Thiol-yne Click Research Articles

Synthesis and Characterization of Alkyne-Functionalized Photo-Cross-Linkable Polyesters.

An alkyne-functionalized elastomer derived from sebacic acid, 1,3-propanediol, and alkyne-functionalized serinol is synthesized via melt condensation. A low-power UV lamp triggers the cross-linking rapidly via thiol–yne click chemistry. The cross-linking behavior is studied by photorheology and NMR spectroscopy. The resultant elastomer possesses mechanical properties similar to those of human soft tissues and exhibits in vitro degradability and good cytocompatibility.

Click Synthesis Enabled Sulfur Atom Strategy for Polymerization‐Enhanced and Two‐Photon Photosensitization

AbstractFacile tailoring of photosensitizers (PSs) with advanced and synergetic properties is highly expected to broaden and deepen photodynamic therapy (PDT) applications. Herein, a catalyst‐free thiol–yne click reaction was employed to develop the sulfur atom‐based PSs by using the in situ formed sulfur “heavy atom effect” to enhance the intersystem crossing (ISC), while such an effect can be remarkably magnified by the polymerization. The introduction of a tetraphenylpyrazine‐based aggregation‐induced emission (AIE) unit was also advantageous in PS design by suppressing their non‐radiative decay to facilitate the ISC in the aggregated state. Besides, the resulting sulfur atom electron donor, together with a double‐bond π bridge and AIE electron acceptor, created a donor‐π‐acceptor (D‐π‐A) molecular system with good two‐photon excitation properties. Combined with the high singlet oxygen generation efficiency, the fabricated polymer nanoparticles exhibited an excellent in vitro two‐photon‐excited PDT towards cancer cells, therefore possessing a huge potential for the deep‐tissue disease therapy.

Click Synthesis Enabled Sulfur Atom Strategy for Polymerization-Enhanced and Two-Photon Photosensitization.

Facile tailoring of photosensitizers (PSs) with advanced and synergetic properties is highly expected to broaden and deepen photodynamic therapy (PDT) applications. Herein, a catalyst-free thiol-yne click reaction was employed to develop the sulfur atom-based PSs by using the in situ formed sulfur "heavy atom effect" to enhance the intersystem crossing (ISC), while such an effect can be remarkably magnified by the polymerization. The introduction of a tetraphenylpyrazine-based aggregation-induced emission (AIE) unit was also advantageous in PS design by suppressing their non-radiative decay to facilitate the ISC in the aggregated state. Besides, the resulting sulfur atom electron donor, together with a double-bond π bridge and AIE electron acceptor, created a donor-π-acceptor (D-π-A) molecular system with good two-photon excitation properties. Combined with the high singlet oxygen generation efficiency, the fabricated polymer nanoparticles exhibited an excellent in vitro two-photon-excited PDT towards cancer cells, therefore possessing a huge potential for the deep-tissue disease therapy.

Cover Picture: 3D Printing of Thiol‐Yne Photoresins through Visible Light Photoredox Catalysis (ChemistrySelect 10/2022)

The cover picture shows the visible light active thiol-yne photoresin formulation and 3D printing of a Chinese Knot under the irradiation of blue light. The thiol-yne photoresin can be photopolymerized via photoredox catalysis mechanism. The use of dual photocatalysts system by Eosin Y and fac-Ir(ppy)3 not only facilitates the faster thiol-yne click reaction but also potentially enables wider visible light wavelength coverage for 3D printing process. This work enriches the photoresin formulations for polymer-based 3D printing industry. The cover artwork was designed by Yimei Wu and Jianyong Jin. More information can be found in the Research Article by Jianyong Jin et al. (DOI: 10.1002/slct.202200319).

Fast Gelation of Poly(ionic liquid)-Based Injectable Antibacterial Hydrogels.

Traditional antibacterial hydrogels have a broad-spectrum bactericidal effect and are widely used as wound dressings. However, the biological toxicity and drug resistance of these antibacterial hydrogels cannot meet the requirements of long-term clinical application. Imidazolium poly(ionic liquids) (PILs) are polymeric antibacterial agents exhibiting strong antibacterial properties, as they contain a strong positive charge. In this study, two imidazolium PILs, namely poly(N-butylimidazolium propiolic acid sodium) (PBP) and poly(N-(3,6-dioxaoctane) imidazolium propiolic acid sodium) (PDP), as high efficiency antibacterial agents, were synthesized by polycondensation reaction. Then, the PILs were compounded with polyethylene glycol (PEG) by a thiol-yne click reaction to prepare injectable antibacterial hydrogels. An in vitro assay showed that the injectable antibacterial hydrogels could not only quickly kill Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), but also had low toxicity for human skin fibroblasts cells (HSFs) and human umbilical vein endothelial cells (HUVECs), respectively. Additionally, the lipopolysaccharide (LPS) inflammation model revealed that the injectable antibacterial hydrogels also had anti-inflammatory effects, which would be advantageous to accelerate wound healing.

