Propargyl or methacrylate end-functionalized polylactides are important intermediates in polymer synthesis towards their application in the biomedical field. Through these intermediates hydrophobic polylactides are post polymerized with hydrophilic monomers or coupled with preformed hydrophilic homopolymers to obtain amphiphilic copolymers that possess qualities that they wouldn’t otherwise have. These systems show a unique property: self-assembly into micellar structures that can be utilized in drug delivery applications. Polylactides (PLA) offer biocompatibility and biodegradability to its non-toxic and non-carcinogenic metabolites for these biomedical applications. Understanding the synthesis, modification and processing of PLA in this light is a cornerstone for successful development of new PLA-based biomaterials. This thesis gives an overview of polylactide end functionalization, their post polymerization and documents attempts to synthesize different end functional polylactides. The experimental part of this thesis focuses on the synthesis of propargyl and methacrylate end-functionalized PLA:s with different chain lengths and their characterization with the appropriate polymer characterization techniques.

Tässä työssä valmistettiin sarja pinta-funktionalisoitavia ja lämpöherkkiä mikrogeelipartikkeleita lääkeainekuljettajiksi. Partikkelit syntetisoitiin dispersiopolymeroinnilla vinyylikaprolaktaamista (VCL), metakryylihaposta (MAA) ja vinyylibentsyyliatsidista (VBA) käyttäen N, N'-bis(akryyli)kystamiinia silloittajana. Komponentit valittiin niiden funktionaalisuuksien ja bioyhteensopivuuden vuoksi, VBA sisällytettiin partikkeleihin sen liittämisreaktioihin sopivan atsidiryhmän takia. Monomeerisuhteita vaihdeltiin parhaimman lopputuloksen aikaansaamiseksi. Partikkeleiden atsidiryhmien reaktiivisuutta testattiin ATRP menetelmällä valmistetuilla alkyyni-pääteryhmäisillä PDMAEMA-ketjuilla. Ne liitettiin partikkeleihin käyttäen kuparikatalysoitua atsidi-alkyyni sykloadditiota (CuAAC). Partikkelien kemiallista rakennetta selvitettiin NMR- ja IR-analyyseillä. Partikkelien koko mitattiin lämpötilan funktiona dynaamisella valonsironnalla. Oikean reagenssisuhteen ja reaktio-olosuhteiden löydyttyä partikkeleita syntetisoitiin onnistuneesti. Niiden todettiin olevan stabiileja vesiliuoksessa ja niiden todettiin muuttavan kokoaan lämpötilan funktiona. Atsidiryhmien reaktiivisuus todettiin havaitsemalla PDMAEMA IR- ja NMR-spektristä intensiivisen puhdistuksen jälkeen.

Ring opening polymerization and click reaction was used to synthesize thermo-responsive glyco-block copolymers consisting of a polyether block with pendant α-D-mannose groups and random copolymer blocks of poly(glycidyl methyl ether)-poly(epoxyhexane). The thermo-responsive block was synthesized as a random copolymer to decrease the phase transition temperature to usable region. Temperature-responsiveness would enable the polymers to switch between dissolved and aggregated states. Such glycopolymers would be interesting candidates for studying carbohydrate-lectin interactions and drug delivery properties. The synthesized polymers were analyzed using nuclear magnetic resonance and Fourier-transform infrared spectroscopy, turbidimetry and differential scanning calorimetry. Both glycopolymers and thermo-responsive copolymers were synthesized. The latter showed good control over the polymerization, leading to clickable azide functionality and desired ratios of monomers in the copolymers. Altering the ratios of glycidyl methyl ether and epoxyhexane in the feed led to variations in the cloud points and glass transition temperatures of the copolymers. The synthesis of glycopolymers proved difficult and could not be initiated using clickable propargyl alcohol. Also, no effective way to purify the glycopolymers initiated using bezyl alcohol was found. Combination of the glycopolymers and thermo-responsive copolymers was attempted using click reaction. A triazole signal was detected using nuclear magnetic resonance spectroscopy suggesting the reaction was successful. However, further studies are required to confirm this.

