Bacteria‐Based Production of Thiol‐Clickable,Genetically Encoded Lipid Nanovesicles

Despite growing research efforts on the preparation of (bio)functional liposomes, synthetic capsules cannot reach the densities of protein loading and the control over peptide display that is achieved by natural vesicles. Herein, a microbial platform for high‐yield production of lipidic nanovesicles with clickable thiol moieties in their outer corona is reported. These nanovesicles show low size dispersity, are decorated with a dense, perfectly oriented, and customizable corona of transmembrane polypeptides. Furthermore, this approach enables encapsulation of soluble proteins into the nanovesicles. Due to the mild preparation and loading conditions (absence of organic solvents, pH gradients, or detergents) and their straightforward surface functionalization, which takes advantage of the diversity of commercially available maleimide derivatives, bacteria‐based proteoliposomes are an attractive eco‐friendly alternative that can outperform currently used liposomes.     

Clickable Nucleic Acids: Sequence‐Controlled Periodic Copolymer/Oligomer Synthesis by Orthogonal Thiol‐X Reactions

Synthetic polymer approaches generally lack the ability to control the primary sequence, with sequence control referred to as the holy grail. Two click chemistry reactions were now combined to form nucleobase‐containing sequence‐controlled polymers in simple polymerization reactions. Two distinct approaches are used to form these click nucleic acid (CNA) polymers. These approaches employ thiol–ene and thiol‐Michael reactions to form homopolymers of a single nucleobase (e.g., poly(A)_n) or homopolymers of specific repeating nucleobase sequences (e.g., poly(ATC)_n). Furthermore, the incorporation of monofunctional thiol‐terminated polymers into the polymerization system enables the preparation of multiblock copolymers in a single reaction vessel; the length of the diblock copolymer can be tuned by the stoichiometric ratio and/or the monomer functionality. These polymers are also used for organogel formation where complementary CNA‐based polymers form reversible crosslinks.     

Secondary‐Ion Mass Spectrometry of Genetically Encoded Targets

Secondary ion mass spectrometry (SIMS) is generally used in imaging the isotopic composition of various materials. It is becoming increasingly popular in biology, especially for investigations of cellular metabolism. However, individual proteins are difficult to identify in SIMS, which limits the ability of this technology to study individual compartments or protein complexes. We present a method for specific protein isotopic and fluorescence labeling (SPILL), based on a novel click reaction with isotopic probes. Using this method, we added ¹⁹F‐enriched labels to different proteins, and visualized them by NanoSIMS and fluorescence microscopy. The ¹⁹F signal allowed the precise visualization of the protein of interest, with minimal background, and enabled correlative studies of protein distribution and cellular metabolism or composition. SPILL can be applied to biological systems suitable for click chemistry, which include most cell‐culture systems, as well as small model organisms.     

High‐Tg Thiol‐Click Thermoset Networks via the Thiol‐Maleimide Michael Addition

Thiol‐click reactions lead to polymeric materials with a wide range of interesting mechanical, electrical, and optical properties. However, this reaction mechanism typically results in bulk materials with a low glass transition temperature (T_g) due to rotational flexibility around the thioether linkages found in networks such as thiol‐ene, thiol‐epoxy, and thiol‐acrylate systems. This report explores the thiol‐maleimide reaction utilized for the first time as a solvent‐free reaction system to synthesize high‐T_g thermosetting networks. Through thermomechanical characterization via dynamic mechanical analysis, the homogeneity and T_gs of thiol‐maleimide networks are compared to similarly structured thiol‐ene and thiol‐epoxy networks. While preliminary data show more heterogeneous networks for thiol‐maleimide systems, bulk materials exhibit T_gs 80 °C higher than other thiol‐click systems explored herein. Finally, hollow tubes are synthesized using each thiol‐click reaction mechanism and employed in low‐ and high‐temperature environments, demonstrating the ability to withstand a compressive radial 100 N deformation at 100 °C wherein other thiol‐click systems fail mechanically.

     

Thiol‐Ene Step‐Growth as a Versatile Route to Functional Polymers

A new use of the thiol‐ene reaction to generate functional, redox‐tunable polymers is described. To illustrate the versatility of this approach, tailored divinyl ether monomers were polymerized with triethylene glycol dithiol to yield polymers containing either a carbonate or zwitterionic phosphocholine within the polymer backbone. Similarly, dithioerythritol was polymerized with triethylene glycol divinyl ether to yield a polymer with pendant diols and show how functional groups can be designed into either the divinyl ether or dithiol monomer. Using the thioether functional group inherent to this polymerization, all three polymers were selectively and quantitatively oxidized to either sulfoxides or sulfones by treatment with dilute hydrogen peroxide or mCPBA, respectively. With these illustrative examples, it is shown that the thiol‐ene polymerization is a broad‐reaching method to access a class of new redox‐active polymers which contain varied and dense functional‐group compositions.     

