. « Synthesis, aggregation behavior and polymerisation of novel amphiphilic (meth)acrylate monomers ». Thesis, University of Strathclyde, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381475.
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Dembowa, Aneta. « Synthesis and Characterization of Amphiphilic Iron-Sulfur Core Dendrimers ». NCSU, 2005. http://www.lib.ncsu.edu/theses/available/etd-01022005-192535/.
Texte intégralRésumé :
Synthesis of water soluble carboxylate-terminated Fe4S4-core was carried out. Convergent method was chosen to build three generations of dendrons. Several synthetic schemes were explored. The syntheses were conducted with 4,4-bis(hydroxyphenyl)penthanol as a repeat unit and N,N-dimethyl thiocarbamate and methyl ester or methoxy-methyl as protecting groups. The conditions for deprotection and ligand exchange have been proposed. 1H, 13C and MALDI-MS were used to characterize synthesized molecules.
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Chambrier, Isabelle. « The synthesis and study of some novel amphiphilic phthalocyanines ». Thesis, University of East Anglia, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293193.
Texte intégralRésumé :
The syntheses of phthalocyanines and particularly substituted phthalocyanines, together with some of their main applications, are described. Asymmetrically octasubstituted phthalocyanines, where the substituents on one benzene ring differ from the substituents on the other three rings are most commonly obtained from statistical mixtures of precursors derived from phthalic acid. The synthesis of a series of such compounds together with their substituted phthalonitrile precursors containing both hydrophilic and hydrophobic side-chain substituents is discussed. This novel series of nonperipherally substituted amphiphilic phthalocyanines were shown to possess liquid crystalline properties. The various liquid crystal discotic mesophases were characterised. As a consequence of their hydrophilic-hydrophobic balance and high solubility in organic solvents, the compounds were studied as Langmuir-Blodgett films. The synthesis and Langmuir monolayer behaviour of peripherally octa-t-butylphthalocyanine is also described. The latter part of this thesis includes a discussion of the mechanisms of the synthesis of phthalocyanines from various precursors and particularly from phthalonitrile, which complements the synthetic aspects of the work. The thesis concludes with an investigation into the feasibility of a stepwise conversion of phthalonitrile precursors into the macrocycle for the preparation of asymmetrically substituted phthalocyanines.
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Batagianni, Eleftheria. « Synthesis and Characterisation of Amphiphilic Copolymers for Bioelectronic Applications ». Thesis, Pau, 2020. http://www.theses.fr/2020PAUU3019.
Texte intégralRésumé :
De nos jours, les dispositifs bioélectroniques ont trouvé un terrain fertile dans une variété d'applications et ont contribué de manière significative à l'amélioration des soins de santé, à la protection de l'environnement et à l'accélération du rythme des progrès scientifiques. Le développement de transistors électrochimiques organiques (OECTs) a trouvé une applicabilité dans divers dispositifs bioélectroniques, car ils peuvent s'interfacer avec des tissus et des organes électriquement actifs pour mesurer l'activité cellulaire. Dans ce domaine en évolution rapide, il existe un besoin émergent de nouveaux matériaux qui peuvent remplacer l'existant une fois en s'attaquant à leurs limites et en aidant à la mise en oeuvre de nouveaux dispositifs améliorés et innovants.L’objectif de notre travail était de préparer des polymères innovants à base de fullerène et des copolymères blocs amphiphiles pour des applications bioélectroniques. À l'Université de Pau et des Pays de l'Adour, nous avons d'abord synthétisé le comonomère et ensuite, en utilisant C60, C70 et PCBM comme monomères, des poly(fullerènes) via une voie de synthèse facile en utilisant matières premières non toxiques. De plus, nous avons utilisé le poly(C60) déjà synthétisé pour obtenir des copolymères blocs amphiphiles avec du poly(oxyde d'éthylène). Nous avons réalisé des études préliminaires et cinétiques pour comprendre l'effet des paramètres de réaction (réactifs, rapport des réactifs, température, temps de polymérisation et solvant). Pour étudier les caractéristiques des produits synthétisés, nous avons effectué la chromatographie GPC, la RMN et les spectroscopies UV-visible, tandis que leur profil thermique a été obtenu par analyse TGA et DSC. Il est fort possible que ces matériaux de type n puissent convenir à des applications médicales telles que les dispositifs bioélectroniques et / ou biocapteurs. Ainsi, lors d'un séjour de trois mois à l'Université de Cambridge, nous avons eu l'occasion d'étudier la conductivité électronique des poly(fullerènes) synthétisés et de ses copolymères blocs amphiphilesNowadays bioelectronic devices have found fertile ground in a variety of applications and have significantly contributed in improving healthcare, offer environmental protection, and accelerating the pace of scientific progress. The development of organic electrochemical transistor (OECT)s have found applicability in various bioelectronic devices since can interface with electrically active tissues and organs to measure cell activity. In this rapidly evolving field there is an emerging need for newmaterials which can replace existing once by tackling their limitations and assisting in the implementation of new improved and innovative devices.The objective of our work was to prepare innovative fullerene based polymers and it’s amphiphilic block copolymers for bioelectronics applications. At the Université de Pau et des Pays de l’Adour we, first, synthesized the co-monomer and following, utilizing C60, C70 and PCBM as monomers, main-chain poly(fullerene)s via a facile one-pot synthetic route using non-toxic starting materials. Moreover, we used the already synthesized poly(C60) to obtain metal-free amphiphilic block copolymers with poly(ethylene oxide). We performed preliminary and kinetic studies to understand the effect of the reaction parameters (reagents, reagents ratio, temperature, polymerization time and solvent). To investigate the characteristics of the synthesized products we performed GPC chromatography, NMR and UV-visible spectroscopies, while their thermal profile was obtained via TGA and DSC analysis. It’s highly possible that these n-type materials can be suitable for medical applications such as bioelectronic and/or biosensing devices. Therefore, during a three month stay at the University of Cambridge, we had the opportunity to study the electron conductivity of the synthesized poly(fullerene)s and its amphiphilic block copolymers
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Liu, Yuqing. « Synthesis and Characterization of Well-Defined, Amphiphilic, Ionic Copolymers ». University of Akron / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=akron1318440986.
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BERTANI, DANIELA. « Synthesis and self-assembly of biocompatible amphiphilic block copolymers ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2018. http://hdl.handle.net/10281/199109.
Texte intégralRésumé :
Il drug delivery attira molto interesse a causa della necessità di migliorare efficienza e selettività delle terapie farmacologiche. Capsule polimeriche per i farmaci sono una strategia promettente per prolungarne i tempi di circolazione, migliorarne il trasporto nel sangue, e modularne nel tempo il rilascio. In questo ambito, l’organizzazione spontanea dei copolimeri a blocchi (CB) in nanoparticelle (NP) compartimentalizzate in ambiente acquoso è uno strumento potente per la fabbricazione di sistemi per il drug delivery.