Poly(2-oxazoline)s consist of a -(CH2-CH2-N)- main chain and an N-acyl substituent. They were reported for the first time in 1966/67. They have been investigated in the bulk, in solutions and in dispersions. The recent interest lies primarily in their chemical versatility and their potential for nanomedical applications. Tailoring materials for such specific applications requires a sound knowledge of their phase behaviors, which depends on intensive parameters. Amongst others, composition and temperature are of particular interest. The phase behaviors of poly(2-propyl-2-oxazoline)s (PPOxs) will be the main focus of this thesis. PPOx homopolymers are investigated as well as block copolymers (BCPs) and blends of poly(2-isopropyl-2-oxazoline) (PiPOx) and poly(lactide) (PLA). The first part describes the synthesis of the polymers. The PPOxs are prepared by cationic ring opening polymerization. They are linear, narrowly dispersed, and bear at the termini one methyl- and one azide-group. Semi-crystalline as well as amorphous PLA is synthesized by ring opening polymerization of L-lactide and DL-lactide, respectively. The linear PLAs are terminated with one propargyl- and one hydroxyl-group. Coupling of the azido- and alkyne-functional homopolymers gives a library of 18 PiPOx-b-PLA BCPs. This approach allows to compare the phase behaviors of the BCPs with those of the individual components. The next part is dedicated to a study of the solution properties of three PPOx homopolymers, namely poly(2-n-propyl-2-oxazoline) (PnPOx), poly(2-cyclopropyl-2-oxazoline) (PcyPOx) and PiPOx in water, in methanol and in water/methanol mixtures. Nuclear magnetic resonance (NMR) spectroscopy of the three polymers reveals significant differences in the side-group’s rotational freedom. Unexpectedly, these differences are reflected in the calorimetric assessment of the coil-to-globule phase transition. The phase diagrams in respect to the water/methanol composition are constructed based on transmittance measurements. Methanol is a good solvent up to its boiling point for the three PPOxs. The solubility of PnPOx in water decreases when up to 40 vol% methanol is added. This behavior termed “cononsolvency” was first reported for ternary polymer/water/methanol mixtures of poly(N-isopropyl acrylamide), a structural isomer of PnPOx and PiPOx. PiPOx and PcyPOx do not exhibit cononsolvency in the investigated ternary system. The PPOxs’ solution behaviors depend on the rotational freedom of the side-groups. In the third part, the bulk phase behavior of PiPOx, its blends with PLA, and PiPOx-b-PLA BCPs is studied. The PiPOx volume fractions in the BCPs varies from 14 to 82 %. PiPOx and PLA are miscible based on the single glass transition criterion and small angle x-ray scattering at a temperature above the melting points of the two polymers. Infrared spectroscopy indicates an attractive dipole-dipole interaction between the carbonyl moieties of the PiPOx amide and the carbonyl of the PLA ester. PiPOx and the stereo-regular PLLA are semi-crystalline. The influence of the miscibility on the crystallization is investigated by polarized optical microscopy, differential scanning calorimetry and wide-angle x-ray scattering. It is found that the presence of PLA increases the crystallization rate of PiPOx. In contrast, PLLA remains amorphous in most of the BCPs. The last part focuses on aqueous dispersions of the self-assembled PiPOx-b-PLA BCPs. The dispersions were prepared by adding a solution of a BCP in THF to water, a non-solvent of PLA but a solvent of PiPOx at low temperature. Contrary to expectation PiPOx resides in the particle interior, together with PLA. It does not form a shell of hydrated chains around the PLA core. This conclusion was attained on the basis of NMR spectroscopy and evaluation of the thermo-responsive properties of the BCP particle dispersions in water. At room temperature the particles are colloidally stable for 20 days at least. The particle morphology is investigated by cryogenic transmission electron microscopy, light scattering and small angle neutron scattering. The particles are spherical and permeated with water over the wide PiPOx volume fraction. Short segments of PiPOx reside on the particle/water interface and stabilize the dispersion. The thermo-responsive properties of the dispersions depend on the configuration and length of these segments. Attractive interactions between soluble and insoluble block are an important factor for the self-assembly of amphiphilic BCPs.

