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The macroscopic alignment of the nematic director within liquid crystalline elastomers (LCEs) amplifies the magnitude of the directional strain response. Theory predicts that the stimuli response o...

The kinetic effects of the substitution and functionality of the thiol in thiol-Michael reactions were investigated using model monofunctional thiols and multifunctional thiols used in various cros...

Microparticle-mediated nucleic acid delivery is a popular strategy to achieve therapeutic outcomes via antisense gene therapy. However, current methods used to fabricate polymeric microparticles suffer from suboptimal properties such as particle polydispersity and low encapsulation efficiency. Here, a new particulate delivery system based on step-growth thiol-Michael dispersion polymerization, is reported in which a low polydispersity microparticle is functionalized with a synthetic nucleic acid mimic, namely click nucleic acids (CNA). CNA oligomers, exhibiting an average length of approximately four nucleic acid repeat units per chain for both adenine and thymine bases, were successfully conjugated to excess thiols present in the microparticles. Effective DNA loading was obtained by simple mixing; and, up to 6 ± 2 pmol of complementary DNA/mg of particle was achieved, depending on the length of DNA used. In addition, DNA loading was orders of magnitude less for noncomplementary sequences and sequences containing an alternating base mismatch. The DNA release properties were evaluated, and it was found that release could be triggered by sudden changes in temperature but was unaffected over a range of pH. Finally, phagocytosis of loaded microparticles was observed by confocal microscopy and corroborated by an increase in cellular metabolic activity up to 90%. Overall, this work suggests that CNA functionalized microparticles could be a promising platform for controlled DNA delivery.

This article describes an efficient enamine organocatalyzed thiol-Michael click reaction and its broad application in cross-linking polymerizations. A series of enamines was shown to catalyze the t...

Controlling the microstructure of heterogeneous, polymer membranes used in gas barrier and gas separation technologies is challenging. Being able to control composite structures is beneficial to achieve an optimum combination of gas permeation and mechanical performance. In addition, unique properties such as anisotropy and confined transport can be controlled by tailoring the size and position of constituent materials. Two-stage reactive polymer (TSRP) networks are an emerging dual-cure polymer material for spatially varying cross-linking density via photopatterning. In this work a thiol–acrylate-based TSRP was used to investigate the effects of pattern geometry on CO₂ permeability and mechanical properties. Line and square patterns of alternating high and low cross-linking density, with characteristic dimension between 1 mm and 10 μm, were generated in TSRP membranes. Notably, synergistic enhanced barrier properties were observed for 10 μm square patterns of lower cross-linking density (or higher permeability) material exhibiting two confined dimensions compared to line gratings with only one confined dimension.

Click nucleic acids (CNAs) are a new, low-cost class of xeno nucleic acid (XNA) oligonucleotides synthesized by an efficient and scalable thiol-ene polymerization. In this work, a thorough characterization of oligo(thymine) CNA-oligo(adenine) DNA ((dA)20) hybridization was performed to guide the future implementation of CNAs in applications that rely on sequence-specific interactions. Microscale thermophoresis provided a convenient platform to rapidly and systematically investigate the effects of several factors (i.e., sequence, length, and salt concentration) on the CNA-DNA dissociation constant (Kapp). Because CNAs have limited water solubility, all studies were performed in aqueous-DMSO mixtures. CNA-DNA hybrids between oligo(thymine) CNA (average length of 16 bases) and (dA)20 DNA have good stability despite the high organic content, a favorable attribute for many emerging applications of XNAs. In particular, the Kapp of CNA-DNA hybrids in 65 vol % DMSO with 10 mM sodium chloride (NaCl) was 0.74 ± 0.1 μM, whereas the Kapp for (dT)20-(dA)20 DNA-DNA was found to be 45 ± 2 μM in a buffer without DMSO but at the same NaCl concentration. CNA hybridized with DNA following Watson-Crick base pairing with excellent sequence specificity, discriminating even a single-base-pair mismatch, with Kapp values of 0.74 ± 0.1 and 3.7 ± 0.6 μM for complementary and single-base-pair mismatch sequences, respectively. As with dsDNA, increasing CNA length led to more stable hybrids as a result of increased base pairing, where Kapp decreased from 5.6 ± 0.8 to 0.27 ± 0.1 μM as the CNA average length increased from 7 to 21 bases. However, unlike DNA-DNA duplexes, which are largely unstable at low salt concentrations, the CNA-DNA stability does not depend on salt concentration, with Kapp remaining consistent between 1.0 and1.9 μM over a NaCl concentration range of 1.25-30 mM.