In questa tesi vengono investigati la sintesi e l’autoassemblaggio (AS) controllati di una serie di CB anfifilici contenenti blocchi idrofilici biocompatibili e biomimetici.
Nel Cap. 3 viene presentato un quadro completo del comportamento di AS di PS-b-PDMA in H2O da DMF. E’ stato preparato un set di campioni con pesi molecolari compresi fra 10 kDa e 57 kDa e fPDMA comprese fra 0.06 e 0.75, e le NP sono state caratterizzate con DLS, TEM, CEM, CET, SEM e AFM. Viene proposta una mappa morfologica, dove le morfologie dominanti sono state correlate con la caratteristiche chimiche dei CB. In particolare, quando fPDMA < 0.15, è stata osservata la formazione di particelle porose con diametri fino ad alcuni micron che assumono una fase spugnosa, stabile alla liofilizzazione.
Nel Cap. 4, una serie di CB biocompatibili e biodegradabili di PEO-b-PLA sono stati sintetizzati tramite ROP controllata di lattide catalizzata da DBU. Il focus di ricerca era sull’effetto del solvente non selettivo sull’AS: NP ottenute da ACT, DX, THF e DMF sono state analizzate con DLS, CEM e CET. Dimensioni e PDI aumentavano nell’ordine ACT < DX < THF ~ DMF. Le NP sono state classificate in tre cluster: micelle (piccolo raggio, basso PDI), polimersomi (medio raggio, medio PDI), e micelle composte (grande raggio, grande PDI). Mentre ACT e DX portano alla formazione preferenziale di micelle, il THF permette di accedere a uno spazio morfologico molto più ampio. Infine, la DMF favorisce fenomeni di aggregazione di secondo ordine.
Nel Cap. 5 vengono valutati la sintesi controllata, la funzionalizzazione terminale e la formazione di di- e triblocchi di polimeri a base di PEtOx biocompatibile tramite una combinazione di ROP e RAFT. Un blocco di PEtOx25 è stato sintetizzato con successo tramite CROP di 2-etil-2-ossazolina con buon controllo; è stato poi usato come macroCTA per la polimerizzazione sequenziale di Sty e t-BA per ottenere il copolimero a tre blocchi PEtOx-b-PS-b-PtBA. Vengono presentati risultati preliminari sul SA in etanolo come solvente selettivo per i blocchi di PEtOx e PtBA, ma non PS.
Nel Cap. 6 è stato studiato l’effetto morfogenico di ACT, DX e DMF sul SA di PS-b-PDMA e PEO-b-PLA usando il rotore molecolare AzeNaph-1 come sonda di viscosità per il monitoraggio in situ dell’aggregazione dei CB. L’evoluzione della viscosità in funzione del contenuto di H2O in PS-b-PDMA è simile sia in DMF che DX: all’aggiunta di H2O, le catene di PS collassano rapidamente, formando core prevalentemente vetrosi. Coerentemente, il DLS mostra poca variazione di dimensioni delle NP fra i due solventi. Anche PEO-b-PLA forma domini vetrosi in DMF/H2O, ma non in ACT o DX. Al contrario, la viscosità locale del core è molto minore in ACT e DX che in DMF su tutto il range di frazione di H2O, ed è dipendente dal tempo. Questa aumentata mobilità molecolare promuove la differenziazione delle NP formate.
Infine, nel Cap. 7 viene esplorato l’AS indotto da polimerizzazione di CB anfifilici basati su glicopolimeri. Tre campioni di PAGA con DP = 25, 50 e 75 sono stati polimerizzati in H2O/MeOH tramite RAFT, con ottimo controllo. L’ottimizzazione delle condizioni di reazioni ha permesso di usare PAGA25 e PAGA50 come stabilizzanti e macroCTA per l’estensione di catena con BA in H2O/MeOH. Il controllo sulla polimerizzazione è stato basso, ma sono state ottenute NP sferiche, stabili e monodisperse.Drug delivery is a trending topic in current research due to the need to improve therapeutic efficiency and selectivity. Polymeric encapsulants for drugs are a promising strategy to prolong circulation times, enhance hydrophobic drug transport through the blood stream, and modulate drug release over time. In this field, amphiphilic block copolymers’ (BCs) spontaneous organization in compartimentalized nanoparticles (NPs) in water is a powerful tool for the fabrication of drug delivery systems. In this Doctoral thesis, the controlled synthesis and self-assembly (S-A) of a series of amphiphilic BCs containing biocompatible, stealthy hydrophilic blocks were investigated. Controlled polymerization techniques were employed to prepare copolymers with narrow molecular weight distributions. In Chapter 3, a complete picture of the previously unreported S-A behaviour of PS-b-PDMA in water from DMF is drawn. A comprehensive sample set spanning molecular weights from 10 kDa to 57 kDa and hydrophilic volume fractions fPDMA from 0.06 to 0.75 was prepared by sequential RAFT, and NPs were characterized by DLS, TEM, CEM, CET, SEM, and AFM. A morphology map is proposed, where predominant morphologies were correlated with BC chemical characteristics. In particular, stable hollow particles with diameters up to several microns when fPDMA drops below 0.15 are formed. Micron-large porous particles exhibiting a sponge phase which can withstand lyophilisation were observed. In Chapter 4, a series of biocompatible and biodegradable PEO-b-PLA BCs were synthesized by controlled ROP of lactide catalyzed by non-toxic DBU. The research focus was on the effect of the non-selective solvent on S-A: NPs obtained from ACT, DX, THF, DMF were analyzed by DLS, CEM and CET. Both size and PDI increased in the order ACT < DX < THF ~ DMF. NPs were classified into three clusters, labeled micelles (small size, low PDI), polymersomes (medium size, medium-low PDI) and large compound micelles (large size, large PDI). While ACT and DX yielded mostly micelles, THF allowed to access a much broader morphological space. Finally, DMF favoured second-order aggregation phenomena. In Chapter 5, controlled synthesis, chain-end functionalization and di- and triblock formation of biocompatible PEtOx-based polymers by a combination of ROP and RAFT techniques were evaluated. Biocompatible PEtOx25 blocks were successfully synthesized by CROP of 2-ethyl-2-oxazoline with good control. PEtOx25 was used as a macroCTA for the sequential polymerization of a Sty and tBA to yield a PEtOx25-b-PS50-b-PtBA25 triblock copolymer. Preliminary results on S-A in ethanol as a selective solvent for both PEtOx and PtBA, but not for PS, are presented. In Chapter 6, the morphogenic effect of ACT, DX and DMF on PS-b-PDMA and PEO-b-PLA S-A was studied using molecular rotor AzeNaph-1 as a local viscosity probe for the in situ monitoring of BC aggregation. Evolution of viscosity as a function of water content in PS-b-PDMA was similar both in DMF and DX: upon the addition of H2O, PS chains rapidly collapsed in NP cores, which were largely glassy. Consistently, DLS shows little variation on particle size between the two solvents. PEO113-b-PLAx also formed glassy domains in DMF/H2O, but not in ACT or DX. Contrarily, local core viscosity was much lower in ACT and DX than in DMF over the whole H2O fraction range, and was time-dependent. This increased chain mobility promoted the differentiation of NP formation. Finally, in Chapter 7, polymerization-induced S-A of glycopolymer-based amphiphilic BCs was investigated. Three PAGA samples with DP = 25, 50 and 75 were polymerized in H2O/methanol mixture by RAFT, with remarkable control. Optimization of reaction conditions allowed the use of PAGA25 and PAGA50 as stabilizers and macroCTAs for chain-extension with n-butylacrylate (BA) in methanol/H2O environment. Control on the polymerization was poor, but stable and monodisperse spherical NPs were obtained.