Preparation of polymer nanoparticles has become of great interest to polymer scientists due to their wide range of applications. Block copolymer nano-objects have been studied for decades, however new production methods are still needed to achieve better commercial viability and thus a wider use of the materials. Polymerization-induced self-assembly (PISA) is a new approach to preparing block copolymer nanoparticles, in which the polymerization of the second block and the self-assembly of the particles are achieved in one step. The method exploits the growing insolubility of the propagating chain to induce the self-assembly already during the polymerization, yielding nano-objects of various morphologies. The approach has gained significant attention in the last few years, and its popularity is expected to grow in the future. This thesis presents the fundamentals of PISA, while offering insight into both the benefits and challenges of the method. The focus of the work is on aqueous emulsion RAFT PISA formulations. Additionally, a new method for the preparation of poly(ethylene glycol)-block-poly(N-vinylcaprolactam) nanoparticles through PISA was developed. The synthesis exploited the lower critical solution temperature behaviour of poly(N-vinylcaprolactam) by conducting the polymerization of said block above its phase transition temperature in water. The polymerizations were carried out as RAFT reactions in emulsion and the resulting particles were characterized by dynamic light scattering. The method yielded particles of 200 nm in diameter that dissolved in water upon cooling to room temperature. Moreover, the purified and dried polymers were analysed using size-exclusion chromatography, NMR spectroscopy and turbidimetry. Preliminary tests showed that the stable particles can be physically crosslinked with salicylic acid to prevent dissolution upon cooling.

Pro Gradussa käsitellään vuorottelevan lisäys-irrotusketjunsiirto- eli RAFT-menetelmän soveltamista alkydi-akrylaattikopolymeerien miniemulsiopolymeroinnissa. Tavoitteena oli valmistaa tuotteita, joilla on kapeampi kokojakauma kuin alkydi-akrylaattikopolymeereilla, jotka on valmistettu perinteisellä miniemulsiopolymeroinnilla. Tiettävästi RAFT-menetelmää ei ole käytetty aiemmin alkydi-akrylaattikopolymeerien miniemulsiopolymeroinnissa. Kokeellisessa osassa alkydista valmistettiin makroketjunsiirtäjä liittämällä alkydiin esterisidoksella ketjunsiirtäjäryhmiä. Liitettävä ketjunsiirtäjä oli joko 3- (bentsyylisulfanyylitiokarbonyylisulfanyyli)-propaanihappo (CTA2) tai 2-(dodekyylisulfanyylitiokarbonyylisulfanyyli)-2-metyylipropaanihappo (DDMAT). Makroketjunsiirtäjiä valmistettiin kolmea eri synteesireittiä, joista jokaisella onnistuttiin liittämään ketjunsiirtäjäryhmiä alkydiin. Liittyneiden ketjunsiirtäjäryhmien määrää ei kyetty määritettämään, ainoastaan vertaamaan ketjunsiirtäjiä toisiinsa. CTA2-pohjaisia alkydimakroketjunsiirtäjiä käytettiin alkydi-butyyliakrylaatti(BA)-kopolymeerien valmistamisessa miniemulsio- ja massapolymerointina. Massapolymeroinnit tehtiin auttamaan miniemulsiopolymerointituotteiden analysoinnissa. Ketjunsiirtäjäryhmien läsnäolon havaittiin vaikuttavan massapolymeroinnissa muodostuvan tuotteen lukukeskimääräiseen moolimassaan (Mn) ja polydisperisteetti-indeksiin (PDI). Kun ketjunsiirtäjäryhmien määrä kasvoi, pieneni muodostuvan tuotteen Mn sekä PDI. Valitettavasti miniemulsiopolymeroinneissa ei havaittu vastaavaa vaikutusta, mikä viittaa siihen, että CTA2-pohjainen alkydimakroketjunsiirtäjä ei kykene kontrolloimaan BA:n miniemulsiopolymerointia. CTA2:ta käytettiin myös vapaana ketjunsiirtäjänä (ilman alkydia) BA:n miniemulsio- ja massapolymeroinnissa. Massapolymeroinneissa onnistuttiin valmistamaan BA-polymeereja, joiden Mn oli 27 000 g/mol ja PDI alle 1,2. Miniemulsiopolymeroinneissa onnituttiin valmistamaan BA-polymeereja, joiden Mn oli 69 000 g/mol ja PDI noin 1,8.