In the present work, the photocatalytic activity was investigated toward a thiol-Michael reaction of different combinations of 9-fluorenylmethyl carbamate (Fmoc) derivatives and photocaged amines (PCA) as base amplifiers and the catalytic base, respectively. This phototriggering approach was systematically studied for evaluating its effect on kinetics between thiol and Michael acceptors like acrylate or sulfone wherein, butyl 3-mercaptopropionate (BMP), 1-hexyl acrylate (HA), and ethyl vinyl sulfone (EVS) were used as model reactants. Interestingly, PCAs exhibited low quantum yields by themselves; NPPOC-Hex (2.5 mol %) which when used with BMP and HA, resulted in only 25% thiol conversion; however, when used along with Fmoc-Hex or Fmoc-TMG (2.5 or 5 mol %), it resulted in a higher thiol conversion of 50–60%. Furthermore, use of NPPOC-DEA (5 mol %) with 1 mol % Fmoc-TMG resulted in >70% thiol conversion for the same system. Upon using BMP and EVS nearly complete conversion of functional groups with 5 mol % NPPOC-DEA and 5 mol % Fmoc-DEA was obtained. This enhancement in reaction kinetics and conversion upon addition of an Fmoc derivative to a monofunctional thiol-Michael system was extended to multifunctional derivatives for polymerizing cross-linked polymer networks. Moreover, the kinetic study on model reactants also demonstrated efficient dark curing, resulting in 50–75% thiol conversion with only 30 s irradiation time, leading to validation of the efficacy of Fmoc derivatives and PCAs as photocatalysts for dark cure. Upon precise characterization in cross-linked systems using Raman spectroscopy for TMPTA/PETMP in the presence of 20 mol % NPPOC-DEA and 1 mol % Fmoc-TMG, the extent of dark cure was evaluated for a distance of 16.5 mm, which was observed to undergo maximum conversion and high dark cure propagation upon heating to 70 °C. Therefore, Fmoc-PCA catalysis is a practically useful approach for improving the photoinitiated efficiency of the thiol-Michael reaction and enabling photopolymerization in the dark with a marked improvement in photosensitivity.

The effect of thiol substitution in radical thiol–ene reactions has been studied by using model, monofunctional thiols as well as multifunctional thiol monomers along with the assessment of their subsequent polymerization reactions and polymer mechanical behavior. FT-IR was used to monitor the polymerization rate and quantify the overall conversion. While the total conversion was observed to range from 70% to 100%, the polymerization rate was found to decrease by as much as 10-fold as the thiol substitution was changed from primary to tertiary. Analogous multi-thiol monomers of similar structure but varying substitution were synthesized to observe the effect of substitution type on polymerization kinetics and polymer behavior. Methylation at the α-carbon was varied from primary to tertiary to observe these differences. Mechanical properties were assessed by using dynamic mechanical analysis and water sorption experiments, where the glass transition temperatures were found to be within 1–2 °C as thiol substitution varied. Furthermore, primary thiol films absorbed 1–3% more water than secondary thiol films. Resin shelf stability experiments were performed by using rheometry to measure storage time-dependent viscosity changes, and it was found that secondary thiol films remained relatively stable for up to 100 times longer than their primary counterparts. It was concluded that while there are differences under relatively slow initiation conditions, at typical initiation rates all three thiol substitutions may be made to react at similar rates for both monofunctional and polymeric systems.

The unique photodynamics of aromatic thiols (relative to alkyl thiols) allowed their employment as effective ultraviolet and visible light photoinitiators (PIs) for acrylate photopolymerizations, r...

Functional nanogels are attractive additives for use in polymer composites. In this study, nanogels with internal allyl sulfide moieties throughout their network structure were prepared via a thiol-Michael addition reaction. The excess thiol-functionalized nanogels were less than 60 nm as discrete particles but act as room-temperature liquids in the bulk state. The reactive nanogels can be dispersed in and swollen by a thiol-ene matrix resin, which upon photopolymerization yields dramatically decreased levels of polymerization shrinkage stress. Furthermore, the postcured nanogel-modified polymers effectively relaxed applied stresses as well as enhanced toughness during exposure to a UV light source that activated the addition-fragmentation as a means for dynamic bond exchange. These nanogels provide a generic approach to introduce adaptable network performance that significantly improves a number of key properties of glassy cross-linked polymer.