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Xu, Rui. « On the role of the carbohydrate vs the lipid moieties in neoglycolipid self-organisation : Synthesis and liquid crystalline properties of two new families of carbohydrate-based amphiphiles ». Phd thesis, INSA de Lyon, 2013. http://tel.archives-ouvertes.fr/tel-00940381.
Texte intégralRésumé :
In this study, we have synthesized two families of new carbohydrate-based amphiphilic derivatives: a series of alkyl glucoside ethers varying in terms of chain length and position on the sugar, and a series of glucosteroids varying in terms of alkyl spacer and, for the disutibstuted systems, in terms of alkyl side chain length. By the means of analytical methods, such as NMR spectroscopy, mass spectroscopy and elementary analysis, the structure of all the compounds was carefully established, as well as their purity. Their liquid crystalline behaviors were studied by the means of transmission light microscopy and differential scanning calorimetry. The two families of compounds which have been studied illustrate how much the behavior can be essentially related to polar interactions (H-bonding), therefore to the sugar moiety, for the ether series, or to hydrophobic interactions (lipid-lipid) in the glucosteroid series. In this latter series, preference for either steroid-stroid or steroid alkyl packing appears as an insight in understanding the behavior of complex lipids, showing potentially more than one conformational structure with important consequences on the supramolecular level, therefore to their potential biological role. This could be regarded as "lipid denaturation" by analogy to the protein denaturation. Also, when we see that compounds like the glycosteroids having an long chain ester -CAG, BbGL-I, are found to exist in Nature, and how much glycolipid-cholesterol interactions were recently shown to be critical in some biological processes, it is hoped that our observations can provide a new vision angle for the study of complex lipids and glycolipids. As a start to develop new probes targeting the "lipid raft" microdomain in membranes, we also explored a sequence towards carbohydrate laurdan hybrids. Further development of this strategy and evaluation of the biological properties is programmed within new collaborative projects.
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Herfurth, Christoph. « Einstufen-Synthese und Charakterisierung amphiphiler Sternpolymere als multifunktionale assoziative Verdicker ». Phd thesis, Universität Potsdam, 2012. http://opus.kobv.de/ubp/volltexte/2012/6244/.
Texte intégralRésumé :
Typische assoziative Verdicker für wässrige Systeme basieren auf linearen, doppelt hydrophob endmodifizierten Poly(ethylenglykolen) (PEGs). Diese Polymere aggregieren aufgrund ihrer Struktur in wässriger Lösung und bilden ein Netzwerk aus verbrückten Polymer-Mizellen. Dabei kann ein Polymer-Molekül maximal zwei Mizellen miteinander verbinden. Bisher ist unklar, wie die Anzahl der Endgruppen eines verzweigten, mehrfach hydrophob endmodifizierten hydrophilen Polymers die Struktur und Dynamik solcher Netzwerke beeinflusst. Die Synthese verzweigter Polymere auf PEG-Basis erfolgt mittels lebender ionischer Polymerisation und ist experimentell aufwändig. Das Einführen hydrophober Endgruppen erfordert zusätzliche Synthese-Schritte.
In dieser Arbeit wurden hydrophile Sternpolymere mit hydrophoben Endgruppen in einem Schritt hergestellt. Dazu wurde die Technik der radikalischen Polymerisation unter Kettenübertragung durch reversible Addition und anschließende Fragmentierung (reversible addition-fragmentation chain transfer, RAFT) genutzt. Die Synthese der Sternpolymere erfolgte von einem multifunktionalen Kern, der die R-Gruppe der RAFT-Kettenüberträger (chain transfer agents, CTAs) bildete. Die dazu benötigten CTAs wurden so konzipiert, dass mit ihrer Hilfe sowohl die Anzahl der Arme des Sternpolymers (von 2 bis 4), als auch die Länge der hydrophoben Endgruppe (C4, C12, C18) variiert werden konnte. Der große Vorteil der RAFT-Polymerisation ist, dass sie viele polare Monomere für die Synthese der hydrophilen Arme des Sternpolymers toleriert. In dieser Arbeit wurden als Modell-Monomere Oligo(ethylenglykol)methylether-acrylat (OEGA) und N,N-Dimethylacrylamid (DMA) eingesetzt. Beide Monomere bilden nicht-ionische hydrophile Polymere. Poly(OEGA) ist ein Kammpolymer, das auf PEG basiert. Poly(DMA) besitzt dagegen eine deutlich kompaktere Struktur.
Die erhaltenen amphiphilen Sternpolymere wurden umfassend molekular charakterisiert. Die Molmassen wurden mit verschiedenen GPC-Systemen bestimmt und der Grad der Endgruppenfunktionalisierung wurde mittels UV/Vis- und 1H-NMR-Spektroskopie überprüft. Die Polymerisation von OEGA zeigt mit den CTAs einige Charakteristika der Polymerisation mit reversibler Deaktivierung (RDRP, auch „kontrollierte radikalische Polymerisation“), wird aber durch Kettenübertragung zum Monomer bzw. Polymer gestört. Diese Nebenreaktion ist auf die Struktur des Monomers als Oligoether zurückzuführen.
Bei allen untersuchten Polymerisationen von DMA mit den multifunktionalen CTAs steigt die Molmasse linear mit dem Umsatz. Die erhaltenen Polymere zeigen durchweg monomodale und enge Molmassenverteilungen (PDI ≤ 1,2). Die Molmassen lassen sich in einem weiten Bereich von 25 kg/mol bis 150 kg/mol einstellen und die Endgruppen der Polymere bleiben zu 90 % erhalten. Während die Polymerisation von DMA sowohl mit den di- als auch den trifunktionalen CTAs innerhalb von 3 h zu quantitativen Umsätzen verläuft, wird der quantitative Umsatz des Monomers bei der Polymerisation mit tetrafunktionalen CTAs erst nach 4 h erreicht. Diese Verzögerung ist auf eine Retardierung in der Anfangsphase der Polymerisation zurückzuführen, die sich aus der besonderen Struktur der tetrafunktionalen CTAs erklärt.
