Dans cette thèse, la fonctionnalisation de surface de nanocristaux de cellulose (NCC) par estérification et polymérisation ATRP a été envisagée, dans le but de développer de nouveaux matériaux avancés. Une méthode pratique permettant de caractériser les polymères greffés en surface des NCC a d’abords été développée, à partir des analyses DLS, DSC et TGA. L’efficacité des méthodes SI-ATRP et SI-ARGET ATRP pour initier le greffage de polystyrène (PS) ou poly(4-vinylpyridine) (P4VP) à la surface des NCC a ensuite été comparée. Les nano-hybrides P4VP-g-NCC pH-responsifs, ont alors été utilisés pour stabiliser des nanoparticules d’or (AuNPs), dans le but de produire des catalyseurs recyclables. L’activité catalytique des matériaux Au@P4VP-g-CNC obtenus – testée avec la réduction du 4-nitrophenol – a été améliorée de manière significative par rapport aux AuNPs seuls. Des polymères UV-responsifs de poly(cinnamoyloxy ethyl methacrylate) (PCEM) ont également été greffés à la surface des NCC, pour produire des particules UV-absorbantes. Les nano-hybrides PCEM-g-CNC obtenus se sont avérés efficaces comme stabilisants UV/thermiques et agents de renforts dans les films PVC. Finalement, une méthode facile pour préparer des colloidosomes à partir d’émulsions de Pickering inverses stabilisées par des NCC modifiés par des groupes cinnamates a été proposée. Des colloidosomes aux parois robustes et permettant un relargage lent de molécules encapsulées comme la rhodamine B ou l’acide désoxyribonucléique fluorescent ont alors été obtenus. / In this thesis, the surface functionalization of cellulose nanocrystals (CNC) by esterification and ATRP reactions was envisaged, with the objective to develop novel advanced materials. A convenient method to characterize the polymers grafted on CNC by Si-ATRP has been first developed, based on DLS, DSC and TGA analyses. The efficiency of the SI-ATRP and SI-ARGET ATRP methods to initiate the grating of polystyrene (PS) or poly(4-vinylpyridine) (P4VP) at the CNC surface were then compared. The pH-responsive P4VP-g-CNC nano-hybrids were subsequently utilized to stabilize gold nanoparticles (AuNPs), in view of producing recyclable catalysts. The catalytic activity of the Au@P4VP-g-CNC material – tested with the reduction of 4-nitrophenol – was significantly improved compared with single AuNPs. UV-responsive poly(cinnamoyloxy ethyl methacrylate) (PCEM) polymers were also grafted on CNC, to produce particles with UV absorbing properties. The PCEM-g-CNC nano-hybrids obtained turned out to be efficient UV/thermal stabilizers and reinforcing agents in PVC films. Finally, a facile method to prepare colloidosomes from w/o inverse Pickering emulsions stabilized by cinnamate-modified CNC was proposed. Colloidosomes with robust shells and allowing the slow release of encapsulated molecules such as rhodamine B or fluorescent deoxyribonucleic acid were then obtained.

