Photoinitiated Reaction Research Articles

Hydrogels with Reversible Mechanics to Probe Dynamic Cell Microenvironments

AbstractThe relationship between ECM mechanics and cell behavior is dynamic, as cells remodel and respond to changes in their local environment. Most in vitro substrates are static and supraphysiologically stiff; thus, platforms with dynamic and reversible mechanical changes are needed. Herein, we developed hyaluronic acid‐based substrates capable of sequential photodegradation and photoinitiated crosslinking reactions to soften and then stiffen the hydrogels over a physiologically relevant range of moduli. Reversible mechanical signaling to adhered cells was demonstrated with human mesenchymal stem cells. In situ hydrogel softening (from ca. 14 to 3.5 kPa) led to a decrease in the cell area and nuclear localization of YAP/TAZ, and subsequent stiffening (from ca. 3.5 to 28 kPa) increased the cell area and nuclear localization of YAP/TAZ. Each photoreaction was cytocompatible and tunable, rendering this platform amenable to studies of dynamic mechanics on cell behavior across many cell types and contexts.

Synthesis of thioether-containing carbosilane dendrimers with sterically shielded sulfur atoms

Carbosilane thiols were synthesized as the first- and second-generation (in silicon) dendrons. It was demonstrated that the resulting bulky thiols successfully undergo the thiol—ene addition to third-generation polyallyl carbosilane dendrimer as a photoinitiated radical reaction to give the corresponding thioether-containing derivatives with sterically shielded sulfur atoms.

Mechanically dynamic PDMS substrates to investigate changing cell environments.

Mechanics of the extracellular matrix (ECM) play a pivotal role in governing cell behavior, such as cell spreading and differentiation. ECM mechanics have been recapitulated primarily in elastic hydrogels, including with dynamic properties to mimic complex behaviors (e.g., fibrosis); however, these dynamic hydrogels fail to introduce the viscoelastic nature of many tissues. Here, we developed a two-step crosslinking strategy to first form (via platinum-catalyzed crosslinking) networks of polydimethylsiloxane (PDMS) and then to increase PDMS crosslinking (via thiol-ene click reaction) in a temporally-controlled manner. This photoinitiated reaction increased the compressive modulus of PDMS up to 10-fold within minutes and was conducted under cytocompatible conditions. With stiffening, cells displayed increased spreading, changing from ∼1300 to 1900μm2 and from ∼2700 to 4600μm2 for fibroblasts and mesenchymal stem cells, respectively. In addition, higher myofibroblast activation (from ∼2 to 20%) for cardiac fibroblasts was observed with increasing PDMS substrate stiffness. These results indicate a cellular response to changes in PDMS substrate mechanics, along with a demonstration of a mechanically dynamic and photoresponsive PDMS substrate platform to model the dynamic behavior of ECM.

Cross-linked supramolecular polymers synthesized by photo-initiated thiol-ene click reaction of supramonomers

Supramonomers refer to monomers fabricated via noncovalent interactions and can be polymerized through conventional covalent methods. In this article, we realized the fabrication of cross-linked supramolecular polymers through photo-initiated thiol-ene click reaction of quadruple hydrogen bonded supramonomers. It is found that the cross-linked supramolecular polymer has a higher critical polymerization concentration than the linear supramolecular polymer, because the orientation of the trifunctional monomer leads to cyclize at low concentrations. It is anticipated that this research can enrich the methodology of fabricating cross-linked supramolecular polymers and provide a new phenomenon to understand the self-assembling behavior of cross-linked supramolecular polymers.

Handheld Co-Axial Bioprinting: Application to in situ surgical cartilage repair

Three-dimensional (3D) bioprinting is driving major innovations in the area of cartilage tissue engineering. Extrusion-based 3D bioprinting necessitates a phase change from a liquid bioink to a semi-solid crosslinked network achieved by a photo-initiated free radical polymerization reaction that is known to be cytotoxic. Therefore, the choice of the photocuring conditions has to be carefully addressed to generate a structure stiff enough to withstand the forces phisiologically applied on articular cartilage, while ensuring adequate cell survival for functional chondral repair. We recently developed a handheld 3D printer called “Biopen”. To progress towards translating this freeform biofabrication tool into clinical practice, we aimed to define the ideal bioprinting conditions that would deliver a scaffold with high cell viability and structural stiffness relevant for chondral repair. To fulfill those criteria, free radical cytotoxicity was confined by a co-axial Core/Shell separation. This system allowed the generation of Core/Shell GelMa/HAMa bioscaffolds with stiffness of 200KPa, achieved after only 10 seconds of exposure to 700 mW/cm2 of 365 nm UV-A, containing >90% viable stem cells that retained proliferative capacity. Overall, the Core/Shell handheld 3D bioprinting strategy enabled rapid generation of high modulus bioscaffolds with high cell viability, with potential for in situ surgical cartilage engineering.

