Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-6587
Authors: Infante Teixeira, Lorena
Title: Thiol-ene miniemulsion photopolymerization towards functional and reactive sulfur polymer latex
Online publication date: 17-Dec-2021
Language: english
Abstract: Polymerization in miniemulsion has drawn a great deal of attention in the last few decades. One of the main reasons for that is the concept of nanoreactors, i.e., every droplet acts as an individual reaction locus. The use of such geometrically restricted environments unravels several advantages and breakthroughs for polymer science. For example, it provides an additional way to control the design of particles and enable the reaction to be performed in a waterborne medium, also appealing to environmental concerns of the industrial sector. Besides being an elegant way to produce well-defined nanoparticles, the confinement effect of the droplets formed in miniemulsion preparations has been reported to be extremely beneficial in other aspects, such as in the encapsulation of sensitive payloads, such as pharmaceuticals and catalysts, and in accelerating and enhancing reactions that occurred within the nanoreactor boundaries. Although many polymer nanoparticles have been prepared by miniemulsion polymerization, the rational design of new nanoparticles is still needed to optimize their composition for specific applications. For example, in the case of biomedical applications for instance, nanoobjects, e.g., particles and capsules could be employed as drug carriers, but they need to have a well-controlled composition and surface chemistry to harness their full potential. This can be difficult to achieve considering the high complexity of the immense number of biochemical interactions possible. To improve delivery, it is necessary to design nanosystems with controlled composition that could protect the encapsulated drug until it reaches its destination, that are inert to foreign interactions, being only responsive to environmental cues that are specific to the targeted tissue, to locally release the cargo and improve the therapeutic effect. To address these challenges, the polymerization using thiol-ene chemistry adds layers of possibilities to tailor the properties of polymer nanomaterials produced by miniemulsion. To begin with, the hydrothiolation can proceed under several mild conditions compatible with biological media and enable a fine control of the structure-property relationship, due to the wide range of thiol- and ene-containing monomers available. In addition, the ubiquitous presence of thiol-moieties in biological molecules makes thiol-ene chemistry an attractive method for the post-polymerization biofunctionalization of polymer materials. In addition, the thiol-ene reaction are extremely fast, oxygen and moisture tolerant, regioselective and quantitative, and display all the advantages of a click-reaction. From an application standpoint, thiol-ene chemistry coupled with miniemulsion technique is a powerful combination to produce several types of polymer nanoparticles. Occurring through a step-growth mechanism, this polymerization allows the formation of functional end-groups on the polymer chain of thiols or enes, especially under off-stoichiometric ratios of monomers, which could be used as anchors for further functionalization of the surfaces of the particles in post-polymerization modifications. Therefore, with the same chemistry, this platform allows not only the formation of polymer networks but also their tailored functionalization. Different from other click-chemistry that have also been used to prepare such nanosystems, thiol-ene provides an extra feature that relies on the sulfur chemistry. Sulfur centers within the main backbone of polysulfide (polythioether) chains are prone to oxidation. These atoms can adopt different oxidation-states. In addition to the sulfide, sulfoxides (IV) and sulfones (VI) can be produced by oxidation, which dramatically changes the physiochemical properties of the material, such as their thermo-mechanical resistance, as well as their hydrophilicity and protein adhesion profile. Consequently, nanocarriers produced by thiol-ene chemistry are widely adaptable for several industrial applications and can be modified both on their surface and in their core network. In this thesis, thiol-ene polymer nanoparticles were prepared via photopolymerization in miniemulsion. The coupling of click-chemistry in dispersed media with photoinitiation confers spatiotemporal selectivity and facilitate tailoring the materials properties. The main goal of this project was to synthesize novel polymer nanoparticles, whose properties could be tailored, either by functionalization with biomolecules through thiol-ene chemistry, or core-modified by oxidation of the sulfur centers and be used as drug-delivery systems. To do so, it was important to control certain aspects of the reaction, in particular, the kinetics under confinement, defining the rate and degree of polymerization. For that, different thiol-ene monomer pairs were prepared and their rates of polymerization were followed by Raman spectroscopy (Section 4.1). The comparison between formulations in bulk, and in miniemulsion provided a full description of the effect of confinement on this step-growth polymerization and how it could be harnessed to favor high-performance properties to the material. The results described could even help understanding the phenomenon in other types of step-growth mechanisms. More interestingly, the polymerizations performed in miniemulsion in the presence of either diene or dithiol monomers show significant improvement in terms of conversion and degree of polymerization compared to the same reaction performed in bulk, and this allow the further thiol-ene functionalization of the excess enes (or thiols) after the polymerization. Post-polymerization functionalization of these particles prepared with an excess of dienes was then employed to functionalize the remaining functional groups on the surface with either thiolated or ene-functionalized biomolecules, such as carbohydrates and peptides, or polymer, such as polyethylene glycol (PEG), well-known in biomedical applications for its role in controlling the interaction between the nanocarriers and the environment (Section 4.3). Furthermore, since hydrophilicity of a nanoparticle is crucial in determining the fate of a nanoparticle in vivo, namely its interactions with proteins, this property was tuned by subsequential oxidation, transforming the parent polysulfide nanoparticles into polysulfoxide and polysulfone latexes (Section 4.2). Moreover, results showed an increase in the hydrodynamic ratio of polysulfoxides and even degradation of the particles under over-oxidation conditions that could be used as release mechanisms in inflamed tissues, which intrinsically exhibit high concentrations of reactive oxidation species that could induce the delivery of the cargo. The outcomes of this thesis are multiple. On one hand, the use of the miniemulsion technique was used to tune the nanoparticles physicochemical properties by controlling their size, distribution, and composition of the initial droplets. On another hand, the thiol-ene step-growth photopolymerization could, within such well-defined droplets, selectively and quantitatively produce modifiable polymer particles either through oxidation or surface modification to optimize the properties of the system for a wide array of specific applications. More generally, this project also provided new insights on reaction kinetics in nanoconfinement.
DDC: 000 Allgemeines
000 Generalities
500 Naturwissenschaften
500 Natural sciences and mathematics
540 Chemie
540 Chemistry and allied sciences
600 Technik
600 Technology (Applied sciences)
660 Technische Chemie
660 Chemical engineering
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 09 Chemie, Pharmazie u. Geowissensch.
Place: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-6587
URN: urn:nbn:de:hebis:77-openscience-5a16d64b-9721-4e79-916d-cadcf253edfd2
Version: Original work
Publication type: Dissertation
License: In Copyright
Information on rights of use: http://rightsstatements.org/vocab/InC/1.0/
Extent: XIV, 124 Seiten
Appears in collections:JGU-Publikationen

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