Auf dem System zur Polymerisation von DMA aufbauend ließen sich Gradienten-Block-Copolymere in Eintopfreaktionen herstellen. Dazu wurde nach Erreichen des quantitativen Umsatzes von DMA ein zweites Monomer zur Reaktionsmischung gegeben. Mit Ethylacrylat (EtA) wurden so lineare amphiphile symmetrische Triblock-Copolymere erhalten. Dabei wurde die Länge des hydrophoben Blocks durch unterschiedliche Mengen an EtA variiert. Mit N,N-Diethylacrylamid (DEA) wurden lineare symmetrische Triblock-Copolymere sowie 3-Arm Stern-Diblock-Copolymere hergestellt, die über einen thermisch schaltbaren zweiten Block verfügen. Bei diesen Polymeren lässt sich die Länge des hydrophoben Teils in situ durch Veränderung der Temperatur variieren.
Das Verhalten der amphiphilen Sternpolymere in wässriger Lösung und in Mikroemulsion wurde im Rahmen einer Kooperation an der TU Berlin mit Hilfe von Kleinwinkel-Neutronenstreuung (SANS), dynamischer Lichtstreuung (DLS) und Rheologie untersucht. Die Polymere wirken durch Assoziation der hydrophoben Endgruppen als effektive Verdicker sowohl allein in wässriger Lösung als auch in Mikroemulsion. Die Struktur des gebildeten Netzwerks hängt dabei von der Konzentration des Polymers in der Lösung und der Länge der Endgruppe (Hydrophobie) ab. Die dynamischen Eigenschaften der Lösungen werden außerdem durch die Anzahl der Arme der Polymere bestimmt.Typically, associative thickeners for aqueous system consist of linear, hydrophobically α,ω-end-capped poly(ethylene glycols) (PEGs). Owing to their structure, these polymers aggregate in aqueous solution, forming a network of bridged micelles. Thus, one polymer molecule can link not more than two micelles. Until now it is unclear whether the structure and dynamics of such networks are influenced by the number of end groups of a branched multiply hydrophobically end-capped hydrophilic polymers. Branched PEG-based polymers are synthesized using the laborious and limited techniques of living ionic polymerization. Introducing hydrophobic end groups demands a multiple-step process. This work presents the one-step synthesis of hydrophilic star polymers with hydrophobic end groups, using reversible addition fragmentation chain transfer (RAFT) polymerization. This radical polymerization method is easy to use and tolerates a large number of polar monomers for the synthesis of the hydrophilic arms of the star polymers. The arms of the polymer were grown from a multifunctional core that formed the R-group of the chain transfer agents (CTAs). The CTAs where tailored to be able to vary the number of arms of the star polymers from 2 to 4 and to vary the length (and therefore the hydrophobicity) of the end groups (C4, C12, C18). Two different polar monomers where used as model monomers: Oligo(ethylene glycol)methyl ether acrylate (OEGA) and N,N-Dimethylacrylamide (DMA). Both monomers yield non-ionic hydrophilic polymers. While poly(OEGA) is a comb polymer based on PEG, poly(DMA) exhibits a more compact structure. The amphiphilic star polymers were characterized extensively. The molar masses were determined using GPC in various solvents and the degree of end functionalisation was monitored using 1H NMR and UV/Vis spectroscopy. The polymerization of OEGA shows some of the expected characteristics of reversible deactivation radical polymerization (RDRP). However, chain transfer to monomer and polymer is a prominent side reaction, limiting the use of this monomer for the fabrication of well-defined material. This reaction can be attributed to the structure of the monomer being an oligoether. For all examined polymerizations of DMA with the multifunctional CTAs the molar mass increased linearly with conversion. The molar mass distributions were monomodal and narrow (PDI ≤ 1.2). Expected values were reached for molar masses from 25 to 150 kg/mol and the end group functionality was about 90 % in all cases. While the polymerization of DMA using di- and trifunctional CTAs proceeded to quantitative conversion within 3 h, an initial retardation period of about 60 min was observed for the polymerization using tetrafunctional CTAs. This retardation was attributed to the peculiar molecular structure of these CTAs. Owing to the well-controlled features of the polymerization of DMA using the multifunctional CTAs, this system was used to obtain tapered block copolymers in a one-pot process. These structures were achieved by adding a second monomer to the reaction mixture after the quantitative conversion of DMA. Using ethyl acrylate (EtA), linear amphiphilic symmetrical triblock copolymers were synthesized. The length of the hydrophobic block was tailored by the addition of varying amounts of EtA. With N,N-Diethylacrylamide as a second monomer, linear symmetric triblock copolymers as well as 3-arm star diblock copolymers were obtained that contain a thermosensitve block. Altering the temperature of aqueous solutions of these polymers varies the length of the hydrophobic block in situ. At the TU Berlin, the behavior of the polymers was studied in aqueous solution as well as in microemulsion. The solutions were characterized by small angle neutron scattering (SANS), dynamic light scattering (DLS) and rheology. The end groups of the polymers aggregate, making the polymers efficient thickeners both in aqueous solution and in microemulsion. The structure of the formed network depends on the concentration of the polymer in solution and on the length of the end group. The dynamic properties of the solutions are governed additionally by the number of arms.
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Liu, Chang. « Giant Molecular Shape Amphiphiles Based on Polyhedral Oligomeric Silsesquioxane : Molecular Design and “Click” Synthesis ». University of Akron / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=akron1367933162.
Texte intégral
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Barouti, Ghislaine. « New poly(hydroxyalkanoate)-based copolymers : from synthesis to tunable self-assembled systems ». Thesis, Rennes 1, 2016. http://www.theses.fr/2016REN1S064/document.
