Ene Chemistry Research Articles

Synthesize Hyperbranched Polymers Carrying Two Reactive Handles via CuAAC Reaction and Thiol–Ene Chemistry

AbstractStructurally defined hyperbranched polymers (HBPs) bearing multiple azido peripheral groups and alkene dangling groups are constructed using the authors' recently developed chain‐growth copper‐catalyzed azide‐alkyne cycloaddition polymerization (CuAACP) of an alkene‐containing AB2 monomer. Sequential integration of CuAAC and photo‐initiated thiol–ene reactions proves highly efficient and chemo‐selective functionalization of polymers at different placements with quantitative yield of both reactive groups. A variety of HBPs carrying both surface and internal functionalities are then produced, achieving quantitative/ratiometric incorporations of guest molecules in most cases. To demonstrate possible conjugation with bioactive ingredients, well‐defined HBPs decorated with peripheral cysteine moieties are produced as an example, showing pH responsiveness in water.

Tailor-Engineered POSS-Based Hybrid Gels for Bone Regeneration.

Organic-inorganic oligo(ethylene glycol)-polyhedral oligomeric silsesquioxanes (OEGn-POSS) hybrid materials are woven into macroscopically shaped entities by thiol-ene chemistry. The mechanical behavior and interfacial nature of the OEGn-POSS materials are easily tailored by changing the length of OEGn. The nanostructured OEGn-POSS materials exhibited excellent bioactivity to form hydroxyapatite, whose morphology was also dependent on the molecular weight of OEGn. Among them, OEG2-POSS materials enhanced the in vitro differentiation of adipose-derived stem cells to osteoblasts and promoted the in vivo bone formation within a femoral condyle defect site, but they could be limited by the mismatch rates between the degradation and new bone formation. Thus, OEG2-POSS could be practically applied for bone regeneration by optimizing the degradation rate based on its key structural features, which would be of great benefit to bone tissue engineering in the future.

Tailored CO2-philic Gas Separation Membranes via One-Pot Thiol–ene Chemistry

Thiol–ene chemistry draws much attention nowadays in the construction of functional polymer materials due to its versatility and fast reaction kinetics, though only a few studies have been reported...

Phosphate-Based Cross-Linked Polymers from Iodo-ene Photopolymerization: Tuning Surface Wettability through Thiol-ene Chemistry.

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.

Ring-Opening Polymerization of Allyl-Functionalized Lactams

Aliphatic polyamides containing pendent allyl groups were prepared by anionic ring-opening copolymerization of e-caprolactam with monomer 1, the substituted lactam 3-(3-propenyl)-2-azepanone. Copolymerization experiments revealed that up to 11 mol % of 1 was integrated successfully into these novel polyamides, which ranged in molecular weight from 27 to 72 kDa. Relative to the well-known commercial polyamide-6 (PA-6), the degree of crystallinity of the copolymers decreased with incorporation of functional monomer. Moreover, the pendent allyl groups afforded rapid access to numerous functional aliphatic polyamides, using photoinitiated thiol–ene chemistry, providing a pathway to cross-linked polyamide films and gels.

Toughness enhancers for bone scaffold materials based on biocompatible photopolymers

ABSTRACTProviding access to the benefits of additive manufacturing technologies in tissue engineering, vinyl esters recently came into view as appropriate replacements for (meth)acrylates as precursors for photopolymers. Their low cytotoxicity and good biocompatibility as well as favorable degradation behavior are their main assets. Suffering from rather poor mechanical properties, particularly in terms of toughness, several improvements have been made over the last years. Especially, thiol–ene chemistry has been investigated to overcome those shortcomings. In this study, we focused on additional means to further improve the toughness of an already established biocompatible vinyl ester‐thiol formulation, eligible for digital light processing‐based stereolithography. All molecules were based on poly(ε‐caprolactone) as building block and the formulations were tested regarding their reactivity and the resulting mechanical properties. They all performed well as toughness enhancer, ultimately doubling the impact resistance of the reference system. © 2018 The Authors. Journal of Polymer Science Part A: Polymer Chemistry published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 110–119