Polysiloxane‐Based Luminescent Elastomers Prepared by Thiol–ene “Click” Chemistry

Side‐chain vinyl poly(dimethylsiloxane) has been modified with mercaptopropionic acid, methyl 3‐mercaptopropionate, and mercaptosuccinic acid. Coordinative bonding of Eu^III to the functionalized polysiloxanes was then carried out and crosslinked silicone elastomers were prepared by thiol–ene curing reactions of these composites. All these europium complexes could be cast to form transparent, uniform, thin elastomers with good flexibility and thermal stability. The networks were characterized by FTIR, NMR, UV/Vis, and luminescence spectroscopy as well as by scanning electron microscopy, thermogravimetric analysis, and X‐ray photoelectron spectroscopy. The europium elastomer luminophores exhibited intense red light at 617 nm under UV excitation at room temperature due to the ⁵D₀→⁷F₂ transition in Eu^III ions. The newly synthesized luminescent materials offer many advantages, including the desired mechanical flexibility. They cannot be dissolved or fused, and so they have potential for use in optical and electronic applications.     

Clickable SBA‐15 to Screen Functional Groups for Adsorption of Antibiotics

Pharmaceutical antibiotics, as emerging contaminants, are usually composed of several functional groups that endow them with the ability to interact with adsorbents through different interactions. This makes the preparation of adsorbents tedious and time‐consuming to screen appropriate functionalized materials. Herein, we describe the synthesis of clickable SBA‐15 and demonstrate its feasibility as a screening material for the adsorption of antibiotics based on similar adsorption trends on materials with similar functional groups obtained by a click reaction and cocondensation/grafting methods.     

Allyl‐Functionalized Dioxynaphthalene[38]Crown‐10 Macrocycles: Synthesis,Self‐Assembly,and Thiol‐ene Functionalization

Five dioxynaphthalene[38]‐crown‐10 ( DNP38C10 ) macrocycles bearing one, two, three, or four allyl moieties have been synthesized and their ability to spontaneously self‐assemble with methyl viologen to form [2]pseudorotaxanes has been evaluated. Association constants between methyl viologen and several of the allyl‐functionalized DNP38C10 macrocycles are found to be comparable to that of methyl viologen and unfunctionalized DNP38C10 , however, the enthalpic and entropic factors that underlie overall binding free energy vary systematically with increasing allyl substitution. These variations are explained through a combination of solution phase and solid‐state analysis of the macrocycles and their complexes. The utility of endowing DNP38C10 macrocycles with allyl moieties is further demonstrated by the ease with which they can be functionalized through thiol‐ene click chemistry.     

Reactive Polymer Coatings: A General Route to Thiol‐ene and Thiol‐yne Click Reactions

Reactive polymer coatings were synthesized via chemical vapor deposition (CVD) polymerization process. These coatings decouple surface design from bulk properties of underlying materials and provide a facile and general route to support thiol‐ene and thiol‐yne reactions on a variety of substrate materials. Through the reported technique, surface functions can be activated through a simple design of thiol‐terminated molecules such as polyethylene glycols (PEGs) or peptides (GRGDYC), and the according biological functions were demonstrated in controlled and low‐fouling protein adsorptions as well as accurately manipulated cell attachments.     

Thiol–Yne Click Reactions on Alkynyl–Dopamine‐Modified Reduced Graphene Oxide

The large‐scale preparation of graphene is of great importance due to its potential applications in various fields. We report herein a simple method for the simultaneous exfoliation and reduction of graphene oxide (GO) to reduced GO (rGO) by using alkynyl‐terminated dopamine as the reducing agent. The reaction was performed under mild conditions to yield rGO functionalized with the dopamine derivative. The chemical reactivity of the alkynyl function was demonstrated by post‐functionalization with two thiolated precursors, namely 6‐(ferrocenyl)hexanethiol and 1H,1H,2H,2H‐perfluorodecanethiol. X‐ray photoelectron spectroscopy, UV/Vis spectrophotometry, Raman spectroscopy, conductivity measurements, and cyclic voltammetry were used to characterize the resulting surfaces.     