This thesis reports the preparation of novel multi-responsive and multiply stimulable triblock copolymers. The resultant polymers were used to coat cotton fabrics and glass to render them amphiphobic. Further, a method was developed for the preparation of poly(ethylene glycol)-block-poly(hydroxyethyl methacrylate) (PEG-b-PHEMA) via anionic polymerization. The multi-responsive copolymer refers to poly(ethylene glycol)-orthonitrobenzyl-poly[2-(perfluorooctyl)ethyl methacrylate)-block-poly(2-cinnamoloxyethyl methacrylate) (PEG-ONB-PFOEMA-b-PCEMA, or P1). P1 was synthesized via atom transfer radical polymerization (ATRP) of FOEMA and a precursory monomer of CEMA using a PEG macroinitiator. The copolymer was multi-responsive or dual light-responsive because the ONB junction cleaves and PCEMA block becomes crosslinked upon UV photolysis. The multiply stimulable copolymers are a series of poly(ethylene glycol)-disulfide-poly[2-(perfluorooctyl)ethyl methacrylate)-block-poly(2-cinnamoloxyethyl methacrylate) (PEG-S2-PFOEMA-b-PCEMA) copolymers. These polymers were synthesized by the end-coupling Py-S2-PFOEMA-b-PHEMA and PEG-SH, and subsequent cinnamation of the PHEMA block. These polymers are multiply stimulable because the S2 junction and PCEMA block respond to different stimulations, such as reducing agents and light, respectively. These synthetic strategies will advance the field of stimuli-responsive polymers by providing novel functional polymers for the generation of durable self-cleaning surfaces. The above polymers form micelles in water or water/organic solvent mixtures because of the water-soluble PEG blocks. Polymer-coated cotton was obtained by immersing cotton in micellar copolymer solutions before subsequent drying and annealing treatment. Upon photolysis, the PEG block was cleaved and the PCEMA anchoring layer became crosslinked. Such a crosslinked and stable layer was rendered amphiphobic because of the exposed PFOEMA block. A similar coating can be obtained from P2. Two types of stimulations including photolysis and reduction treatment need to be applied to yield amphiphobic textiles. This coating strategy is unique and environmentally friendly because the water- and oil-repellent coatings were prepared from an aqueous solution for the first time. In a further study, a novel and long-sought method was developed for the anionic polymerization of PEG-b-PHEMA. A PEG-DPE macroinitiator was synthesized and subsequently converted into an active initiator by reaction with sec-butyl lithium. Consequently, the active initiator underwent polymerization with HEMA-TMS to yield PEG-b-P(HEMA-TMS). Upon post-polymerization modification, PEG-b-PHEMA was obtained with a low polydispersity of 1.08. / Thesis (Ph.D, Chemistry) -- Queen's University, 2013-04-29 12:25:54.593

O objetivo do presente estudo visa o desenvolvimento de um copolímero em bloco constituído por metacrilato de metila (MMA) e de dimetilaminoetila (DMAEMA), tendo como macroniciador poli--caprolactona dibromada (Br-PCL-Br), e que permite formar nanocápsulas sensíveis ao pH, contendo ou não o tripeptídeo leucina-ácido aspártico-valina (LDV) na superfície para a vetorização ativa de anti-neoplásicos. Os métodos envolveram diferentes abordagens sintéticas testadas, sendo que a técnica de transferência eletrônica por regeneração de ativadores (ATRP-ARGET) permitiu obter o copolímero PCL-P(MMA-DMAEMA)2 de forma mais prática e com rendimentos entre 30 e 70%. Por fim, o tripeptídeo LDV foi conjugado ao copolímero por meio do ligante metacrilato de 2-isocianato de etila (IEM). Um método por cromatografia líquida de alta eficiência (CLAE) foi adaptado para a quantificação da doxorrubicina e as nanopartículas foram preparadas por nanoprecipitação e avaliadas quanto à capacidade de expandir em diferentes pHs e citotoxicidade em células de câncer de mama. Os resultados do copolímero demonstram, por análises de infravermelho (IR-FT), sinais característicos em 2900 cm-1 e 1720 cm-1 correspondentes às funções –CH e –C=O. A análise de ressonância magnética nuclear de hidrogênio (RMN 1H) mostra a caracterização das cadeias hidrocarbônicas do copolímero, sendo que os deslocamentos químicos em 2,8 ppm e 3,8 ppm correspondem aos sinais dos grupamentos –CH2-N do DMAEMA e -OCH3 do MMA. As nanocápsulas preparadas a partir do copolímero expandiram de diâmetro quando expostas à pH ácido. Uma vez que o PMMA foi identificado como componente mais citotóxico, o copolímero foi otimizado por meio da redução da quantia de MMA. A quantificação da doxorrubicina encapsulada nas nanopartículas preparadas a partir dos copolímeros não otimizado (ARGET-A) e otimizado (ARGETB) foi de 61,42% e 64,88%, respectivamente. No estudo de citotoxicidade, as nanopartículas preparadas a partir do copolímero ARGET-B apresentaram-se eficazes no controle da proliferação celular de MCF-7. Conclui-se que o método de síntese ATRP-ARGET-B foi o mais apropriado para a produção do copolímero empregado no desenvolvimento de nanopartículas pH responsivas eficazes no 6 controle da proliferação de células tumorais. Ainda, existe a possibilidade do emprego do copolímero contendo o tripeptídeo LDV para alcançar uma vetorização ativa em células de câncer por meio da interação com integrinas específicas. Entretanto, até o presente, não foi realizada a avaliação das nanopartículas contendo LDV. / The objective of the present study looks for the development of a block copolymer constituted by methyl methacrylate (MMA) and dimethylaminoethyl methacrylate (DMAEMA), having poly--caprolactone dibromated (Br-PCL-Br) as a macroinitiator and, that could form pH sensible nanocapsules with or without the tripeptide leucineaspartic acid-valine (LDV) in its surface for active vectorization of anti-neoplasics. The methods employed different synthetic approaches tested, being that the activator regenerated by eletron transfer technique (ATRP-ARGET) allowed to obtain the copolymer PCL-P(MMA-DMAEMA)2 in a practicle way and with incomes between 30 and 70%. Finally, the tripeptide LDV was linked to the copolymer through the 2- isocyanatoethyl methacrylate (IEM). A high performance liquid chromatography method (HPLC) was adapted to doxorubicin quantification and, the nanopartircles were prepared by nanoprecipitation and evaluated conserning its ability to expand in different environments and citotoxycity in mammary cancer cells. The results from the copolymer demonstrated, by infrared (FT-IR), characteristic signals of 2900 cm-1 and 1720 cm-1 from the functions –CH and –C=O. And hydrogen nuclear magnetic resonance (RMN 1H) analysis allowed the characterization of the hydrogen-carbonic chains of the copolymer, being that the chemical displacement in 2,8 ppm and 3,8 ppm corresponds to the signals of the groups –CH2-N from DMAEMA and –O-CH3 from MMA. The nanocapsules prepared from the copolymer expanded its diameter when exposed to acidic pH. Once PMMA was identified as the most toxic component the copolymer was optimized by the reduction of MMA amount. Doxorubicin quantification in the nanocapsules prepared with the copolymers not optimized (ARGET-A) and optimized (ARGET-B) was 61,42% and 64,88%, respectively. In the cytotoxicity study, the nanocapsules prepared from copolymer ARGET-B showed to be efficient to control the cellular proliferation of MCF-7. It can be concluded that the ATRP-ARGET-B method was the more appropriate one for the copolymer production, which was employed in nanocapsules pH responsive effective to control 8 tumor proliferation. Besides, there is the possibility to use the copolymer functionalized with LDV to achieve an active delivery to cancer cells by it interaction with specific integrins. However, till the present, it was not realized the evaluation of the nanocapsules with LDV.

