Thiol-yne Chemistry Research Articles

Structurally Defined Amphiphilic AAO Membranes Using UV-Assisted Thiol-Yne Chemistry: Applications in Anti-Counterfeiting and Electronics.

In this study, we fabricate and characterize amphiphilic anodic aluminum oxide (AAO) membranes using UV-triggered thiol-yne click reactions and photomasks for various innovative applications, including driven polymer nanopatterns, anti-counterfeiting, and conductive pathways. Specifically, we synthesize 10-undecynyl-terminated-AAO membranes and subsequently prepare amphiphilic AAO membranes with superhydrophilic and superhydrophobic regions. Various analytical methods, including grazing angle X-ray photoelectron spectroscopy (GIXPS), energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), nanofocused synchrotron X-ray techniques (nano-XRD and nano-XRF), and water contact angle measurements, confirm the modifications and distinct properties of the modified areas. This work achieves a series of applications, such as driven polymer nanopatterns, solvent- and light-triggered anti-counterfeiting, and region-selective conductive pathways using silver paint with lower resistivity. Besides, the amphiphilic AAO membrane exhibits successful stability, durability, and reusability. To sum up, this study highlights the versatility and potential of amphiphilic AAO membranes in advanced material design and smart applications.

Monolithic conjugated microporous polymers with antibacterial activity for air filtration

The air pollution caused by particulate matters (PMs) poses a severe threat to the human health. In particular, the fine particles with diameter smaller than 2.5 μm (PM2.5) can be carriers of various bacteria and viruses, accelerating spread of epidemic. In this work, we synthesized two robust and flexible conjugated microporous polymer (CMP) aerogels for PMs removal, via one-step coupling polymerization of arylethynylenes and aryl halides with different molecular configuration. The resulting CMP aerogels comprise of hollow nanotubes with 3D porous network and high surface areas up to 660 m2/g. The efficiency of CMP aerogels for PM2.5 and PM10 was 99.5 ± 0.3 % and 99.8 ± 0.1 % with a long-term durability. In combination with their physicochemical stability and inherent surface hydrophobicity, a high efficiency for PM2.5 filtration more than 99.6 ± 0.1 % also can be obtained at a high humidity at room temperature both for the two CMP aerogels. In addition, benefiting from the rich alkynyl groups in skeletons, post-modification of the resulting CMP aerogels with thiol-yne chemistry followed by silver ion uptake gives rise to antibacterial materials with outstanding activity for gram-positive strains far superior to other porous organic polymer materials. This work provides a new avenue to fabricate bifunctional CMPs derived porous aerogels for air filtration with high performance and antibacterial activity, and is expected to expand the application of CMPs in environmental purification.

Tailoring Network Topology in Mechanically Robust Hydrogels for 3D Printing and Injection.

Tissue engineering and regenerative medicine are confronted with a persistent challenge: the urgent demand for robust, load-bearing, and biocompatible scaffolds that can effectively endure substantial deformation. Given that inadequate mechanical performance is typically rooted in structural deficiencies─specifically, the absence of energy dissipation mechanisms and network uniformity─a crucial step toward solving this problem is generating synthetic approaches that enable exquisite control over network architecture. This work systematically explores structure-property relationships in poly(ethylene glycol)-based hydrogels constructed utilizing thiol-yne chemistry. We systematically vary polymer concentration, constituent molar mass, and cross-linking protocols to understand the impact of architecture on hydrogel mechanical properties. The network architecture was resolved within the molecular model of Rubinstein-Panyukov to obtain the densities of chemical cross-links and entanglements. We employed both nucleophilic and radical pathways, uncovering notable differences in mechanical response, which highlight a remarkable degree of versatility achievable by tuning readily accessible parameters. Our approach yielded hydrogels with good cell viability and remarkably robust tensile and compression profiles. Finally, the hydrogels are shown to be amenable to advanced processing techniques by demonstrating injection- and extrusion-based 3D printing. Tuning the mechanism and network regularity during the cell-compatible formation of hydrogels is an emerging strategy to control the properties and processability of hydrogel biomaterials by making simple and rational design choices.

Rapid polythioether synthesis and thioether network formation using thiol-yne chemistry of electron-deficient alkynes

The preparation of polythioethers has gained importance again after the development of click chemistry reactions. The thiol-X reactions, i.e., thiol-ene reactions based on free radical mechanism facilitated by light or heat, and thiol-Michael and thiol-epoxy reactions, which are the main synthetic pathways for the synthesis of polymers (linear, hyperbranched (HB), and network) with thioether linkages and meet most of the features of click reactions strategy, have currently been revisited. For a while, our group has focused on synthesizing linear, HB, and network polythioethers based on electron-deficient alkyne-containing precursors. We have shown that electron-deficient alkyne-containing monomers and polymers offer a suitable platform for thiol-Michael (i.e., thiol-yne) click reactions to yield linear, HB, and network structures rapidly under ambient conditions. The central structure in these polythioether syntheses is electron-deficient alkyne bonds of acetylenedicarboxylates, which are then reacted with dithiols in chloroform through an organobase 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) at ambient temperatures. Moreover, acetylenedicarboxylates are functionalized using copper-free azide-alkyne cycloaddition reaction followed by reacting with multifunctional allyl and SH derivatives through thiol-ene photopolymerization resulting in polymeric networks with thioether linkages. This feature article highlights our contribution to the synthesis of linear, HB, and network polythioether based on various electron-deficient alkyne precursors.