Visible‐Light‐Mediated Thiol‐Ene Hydrogelation Using Eosin‐Y as the Only Photoinitiator

The utility of visible‐light‐mediated polymerization in tissue engineering has been limited due to the necessary use of potentially cytotoxic coinitiator and comonomer. Here, we report a visible‐light‐mediated thiol‐ene hydrogelation scheme using eosin‐Y as the only photoinitiator. Under visible light exposure, rapid and highly tunable step‐growth gelation is achieved using PEG‐norbornene and a model cross‐linker dithiothreitol. In addition to investigating the gelation kinetics and properties of thiol‐ene hydrogels formed by this new gelation scheme, we also report high cytocompatibility of these hydrogels using human mesenchymal stem cells (hMSCs) and pancreatic MIN6 β‐cells.     

Thiol‐yne Click Adamantane Monolithic Stationary Phase for Capillary Electrochromatography

A porous crosslinked organic polymer based on N‐acryloxysuccinimide (NAS) and ethylene dimethacrylate (EDMA) was prepared inside 75 µm i.d. fused silica capillary as functionalizable monolithic stationary phase for electrochromatographic applications. Succinimide groups on the monolith surface provide reactive sites able to react readily through standard electrophile‐nucleophile chemistry. Propargylamine was used to prepare alkyne functionalized poly(NAS‐co‐EDMA). Onto this thiol‐reactive polymer surface was grafted adamantane units via a photochemically‐driven addition reaction. Chemical characterization was performed in situ after each synthetic step by means of Raman spectroscopy and grafting kinetics was investigated to ensure quantitative grafting of 1‐adamantanethiol. The as‐designed monolithic stationary phase exhibited typical reversed‐phase separation mechanism as evidenced by the linear increase of the logarithm of retention factor of neutral aromatic solutes with the increase of the aqueous buffer content in the mobile phase.     

Polythioethers by Thiol‐Ene Click Polyaddition of α,ω‐Alkylene Thiols

The straightforward synthesis of a series of poly(thioether)s by photoinduced thiol‐ene click polyaddition of α,ω‐alkylene thiols is reported. It is found that linear and telechelic poly(thioether)s can be directly obtained from α,ω‐alkylene thiols with, for example, alkyl chain length of m = 1,2,3, and 9. The reaction proceeds without additives such as (radical) initiators or metal compounds and can simply be carried out by UV‐irradiation of the bulk monomer or monomer solution. Ex situ kinetic studies reveal that the reaction proceeds by a typical a step‐growth polyaddition mechanism. As the homologue series of poly(thioether)s are now synthetically accessible, new direct pathways to tailored poly(alkyl sulphoxide)s and poly(alkyl sulfone)s are now possible.

     

Synthesis of Upconverting Hydrogel Nanocomposites Using Thiol‐Ene Click Chemistry: Template for the Formation of Dendrimer‐Like Gold Nanoparticle Assemblies

The synthesis of upconverting hydrogel nanocomposites by base‐catalyzed thiol‐ene click reaction between 10‐undecenoic acid capped Yb³⁺/Er³⁺‐doped NaYF₄ nanoparticles and pentaerythritol tetrakis(3‐mercaptopropionate) (PETMP) as tetrathiol monomer is reported. This synthetic strategy for nanocomposite gels is quite different from works where usually the preformed gels are mixed with the nanoparticles. Developing nanocomposites by surface modification of capping ligands would allow tuning and controlling of the separation of the nanoparticles inside the gel network. The hydrogel nanocomposites prepared by thiol‐ene click reaction show strong enhancement in luminescence intensity compared to 10‐undecenoic acid‐capped Yb³⁺/Er³⁺‐doped NaYF₄ nanoparticles through the upconversion process (under 980 nm laser excitation). The hydrogel nanocomposites display strong swelling characteristics in water resulting in porous structures. Interestingly, the resulting nanocomposite gels act as templates for the synthesis of dendrimer‐like Au nanostructures when HAuCl₄ is reduced in the presence of the nanocomposite gels.     

Synthesis of New Lipid‐Inspired Ionic Liquids by Thiol‐ene Chemistry: Profound Solvent Effect on Reaction Pathway

The synthesis of a series of new lipid‐inspired ionic liquids through thiol‐ene “click” reaction with a single‐step process. This synthesis offers considerable promise as an efficient and orthogonal method to construct structurally diverse imidazolium‐type ionic liquids with linear and branched cationic tails, as well as versatility in the placement of the sulfur heteroatom. Profound solvent effect in this ene reaction regioselectivity has been observed.