Synthesis of vegetable oil-based hyperbranched polyol via thiol-yne click reaction and their application in polyurethane

A novel bio-based hyperbranched polyol (HBP) with high functionality was prepared from grapeseed oil (GSO) through the following sequential steps: i) epoxidation, ii) propargylation and iii) thiol-yne click reaction. Structural analysis confirmed that the GSO-based HBP was synthesized successfully; and the hydroxyl value of the synthesized HBP was 612 mg KOH/g, which is close to that of commercialized HBP. Furthermore, the prepared HBP was employed as a crosslinker to fabricate bio polyurethane (PU) films via a two-step prepolymer polymerization. The successful synthesis of hyperbranched PUs was confirmed by Fourier transform infrared analysis. Moreover, according to the results of X-ray diffraction analysis, the crystallinity of the prepared hyperbranched PUs decreased because the crosslinked networks hindered the formation of crystalline structures. Based on the mechanical property analysis, it was confirmed that the tensile strength and elongation of PU using HBP reached 27 MPa and 2315%, respectively. From these results, it can be confirmed that the tensile strength and tensile elongation of the PUs significantly increased upon the introduction of a crosslinker with a hyperbranched structure.

Porous organic polymers (POPs) membrane via thiol-yne click chemistry for efficient particulate matter capture and microplastics separation

In viewing the serious environmental issues caused by microplastics and air pollution, it is of great significance to capture microplastics in water and harmful particulate matter (PM) in atmosphere for maintaining human health. In this study, we report the synthesis of porous composite membrane, which was fabricated using 1,4-phenyldimercaptans and 1,3,5-triacetylbenzene as building blocks via a click chemistry, for microplastics filtration and PM capture. By using polystyrene fluorescent microspheres with a diameter of 0.1 μm as simulated microplastics, the filtration efficiency of the as-resulted porous composite membrane (PCM) was measure to be 90.92% by fluorescence analysis. The results obtained from infrared microspectrography also show that the PCM has superior removal performance for microplastics in terms to urban domestic wastewater. In the case of PM capture, the removal efficiencies of PCM for PM 2.5 and PM 10 were measured as high as 99.90% ± 0.42% and 99.93% ± 0.26%, respectively. Moreover, its removal efficiency for PM can remain nearly unchanged within 30 h. Owing to the flexible kapok fibers as supporting layer of PCM, the PCM possesses good mechanical properties and could be prepared without limitation in size and shape on a large scale under mild conditions, thus showing great potential for practical applications of microplastic removal and PM capture. • A porous composite membrane based on porous organic polymers (POPs) was prepared. • The POPs was synthesized via a thiol-yne click chemistry. • The porous composite membrane has excellent flexibility and mechanical strength. • The porous composite membrane possesses high efficiency for PM capture. • The porous composite membrane shows high efficiency for microplastics separation.

Synthesis and structural studies of Cu(i) methylthiosalicylate complexes and their catalytic application in thiol-yne click reaction

Three complexes of Cu(i), [Cu(PPh3)2(mts)] (1), [Cu(dppf)(mts)] (2) and [Cu(dppe)(mts)]2 (3) (mts = methylthiosalicylate; dppf = diphenylphosphinoferrocene; dppe = diphenylphosphinoethane), have been synthesized and characterized.

Development of a highly efficient in-tube solid-phase microextraction system coupled with UHPLC-MS/MS for analyzing trace hydroxyl polycyclic aromatic hydrocarbons in biological samples.

Hydroxyl polycyclic aromatic hydrocarbons are considered active mutagenic and carcinogenic substances and are found in extremely low levels (ng/g) in biological samples. As a result, their determination in urine and blood samples is challenging, and a sensitive and effective method for the analysis of trace hydroxyl polycyclic aromatic hydrocarbons in complex biological matrices is required. In this work, a novel macroporous in-tube solid-phase microextraction monolith was prepared via a thiol-yne click reaction, and a highly efficient analytical method based on in-tube solid-phase microextraction coupled with UHPLC-MS/MS was developed to determine hydroxyl polycyclic aromatic hydrocarbons with low detection limits of 0.137-11.0ng/L in complex biological samples. Four hydroxyl polycyclic aromatic hydrocarbons, namely, 2-hydroxyanthraquinone, 1-hydroxypyrene, 1,8-dihydroxyanthraquinone, and 6-hydroxychrysene, were determined in the urine samples of smokers, non-smokers, and whole blood samples of mice. Satisfactory recoveries were achieved in the range of 83.1-113% with relative standard deviations of 3.2-9.7%. It was found that implementation of the macroporous monolith gave a highly efficient approach for enriching trace hydroxyl polycyclic aromatic hydrocarbons in biological samples.