Because of facile implementation, quantitative conversions, and an insensitivity to oxygen, water, and most organic functional groups, radical-mediated thiol-ene coupling (TEC) reactions have emerged as a valuable tool in macromolecule synthesis. It was recently demonstrated that the kinetics and conversions of thiyl radical-mediated reactions are adversely affected in the presence of basic amines by the formation of retardive thiolate anions. Herein, the performance of TEC polymerizations is evaluated under a variety of reaction environments with the intention to aid in the optimal formulation design of TEC reactions in the presence of amines. Results from both bulk and aqueous-phase network photopolymerizations established that sensitivity to amine basicity and pH is dependent on the thiol acidity, although norbornene-type alkenes exhibit a unique ability to achieve high conversions, where allyl ethers, vinyl ether, and vinyl siloxanes are highly inhibited. Additionally, the protic solvents such as alcohols and acetic acid are established as ideal solvents or additives to suppress or eliminate amine-induced retardation.

Motivated by the various reported potential applications of poly(phosphine oxide) materials, a visible light photoinitiated iodo-ene reaction was successfully employed in network polymerization between the phosphorus-containing multifunctional monomer, tris(allyloxymethyl)phosphine oxide (TAOPO), and diiodoperfluorobutane. The cross-linked poly(phosphine oxide) network exhibited a higher glass transition temperature than a similarly cross-linked polymer formulated with trimethylolpropane triallyl ether (TMPTAE). Interestingly, the TMPTAE/DIPFB cross-linked polymer, changed color from clear to yellow within 10 min of exposure to air, whereas the cross-linked poly(phosphine oxide) underwent a similar change only upon heating. Upon investigation, it was determined that alkenes were generated within the polymer network, presumably via elimination, accounting for the observed color. These double bonds, formed in the polymer matrix, permitted surface modification via radical thiol-ene reaction. The successful surface functionalization with PEG-SH resulted in increasing the surface wettability. Additionally, the phosphorus-containing network polymer with double bonds in the polymer matrix showed shape memory capability, this representing an exciting and versatile materials platform.

A new group of nitrogen-centered nucleophilic catalysts for the thiol-Michael addition “click” reactions is examined. These nucleophiles showed efficient catalytic activities as compared with traditional base catalysts, such as triethylamine, and are demonstrated to be a viable strategy for cross-linking polymerization reactions. Additionally, an experimental and computational mechanistic study was performed, suggesting a pathway for the nitrogen-centered catalyst to undergo the nucleophilic addition mechanism.

A visible-light base generating system was successfully employed in catalyzing the thiol-Michael addition reaction to yield cross-linked polymers from a stoichiometric mixture of model thiol and vinyl monomers. Implementation of the radical inhibitor TEMPO with a combination of a photosensitizer (isopropylthioxanthone, ITX) and a photobase generator (triazabicyclodecene tetraphenylborate, TBD·HBPh4) resulted in suppression of radical mediated side reactions and provided stoichiometric and complete conversion of both thiol and vinyl functional groups. The new initiating system acts as an efficient visible-light photobase generator that improves the orthogonality of the thiol-Michael addition with respect to off-stoichiometric radical thiol-vinyl addition/vinyl chain reactions. This approach opens up a variety of possibilities for base-catalyzed reactions in multiple applications such as coatings and biomaterials that require biocompatible, environmentally friendly, and low-energy visible-light initiation.