A pOH Jump Driven by N═N Out-of-Plane Motion in the Photoisomerization of Water-Solvated Triazabutadiene.

Utilization of photoinitiated isomerization reaction has recently emerged as a very promising platform to modulate the basicity of compounds; however, theoretical insight into its regulatory mechanism remains largely unknown and needs to be addressed. For the first time, an unexpected trans-cis photoisomerization via the N═N out of plane (NOOP) motion triggered by an in-plane inversion of N-N═N moiety was computationally demonstrated to regulate the pOH jump of water-solvated triazabutadiene by using the multiconfigurational perturbation theory together with the calculation of rate constants of protonation-deprotonation reactions. Kinetic analyses show that the dramatic pOH change can be attributed to the reinforced intramolecular hydrogen bonding resulting from water cluster reorientation and the enhanced coupling between the rotated π orbital and N lone pair of triazabutadiene in the remarkable trans-cis photoisomerization.

Covalent Incorporation of Ionic Liquid into Ion-Conductive Networks via Thiol-Ene Photopolymerization.

Ene-functionalized ionic liquids with a range of different cationic groups and counteranions react stoichiometrically within a tetrathiol-divinyl ether formulation within 20 minutes to form thiol-ene polymers with measurable ionic conductivities via a photoinitiated polymerization and crosslinking reaction. Dynamic mechanical analysis indicates that these networks are more spatially heterogeneous and possess higher glass transition temperatures (Tg ) compared with thiol-ene formulations without charge. While tuning the molar content of ionic liquid monomer is one method for adjusting the crosslink and charge densities of the thiol-ene polymeric ionic liquid networks, the presence of cation-anion interactions also plays a critical role in dictating the thermomechanical and conductive properties. Particularly, while cationic structure effects are not significant on the polymer properties, the use of a weakly coordinating hydrophobic anion (bistriflimide) instead of bromide-based networks results in an apparent decrease in hydrated ion conductivity (7.4 to 1.5 mS cm-1 ) and Tg (-9.6 to -17.8 °C).

Emulsion-templated porous polymers prepared by thiol-ene and thiol-yne photopolymerisation using multifunctional acrylate and non-acrylate monomers

The chemical and mechanical properties of macroporous polymer substrates play a crucial role in the determination of their end-application. The preparation of highly (macro)porous monolithic polymers (polyHIPEs) by emulsion templating and thiol-ene/yne photopolymerisation, using multifunctional acrylate, allyl ether and alkyne-based monomers with trimethylolpropane tris (3-mercaptopropionate) (TMPTMP), is described in this work. Issues associated with monomer solubility and/or stability of the produced high internal phase emulsions (HIPEs) are tackled. Scanning electron microscopy (SEM) is used to study the morphology and porosity (average void diameters) of the obtained materials. Due to the nature of the photoinitiated thiol-ene reactions, materials obtained from acrylate monomers display residual thiols that are quantified by a colourimetric (Ellman's) assay. Raman spectroscopy is also shown to be a complementary technique to evaluate the residual thiol content. The influence of the monomer functionality on the mechanical properties of the material is explored using compression tests. Significant differences in the surface functionality and mechanical behavior between materials prepared with comonomers able to homopolymerise (acrylates) and those unable to homopolymerise (allyl ethers; alkynes) are demonstrated.

Photoinitiated Thiol‐Ene “Click” Reaction: An Organocatalytic Alternative

AbstractThe thiol‐ene coupling (TEC) reaction has attracted a lot of scientific attention during the last years, particularly in the fields of polymers, materials and more recently in drug design. The combination of organocatalysis and photocatalysis has enabled the development of an efficient synergistic protocol for the addition of various thiols to a plethora of olefins. Utilizing phenylglyoxylic acid as the catalyst‐initiator and common household bulbs as the light source, we report an organocatalytic photoinitiated TEC reaction showing exceptional tolerance in the presence of various functionalities, untangling previously unsolved problems.magnified image

Preparation and characterization of hydrophilic hybrid monoliths via thiol-ene click polymerization and their applications in chromatographic analysis and glycopeptides enrichment

A macroporous hydrophilic organic-silica hybrid monolithic column was synthesized via photoinitiated thiol-ene click polymerization reaction of 1-thioglycerol-modified polyhedral oligomeric vinylsilsesquioxane (vinylPOSS) and dithiothreitol (DTT) in a binary porogenic system consisting of tetrahydrofuran (THF) and dodecanol. 1-Thioglycerol was used to modify vinylPOSS in order to form a precursor with good solubility in the binary porogenic system. The influences of both the ratio of 1-thioglycerol/vinylPOSS and the porogenic solvents on the morphology and permeability of hybrid monoliths were studied in detail. The physical properties of hybrid monolith were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy and nitrogen adsorption/desorption measurement. The chromatographic performance was evaluated by separation of neutral polar compounds in capillary liquid chromatography (cLC). The resulting column possessed homogeneous macroporous structure and showed hydrophilic interaction liquid chromatography (HILIC) separation mechanism with high efficiency of 65,000Nm−1 for formamide. Ultimately, the hybrid matrix was grafted with hydrazine groups and then exhibited the ability of glycopeptides enrichment.