Texte intégralRésumé :
Les copolymères à blocs amphiphiles s’auto-assemblent en solution aqueuse grâce à l’association de leurs segments hydrophobes. Les nanoparticules formées à partir de copolymères biocompatibles et biodégradables tels que les poly(hydroxyalkanoates) (PHAs) sont particulièrement attractives pour la conception de systèmes à libération prolongée de principes actifs. La relation entre la composition/structure chimique du copolymère, ses propriétés d’auto-assemblage et ses effets sur les cellules in-vitro doit être étudiée. Des copolymères à blocs poly(acide malique)-b-poly(3-hydroxybutyrate) (PMLA-b-PHB), PMLA-b-PHB-b-PMLA et poly(triméthylène carbonate)-b-poly(acide-malique) (PTMC-b-PMLA) ont été synthétisés par polymérisation par ouverture cycle (ROP) des monomères correspondants, suivie d’une hydrogénolyse. Une gamme de copolymères bien définis, caractérisés par spectroscopie RMN 1H, 13C{1H}, HSQC, HMBC, et DOSY, par analyses SEC, DSC, TGA, et mesure des angles de contact, présentant des balances hydrophile/hydrophobe modulables, a été obtenue grâce au control précis de la fraction hydrophile f (11-82%). Des auto-assemblages modulables ont été formés par nanoprécipitation des copolymères en l’absence d’agent tensio-actif. De larges agrégats ainsi que des micelles cœur-couronne (Rh = 16-335 nm) ont été obtenus en fonction du copolymère utilisé (dibloc vs. tribloc). Des micelles stables pendant 10 jours à 37 °C en solution aqueuse ont été obtenues pour les copolymères avec f allant jusqu’à 50%. Les copolymères PMLA-b-PHB et PTMC-b-PMLA n’ont pas révélé de toxicité aigüe in-vitro. De plus, l’utilisation du PHB a avantageusement permis de diminuer la captation des nano-objets par les macrophages et d’augmenter la captation par les cellules hépatiquesAmphiphilic block copolymers are able to form self-assembled systems in aqueous solution by association of their hydrophobic segments. Nanoparticles formed from biodegradable and biocompatible polymers such as poly(hydroxyalkanoate) copolymers are particularly attractive for drug delivery applications. The relationship between the chemical structure/composition of the macromolecule, its self-assembly properties and its effect on cells in-vitro has to be studied.The synthesis of poly(-malic acid)-b-poly(3-hydroxybutyrate) (PMLA-b-PHB), PMLA-b-PHB-b-PMLA, and poly(trimethylene carbonate)-b-poly(-malic acid) (PTMC-b-PMLA) was established through the ring-opening polymerization (ROP) of the corresponding monomers followed by hydrogenolysis. A range of well-defined copolymers characterized by 1H, 13C{1H}, HSQC, HMBC, DOSY NMR spectroscopy, SEC, DSC, TGA, contact angle analyses, with tunable hydrophilic/hydrophobic balance were thus obtained through the precise control of the hydrophilic weight fraction f (11-82%). Tunable self-assembled systems were obtained by nanoprecipitation of the amphiphilic PHA-based copolymers without the use of a surfactant. Large aggregates and core-shell micelles (Rh = 16-335nm) were obtained depending on the polymer topology. PHB-based copolymers with f up to 50% formed highly stable micelles at 37 °C over a period of 10 days in aqueous solution. PMLA-b-PHB as well as PTMC-b-PMLA copolymers revealed no acute in-vitro cytotoxicity. The use of PHB as hydrophobic segment enabled to minimize the non-specific scavenging by macrophages cells while the cellular uptake by hepatocytes was favored
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Weiß, Jan. « Synthesis and self-assembly of multiple thermoresponsive amphiphilic block copolymers ». Phd thesis, Universität Potsdam, 2011. http://opus.kobv.de/ubp/volltexte/2011/5336/.
Texte intégralRésumé :
In the present thesis, the self-assembly of multi thermoresponsive block copolymers in dilute aqueous solution was investigated by a combination of turbidimetry, dynamic light scattering, TEM measurements, NMR as well as fluorescence spectroscopy. The successive conversion of such block copolymers from a hydrophilic into a hydrophobic state includes intermediate amphiphilic states with a variable hydrophilic-to-lipophilic balance. As a result, the self-organization is not following an all-or-none principle but a multistep aggregation in dilute solution was observed. The synthesis of double thermoresponsive diblock copolymers as well as triple thermoresponsive triblock copolymers was realized using twofold-TMS labeled RAFT agents which provide direct information about the average molar mass as well as residual end group functionality from a routine proton NMR spectrum. First a set of double thermosensitive diblock copolymers poly(N-n-propylacrylamide)-b-poly(N-ethylacrylamide) was synthesized which differed only in the relative size of the two blocks. Depending on the relative block lengths, different aggregation pathways were found. Furthermore, the complementary TMS-labeled end groups served as NMR-probes for the self-assembly of these diblock copolymers in dilute solution. Reversible, temperature sensitive peak splitting of the TMS-signals in NMR spectroscopy was indicative for the formation of mixed star-/flower-like micelles in some cases. Moreover, triple thermoresponsive triblock copolymers from poly(N-n-propylacrylamide) (A), poly(methoxydiethylene glycol acrylate) (B) and poly(N-ethylacrylamide) (C) were obtained from sequential RAFT polymerization in all possible block sequences (ABC, BAC, ACB). Their self-organization behavior in dilute aqueous solution was found to be rather complex and dependent on the positioning of the different blocks within the terpolymers. Especially the localization of the low-LCST block (A) had a large influence on the aggregation behavior. Above the first cloud point, aggregates were only observed when the A block was located at one terminus. Once placed in the middle, unimolecular micelles were observed which showed aggregation only above the second phase transition temperature of the B block. Carrier abilities of such triple thermosensitive triblock copolymers tested in fluorescence spectroscopy, using the solvatochromic dye Nile Red, suggested that the hydrophobic probe is less efficiently incorporated by the polymer with the BAC sequence as compared to ABC or ACB polymers above the first phase transition temperature. In addition, due to the problem of increasing loss of end group functionality during the subsequent polymerization steps, a novel concept for the one-step synthesis of multi thermoresponsive block copolymers was developed. This allowed to synthesize double thermoresponsive di- and triblock copolymers in a single polymerization step. The copolymerization of different N-substituted maleimides with a thermosensitive styrene derivative (4-vinylbenzyl methoxytetrakis(oxyethylene) ether) led to alternating copolymers with variable LCST. Consequently, an excess of this styrene-based monomer allowed the synthesis of double thermoresponsive tapered block copolymers in a single polymerization step.Die Selbstorganisation von mehrfach thermisch schaltbaren Blockcopolymeren in verdünnter wässriger Lösung wurde mittels Trübungsphotometer, dynamischer Lichtstreuung, TEM Messungen, NMR sowie Fluoreszenzspektroskopie untersucht. Die schrittweise Überführung eines hydrophilen in ein hydrophobes Blockcopolymer beinhaltet ein oder mehr amphiphile Zwischenstufen mit einstellbarem hydrophilen zu lipophilen Anteil (HLB). Dies führt dazu, dass die Selbstorganisation solcher Polymere in Lösung nicht nur einem Alles-oder-nichts-Prinzip folgt sondern ein mehrstufiges Aggregationsverhalten beobachtet wird. Die Synthese von doppelt thermisch schaltbaren Diblockcopolymeren und dreifach thermisch schaltbaren Triblockcopolymeren wurde durch sequenzielle RAFT Polymerisation realisiert. Dazu wurden zweifach TMS-markierte RAFT Agentien verwendet, welche die Bestimmung der molaren Masse sowie der verbliebenen