Thiol−Ene Coupling in a Continuous Photo‐Flow Regime

AbstractPhotoinitiated thiol−ene chemistry is a promising technique for use in chemical synthesis and related sciences. In view of scaling, the process was successfully transferred to a continuous flow regime with compelling results in terms of selectivity, efficiency, and productivity. A series of selected thiols and enes were reacted using 2,2‐dimethoxy‐2‐phenylacetophenone as radical initiator to respond to the 365 nm UV‐LED source. Process parameters were evaluated and chemical cross‐reactivity of the different substrates was assessed. Optimization of conditions gave high productivity of the thio‐ether resulting from the model reaction between benzyl thiol and 1‐decene when performed under neat conditions. The robustness of this method was demonstrated by running it under continuous operation for an extended period of time, with product output reaching constant yields of 90–92 % as soon as the steady‐state regime was installed. The corresponding space–time yield was 9.75 kg l−1 h−1, an impressive value that further demonstrates scale‐up potential.

Solid‐Phase Thiol–Ene Lipidation of Peptides for the Synthesis of a Potent CGRP Receptor Antagonist

AbstractWe report a new method herein coined SP‐CLipPA (solid‐phase cysteine lipidation of a peptide or amino acid) for the synthesis of mono‐S‐lipidated peptides. This technique utilizes thiol–ene chemistry for conjugation of a vinyl ester to a free thiol of a semiprotected, resin‐bound peptide. Advantages of SP‐CLipPA include: ease of handling, conversions of up to 91 %, by‐product removal by simple filtration, and a single purification step. Additionally, the desired lipidated products show high chromatographic separation from impurities, thus facilitating RP‐HPLC purification. To showcase the utility of SP‐CLipPA, we synthesized a potent calcitonin gene‐related peptide (CGRP) receptor antagonist peptide in excellent yield and purity. This peptide, selected from a series of lipidated analogues of CGRP8–37 and CGRP7–37, has potential for the treatment of migraine.

Solid-Phase Thiol-Ene Lipidation of Peptides for the Synthesis of a Potent CGRP Receptor Antagonist.

We report a new method herein coined SP-CLipPA (solid-phase cysteine lipidation of a peptide or amino acid) for the synthesis of mono-S-lipidated peptides. This technique utilizes thiol-ene chemistry for conjugation of a vinyl ester to a free thiol of a semiprotected, resin-bound peptide. Advantages of SP-CLipPA include: ease of handling, conversions of up to 91 %, by-product removal by simple filtration, and a single purification step. Additionally, the desired lipidated products show high chromatographic separation from impurities, thus facilitating RP-HPLC purification. To showcase the utility of SP-CLipPA, we synthesized a potent calcitonin gene-related peptide (CGRP) receptor antagonist peptide in excellent yield and purity. This peptide, selected from a series of lipidated analogues of CGRP8-37 and CGRP7-37 , has potential for the treatment of migraine.

Optical Properties of Photopolymerized Thiol–Ene Polymers Fabricated Using Various Multivinyl Monomers

A common tetrathiol was combined with various multivinyl monomers via photoinitiated thiol–ene chemistry reactions to determine the impact of divinyl comonomers on the optical properties of the resulting polymers in comparison with the use of tetravinyl comonomers. The optical properties, thermal properties, and hydrophilic character of the resulting polymers were determined and compared with each other. The reactions resulted in transparent, hydrophilic materials that could be polymerized and molded. The results showed that divinyl comonomers polymerized with the common tetrathiol comonomer tended to have greater transmissive character but lower refractive indices than tetravinyl comonomers polymerized with the common tetrathiol comonomer. It was ultimately determined that the varying polymers could all be useful in optical applications that require transparent, soft, or nonhydrophobic materials.

Surfaces Decorated with Polymeric Nanocompartments for pH Reporting

Here we present a novel active surface that demonstrates pH responsiveness and can be used as a platform for designing ‘smart labels’. To generate our active surfaces, we immobilized polymer nanocompartments onto glass surfaces using thiol–ene chemistry. Prior to surface attachment, a pH responsive model dye was encapsulated within nanocompartments at two different pH values. We confirmed the attachment and distribution of dye‐loaded polymersomes and established the pH responsiveness of the active surface construct. The strategy presented here was carefully chosen to obtain small sized functional surfaces from commercially available materials that can be easily integrated into intelligent packaging systems. The ability to miniaturize such smart labels, while still being able to detect their response to the environment, is a crucial step towards developing active surfaces suitable for food packaging applications.