The use of living radical polymerization methods has shown significant potential to control grafting of polymers from inert polymeric substrates. The objective of this thesis is to create advanced substrates for use in combinatorial chemistry applications through the use of g-radiation as a radical source, and the use of RAFT, ATRP and RATRP living radical techniques to control grafting polymerization. The substrates grafted were polypropylene SynPhase lanterns from Mimotopes and are intended to be used as supports for combinatorial chemistry. ATRP was used to graft polymers to SynPhase lanterns using a technique where the lantern was functionalized by exposing the lanterns to gamma-radiation from a 60Co radiation source in the presence of carbon tetra-bromide, producing short chain polystyrene tethered bromine atoms, and also with CBr4 directly functionalizing the surface. Styrene was then grafted off these lanterns using ATRP. MMA was graft to the surface of SynPhase lanterns, using g-radiation initiated RATRP at room temperature. It was found that the addition of the thermal initiator, AIBN, successfully increased the concentration of radicals to a level where we could achieve proper control of the polymerization. RAFT was used to successfully control the grafting of styrene, acrylic acid and N,N???-dimethylacrylamide to polypropylene SynPhase Lanterns via a -initiated RAFT agent mediated free radical polymerization process using cumyl phenyldithioacetate and cumyl dithiobenzoate RAFT agents. Amphiphilic brush copolymers were produced with a novel combined RAFT and ATRP system. Polystyrene-co-poly(vinylbenzyl chloride) created using gamma-radiation and controlled with the RAFT agent PEPDA was used as a backbone. The VBC moieties were then used as initiator sites for the ATRP grafting of t-BA to give a P(t-BA) brush that was then hydrolyzed to produce a PAA brush polymer. FMOC loading tests were conducted on all these lanterns to assess their effectiveness as combinatorial chemistry supports. It was found that the loading could be controlled by adjusting the graft ratio of the lanterns and had a comparable loading to those commercially produced by Mimotopes.

