Antimicrobial Materials via Thiol-ene Chemistry

With the increasing prevalence of antimicrobial resistance, the escalation of opportunistic/pathogenic infections is a looming global crisis. To avoid the pitfalls of conventional antibiotics, this dissertation focuses on developing macromolecular solutions to develop novel antimicrobial materials based on essential oils (thymol, carvacrol, and aldehydes). It is well established that essential oil derivatives exhibit high potency towards a wide range of pathogenic microbes. The rapid photopolymerization kinetics, limited by-products, and homogeneous network formation afforded by thiol-ene photopolymerization are utilized to either encapsulate essential oil derivatives or convert them into monomers which can subsequently be incorporated into new antimicrobial materials with new structure-function relationships. The first chapter of this dissertation outlines the need for alternatives to traditional antibiotics and the motivation for developing essential oil-based therapies. In the second chapter, the utilization of thiol-ene chemistry in the design of drug delivery and encapsulation are reviewed. The third chapter of this dissertation focus on the development of one-pot/solvent-free thiol-ene miniemulsion technique to synthesize thymol/carvacrol-loaded nanoparticles with high loading capacity (≈50% w/w), excellent encapsulation efficiencies (\u3e95%), and potent antimicrobial activity. In the following chapters, new pro-antimicrobial networks via degradable acetals (PANDAs) were fabricated as a new paradigm for the sequestration and triggered release of volatile, antimicrobial aldehydes. PANDAs are crosslinked networks in which every crosslink junction contains a degradable acetal linkage. When PANDAs are exposed to neutral to acidic conditions (pH \u3c 8), the PANDAs undergo surface erosion and exhibit sustained aldehyde release from days to months. Chapter IV details the fabrication of PANDAs with a synthetic aldehyde, chlorobenzaldehyde, while chapter V emphases on the use of the plant-derived, p-anisaldehyde (an extract from star anise). In both chapters, the synthesis of PANDAs, thermal/mechanical properties, aldehyde release kinetics, as well as antimicrobial efficacy and cytotoxicity were elucidated

Functional, Sub-100 nm Polymer Nanoparticles \u3ci\u3evia\u3c/i\u3e Thiol-ene Miniemulsion Photopolymerization

In this work, sub-100 nm crosslinked polythioether nanoparticles were synthesized via thiol–ene photopolymerization in miniemulsion using high-energy homogenization. The effects of the miniemulsion formulation and homogenization parameters – including inhibitor concentration, surfactant concentration, organic weight fraction, ultrasonication time and amplitude – on nanoparticle size and size distribution were investigated. Thiol–ene nanoparticles with a mean particle diameter of 46 nm were obtained under optimized conditions for the current system at 2.5 wt% organic fraction and 20 mM surfactant concentration. In an effort to demonstrate potential utility of thiol–ene nanoparticles, we exploit the step-growth radical mechanism of thiol–ene photopolymerization under non-stoichiometric conditions to fabricate functional nanoparticles that express excess thiol or alkene at the particle surface. We show that these excess functional groups can be utilized as reactive handles in thiol-Michael and radical-mediated thiol–ene reactions for immobilization of fluorescent moieties via postpolymerization modification

Architected Polymer Foams Via Direct Bubble Writing

Polymer foams are cellular solids composed of solid and gas phases, whose mechanical, thermal, and acoustic properties are determined by the composition, volume fraction, and connectivity of both phases. A new high-throughput additive manufacturing method, referred to as direct bubble writing, for creating polymer foams with locally programmed bubble size, volume fraction, and connectivity is reported. Direct bubble writing relies on rapid generation and patterning of liquid shell–gas core droplets produced using a core–shell nozzle. The printed polymer foams are able to retain their overall shape, since the outer shell of these bubble droplets consist of a low-viscosity monomer that is rapidly polymerized during the printing process. The transition between open- and closed-cell foams is independently controlled by the gas used, while the foam can be tailored on-the-fly by adjusting the gas pressure used to produce the bubble droplets. As exemplars, homogeneous and graded polymer foams in several motifs, including 3D lattices, shells, and out-of-plane pillars are fabricated. Conductive composite foams with controlled stiffness for use as soft pressure sensors are also produced