Thiol-substituted copolylactide: synthesis, characterization and post-polymerization modification using thiol–ene chemistry

A copolylactide that is substituted with pendent thiol groups (thiol-PL) undergoes coupling with a variety of electrophiles under mild conditions via thiol–ene addition.

Utilizing thiol–ene chemistry for crosslinked nickel cation‐based anion exchange membranes

ABSTRACTMetal cation‐based anion exchange membranes (AEMs) are a unique class of materials that have shown potential to be highly stable AEMs with competitive conductivities. Here, we expand upon previous work to report the synthesis of crosslinked nickel cation‐based AEMs formed using the thiol–ene reaction. These thiol–ene‐based samples were first characterized for their morphology, both with and without nickel cations, where the nickel‐containing membranes demonstrated a disordered scattering peak characteristic of ionic clusters. The samples were then characterized for their water uptake, chemical and mechanical stability, and conductivity. They showed a combination of high water content and extreme brittleness, which also resulted in fairly low conductivity. The brittleness resulted from large water swelling as well as the need for each nickel cation to act as a crosslinker, necessary with the current nickel‐coordination chemistry. Therefore, increasing the ion exchange capacity (IEC) for these types of AEMs, important for enhancing conductivity, also increased the crosslink density. The low conductivity and brittleness seen in this work demonstrated the need to develop non‐crosslinking metal‐complexes. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 328–339

Renewable Thiol–Ene Thermosets Based on Refined and Selectively Allylated Industrial Lignin

Aromatic material constituents derived from renewable resources are attractive for new biobased polymer systems. Lignin, derived from lignocellulosic biomass, is the most abundant natural source of such structures. Technical lignins are, however, heterogeneous in both structure and polydispersity and require a refining to obtain a more reproducible material. In this paper the ethanol-soluble fraction of Lignoboost Kraft lignin is selectively allylated using allyl chloride by means of a mild and industrially scalable procedure. Analysis using 1H-, 31P-, and 2D HSQC NMR give a detailed structural description of lignin, providing evidence of its functionalization and that the suggested procedure is selective toward phenols with a conversion of at least 95%. The selectively modified lignin is subsequently cross-linked using thermally induced thiol–ene chemistry. FT-IR is utilized to confirm the cross-linking reaction, and DSC measurements determined the Tg of the thermosets to be 45–65 °C depending on reactiv...

Thiol–Ene (Click) Reactions as Efficient Tools for Terpene Modification

AbstractThis Focus Review highlights the application of thiol–ene (click) chemistry to the production of a diverse range of materials that are derived from terpenes. To present an overview concerning the potency of terpenes as renewable resources, recent advances in their development by using synthetic organic chemistry are initially discussed. In addition, the use of thiol–ene chemistry as an efficient approach and versatile tool for noncatalytic carbon−heteroatom bond formation is briefly presented, including mechanistic and kinetic aspects, as well as some structural considerations, that is, the influence of the thiol and olefin structures, which should be well‐thought‐out before applying such chemistry. This discussion also covers how an initiator works and its effect on the reaction rate. Moreover, the utilization of thiol–ene reactions for the synthesis of terpene‐based valuable platform chemicals, monomers, and polymers, including recent examples that demonstrate its broad utility, are highlighted.

An Approach to the High-Throughput Fabrication of Glycopolymer Microarrays through Thiol–Ene Chemistry

The fabrication of microarrays consisting of well-defined glycopolymers is described. This was achieved by postfunctionalization of an immobilized poly(allyl glycidyl ether) using unprotected thiol-modified carbohydrates through thiol–ene conjugation chemistry. This enabled the fabrication of glycopolymer microarrays in which the density and composition of the carbohydrate moieties varied along each of the polymer chains displayed across the array. These glycopolymer microarrays were applied in the evaluation of multivalent ligand–protein interactions with the determination of surface dissociation constants (KD) with concanavalin A and Ricinus communis agglutinin I for surface immobilized mannose-, glucose-, and galactose-containing glycopolymers and validated in solution with ITC.