A photoinitiation system that utilizes phosphonium tetraphenylborate as the key component was developed for the visible light-triggered nucleophile-catalyzed thiol-Michael addition reaction. This highly reactive catalyst was composed of a photocaged phosphine (methyldiphenylphosphonium tetraphenylborate, MDPP·HBPh

Enrichment of mRNA is a key step in a number of molecular biology techniques, particularly in the rapidly growing field of transcriptomics. Currently, mRNA is isolated using oligo(thymine) DNA (oligo(dT)) immobilized on solid supports, which binds to the poly(A) tail of mRNA to pull the mRNA out of solution through the use of magnets or centrifugal filters. Here, a simple method to isolate mRNA by complexing it with synthetic click nucleic acids (CNAs) is described. Oligo(T) CNA bound efficiently to mRNA, and because of the insolubility of CNA in water, >90% of mRNA was readily removed from solution using this method. Simple washing, buffer exchange, and heating steps enabled mRNA’s enrichment from total RNA, with a yield of 3.1 ± 1.5% of the input total RNA by mass, comparable to the yield from commercially available mRNA enrichment beads. Further, the integrity and activity of mRNA after CNA-facilitated pulldown and release was evaluated through two assays. In vitro translation of EGFP mRNA confirmed the translatability of mRNA into functional protein and RT-qPCR was used to amplify enriched mRNA from total RNA extracts and compare gene expression to results obtained using commercially available products.

Thermally transformable/responsive (meth)acrylate photopolymer networks were constructed from commercial (meth)acrylate esters and synthetic di- and mono(meth)acylate monomers bearing thioester functionalities. The thermal responsiveness, here self-limited exchange, relied on the catalytic metamorphosis of thioesters into esters with the concomitant depletion of hydroxyls and subsequent generation of free thiols. The thioester–hydroxyl cross-exchange was demonstrated in network systems with interchain thioesters as well as in networks with side-chain pendant thioacetyls. The interchain metamorphosis resulted in close to 80% conversion of thioesters into esters when 2 equiv of hydroxyl groups was initially present. In practical terms, such an outcome enabled efficient stress relaxation (60%) and good shape adaptation (90% shape fixity) in 1 h at 105 °C. On the other hand, side-chain S → O acyl transfer reactions were found to vary in efficiency depending on the vicinity of thioesters and hydroxyls. When in...

Free-radical polymerizations are used for a wide range of applications but are detrimentally impacted by the presence of oxygen. Zinc phthalocyanines have been previously used as singlet oxygen generators to excite radical-consuming ground-state triplet oxygen into its less reactive singlet state prior to photoexcitation of a photoinitiator. We report for the first time that polymerization can be achieved via irradiation of UV band of phthalocyanine and that photosensitization and photoinitiation can be independently achieved via irradiation of its two distinct absorption bands to reduce oxygen inhibition and initiate polymerization without the need for additional treatment. We propose a mechanism for this unique photoinitiation phenomenon and verify its feasibility via computational and experimental approaches. This new class of dual-photosensitive molecules shows promising utility in applications that are adversely impacted by the presence of oxygen, such as coatings and stereolithography.

In the present study, the photo-initiated copper-catalyzed azide-alkyne cycloaddition (CuAAC) polymerization was utilized to form structurally diverse glassy polymer networks. Systematic alterations in the monomer backbone rigidity (e.g., cyclic or aliphatic groups with a different length of backbone) and the reactive functional group density (e.g., tetra-, tri-, di-, and mono-functional azide and alkyne monomers) were used to provide readily tailorable network structures with crosslink densities (estimated from the rubbery modulus) varying by a factor of over 20. All eight of the resultant networks exhibited glass transition temperatures (T(g)) between 50 and 80 °C with tensile toughness ranging from 28 to 61 MJ m(−3). A nearly linear dependence of yield stress and elongation at break (broadly defined as strength and ductility, respectively) on the T(g) and rubbery modulus was established in these triazole networks. When a flexible di-alkyne monomer (5 carbon spacing between alkynes) was incorporated in a network composed of a tri-alkyne and di-azide monomer, the elongation at break was improved from 166 to 300 %, while the yield stress was reduced from 36 to 23 MPa. Additionally, the polymer ductility was also varied by incorporating mono-functional azides as chain ends in the network - replacing a sterically hindered stiff mono-azide with a more flexible mono-azide increased the elongation at break from 24 to 185 % and the tensile toughness from 6 to 28 MJ m(−3).