Endgruppenfunktionalität direkt aus einem Protonen NMR Spektrum erlauben. Mit diesen RAFT Agentien wurde zunächst eine Serie von doppelt thermisch schaltbaren Diblockcopolymeren aus Poly(N-n-propylacrylamid)-b-Poly(N-ethylacrylamid), welche sich lediglich durch die relativen Blocklängen unterscheiden, hergestellt. In Abhängigkeit von der relativen Blocklänge wurde ein unterschiedliches Aggregationsverhalten der Diblockcopolymere in verdünnter wässriger Lösung beobachtet. Des Weiteren wirken die komplementär TMS-markierten Endgruppen als NMR-Sonden während der schrittweisen Aggregation dieser Polymere. Reversible, temperaturabhängige Peakaufspaltung der TMS-Signale in der NMR Spektroskopie spricht für eine Aggregation in gemischte stern-/blumenartige Mizellen, in denen ein Teil der hydrophoben Endgruppen in den hyrophoben Kern zurückfaltet. Obendrein wurden dreifach thermisch schaltbare Triblockcopolymere aus Poly(N-n-propylacrylamid) (A), Poly(methoxydiethylen glycol acrylat) (B) und Poly(N-ethylacrylamid) (C) in allen möglichen Blocksequenzen (ABC, BAC, ACB) durch schrittweisen Aufbau mittels RAFT Polymerisation erhalten. Das Aggregationsverhalten dieser Polymere in verdünnter wässriger Lösung war relativ komplex und hing stark von der Position der einzelnen Blöcke in den Triblockcopolymeren ab. Besonders die Position des Blocks mit der niedrigsten LCST (A) war ausschlaggebend für die resultierenden Aggregate. So wurde oberhalb der ersten Phasenübergangstemperatur nur Aggregation der Triblockcopolymere beobachtet, wenn der A Block an einem der beiden Enden der Polymere lokalisiert war. Wurde der A Block hingegen in der Mitte der Polymere positioniert, entstanden unimere Mizellen zwischen der ersten und zweiten Phasenübergangstemperatur, welche erst aggregierten, nachdem der zweite Block (B) seinen Phasenübergang durchlief. Die Transportereigenschaften dieser Triblockcopolymere wurden mittels Fluoreszenzspektroskopie getestet. Dazu wurde die Einlagerung eines hydrophoben, solvatochromen Fluoreszenzfarbstoffes, Nilrot, in Abhängigkeit der Temperatur untersucht. Im Gegensatz zu den Polymeren mit der Blocksequenz ABC oder ACB, zeigten die Polymere mit der Sequenz BAC eine verminderte Aufnahmefähigkeit des hydrophoben Farbstoffes oberhalb des ersten Phasenübergangs, was auf die fehlende Aggregation und die damit verbundenen relativ kleinen hydrophoben Domänen der unimolekularen Mizellen zwischen der ersten und zweiten Phasenübergangstemperatur zurückzuführen ist. Aufgrund des zunehmenden Verlustes von funktionellen Endgruppen während der RAFT Synthese von Triblockcopolymeren wurde ein neuartiges Konzept zur Einschrittsynthese von mehrfach schaltbaren Blockcopolymeren entwickelt. Dieses erlaubt die Synthese von mehrfach schaltbaren Diblock- und Triblockcopoylmeren in einem einzelnen Reaktionsschritt. Die Copolymeriation von verschiedenen N-substituierten Maleimiden mit einem thermisch schaltbaren Styrolderivat (4-Vinylbenzylmethoxytetrakis(oxyethylene) ether) ergab alternierende Copolymere mit variabler LCST. Die Verwendung eines Überschusses dieses styrolbasierten Monomers erlaubt ferner die Synthese von Gradientenblockcopolymeren in einem einzelnen Polymerisationsschritt.
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Balster, Russell. « Synthesis and characterisation of initiators and amphiphilic miktoarm star polymers ». Thesis, Durham University, 2016. http://etheses.dur.ac.uk/11638/.
Texte intégralRésumé :
This project involves the development of several novel heterofunctional initiators with a calix[4]arene centre that can facilitate a “core” first method for the synthesis of miktoarm star polymers. Chapter 1 introduces main concepts on calixarenes, single electron transfer living radical polymerisation and the ring opening polymerisation of ε-caprolactone. Chapter 2 describes the synthetic strategy employed for the synthesis of a novel A2B2 heterofunctional initiator that incorporated an alkyl halogen moiety and a primary hydroxyl. p-tert-butylcalix[4]arene was modified via a six step process to introduce the required functionality and was fully characterised at each stage using 1D and 2D NMR spectroscopy, ASAP MS and IR spectroscopy. Chapter 3 describes how the A2B2 heterofunctional initiator was used to synthesise a novel 2-armed PCL polymer centred on a calixarene core. This was further used for copper(0) mediated polymerisation of 2-hydroxyethylacrylate due to the alkyl halide moieties remaining in the calixarene core, leading to the formation of several amphiphilic A2B2 miktoarm star polymers. Both polymers were fully characterised using 1D and 2D NMR spectroscopy, SEC, DSC, TGA and IR spectroscopy. Chapter 4 describes the synthetic strategy employed for the synthesis of a novel A4B4 heterofunctional initiator that incorporated an alkyl halogen moiety and a primary hydroxyl. p-tert-butylcalix[4]arene was modified via a seven step process to introduce the required functionality and was fully characterised at each stage using 1D and 2D NMR spectroscopy, ASAP MS and IR spectroscopy. Chapter 5 describes how the A4B4 heterofunctional initiator was used to synthesise a novel 4-armed star PCL polymer centred on a calixarene core. This was further used for copper(0) mediated polymerisation of 2-hydroxyethylacrylate due to the alkyl halide moieties remaining in the calixarene core, leading to the formation of several amphiphilic A4B4 miktoarm star polymers. Both polymers were fully characterised using 1D and 2D NMR spectroscopy, SEC, DSC, TGA and IR spectroscopy. Chapter 6 described the self-assembly of A2B2 and A4B4 amphiphilic miktoarm star polymers calixarene-A2B2starPCL100PHEAm, 8-10, where m = 75, 100 and 270, respectively and calixarene-A4B4starPCL20PHEAm, 18, 19 and 20 where m = 10, 25 and 48, respectively). The TEM analysis on polymer systems 8 - 10 and 18 - 20, revealed spherical micelles, with the size of the micelle decreasing as the proportion of hydrophilic PHEA increased. The CMC determinations for polymers 8 – 10 revealed that the length of the hydrophilic chain does not appear to have a significant effect on the CMC. For polymers 18 – 20, the CMC increases as the length of the hydrophilic polymer chain increases. For both polymeric systems 8 - 10 and 18 - 20, low CMC values were calculated. This work showed the system has a potential in medical applications, with their ability to form micelles in the range of 5 to 110 nm and have the ability to encapsulate highly hydrophobic material, such as the fluorescent probe pyrene. In chapter 7 general conclusions and future perspectives for the work are discussed.
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Carmichael-Baranauskas, Anita Yvonne. « Synthesis of Amphiphilic Block Copolymers for Use in Biomedical Applications ». Thesis, Virginia Tech, 2010. http://hdl.handle.net/10919/31737.
Texte intégralRésumé :
The research presented in this thesis focuses on the synthesis of three amphiphilic block copolymer systems containing poly(ethylene oxide) (PEO) blocks. The polymer systems were developed for use in biomedical applications. The first of these is a series of poly(ethylene oxide-b¬-oxazoline) (PEO-b-POX) diblock copolymers for use in the progress towards novel non-viral gene transfer vectors. Poly(ethylene oxide-b¬-2-ethyl-2-oxazoline) (PEO-b-PEOX) and poly(ethylene oxide-b¬-2-methyl-2-oxazoline) (PEO-b-PMOX) were investigated. The PEOX block was hydrolyzed with acid to form linear polyethylenimine (L-PEI). The polycation L-PEI is well known for its DNA binding efficiency but the water solubility of the resulting DNA/polymer complex is limited. Addition of a PEO block is directed towards the formation of a water dispersible DNA/copolymer complex. Dynamic light scattering of the PEO-b-PEOX and PEO-b-PEI block copolymers indicated that both systems existed as single chains in aqueous solution at pH 7.