Photochemical synthesis of 6-substituted 12-oxo-6,12-dihydroazepino[2,1-b]quinazolines

A method for the synthesis of 6-substituted 12-oxo-6,12-dihydroazepino[2,1-b]quinazolines via a photoinitiated reaction of orthosubstituted aryl azides with sodium 2-aminobenzoate is proposed. Stepwise annulation of the quinazoline system to the azepine ring occurs during nucleophilic addition of an amine to a cyclic keteneimine generated by photolysis of an aryl azide and subsequent intramolecular condensation of the intermediate product.

Oxygen-Purged Microfluidic Device to Enhance Cell Viability in Photopolymerized PEG Hydrogel Microparticles.

Encapsulating cells within biocompatible materials is a widely used strategy for cell delivery and tissue engineering. While cells are commonly suspended within bulk hydrogel-forming solutions during gelation, substantial interest in the microfluidic fabrication of miniaturized cell encapsulation vehicles has more recently emerged. Here, we utilize multiphase microfluidics to encapsulate cells within photopolymerized picoliter-volume water-in-oil droplets at high production rates. The photoinitiated polymerization of polyethylene glycol diacrylate (PEGDA) is used to continuously produce solid particles from aqueous liquid drops containing cells and hydrogel forming solution. It is well understood that this photoinitiated addition reaction is inhibited by oxygen. In contrast to bulk polymerization in which ambient oxygen is rapidly and harmlessly consumed, allowing the polymerization reaction to proceed, photopolymerization within air permeable polydimethylsiloxane (PDMS) microfluidic devices allows oxygen to be replenished by diffusion as it is depleted. This sustained presence of oxygen and the consequential accumulation of peroxy radicals produce a dramatic effect upon both droplet polymerization and post-encapsulation cell viability. In this work we employ a nitrogen microjacketed microfluidic device to purge oxygen from flowing fluids during photopolymerization. By increasing the purging nitrogen pressure, oxygen concentration was attenuated, and increased post-encapsulation cell viability was achieved. A reaction-diffusion model was used to predict the cumulative intradroplet concentration of peroxy radicals, which corresponded directly to post-encapsulation cell viability. The nitrogen-jacketed microfluidic device presented here allows the droplet oxygen concentration to be finely tuned during cell encapsulation, leading to high post-encapsulation cell viability.

Highly efficient and selective pressure-assisted photon-induced polymerization of styrene

The polymerization process of condensed styrene to produce polystyrene as an industrially important polymeric material was investigated using a novel approach by combining external compression with ultraviolet radiation. The reaction evolution was monitored as a function of time and the reaction products were characterized by in situ Fourier transform infrared spectroscopy. By optimizing the loading pressures, we observed highly efficient and selective production of polystyrene of different tacticities. Specifically, at relatively low loading pressures, infrared spectra suggest that styrene monomers transform to amorphous atactic polystyrene (APS) with minor crystalline isotactic polystyrene. In contrast, APS was found to be the sole product when polymerization occurs at relatively higher loading pressures. The time-dependent reaction profiles allow the examination of the polymerization kinetics by analyzing the rate constant and activation volume as a function of pressure. As a result, an optimized pressure condition, which allows a barrierless reaction to proceed, was identified and attributed to the very desirable reaction yield and kinetics. Finally, the photoinitiated reaction mechanism and the growth geometry of the polymer chains were investigated from the energy diagram of styrene and by the topology analysis of the crystal styrene. This study shows strong promise to produce functional polymeric materials in a highly efficient and controlled manner.

Multireactive Poly(2-oxazoline) Nanofibers through Electrospinning with Crosslinking on the Fly.

Crosslinked hydrophilic poly(2-oxazoline)-based nanofibers amenable to facile multifunctionalization are fabricated using alkene-containing poly(2-alkyl-2-oxazoline)s (PAOx) via in situ photoinitiated radical thiol-ene crosslinking during electrospinning. The resulting crosslinked nanofibers are demonstrated to be multifunctionalizable using different chemistries as they contain two functional handles, being the alkene moieties from the parent copolymer and the residual thiol groups from the tetra-thiol-based crosslinker. While the thiol groups in these nanofibers could be passivated or conjugated to install functional molecules through thiol-maleimide conjugation, the alkene groups could sequentially be modified with thiol-containing molecules using photoinitiated radical thiol-ene reactions. Utilization of the photochemically induced conjugation of thiol-bearing molecules to the alkene groups on the nanofibers is used to obtain functionalization in a spatially controlled manner.