Robust, Uniform, and Highly Emissive Quantum Dot-Polymer Films and Patterns Using Thiol-Ene Chemistry.

This work demonstrates a facile and versatile method for generating low scattering cross-linked quantum dot (QD)-polymer composite films and patterned highly emissive structures with ultrahigh QD loading, minimal phase separation, and tunable mechanical properties. Uniform QD-polymer films are fabricated using thiol-ene chemistry, in which cross-linked polymer networks are rapidly produced in ambient conditions via fast UV polymerization in bulk to suppress QD aggregation. UV-controlled thiol-ene chemistry limits phase separation through producing highly QD loaded cross-linked composites with loadings above majority of those reported in the literature (<1%) and approaching 30%. As the QD loading is increased, the thiol and ene conversion decreases, resulting in nanocomposites with widely variable and tailorable mechanical properties as a function of UV irradiation time with an elastic modulus decreasing to 1 GPa being characteristic of reinforced elastomeric materials, in contrast to usually observed stiff and brittle materials under these loading conditions. Furthermore, we demonstrate that the thiol-ene chemistry is compatible with soft-imprint lithography, making it possible to pattern highly loaded QD films while preserving the optical properties essential for high gain and low optical loss devices. The versatility of thiol-ene chemistry to produce high-dense QD-polymer films potentially makes it an important technique for polymer-based elastomeric optical metamaterials, where efficient light propagation is critical, like peculiar waveguides, sensors, and optical gain films.

Nanostructured Surfaces through Immobilization of Self‐Assembled Polymer Architectures Using Thiol–Ene Chemistry

An efficient strategy for engineering nanostructured surfaces by coupling soft polymeric nanoarchitectures to functionalized surfaces is presented. Self‐assembly of polymeric nanoarchitectures from amphiphilic triblock copolymers can yield both filled and hollow spherical nanoarchitectures, depending on the properties of the polymer chosen. These nanoarchitectures are immobilized on solid substrates via a biocompatible thiol–ene reaction, and conditions are optimized to maintain structural integrity of polymeric assemblies. Two routes of surface modification are also implemented to allow inclusion of a polymeric spacer that can mediate between soft polymeric assemblies and solid substrates. Nanostructured surfaces with both filled and hollow nanoarchitectures attached to the surface directly or with a spacer are successfully generated with this protocol. This concept of generating nanostructured surfaces using preassembled polymeric architectures is an important step toward active surfaces, because entrapment of active molecules in the nanoarchitectures prior to their immobilization opens the door to easy generation of surfaces with predetermined activities. image

Fully degradable protein nanocarriers by orthogonal photoclick tetrazole–ene chemistry for the encapsulation and release

The encapsulation of sensitive drugs into nanocarriers retaining their bioactivity and achieving selective release is a challenging topic in current drug delivery design. Established protocols rely on metal-catalyzed or unspecific reactions to build the (mostly synthetic) vehicles which may inhibit the drug's function. Triggered by light, the mild tetrazole-ene cycloaddition enables us to prepare protein nanocarriers (PNCs) preserving at the same time the bioactivity of the sensitive antitumor and antiviral cargo Resiquimod (R848). This catalyst-free reaction was designed to take place at the interface of aqueous nanodroplets in miniemulsion to produce core-shell PNCs with over 90% encapsulation efficiency and no unwanted drug release over storage for several months. Albumins used herein are major constituents of blood and thus ideal biodegradable natural polymers for the production of such nanocarriers. These protein carriers were taken up by dendritic cells and the intracellular drug release by enzymatic degradation of the protein shell material was proven. Together with the thorough colloidal analysis of the PNCs, their stability in human blood plasma and the detailed protein corona composition, these results underline the high potential of such naturally derived drug delivery vehicles.

Synthesis and functionalization of polymer networks via germane–ene chemistry

Germane–ene polymer networks are prepared by utilizing Ge–H bonds with suitable crosslinkers; the materials are ideally suited for post polymer functionalization.