PEO copolymers also play a significant role in the formation of magnetic magnetite nanoparticles, which are dispersible in water at biological pH (pH =7). There is significant interest in the design of magnetic nanoparticle fluids for biomedical applications including magnetic field-directed drug delivery, magnetic cell separations, and blood purification. For use in vivo, the magnetite nanoparticles must be coated with biocompatible materials. Such polymers render the nanoparticles dispersible in water. Harris1 et al. synthesized PEO based, polyurethane triblocks with pendant carboxylic acid groups for use in formation of stable aqueous magnetic fluids.
Building from this work, two polyurethane and polyurethaneurea systems were synthesized with 1300 g/mol PEOX and 2500 g/mol and PEOX2070 g/mol poly(ethylene oxide-co-propylene oxide) tailblocks, respectively. The PEO/PPO random copolymer contained about 25 weight percent PPO, and this disrupted the capacity of the PEO to crystallize. The PEOX based urethane triblocks were synthesized through reacting the tailblocks with the monomers for the center block whereas the PEO/PPO based polyurethaneurea was synthesized through forming the central urethane block with pendant acid groups first and then terminating the copolymer with the monofunctional copolymer. Terminal amine groups on the PEO/PPO tailblock afforded a triblock linked with two urea groups. The new polyurethanes with the PEOX tailblocks and the new polyurethaneurea with the PEO/PPO tailblocks could be utilized to efficiently stabilize magnetite nanoparticles in water.Master of Science
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Bansal, Kuldeep Kumar. « Novel amphiphilic polymers from renewable feedstock : synthesis, characterisation and applications ». Thesis, University of Nottingham, 2015. http://eprints.nottingham.ac.uk/30858/.
Texte intégralRésumé :
Development of novel biodegradable polymers from renewable resources has attracted attention due to the limitations associated with polymers obtained from petroleum resources. The objective of the work presented in this thesis was to develop various novel biodegradable amphiphilic block copolymers from commercially available sustainable feedstocks for drug delivery applications. Synthesis was performed using a reported method under mild reaction conditions. Renewable δ-decalactone was chosen as a key monomer to synthesise novel amphiphilic block copolymers via ROP using PEG as initiator. A diblock (i.e. mPEG-b-PDL) and a triblock (i.e. PDL-b-PEG-b-PDL) copolymer of poly(decalactone) (PDL) was synthesised and purified successfully. Additionally, a novel triblock copolymer (i.e. mPEG-b-PDL-b-PPDL) was synthesised using ω-pentadecalactone as monomer and mPEG-b-PDL as initiator via ROP to generate a copolymer with different physical properties. Further, a di-block copolymer of ε-caprolactone (i.e. mPEG-b-PCL) was synthesised for comparative studies with novel block copolymers. Micelles of synthesised block copolymers were fabricated using a reported nanoprecipitation method. Micelles fabricated from these novel block copolymers were of sizes <200nm and possessed low critical micelle concentration (CMC) values. Curcumin and Amphotericin B were successfully encapsulated in the novel block copolymer micelles via nanoprecipitation method. The results obtained from curcumin loading and release studies suggested that these novel PDL block copolymers could perform in similar fashion when compared with poly(caprolactone) (PCL) block copolymer micelles. However, in subsequent study micelle of mPEG-b-PDL gave high loading content compared to mPEG-b-PCL micelles when amphotericin B was used as a drug. Further, a preliminary in vitro degradation study of mPEG-b-PDL micelles was performed and the results proposed that the ester linkage of PDL chain were susceptible to hydrolytic degradation in physiological condition. Additionally, in vitro cytotoxicity studies performed on HCT-116 human colon cancer cells revealed that the novel mPEG-b-PDL micelles have similar toxicity profiles when compared to the well-established mPEG-b-PCL micelles. Ligand mediated targeting efficiency of novel diblock copolymer micelles was also studied for potential future applications in cancer therapy. Amphiphilic block copolymers using PEG and PDL were synthesised via click chemistry to generate functionalised block copolymers. Folic acid and rhodamine B were used as targeting ligand and tracker dye respectively. Mixed micelles fabricated from functionalised block copolymers (i.e. FA-PEG-b-PDL, RhB-PEG-b-PDL and mPEG-b-PDL) were tested on folate receptor positive (MCF-7 FR+ve) and folate receptor negative (A549 FR-ve) human cancer cell lines for receptor mediated endocytosis. The acquired confocal images demonstrated the nonspecific uptake of the PEG-b-PDL micelles formulations (targeted and non-targeted) in both cell lines selected in current study. The results obtained from this thesis study suggested that the synthesised novel PDL block copolymer micelles have potential to act as a novel drug delivery system. However, further studies have been proposed to explore the possible applications of these renewable block copolymers.
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AMABILI, PAOLO. « α-Hydrazido acids for the synthesis of bioactive amphiphilic compounds ». Doctoral thesis, Università Politecnica delle Marche, 2017. http://hdl.handle.net/11566/245568.
Texte intégralRésumé :
Con lo scopo di ottenere nuovi foldameri (oligomeri con un folding prevedibile), sono stati sintetizzati nuovi mimici di β-peptidi caratterizzati dalla formale sostituzione Cβ→Nβ(acile) modificando β-amminoacidi a base pirrolidin-2-onica, utilizzati precedentemente nei nostri laboratori per la preparazione di esameri. Sono stati quindi sintetizzati nuovi oligomeri di α-idrazidoacidi conformazionalmente costretti in un anello imidazolidinonico (AOPIC) che sono stati poi analizzati usando tecniche spettroscopiche (NMR e CD) e computazionali (MD). Lo studio computazionale, oltre a fornire la prova teorica della presenza di un’elica-8 come unica struttura stabile, ha evidenziato anche la forte tendenza alla formazione di una sequenza “hydrazido-turn”, in cui cicli addizionali a 5-termini sono presenti contemporaneamente ai cicli ad 8-termini.