Rapid “one-pot” preparation of polymeric monolith via photo-initiated thiol-acrylate polymerization for capillary liquid chromatography

A facile approach was exploited for fast preparation of polymer-based monoliths in UV-transparent fused-silica capillaries via “one-pot” photo-initiated thiol-acrylate polymerization reaction of dipentaerythritolpenta-/hexaacrylate (DPEPA) and 1-octadecanethiol (ODT) in the presence of porogenic solvents (1-butanol and ethylene glycol). Due to relative insensitivity of oxygen inhibition in thiol-ene free-radical polymerization, the polymerization could be performed within 5 min. The effects of composition of prepolymerization solution on the morphology and permeability of poly(ODT-co-DPEPA) monoliths were investigated in detail by adjusting the content of monomer and binary porogen ratio. The physical properties of poly(ODT-co-DPEPA) monoliths were characterized by Fourier transform infrared spectroscopy (FT-IR), mercury intrusion porosimetry (MIP) and nitrogen adsorption/desorption measurement. The evaluation of chromatographic performance was carried out by capillary liquid chromatography (cLC). The results indicated that the poly(ODT-co-DPEPA) monolith was homogeneous and permeable, and also possessed a typical reversed-phase retention mechanism in cLC with high efficiency (∼75,000 N m−1) for separation of alkylbenzenes. Eventually, the further separation of tryptic digest of proteins by cLC tandem mass spectrometry (cLC-MS/MS) demonstrated its potential in the analysis of biological samples.

ChemInform Abstract: Using Photo‐Initiated Polymerization Reactions to Detect Molecular Recognition

AbstractReview: 50 refs.

Thiol-yne/thiol-epoxy hybrid crosslinked materials based on propargyl modified hyperbranched poly(ethyleneimine) and diglycidylether of bisphenol A resins

Photoinitiated thiol-yne reaction was combined with thermal thiol-epoxy to get thermosets by dual curing from propargyl decorated poly(ethyleneimine) and DGEBA.

Using photo-initiated polymerization reactions to detect molecular recognition.

Widely used medical diagnostic devices and assays that sense the presence of a particular molecule in a bodily fluid often rely on either a nanoparticle label or an enzymatic reaction to generate a signal that is easily detectable. In many cases, it is desirable if the magnitude of the signal correlates with the concentration of the molecule of interest. Photo-initiated polymerization reactions are an alternative means of generating amplified signals that can be used to quantify biological molecules in complex fluids. In this case, the formation of a polymer, typically a cross-linked hydrogel, signifies the presence of the molecule of interest. This tutorial review explains how photo-initiated polymerization reactions have been used in a conditional manner to detect and quantify molecular recognition events. We weigh the advantages and disadvantages of using photo-initiated reactions in comparison with other approaches and highlight exciting directions and opportunities in this area.

Surface functionalization of conjugated microporous polymer thin films and nanomembranes using orthogonal chemistries

The synthesis and surface modification of CMP thin films and nanomembranes was performed using orthogonal click chemistries. The surface modification can tune the nanomembrane properties for desired applications; the use of photo-initiated reactions provides the additional opportunity to photo-pattern the CMP materials.

Synthesis and Physical Properties of Thiol–Ene Networks Utilizing Plant-Derived Phenolic Acids

Elastomeric polymer films synthesized through thiol–ene chemistry, suitable in applications as coatings and adhesives due to their ease of preparation and superior physical properties, are traditionally derived from petroleum sources. Of recent interest is the exploration of sustainable alternatives for the precursors to these materials. Here, we report the synthesis of thiol–ene networks through the photoinitiated reaction between allylated plant-based phenolic acids (salicylic acid and 4-hydroxybenzoic acid) and a multifunctional thiol, followed by isothermal annealing. Plant-sourced phenolic acids offer many advantages as biorenewable monomers: their rigid aromatic rings are expected to provide mechanical strength to the resulting polymers and the presence of multiple hydroxyl and carboxyl groups leads to ease of functionalization. Both phenolic acids produced networks with high degrees of homogeneity and few defects, as evidenced by narrow glass transitions and consistency of their tensile behavior with the ideal elastomer model at low-to-moderate strains. The 4-hydroxybenzoic acid based network, which had a higher cross-link density, exhibited a higher glass transition temperature, modulus, tensile strength, and elongation at break as compared to the salicylic acid based network. This work develops fundamental relationships between the molecular structure of the phenolic acids and the physical properties of the resulting networks.