International audience; Surface modifications are typically permanent in shape and chemistry. Herein, vinylogous urethane (VU) chemistry is presented as an easily accessible and versatile platform for rapid, facile, and reworkable surface modification. It is demonstrated that both physical and chemical post-modification of permanent, yet dynamic elastic polymer networks are achieved. Surface patterns with high regularity are created, both via a straightforward replication process using a polydimethylsiloxane stamp (resolution ca. 10-100 µm) as well as using thermally activated nano-imprint lithography (NIL) to form hole, pillar, or line patterns (ca. 300 nm) in elastic VU-based vitrimers. The tunable, rapid exchange allows patterning at 130 °C in less than 15 min, resulting in an increased water contact angle and surface-structure induced light reflection. Moreover, it is also demonstrated that the use of a single dynamic covalent chemistry makes it possible to strongly adhere to fluorinated and non-fluorinated materials based on incompatible matrices, causing cohesive failure in a peel test. In a topography scan, the visibly transparent interface is shown to possess a continuous phase without a gap, while maintaining distinctively separated (non)-fluorinated domains. Finally, this approach allowed for a straightforward coating of a non-fluorinated material with a fluorinated monomer to minimize the overall fluorinated content.

The simultaneous delivery of multiple therapeutics to a single site has shown promise for cancer targeting and treatment. However, because of the inherent differences in charge and size between drugs and biomolecules, new approaches are required for colocalization of unlike components in one delivery vehicle. In this work, we demonstrate that triblock copolymers containing click nucleic acids (CNAs) can be used to simultaneously load a prodrug enzyme (cytosine deaminase, CodA) and a chemotherapy drug (doxorubicin, DOX) in a single polymer nanoparticle. CNAs are synthetic analogs of DNA comprised of a thiolene backbone and nucleotide bases that can hybridize to complementary strands of DNA. In this study, CodA was appended with complementary DNA sequences and fluorescent dyes to allow its encapsulation in PEG-CNA-PLGA nanoparticles. The DNA-modified CodA was found to retain its enzyme activity for converting prodrug 5-fluorocytosine (5-FC) to active 5-fluorouracil (5-FU) using a modified fluorescent assay. The DNA-conjugated CodA was then loaded into the PEG-CNA-PLGA nanoparticles and tested for cell cytotoxicity in the presence of the 5-FC prodrug. To study the effect of coloading DOX and CodA within a single nanoparticle, cell toxicity assays were run to compare dually loaded nanoparticles with nanoparticles loaded only with either DOX or CodA. We show that the highest level of cell death occurred when both DOX and CodA were simultaneously entrapped and delivered to cells in the presence of 5-FC.

Through thiol-ene photopolymerization of presynthesized oligomers, advanced clickable nucleic acids (CNA-2G) are synthesized with sequence-controlled repeating units. As examples, poly(thymine-adenine) (polyTA) CNA-2G and poly(thymine-thymine-cytosine) CNA-2G are synthesized by polymerizing thiol-ene heterofunctional dimers with pendant thymine-adenine nucleobases and trimer with pendant thymine-thymine-cytosine nucleobases. Based on size exclusion chromatography (SEC) analysis, polyTA and polyTTC have number average molecular weights of 2000 and 1800, respectively, which contain 7-8 pendant nucleobases. Based on the different behavior of the CNA-2G monomers and CNA-2G oligomers with two or more pendant nucleobases in photopolymerization, an unusual thiol-ene chain-growth propagation mechanism is observed for the former and a common thiol-ene step-growth propagation mechanism for the latter. The uncommon thiol-ene chain-growth propagation is hypothesized to rely on a six-membered ring mediated intramolecular hydrogen atom transfer process.

Efficient intracellular delivery of biomacromolecules such as proteins continues to remain a challenge despite its potential for medicine. In this work, we show that mScarlet, a non cytotoxic red fluorescent protein (RFP) conjugated to Click Nucleic Acid (CNA), a synthetic analog of DNA, undergo cell uptake significantly more than either native proteins or proteins conjugated with similar amounts of DNA in MDA-MB-468 cells. We further demonstrate that the process of cell uptake is metabolically driven and that scavenger receptors and caveolae mediated endocytosis play a significant role. Co-localization studies using anti-scavenger receptor antibodies suggest that scavenger receptors are implicated in the mechanism of uptake of CNA modified proteins.