Ci siamo poi dedicati alla ricerca di nuovi analoghi dei precedenti oligomeri che non fossero però chirali e conformazionalmente costretti, quindi più facili ed economici da sintetizzare, con lo scopo di ottenere la stessa struttura secondaria ma con minore sforzo sintetico e una migliore versatilità nella sostituzione delle catene laterali. Infatti, un’appropriata disposizione delle catene laterali, può essere un ottimo punto di partenza per la realizzazione di foldameri anfifilici da testare come antibiotici. Sono infatti molte le problematiche associate all’utilizzo di farmaci a base peptidica e, a causa del rapido e preoccupante sviluppo di fenomeni di resistenza agli antibiotici, i mimici sintetici degli AMPs (SMAMPs) stanno ricevendo molta attenzione come nuovi potenziali farmaci. A questo proposito, abbiamo sviluppato la sintesi di derivati anfifilici a base di α-idrazidoacidi anfifilici che possono rappresentare una nuova classe di piccoli mimici sintetici di peptidi antimicrobici (SMMAMPs). Da primi esperimenti di valutazione dell’attività antimicrobica mediante la valutazione della concentrazione inibente minima (MIC), i nostri composti sono risultati essere promettenti agenti antimicrobici, utili per applicazioni biologiche eventualmente a seguito di un’ottimizzazione strutturale per migliorarne le proprietà farmacologiche.Novel mimics of β-peptides based on the formal substitution Cβ→Nβ(acyl) were synthesized with the aim to obtain new foldamers (oligomers with a predictable folding). Thus, we modified pirrolidin-2-one tethered β-amino acids, previously used in our laboratory to prepare hexamers, devised a new imidazolidinone-tethered α-hydrazido acid (AOPIC) suitable to give oligomers that were analysed using spectroscopic (NMR and CD) and computational (MD) techniques. The computational analysis, besides furnishing the theoretical proof of the 8-helix as the only stable structure, strongly evidenced a “hydrazido-turn” sequence, where additional 5-membered H-bonded cycles were enclosed within the 8-membered ones. In the search for simpler and cheaper analogues, we directed our attention towards analogues of the previously employed oligomers, where constrictions and chirality were missing, with the aim to obtain a secondary structure with minor synthetic effort and increased versatility in side chains substitution. In fact, an appropriate disposition of side chains could be a good starting point for the synthesis of amphiphilic foldamers to be tested as antibacterial agents. Since many difficulties are connected with the use of peptide drugs, synthetic mimics of AMPs (SMAMPs) are receiving ever more interest and importance as new drug candidates, owing to the rapid and widespread development of antibiotic resistances. Thus, within this topic, we carried out the synthesis of amphiphilic α-hydrazido acid derivatives, which could be novel lead compounds for developing a new class of SMMAMPs. The Minimum Inhibitory Concentration (MIC) was evaluated for a few properly derivatized α-hydrazido acid monomers, and the preliminary results showed a promising antimicrobial activity suitable for biological applications, eventually leading to a structure optimization for improvement of the pharmacological properties.
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Jiang, Jing. « Giant Shape Amphiphiles Based on Polyoxometalates (POMs)-Polyhedra Oligomeric Silsesquioxane (POSS) Hybrids : Synthesis and Characterization ». University of Akron / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=akron1366811690.
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Yue, Kan. « Design, Synthesis and Self-Assembly of Shape Amphiphiles Based on Polyhedral Oligomeric Silsesquioxane-Polymer Conjugates ». University of Akron / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=akron1384817970.
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Assem, Yasser [Verfasser]. « Biodegradable Amphiphilic Block Copolymers : Synthesis, Characterization and Properties Evaluation / Yasser Assem ». Marburg : Philipps-Universität Marburg, 2011. http://d-nb.info/1016532830/34.
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KIM, NAMJIN. « Synthesis and Characterization of Amphiphilic Fe4S4-Core Dendrimers as Protein Models ». NCSU, 2006. http://www.lib.ncsu.edu/theses/available/etd-07052006-133137/.
Texte intégralRésumé :
The ultimate goal of this research is to clarify the structural effects on the rate and driving force for electron transfer in amphiphilic iron-sulfur core dendrimers, which can eventually be used as protein models. These dendrimers were synthesized by ligand exchange reactions, including the synthesis of dendrons via a modular synthesis approach. Their structure-property relationships were then investigated using electrochemical methods. Three different routes were used to synthesize thiol dendrons with both cationic and anionic peripheral units. The first utilized the disulfide linkage as a focal and protecting group. However, due to difficulties associated with generating free thiol from the disulfide, only partially-substituted dendrimers were prepared in ligand exchange reaction. Similar problems were encountered with the next two methods, which used thiocarbamate and trityl protecting groups, respectively. First generation dendrimers were successfully prepared and characterized using the thiocarbamate group; however, low thiol concentration resulted in only partially substituted dendrimers for the second generation. All synthetic attempts using the trityl focal group resulted in only partial substitution. Because the concentration of free thiol was the factor limiting the synthesis of these amphiphilic iron-sulfur core dendrimers, a protocol was established to measure the thiol concentration using Ellman?s reagent test. However, this proved to be inaccurate due to oxygen dissolved in solution and then re-oxidized thiols during the course of the test. The electrochemical properties of these cationic and anionic dendrimers were measured and compared to G1-flexible dendrimer previously studied by the Gorman Group. G1-cationic dendrimer exhibited more effective attenuation of the electron transfer rate than G1-flexible dendrimer. This was attributed to the difference of molecular weight in both dendrimers. The redox potential in the cationic dendrimer was shifted more positively by about 100 mV due to polar microenvironment around the iron-sulfur core. Cyclic voltammogram of G1-anionic dendrimer exhibited an unexpected peak so other electrochemical properties could not be measured. Only an approximate redox potential was obtained and exhibited a positive shift by about 60 mV compared to G1-flexible dendrimer.
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Grainger, Andrew McAngus. « Synthesis and characterisation of new amphiphilic molecules for non-linear optics ». Thesis, Durham University, 1991. http://etheses.dur.ac.uk/6028/.
Texte intégralRésumé :
New amphiphilic donor-n-acceptor chromophores have been prepared and characterised. The LB film forming and second order non-Linear optical properties of these amphiphiles have been Investigated. New electron acceptors have been prepared using the reagent 2-chlorobenzylthiocyanate. The scope of the reagent for the preparation of TCNQ derivatives has been Investigated. New DCNQI and N, 7, 7-tricyanoquinomethaneimines have been prepared and characterised. Attempts to prepare novel donor-n-acceptor compounds from these electron acceptors were unsuccessful. The synthesis, LB deposition and CT spectra of R-Q3CNQ (R = C(_6)H(_13) to C(_20)H(_41) and four substituted analogues have been studied. The second harmonic Intensity from Z-type films of C(_16)H(_33)-Q3CNQ was found to Increase quadratically with the number of LB layers. Zwitterionic amphiphiles with benzothiazolium and thiazolium donor groups (C(_16)H(_33)-BT3CNQ and C(_6)H(_13)-T3CNQ have been prepared and characterised. No SHG was observed from films of C(_4),H(_13)-T3CNQ. Films of C(_16)H(_33)-BT3CNQ are Y-type and optical SHG has been observed from odd numbers of layers. A variation In SH Intensity with the number of laser pulses has been observed. The synthesis, CT spectra and LB deposition of some new hemicyanine derivatives have been studied. The LB films have a Y-type structure and SHG was observed from films with odd numbers of layers. Novel push-pull chromophores with the 1,3-dithiole donor group have been prepared and characterised. The LB deposition, CT spectra and NLO properties have been studied.