Synthesis and branching structure detection of long-subchain hyperbranched polymers via pyrene-labelled methodology

Long-subchain hyperbranched polymers (LHPs) are macromolecules with complex topological structures that have been extensively studied by researchers. However, the interior branching structure characterization of LHPs remains a challenging topic. In this contribution, LHPs were fabricated through stepwise growth of anionic polymerized AB2 polystyrene macromonomers bearing one Si–H group and two alkyne groups using a hydrosilylation coupling reaction. By varying the reaction solution concentration, LHPs with diverse weight-average degree of polymerization (Dpw) and branching factors (g’) were obtained. Pyrene moieties were efficiently attached to the obtained LHPs by thiol-yne click reaction, and the fluorescence manners of the pyrene chromophores on the LHPs were investigated. The fraction of residual double alkyne (DA) to total alkynes-fDA was proposed as a new parameter to describe the branching structure perfectness of LHPs. IE/IM to fDA calibration curves were built. fDA can be easily determined by IE/IM obtained from fluorescence tests. This study will offer a feasible method to character branching structure perfectness of complex topological polymers.

A facile method for grafting hyperbranched poly(thiol ether-ester) onto MWCNTs via thiol-yne click chemistry and their dispersion and oxidation responsive properties

A novel and facile approach was described to graft hyperbranched poly(thiol ether-ester) (HPTEE) onto the multi-walled carbon nanotubes (MWCNTs) via thiol-yne click chemistry. The covalent grafting between HPTEE and MWCNTs was characterized through FT-IR, TGA, XPS and TEM techniques. Experimental results indicate that HPTEE chains were covalently grafted onto MWCNTs surface. The grafting content of HPTEE is about 22.9%, and the thickness of HPTEE grafted on MWCNTs is about 3–5 nm. The results of dispersibility test indicate that the dispersion stability of the MWCNTs-HPTEE in water was greatly improved as compared with the raw MWCNTs. Additionally, we demonstrate that the obtained MWCNTs-HPTEE were tested to be oxidation responsive because of the presence of oxidizable thioether groups in the grafting of hyperbranched polymers on the MWCNTs surface.

Highly Refractive Polyimides Derived from Efficient Catalyst-Free Thiol–Yne Click Polymerization

Polyimides (PIs), owing to their inherent high refractive index and excellent physical properties, are required in advanced optical applications. They are traditionally synthesized through conventional two-step polycondensation, followed by high-temperature or chemical imidization, inevitably increasing energy consumption, environmental pollution, and production duration. Herein, for the first time, we synthesized PIs consisting of vinylene sulfide linkages via an efficient catalyst-free thiol–yne click polymerization, which would be accomplished within 2 h at 25 °C by simply mixing the dithiols and bisimide-containing diynes in THF, affording PIs with tensile strength ranging from 106.3 to 114.9 MPa, glass transition temperature up to 238 °C, thermal decomposition temperature as high as 381 °C, and desirable solubility, so that it was easily cast from solution into tough films. Moreover, the BPADA-TBT PI film demonstrates good optical performance, with its refractive index exceeding 1.70 at 633 nm and transmittance above 81% at 450 nm, making it a potential candidate in advanced optical applications.

Thiol-Yne Click Postsynthesis of a Sulfonate Group-Enriched Magnetic Microporous Organic Network for Efficient Extraction of Benzimidazole Fungicides.