The use of living radical polymerization methods has shown significant potential to control grafting of polymers from inert polymeric substrates. The objective of this thesis is to create advanced substrates for use in combinatorial chemistry applications through the use of g-radiation as a radical source, and the use of RAFT, ATRP and RATRP living radical techniques to control grafting polymerization. The substrates grafted were polypropylene SynPhase lanterns from Mimotopes and are intended to be used as supports for combinatorial chemistry. ATRP was used to graft polymers to SynPhase lanterns using a technique where the lantern was functionalized by exposing the lanterns to gamma-radiation from a 60Co radiation source in the presence of carbon tetra-bromide, producing short chain polystyrene tethered bromine atoms, and also with CBr4 directly functionalizing the surface. Styrene was then grafted off these lanterns using ATRP. MMA was graft to the surface of SynPhase lanterns, using g-radiation initiated RATRP at room temperature. It was found that the addition of the thermal initiator, AIBN, successfully increased the concentration of radicals to a level where we could achieve proper control of the polymerization. RAFT was used to successfully control the grafting of styrene, acrylic acid and N,N???-dimethylacrylamide to polypropylene SynPhase Lanterns via a -initiated RAFT agent mediated free radical polymerization process using cumyl phenyldithioacetate and cumyl dithiobenzoate RAFT agents. Amphiphilic brush copolymers were produced with a novel combined RAFT and ATRP system. Polystyrene-co-poly(vinylbenzyl chloride) created using gamma-radiation and controlled with the RAFT agent PEPDA was used as a backbone. The VBC moieties were then used as initiator sites for the ATRP grafting of t-BA to give a P(t-BA) brush that was then hydrolyzed to produce a PAA brush polymer. FMOC loading tests were conducted on all these lanterns to assess their effectiveness as combinatorial chemistry supports. It was found that the loading could be controlled by adjusting the graft ratio of the lanterns and had a comparable loading to those commercially produced by Mimotopes.

The use of living radical polymerization methods has shown significant potential to control grafting of polymers from inert polymeric substrates. The objective of this thesis is to create advanced substrates for use in combinatorial chemistry applications through the use of g-radiation as a radical source, and the use of RAFT, ATRP and RATRP living radical techniques to control grafting polymerization. The substrates grafted were polypropylene SynPhase lanterns from Mimotopes and are intended to be used as supports for combinatorial chemistry. ATRP was used to graft polymers to SynPhase lanterns using a technique where the lantern was functionalized by exposing the lanterns to gamma-radiation from a 60Co radiation source in the presence of carbon tetra-bromide, producing short chain polystyrene tethered bromine atoms, and also with CBr4 directly functionalizing the surface. Styrene was then grafted off these lanterns using ATRP. MMA was graft to the surface of SynPhase lanterns, using g-radiation initiated RATRP at room temperature. It was found that the addition of the thermal initiator, AIBN, successfully increased the concentration of radicals to a level where we could achieve proper control of the polymerization. RAFT was used to successfully control the grafting of styrene, acrylic acid and N,N???-dimethylacrylamide to polypropylene SynPhase Lanterns via a -initiated RAFT agent mediated free radical polymerization process using cumyl phenyldithioacetate and cumyl dithiobenzoate RAFT agents. Amphiphilic brush copolymers were produced with a novel combined RAFT and ATRP system. Polystyrene-co-poly(vinylbenzyl chloride) created using gamma-radiation and controlled with the RAFT agent PEPDA was used as a backbone. The VBC moieties were then used as initiator sites for the ATRP grafting of t-BA to give a P(t-BA) brush that was then hydrolyzed to produce a PAA brush polymer. FMOC loading tests were conducted on all these lanterns to assess their effectiveness as combinatorial chemistry supports. It was found that the loading could be controlled by adjusting the graft ratio of the lanterns and had a comparable loading to those commercially produced by Mimotopes.

Atom transfer radical polymerisation (ATRP) technique was used to synthesize poly(methacrylic acid-block-methyl methacrylate) (P(MAA₁₀₂-b-MMA₁₀)) copolymer in order to study the aggregation behavior in aqueous solution over the course of neutralization. A combination of static and dynamic light scattering (SLS, DLS) and potentiometric titration techniques were used to investigate the size and shape of the micelle at various degrees of neutralization. The hydrodynamic radius (Rh) determined from dynamic light scattering increases from ~26nm (for unneutralized) to ~42nm (for completely neutralized sample). Both potentiometric and laser light scattering studies indicate the formation of a core shell micelle. The weighted average molecular weights of the polymer and micelle are 1.18x10⁴ and 2.25 x 10⁵ g/mol respectively, which suggests that the aggregation number of the micelle is ~20. / Singapore-MIT Alliance (SMA)