A photocleavable membrane component was introduced into synthetic liposomes to achieve light-triggered pinocytosis-like behavior as a potential solution to the feeding requirement in protocell and bottom-up artificial cell systems. Light-triggered pinocytosis was observed in both elongated liposomes, prepared by lipid film hydration, and osmotically stressed spherical vesicles prepared by the pull-down method. Liposomes formed via lipid film hydration consistently underwent pinocytosis in cases of lobed structures or in prolate ellipsoidal structures with aspect ratios ≥2, suggesting that a critical volume-to-surface-area ratio is necessary to drive pinocytosis. When liposomes formed by the pull-down method were osmotically deformed prior to irradiation, an average of 44% exhibited pinocytosis. This light-driven pinocytosis behavior is hypothesized to be due to an asymmetric distribution of photocleavable lipid between the inner and outer leaflet, consistent with the observation that liposomes assembled a...

Here, a process is introduced for forming dual stage thiol-Michael/acrylate hybrid networks photocured by two different wavelengths, demonstrating its use in nanoimprint lithography (NIL) and shape memory materials. Initiated with a visible light sensitive photobase and a UV-sensitive radical initiator, thiol-Michael-acrylate hybrid polymerizations were programmed to proceed sequentially and orthogonally, with base-catalyzed thiol-Michael photopolymerization as the first stage and radical mediated acrylate photopolymerization as the second stage. By regulating the photopolymerization formulations, i.e. thiol-to-acrylate ratios, initiator loadings and irradiation conditions, a series of materials with highly tunable mechanical performance was achieved, with ultimate T(g) values ranging from 23 to 70 °C. With a photopatternable first stage and a readily reconfigurable second stage, its implementation in nanoimprint lithography (NIL) enabled surface features on the scale of 10 nm to be formed on a photopatterned substrate. Additionally, the dual stage polymer results in a relatively homogenous polymer network with a narrow glass transition temperature (Tg), which enables rapid response in applications as shape memory materials, with shape-fixity values above 95% and shaperecovery values above 99%. With its unique photocuring process and programmable mechanical properties, the two color light controlled photopolymerization can be exploited as a useful tool in a wide range of materials science applications.

Polymers that possess dynamic covalent bonds activated at ambient conditions are ideal platforms for smart, responsive materials. Herein, a class of dynamic covalent polymerizations is developed based on the thiol-thioester exchange, that is, transthioesterification, reaction. Shifts in the equilibrium extent of the exchange reactions are deliberately utilized to drive the formation of oligomers and polymers. In particular, a series of AB and A

Kinetic parameters and their influence on the overall rates of base-catalyzed thiol–Michael reactions proceeding via an alternating propagation and chain transfer cycle were evaluated. A kinetic model was developed that enables the determination and accurate prediction of the reaction kinetic paths for the thiol–Michael addition reaction and its accompanying polymerization. Individual kinetic parameters for propagation and chain transfer steps were evaluated for three commonly used thiol and vinyl functional monomers. Chain transfer and propagation kinetic parameters were determined in binary combinations of monomers from analysis of experimental data for the reaction rates. Subsequently, eight ternary thiol–Michael systems composed of thiol–acrylate–vinyl sulfone and thiol 1-thiol 2-vinyl were analyzed based on the binary kinetic model parameters. It was clearly demonstrated that the kinetic parameters determined from the binary reactions enabled an accurate prediction of the relative reactivity and sele...

This work details a novel polyurethane liquid crystal elastomer (PULCE) with exchangeable carbamate functional groups that enable programming of a uniformly aligned monodomain sample through the ap...

In this contribution, three o-nitrobenzyl-based photobase systems were synthesized and evaluated for visible light initiated thiol-Michael addition polymerizations. With a modified structure, the (3,4-methylenedioxy-6-nitrophenyl)-propyloxycarbonyl (MNPPOC) protected base performance exceeds that of the nonsubstituted 2-(2-nitrophenyl)-propyloxycarbonyl (NPPOC) protected base and an ITX sensitized photobase system, with respect to both long-wavelength light sensitivity and photolytic efficiency. In material synthesis, MNPPOC-TMG is capable of initiating photo thiol-Michael polymerization efficiently and orthogonally with only limited visible light exposure and generating a highly homogeneous cross-linked polymer network. This approach enables the thiol-Michael “click” reaction to be conducted with a low-energy, visible light irradiation and, thus, expands its applications in biocompatible and UV sensitive materials.