Dually thermoresponsive poly(sulfobetaine methacylate)-graft-(poly(poly(ethylene glycol) methyl ether methacrylate)-co-poly(di(ethylene glycol) methyl ether methacrylate) were synthesized via single electron transfer living radical polymerization (SET-LRP). Two different such graft copolymers S70-g-P25D25 and S70-g-P70D280 with different side chain lengths were prepared and studied. These polymers showed 'schezophrenic' self-assembly behavior in response to temperature and ionic strength in aqeuous solution in water. S70-g-P25D25 formed nanostructures at temperatures both above the lower critical solution temperature (LCST) and below the upper critical solution temperature (UCST) with inversed core-shell nature in aqueous solution. Under saline condition no nano structure could be observed at temperatures below the UCST. For S70-g-P70D280, LCST type self-assembly was observed with the formation of similar nanostructures, but at temperatures below UCST, instead of intermolecular aggregation, unimolecular self-assembly was obsverved due to the much more crowded side chains.

Recent years have seen an increasing interest in green chemistry and an emphasis on renewable resources. New methods for more efficient fractioning and processing of biomass have been explored as a potential replacement for the current pulping industry. It was found that a number of imidazolium based ionic liquids are capable of dissolving cellulose, lignin and even wood as a whole. Although many ionic liquids have been studied for their dissolution properties, the exact dissolution mechanism is not yet fully understood. In the current research, solid state NMR was applied to study the dissolution process of woodpulp in an ionic liquid. A set of spectral techniques, 13C CPMAS, HETCOR, 1H HRMAS and NOESY, was applied to partly dissolved softwood dissolving pulp. The ionic liquid 1-ethyl-3-methylimidazolium acetate (EMIMAc) was used as a solvent. The used samples were 66 wt%, 50 wt%, 33 wt% and 25 wt% pulp in EMIMAc. The CPMAS spectra proved useful in studying the breakdown of the cellulose crystalline structure. Cellulose fibril surfaces were effected already in the 66 wt% pulp sample. The in core crystallinity remained mainly intact up to 33 wt% pulp and then almost completely disappeared for the 25 wt% sample. The HETCOR experiments yielded no information on specific interactions between cellulose and EMIMAc because of too low signal intensities. The HRMAS spectra showed large changes in chemical shifts between the samples for EMIMAc and cellulose protons. The largest changes 0.3-0.7 ppm, were observed for the acidic EMIMAc protons and water. This means a change in hydrogen bonding interactions is taking place for both EMIMAc and cellulose upon increasing the EMIMAc concentration. The NOESY spectra showed that in the 50 wt% sample cellulose mainly interacts with water. In the 25 wt% sample water is largely replaced by acetate anions at the cellulose chains.