Destruction of Opportunistic Pathogens Via Polymer Nanoparticle-Mediated Release of Plant-Based Antimicrobial Payloads

The synthesis of antimicrobial thymol/carvacrol‐loaded polythioether nanoparticles (NPs) via a one‐pot, solvent‐free miniemulsion thiol‐ene photopolymerization process is reported. The active antimicrobial agents, thymol and carvacrol, are employed as “solvents” for the thiol‐ene monomer phase in the miniemulsion to enable facile high capacity loading (≈50% w/w), excellent encapsulation efficiencies (\u3e95%), and elimination of all postpolymerization purification processes. The NPs serve as high capacity reservoirs for slow‐release and delivery of thymol/carvacrol‐combination payloads that exhibit inhibitory and bactericidal activity (\u3e99.9% kill efficiency at 24 h) against gram‐positive and gram‐negative bacteria, including both saprophytic (Bacillus subtilis ATCC 6633 and Escherichia coli ATCC 25922) and pathogenic species (E. coli ATCC 43895, Staphylococcus aureus RN6390, and Burkholderia cenocepacia K56‐2). This report is among the first to demonstrate antimicrobial efficacy of essential oil‐loaded nanoparticles against B. cenocepacia – an innately resistant opportunistic pathogen commonly associated with debilitating respiratory infections in cystic fibrosis. Although a model platform, these results point to promising pathways to particle‐based delivery of plant‐derived extracts for a range of antimicrobial applications, including active packaging materials, topical antiseptics, and innovative therapeutics

Synthesis and evaluation of thermally-responsive coatings based upon Diels–Alder chemistry and renewable materials

A soybean based coating with thermally responsive Diels–Alder linkages has been prepared following an automotive 2-component formulation. The resulting coatings displayed the capability to be healed following physical deformation by a thermal stimulus, and such a material has significant potential for end users. Various curing agents were employed, and resulted in variation of scratch resistance and re-healablity. Different thermally responsive soybean resins were synthesized to have varying amounts reversible and nonreversible linkages when incorporated into the coating. Additionally, different isocyanates were added at differing ratios of NCO:OH in search of the optimum coating. It was found through the analysis of rehealability, hardness, gloss, and adhesion that the optimal combination was an acetylated resin (no irreversible crosslinks) with 54% reversible Diels–Alder linkages at an NCO:OH ratio of 5:1 using isophorone diiscocyanate. Materials were evaluated via differential scanning calorimetry (DSC), scratch resistance, Koenig hardness, gloss measurements, and topographical analysis

A Bio-Based Pro-Antimicrobial Polymer Network Via Degradable Acetal Linkages

The synthesis of a fully degradable, bio-based, sustained release, pro-antimicrobial polymer network comprised of degradable acetals (PANDA) is reported. The active antimicrobial agent – p-anisaldehyde (pA) (an extract from star anise) – was converted into a UV curable acetal containing pro-antimicrobial monomer and subsequently photopolymerized into a homogenous thiol-ene network. Under neutral to acidic conditions (pH \u3c 8), the PANDAs undergo surface erosion and exhibit sustained release of pA over 38 days. The release of pA from PANDAs was shown to be effective against both bacterial and fungal pathogens. From a combination of confocal microscopy and transmission electron microscopy, we observed that the released pA disrupts the cell membrane. Additionally, we demonstrated that PANDAs have minimal cytotoxicity towards both epithelial cells and macrophages. Although a model platform, these results point to promising pathways for the design of fully degradable sustained-release antimicrobial systems with potential applications in agriculture, pharmaceuticals, cosmetics, household/personal care, and food industries