The lack of functional groups or binding sites largely hindered the broad application of microporous organic networks (MONs). Herein, we report the fabrication of the sulfonate group-enriched magnetic MON composite (MMON-SO3H@SO3Na) via the combination of the sulfonic acid group containing the monomer and thiol-yne click postmodification for efficient magnetic solid-phase extraction (MSPE) of benzimidazole fungicides (BZDs) from complex sample matrices. The well-defined core-shell-structured MMON-SO3H@SO3Na was obtained and served as an advanced adsorbent for MSPE for concentrating and monitoring trace BZDs. The MMON-SO3H@SO3Na with numerous sulfonate groups provides plenty of ion-exchange, hydrogen-bonding, and π-π sites, leading to the favorable affinity to BZDs via multiple interaction mechanisms. The MMON-SO3H@SO3Na-based MSPE-high-performance liquid chromatography method afforded a wide linear range, low limits of detection, large enrichment factors, good precisions, and reusability for BZDs. Trace BZDs in complex vegetables and fruit samples were successfully detected by the established method. The MMON-SO3H@SO3Na also exhibited good selectivity toward multiple types of polar contaminants containing hydrogen-bonding sites and aromatic structures. This work provided a new postsynthesis strategy for constructing novel and multifunctioned magnetic MONs for preconcentration of trace analytes in a complex matrix.

Free radical polymerization of acrylates bearing acetylene for preparation of clickable polymers

It is still a challenge to directly, without any control means, synthesize polymers bearing acetylene groups by normal free radical polymerization (FRP) of acetylenyl vinyl monomers, such as propargyl (meth)acrylates, because the reactive acetylene groups result in chain branching and gelation. Some propargyl acrylates with alkyl substitutes, however, can afford linear and soluble polymers. To clarify the substitute effects the FRP behaviours of a series of acrylates bearing acetylene groups with or without substitutes are studied. Homopolymerizations of acetylenyl acrylates without or with mono-substitute on propargyl led to branched polymers at early reaction stage, and became gelled after 0.5 h with monomer conversion over 12% and gel content over 50%. The acetylenyl acrylates with di-substitutes on propargyl can afford linear and soluble homo- and copolymers with‾Mn up to over 10,000 and with 45–75% monomer conversion, except for monomer 2-(2-methylbut-3-yn-2-yloxy)ethyl acrylate (DMPOEA) which has di-substitutes and a spacer connecting to the propargyl. Reactivities of vinyl and acetylene groups were found within 20 times difference by laser flash photolysis (LFP) experiments. The substitute effects of acetylenyl acrylates on FRP are explained by the intramolecular cycloaddition between CC and CC to form lactone from the s-cis conformers of the di-alkyl substituted acetylenyl acrylates. Propagating radicals can transform to stable allyl radicals by α-H atom transfer and thus the chain propagations stop. Both real-time FT-IR monitoring of photo-polymerization and high resolution 13C NMR spectra of the polymer confirmed the existence of lactone units on polymer chains. The hypothesis is also accordance with facts obsorved in the FRP. Finally postpolymerization modification through acetylene groups on polymer chains by photo thiol-yne click reaction is exemplified.

Thiol-yne click reaction mediated photoelectrochemical detection of multi-sulfhydryl compounds based on diacetylene functionalized conjugated polymer

Most existing solutions for thiol detection require the addition of extra chemical agents to produce detection signals. However, the tedious operations in the sensing process are unfavorable for the real-time dynamic detection of thiol molecules. Herein, we present an all-organic graphene/poly(1,3,5-triethynylbenzene) (PTEB) composite for rapid and direct photoelectrochemical (PEC) analysis of multi-sulfhydryl compounds through specific thiol-yne click reaction. The non-covalent interfacial π-π interaction between the graphene and PTEB improves the optoelectronic properties of PTEB, which sensitizes the photocathode toward thiol detection with high sensitivity, broad linear range, and low detection limit. The theoretical calculation reveals that abundant 1,3-diyne linkages of PTEB are -SH sensitive active sites in PEC detection. Furthermore, a homemade sensing instrument has achieved real-time monitoring of thiol, suggesting its feasibility as an online sensor or a reaction monitor embedded in the industrial production line. Such progress holds promise for developing a diacetylene functionalized conjugated polymers-based -SH responsive platform for practical application in chemical production and quality control.

Room-Temperature Synthesis of a Hollow Microporous Organic Polymer Bearing Activated Alkyne IR Probes for Nonradical Thiol-yne Click-Based Post-Functionalization.

This work shows that hollow microporous organic polymer (H-MOP-A) with activated internal alkynes as IR probes can be prepared by template synthesis based on acyl Sonogashira-Hagihara coupling at room temperature. The H-MOP-A is a versatile platform in the main chain PSM based on nonradical thiol-yne click reaction. Moreover, an IR peak of internal alkynes in the H-MOP-A is very intense and could be utilized in the monitoring of thiol-yne click-based main chain PSM. The functionalized H-MOP-A with carboxylic acids (H-MOP-CA) showed efficient adsorption toward Ag+ ions. The resultant H-MOP-CA-Ag showed excellent performance in the CO2 fixation to α-alkylidene cyclic compounds.