The recently developed synthetic oligonucleotides referred to as "click" nucleic acids (CNAs) are promising due to their relatively simple synthesis based on thiol-X reactions with numerous potential applications in biotechnology, biodetection, gene silencing, and drug delivery. Here, the cytocompatibility and cellular uptake of rhodamine tagged, PEGylated CNA copolymers (PEG-CNA-RHO) were evaluated. NIH 3T3 fibroblast cells treated for 1 h with 1, 10, or 100 μg/mL PEG-CNA-RHO maintained an average cell viability of 86%, which was not significantly different from the untreated control. Cellular uptake of PEG-CNA-RHO was detected within 30 s, and the amount internalized increased over the course of 1 h. Moreover, these copolymers were internalized within cells to a higher degree than controls consisting of either rhodamine tagged PEG or the rhodamine alone. Uptake was not affected by temperature (i.e., 4 or 37 °C), suggesting a passive uptake mechanism. Subcellular colocalization analysis failed to indicate significant correlations between the internalized PEG-CNA-RHO and the organelles examined (mitochondria, endoplasmic reticulum, endosomes and lysosomes). These results indicate that CNA copolymers are cytocompatible and are readily internalized by cells, supporting the idea that CNAs are a promising alternative to DNA in antisense therapy applications.

Multifunctional vinyl sulfonates and vinyl sulfonamides were conveniently synthesized and assessed in thiol-Michael crosslinking polymerizations. The monomer reactivities, mechanical behavior and hydrolytic properties were analyzed and compared with those of analogous thiol-acrylate polymerizations. Materials with a broad range of mechanical properties and diverse hydrolytic stabilities were obtained.

Here, we introduce photocuring as a tool for the spatiotemporal control of vitrimer network synthesis via a photoinitiated thiol–ene polymerization. A difunctional norbornene monomer was synthesized containing ester linkages and pendant alcohol groups to participate in transesterification bond reshuffling reactions. The transesterification catalyst 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) was shown to be highly effective in promoting transesterification in these networks at high temperatures, without interfering with external spatiotemporal, photoinitiated control over the thiol–ene polymerization and associated network formation. A strong Arrhenius dependence of the stress relaxation time with inverse temperature was observed from 145 to 175 °C, which suggests a relaxation controlled by the transesterification reaction rate, similar to previously studied thermally cured vitrimers. These thiol–ene vitrimers are implemented in nanoimprint lithography (NIL) for creating surface features, where imprinting m...

We report the synthesis of polymeric particles using radical mediated step-growth thiol-ene and thiol-yne ‘click’ dispersion polymerizations in alcoholic solvents. Various alkene, alkyne and thiol monomers were used, and thermal, photo- or redox initiation methods were all shown to be effective means to initiate polymerization. Polymer particles typically were formed with diameters in the range of several hundred nanometers, with narrow size distributions though broader than typical free-radical chain-growth dispersion polymerizations. Photoinitiation yielded the smallest sizes due to the rapid nucleation of particles as compared to redox and thermal initiation methods. Reaction kinetics were monitored by FT-IR spectroscopy for aliquot samples taken at various reaction durations. The reaction achieved full conversion in photoinitiated systems within five minutes, while it took three hours for both thermal and redox initiation to be completed. The effects of polymerization conditions on particle size particularly the impact of monomer, stabilizer, and initiator concentrations were studied. Generally, average particle size increased with higher monomer concentration and decreased with additional stabilizer or initiator. Combinations of monomers with varying number of functional groups were investigated to form particles of various mechanical and physical behavior, including both linear and crosslinked systems.

A kinetic mechanism and the accompanying mathematical framework are presented for base-mediated thiol–Michael photopolymerization kinetics involving a photobase generator. Here, model kinetic predictions demonstrate excellent agreement with a representative experimental system composed of 2-(2-nitrophenyl)propyloxycarbonyl-1,1,3,3-tetramethylguanidine (NPPOC-TMG) as a photobase generator that is used to initiate thiol–vinyl sulfone Michael addition reactions and polymerizations. Modeling equations derived from a basic mechanistic scheme indicate overall polymerization rates that follow a pseudo-first-order kinetic process in the base and coreactant concentrations, controlled by the ratio of the propagation to chain-transfer kinetic parameters (kp/kCT) which is dictated by the rate-limiting step and controls the time necessary to reach gelation. Gelation occurs earlier as the kp/kCT ratio reaches a critical value, wherefrom gel times become nearly independent of kp/kCT. The theoretical approach allowed determining the effect of induction time on the reaction kinetics due to initial acid–base neutralization for the photogenerated base caused by the presence of protic contaminants. Such inhibition kinetics may be challenging for reaction systems that require high curing rates but are relevant for chemical systems that need to remain kinetically dormant until activated although at the ultimate cost of lower polymerization rates. The pure step-growth character of this living polymerization and the exhibited kinetics provide unique potential for extended dark-cure reactions and uniform material properties. The general kinetic model is applicable to photobase initiators where photolysis follows a unimolecular cleavage process releasing a strong base catalyst without cogeneration of intermediate radical species.