Hyaluronic acid (HA) hydrogels are interesting biomaterials for drug delivery and tissue engineering applications. Glycidyl ether derivatives have gained much interests due to their thermo-responsive properties. Thermo-responsive random copolymers of glycidyl methyl ether (GME) and epoxyhexane (EH) were synthesized. Once their properties were studied, they were grafted onto hyaluronic acid to obtain gelation at temperatures above the phase transition temperature of poly (GME-EH). PGME is a water-soluble polymer at low temperatures, but phase separates at 57.3oC. The transition temperature of PGME is too high to be utilized in medical applications. Thus a hydrophobic monomer EH was used to decrease the transition temperature of PGME via copolymerization. Several samples of random copolymers poly (GME-EH) were successfully synthesized by anionic ring opening polymerization (AROP). The transition temperature of copolymers was characterized by NMR, turbidimetry and micro-calorimetry respectively to study the phase transition behavior. Tetraoctylammonium bromide was used as initiator resulting with a bromide as the end group. Bromide was substituted by azide group to be used in click chemistry reaction with alkyne-functional HA. The reaction of the azide group on the end of copolymer chain was detected by FT-IR spectroscopy. Grafting was achieved by click chemistry following copper-catalyzed azide-alkyne cycloaddition (CuAAC) procedure. Rheology was used to study the gelation of the final product: thermo-responsive hyaluronic acid hydrogel. However, for different reasons the final product failed to form a gel.

In this master's thesis research reversible addition-fragmentation chain-transfer polymerization (RAFT) was utilized to synthesize primary and tertiary amine-based cationic copolymers to be utilised as micelles for gene transfer. Materials that were synthesized included 2-aminoethyl methacrylamide hydrochloride (AEMA.HCl) monomer, homopolymers such as polymethyl methacrylate (PMMA) and poly (N,N-dimethylamino ethyl methacrylate) (PDAMEMA), and copolymers such as polymethyl methacrylate-block-poly (2-dimethylamino) ethyl methacrylate (PMMA-b-PDMAEMA), polymethylmethacrylate-block-poly(dimethylamino ethyl methylcrylate-statistical-2-aminoethyl methacrylamide hydrochloride) (PMMA-b-P[DMAEMA-co-AEMA.HCl]) and poly (dimethylamino ethyl methylcrylate-statistical-2-aminoethyl methacrylamide hydrochloride) (P[DMAEMA-co-AEMA.HCl]). Prepared polymers were characterized using nuclear magnetic resonance (NMR) spectroscopy and size exclusion chromatography (SEC) methods. Also, via dialysis method aqueous micelles of PMMA-b-PDMAEMA block copolymer were prepared, and charaterized using dynamic light scattering (DLS). AEMA-hydrochloride monomer was synthesized via amidation process using methacrylic anhydride, and purified by recrystallization in isopropanol. Proton Neutron Magnetic Resonance (1HNMR) results revealed successful synthesis and production of a highly pure monomer. PMMA and PDMAEMA homopolymers of narrow molecular weight distribution were synthesized via RAFT using azobisisobutyronitrile (AIBN) initiator and 4-cyano-4-(phenylcarbonothioylthio) pentanoic acid (CPA) as chain transfer agent (CTA). With PMMA as a macro-CTA and AIBN initator DMAEMA was polymerized resulting in the formation of PMMA-b-PDMAEMA cationic block copolymer. 1HNMR analysis revealed a polymer consisting of PMMA and PDMAEMA blocks, and size exclusion chromatography (SEC) results also indicated production of a polymer with narrow molecular weight distribution. Results from dynamic light scattering (DLS) study showed PMMA-b-PDMAEMA (Mn=~23000 g/mol) diblock copolymer forms micelles with hydrodynamic radius in the range of 10-100 nm when THF-based copolymer solution was dialyzed in water. The size of micelle decreased at higher pH values. With respect to size PMMA-b-PDMAEMA copolymer micelles could be considered suitable for DNA transfer. Also, with AIBN initiator CPA and PMMA were used as CTA and a macro-CTA in two separate reactions to polymerize DMAEMA and AEMA-hydrochloride monomers simultaneously leading to formation of P(DMAEMA-co-AEMA.HCl) and PMMA-b-P(DMAEMA-co-AEMA.HCl) copolymers respectively. It was observed through SEC polymerization occured in both cases and resulting polymers exhibit very narrow molecular weight distribution. However, the molecular nature and composition of both copolymers cannot be reliably predicted based on 1HNMR results due to complications as a result of polymers poor solubility in various NMR solvents.