High Refractive Index Photopolymers by Thiol-Yne "Click" Polymerization.

A scalable synthesis of high refractive index, optically transparent photopolymers from a family of low-viscosity multifunctional thiol and alkyne monomers via thiol-yne "click" is described herein. The monomers designed to incorporate high refractive index cores consisting of aryl and sulfide groups with high intrinsic molar refraction were synthesized starting from commercially available low-cost raw materials. The low-viscosity (<500 cP) thiol-yne resins formulated with these new multifunctional monomers and a phosphine oxide photoinitiator underwent efficient thiol-yne polymerizations upon exposure to 405 nm light at 30 mW/cm2. In contrast to the previously reported thiol-ene systems, the kinetic profile of these photopolymerizations showed significant dependence on the nature of the thiol and alkyne monomers. However, the ability of the thiol-yne reaction to introduce a large number of sulfide linkages compared to that of thiol-ene systems yielded cross-linked high optical quality photopolymers with a polymer refractive index that exceeds 1.68 (nD/20 °C). Interestingly, the photopolymer formed from the least sterically hindered alkynyl thioether monomer 2b with flexible thioether core and the dithiol 1a exhibited unprecedented difference in the polymer refractive index as compared to that of the resin with polymerization-induced changes reaching up to 0.08. Furthermore, the implementation of these low-viscosity thiol-yne resins was demonstrated by preparing two-stage photopolymeric holographic materials with a dynamic range of ∼0.02 and haze < 1.5% in two-dimensional high refractive index structures.

Two-step immobilization of metronidazole prodrug on TEMPO cellulose nanofibrils through thiol-yne click chemistry for in situ controlled release

Nowadays, drug encapsulation and drug release from cellulose nanofibrils systems are intense research topics, and commercial grades of cellulose nanomaterials are currently available. In this work we present an ester-containing prodrug of metronidazole that is covalently bound to cellulose nanofibrils in aqueous suspension through a two-step immobilization procedure involving green chemistry principles. The presence of the drug is confirmed by several characterization tools and methods such as Raman spectroscopy, elemental analysis, Dynamic Nuclear Polarization enhanced NMR. This technique allows enhancing the sensitivity of NMR by several orders of magnitude. It has been used to study cellulose nanofibrils substrates and it appears as the ultimate tool to confirm the covalent nature of the binding through thiol-yne click chemistry. Moreover, the ester function of the immobilized prodrug can be cleaved by specific enzyme activity thus allowing controlled drug release.

Selective removal of toxic organic dyes using Trӧger base-containing sulfone copolymers made from a metal-free thiol-yne click reaction followed by oxidation.

Three copolymers TCP1–3 bearing Trӧger's base (TB) units intercalated with various thioether groups were synthesized using a catalyst-free thiol-yne click reaction. TCP1–3 display excellent solubility in common organic solvents allowing for their structural, and photophysical characterization. The thioether groups in TCP1–3 were selectively oxidized into their respective sulfone derivatives under mild oxidation reaction conditions affording the postmodified copolymers TCP4–6. Investigation of organic dye uptake from water by TCP1–6 proved their efficiency as selective adsorbents removing up to 100% of the cationic dye methylene blue (MEB) when compared to anionic dyes, such as Congo red (CR), methyl orange (MO) and methyl blue (MB). The sulfone-containing copolymers TCP4–6 display superior and faster MEB removal efficiencies with respect to their corresponding synthons TCP1–3.

Thiol-yne click reaction: an interesting way to derive thiol-provided catechols.

The hydrothiolation of activated alkynes is presented as an attractive and powerful way to functionalize thiols bearing catechols. The reaction was promoted by a heterogeneous catalyst composed of copper nanoparticles supported on TiO2 (CuNPs/TiO2) in 1,2-dichloroethane (1,2-DCE) under heating at 80 °C. The catalyst could be recovered and reused in three consecutive cycles, showing a slight decrease in its catalytic activity. Thiol derivatives bearing catechol moieties, obtained through a versatile Michael addition, were reacted with different activated alkynes, such as methyl propiolate, propiolic acid, propiolamide or 2-ethynylpyridine. The reaction was shown to be regio- and stereoselective towards anti-Markovnikov Z-vinyl sulfide in most cases studied. Finally, some catechol derivatives obtained were tested as ligands in the preparation of coordination polymer nanoparticles (CNPs), by taking the advantage of their different coordination sites with metals such as iron and cobalt.