Polysulfide network oxidative modification is presented. Fundamental differences between the properties of sufide-based and sulfone-based networks are discussed, and a method for producing the sulfone-based materials from thioether-based materials is developed. Oxidation enables significant mechanical property enhancements of polysulfide materials without any deleterious effects that typically accompany cross-linking polymerizations. Various application examples such as sulfide-containing particle modification and hardening of soft lithography or thiol–ene 3D microprinted objects are also shown.

In this letter, we present a robust covalent adaptable network (CAN) that relies on dynamic, exchangeable thiourethanes. A primary aliphatic isocyanate, hexamethylene diisocyanate (HDI), and a primary aliphatic thiol, ethoxylated-trimethylolpropane tri(3-mercaptopropionate) (EETMP), are employed to form a network that can fully relieve an applied stress at 90 °C in under 40 min through the thiourethane bond exchange with a low loading (1 mol%) of catalyst, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN). Based on the kinetic behavior of the dynamic chemistry, and as monitored via real-time FT-IR, synergetic dissociation and association mechanisms of the thiourethane bond exchange are proposed to explain the higher catalyst efficiency of the combined basic and nucleophilic catalyst, DBN, as compared to the strong basic catalyst, potassium tert-butoxide, and the strong nucleophilic catalyst, N-hetero carbene. Moreover, this thiourethane network exhibits excellent reprocessablity under relatively mild conditions (110 °C), which makes it a promising potential alternative to urethane materials in industry.

Due to the ability to generate oligomers of precise sequence, sequential and stepwise solid-phase synthesis has been the dominant method of producing DNA and other oligonucleotide analogues. The requirement for a solid support, however, and the physical restrictions of limited surface area thereon significantly diminish the efficiency and scalability of these syntheses, thus, negatively affecting the practical applications of synthetic polynucleotides and other similarly created molecules. By employing the robust photoinitiated thiol-ene click reaction, we developed a new generation of clickable nucleic acids (CNAs) with a polythioether backbone containing repeat units of six atoms, matching the spacing of the phosphodiester backbone of natural DNA. A simple, inexpensive, and scalable route was utilized to produce CNA monomers in gram-scale, which indicates the potential to dramatically lower the cost of these DNA mimics and thereby expand the scope of these materials. The efficiency of this approach was demonstrated by the completion of CNA polymerization in 30 seconds, as characterized by size-exclusive chromatography (SEC) and infrared (IR) spectroscopy. CNA/DNA hybridization was demonstrated by gel electrophoresis and used in CdS nanoparticle assembly.

Thiol lysolipids undergo thiol–thioester exchange with two phenyl thioester-functionalized tails to produce phospholipid structures that assemble into liposomes with differences in exchange rates, temperature sensitivity, permeability, and continued exchange behavior. This in situ formation reaction imparts dynamic characteristics into the membrane for downstream liposome functionalization and mimics native membrane remodeling.

Bulk photopolymerization of a library of synthesized multifunctional azides and alkynes was carried out toward developing structure–property relationships for CuAAC-based polymer networks. Multifunctional azides and alkynes were formulated with a copper catalyst and a photoinitiator, cured, and analyzed for their mechanical properties. Material properties such as the glass transition temperatures (Tg) show a strong dependence on monomer structure with Tg values ranging from 41 to 90 °C for the series of CuAAC monomers synthesized in this study. Compared to the triazoles, analogous thioether-based polymer networks exhibit a 45–49 °C lower Tg whereas analogous monomers composed of ethers in place of carbamates exhibit a 40 °C lower Tg. Here, the formation of the triazole moiety during the polymerization represents a critical component in dictating the material properties of the ultimate polymer network where material properties such as the rubbery modulus, cross-link density, and Tg all exhibit strong depen...