RE-HEALABLE COATING BASED UPON THERMALLY RESPONSIVE LINKAGES

The goal of this thesis was to design thermally responsive polyol resins that would be compatible with isocyanates. Two approaches were made to reach this goal, the first involved functionalizing soybean oil and the second involved post-polymerization modification of a methacrylate based resin. A soybean based coating with thermally responsive Diels-Alder linkages has been prepared following an automotive two-component formulation. The resulting coatings displayed the capability to be healed following physical deformation by a thermal stimulus, and such a material has significant potential for end users. Various curing agents were employed, and resulted in variation of scratch resistance and re-healablity. Different thermally responsive soybean resins were synthesized to have varying amounts of reversible and nonreversible linkages when incorporated into the coating. Additionally, different isocyanates were added at differing ratios of NCO:OH in search of the optimum coating. It was found through the analysis of re-healabilty, hardness, gloss, and adhesion that the optimal combination was an acetylated resin (no irreversible crosslinks) with 54% reversible Diels Alder linkages at an NCO:OH ratio of 5:1 using isophorone diiscocyanate. Materials were evaluated via differential scanning calorimetry (DSC), scratch resistance, Koenig hardness, gloss measurements, and topographical analysis. In the second project, copolymerization of methyl methacrylate and 2-isocyanatoethyl methacrylate via free radical polymerization was done to synthesize a polymer with pendant isocyanates. The isocyanate was used as a chemical handle to incorporate Diels-Alder linkages into the PMMA resin. The PMMA resin with Diels-Alder linkages was successfully synthesized and incorporated into a polyurethane gel as proven via 1H NMR and IR. The gel showed thermal reversibility at 120°C due to retro-DA reaction via DSC as well as thermally reversible bulk properties

Programmable Porous Polymers Via Direct Bubble Writing With Surfactan-Free Inks

Fabrication of macroporous polymers with functionally graded architecture or chemistry bears transformative potential in acoustic damping, energy storage materials, flexible electronics, and filtration, but is hardly reachable with current processes. Here, we introduce thiol-ene chemistries in direct bubble writing, a recent technique for additive manufacturing of foams with locally controlled cell size, density and macroscopic shape. Surfactant-free and solvent-free graded 3D foams without drying-induced shrinkage were fabricated by direct bubble writing at an unparalleled ink viscosity of 410 cP (40 times higher than previous formulations). Functionalities including shape memory, high glass transition temperatures ( \u3e25 °C), and chemical gradients were demonstrated. These results extend direct bubble writing from aqueous inks to non-aqueous formulations, while the liquid flow rate (3 mL min-1) exceeds chip microfluidic techniques. Altogether, direct bubble writing with thiol-ene inks promises rapid one-step fabrication of functional materials with locally controlled gradients in the chemical, mechanical, and architectural domains

Architected Polymer Foams via Direct Bubble Writing

Polymer foams are cellular solids composed of solid and gas phases, whose mechanical, thermal, and acoustic properties are determined by the composition, volume fraction, and connectivity of both phases. A new high‐throughput additive manufacturing method, referred to as direct bubble writing, for creating polymer foams with locally programmed bubble size, volume fraction, and connectivity is reported. Direct bubble writing relies on rapid generation and patterning of liquid shell–gas core droplets produced using a core–shell nozzle. The printed polymer foams are able to retain their overall shape, since the outer shell of these bubble droplets consist of a low‐viscosity monomer that is rapidly polymerized during the printing process. The transition between open‐ and closed‐cell foams is independently controlled by the gas used, while the foam can be tailored on‐the‐fly by adjusting the gas pressure used to produce the bubble droplets. As exemplars, homogeneous and graded polymer foams in several motifs, including 3D lattices, shells, and out‐of‐plane pillars are fabricated. Conductive composite foams with controlled stiffness for use as soft pressure sensors are also produced

Utilizing Intrinsic Properties of Polyaniline to Detect Nucleic Acid Hybridization Through UV-Enhanced Electrostatic Interaction

Detection of specific RNA or DNA molecules by hybridization to “probe” nucleic acids via complementary base-pairing is a powerful method for analysis of biological systems. Here we describe a strategy for transducing hybridization events through modulating intrinsic properties of the electroconductive polymer polyaniline (PANI). When DNA-based probes electrostatically interact with PANI, its fluorescence properties are increased, a phenomenon that can be enhanced by UV irradiation. Hybridization of target nucleic acids results in dissociation of probes causing PANI fluorescence to return to basal levels. By monitoring restoration of base PANI fluorescence as little as 10–11 M (10 pM) of target oligonucleotides could be detected within 15 min of hybridization. Detection of complementary oligos was specific, with introduction of a single mismatch failing to form a target–probe duplex that would dissociate from PANI. Furthermore, this approach is robust and is capable of detecting specific RNAs in extracts from animals. This sensor system improves on previously reported strategies by transducing highly specific probe dissociation events through intrinsic properties of a conducting polymer without the need for additional labels