Di-block copolymer of poly[methacrylic acid-block-2-(diethylamino)ethyl methacrylate] [P(MAA-b-DEA)] with narrow molecular weight distribution was synthesized using the atom transfer radical polymerization (ATRP) technique. The micellization behavior of the P(MAA-b-DEA) copolymer in aqueous solution at room temperature and different pH values were examined by potentiometric and conductivity titration, UV-Visible spectrophotometry, ¹H-NMR, static and dynamic laser light scattering. At low pH (< 4.2), core-shell micelles were formed with MAA core and protonated DEA shell. At moderate pH values, the polymer precipitated from water and formed a cloudy solution, where the polymer chains aggregated into larger particles resembling that of a hard sphere induced by electrostatic interactions. At high pH (> 9.5), core-shell like micelles consisting of hydrophobic DEA core and ionized MAA shell were re-established. / Singapore-MIT Alliance (SMA)

We present a systematic methodology to functionalize magnetic nanoparticles through surface-initiated atom-transfer radical polymerization (ATRP). The magnetite nanoparticles are prepared according to the method proposed by Sun et al. (2004), which leads to a monodisperse population of ~ 6 nm particles stabilized by oleic acid. The functionalization of the nanoparticles has been performed by transforming particles into macro-initiators for the ATRP, and to achieve this two different routes have been explored. The first one is the ligand-exchange method, which consists of replacing some oleic acid molecules adsorbed on the particle surface with molecules that act as an initiator for ATRP. The second method consists in using the addition reaction of bromine to the oleic acid double bond, which turns the oleic acid itself into an initiator for the ATRP. We have then grown polymer brushes of a variety of acrylic polymers on the particles, including polyisopropylacrylamide and polyacrylic acid. The nanoparticles so functionalized are water soluble and show responsive behavior: either temperature responsive behavior when polyisopropylacrylamide is grown from the surface or PH responsive in the case of polyacrylic acid. This methodology has potential applications in the control of clustering of magnetic nanoparticles. / Singapore-MIT Alliance (SMA)

Polycationic nanoparticles were synthesized with an activators regenerated by electron transfer for atom transfer radical polymerization-based (ARGET ATRP-based) emulsion in water method and investigated for their utility as biomaterials for drug delivery. The polycationic nanoparticles were composed of 2-(diethylamino)ethyl methacrylate (DEAEMA) for pH-responsiveness, poly(ethylene glycol) methyl ether methacrylate (PEGMA) for improved biocompatibility, tert-butyl methacrylate (tBMA) to impart hydrophobicity, and a tetraethylene glycol dimethacrylate (TEGDMA) cross-linking agent for enhanced colloidal stability. Dynamic light scattering demonstrated pH-responsive swelling, and cell-based assays demonstrated pH-dependent membrane disruption. The polycationic nanoparticles demonstrated low toxicity to cells. The polycationic nanoparticles were evaluated for use as drug delivery biomaterials by investigating the interactions with the drug and cells. Delivery remains a major challenge for translating small interfering RNA (siRNA) to the clinic, and overcoming the delivery challenge requires effective siRNA delivery vehicles. The polycationic nanoparticles demonstrated efficient siRNA loading. Evidence of siRNA-induced knockdown in cells was observed following transfection with the polycationic nanoparticle/siRNA complexes. Imaging techniques confirmed enhanced siRNA internalization using the polycationic nanoparticle/siRNA complexes compared to naked siRNA. An array of polycationic nanoparticles synthesized using ARGET ATRP or UV-initiated polymerization methods was characterized to examine the effect of polymerization method on material properties and the connection to molecular structure. An improved understanding of molecular structure, and its connection to polymerization method and material characteristics, may aid the design of advanced materials. The ARGET ATRP polycationic nanoparticles demonstrated increased nanoscale homogeneity compared to the UV-initiated polymerization polycationic nanoparticles; increased nanoscale heterogeneity in the UV-initiated polymerization polycationic nanoparticles was associated with broader transitions. The polycationic nanoparticles promoted cellular uptake of siRNA and induced knockdown, thus demonstrating potential as siRNA delivery vehicles. The ARGET ATRP method provides an alternative route to creating polycationic nanoparticles with improved nanoscale homogeneity. / text