Thiol-yne chemistry of diferrocenylacetylene: from synthesis and electrochemistry to theoretical studies.

The thiol-yne coupling chemistry of diferrocenylacetylene (FcCCFc) 1, bearing two electron rich and redox-active ferrocenyl units (Fc = Fe(η5-C5H4)(η5-C5H5)) and an internal triple bond, has been investigated for the first time. In order to determine whether steric limitations might affect hydrothiolation, a model reaction using a functionalized monothiol was tested, namely 2-mercaptoethanol I. The thiol-diferrocenylacetylene reactions were initiated either thermally (in toluene with AIBN) or by UV light irradiation (in THF and in the presence of DMPA as the photoinitiator). The outcomes of these thiol-yne reactions showed a strong dependence on the initiation method used, with the thermally initiated one being the most efficient. These thiol-diferrocenylacetylene reactions mainly afforded the (Z)-stereoisomer of the newly obtained vinyl thioether sulfide FcCHC(Fc)S-(CH2)2OH (2), unlike the more common (E)-vinyl sulfides found in other additions to alkynes. The hydrothiolation of the internal -CC- bond in 1 was successfully extended to dithiol 2,2'-(ethylenedioxy)diethanethiol II, leading to the formation of the (ZZ)-isomer, with four ferrocenyl units, as the major product. According to the electrochemical studies, the new asymmetrical ferrocenyl-vinyl sulfides show iron-iron electronic and electrostatic interactions. Theoretical results for the (Z)-stereoisomer (2) suggest that adiabatic oxidation would lead to the loss of almost one electron on the ferrocenyl subunit closer to the thioether chain. Furthermore, the thiol-yne chemistry of the internal -CC- bond in diferrocenylacetylene has been compared to the external triple bond in ethynylferrocene, the theoretical results of which helped us to rationalize the very different reactivities observed in both metallocenes.

Molecularly imprinted polymers by thiol–yne chemistry: making imprinting even easier

Molecularly imprinted polymers (MIPs) are synthetic, bio-mimetic materials with recognition properties on a par with those of antibodies, which feature superior physical and chemical stability.

Thiol–yne chemistry for 3D printing: exploiting an off-stoichiometric route for selective functionalization of 3D objects

An alkyne monomer, bis(propargyl) fumarate, is synthesized and mixed to a thiol monomer to produce DLP-3D printable formulations. Using off-stoichiometric formulations it is possible to print functionalizable objects.

Hyperbranched poly(ethylenimine-co-oxazoline) by thiol–yne chemistry for non-viral gene delivery: investigating the role of polymer architecture

Synthesis of long-chain hyperbranched poly(ethylenimine-co-oxazoline)s by AB2thiol–yne chemistry is reported, and their application as pDNA transfection agents studied.

Selective Functionalization with PNA of Silicon Nanowires on Silicon Oxide Substrates.

Silicon nanowire chips can function as sensors for cancer DNA detection, whereby selective functionalization of the Si sensing areas over the surrounding silicon oxide would prevent loss of analyte and thus increase the sensitivity. The thermal hydrosilylation of unsaturated carbon–carbon bonds onto H-terminated Si has been studied here to selectively functionalize the Si nanowires with a monolayer of 1,8-nonadiyne. The silicon oxide areas, however, appeared to be functionalized as well. The selectivity toward the Si–H regions was increased by introducing an extra HF treatment after the 1,8-nonadiyne monolayer formation. This step (partly) removed the monolayer from the silicon oxide regions, whereas the Si–C bonds at the Si areas remained intact. The alkyne headgroups of immobilized 1,8-nonadiyne were functionalized with PNA probes by coupling azido-PNA and thiol-PNA by click chemistry and thiol–yne chemistry, respectively. Although both functionalization routes were successful, hybridization could only be detected on the samples with thiol-PNA. No fluorescence was observed when introducing dye-labeled noncomplementary DNA, which indicates specific DNA hybridization. These results open up the possibilities for creating Si nanowire-based DNA sensors with improved selectivity and sensitivity.

Design of synthetic extracellular matrices for probing breast cancer cell growth using robust cyctocompatible nucleophilic thiol-yne addition chemistry

Controlled, three-dimensional (3D) cell culture systems are of growing interest for both tissue regeneration and disease, including cancer, enabling hypothesis testing about the effects of microenvironment cues on a variety of cellular processes, including aspects of disease progression. In this work, we encapsulate and culture in three dimensions different cancer cell lines in a synthetic extracellular matrix (ECM), using mild and efficient chemistry. Specifically, harnessing the nucleophilic addition of thiols to activated alkynes, we have created hydrogel-based materials with multifunctional poly(ethylene glycol) (PEG) and select biomimetic peptides. These materials have definable, controlled mechanical properties (G’ = 4–10 kPa) and enable facile incorporation of pendant peptides for cell adhesion, relevant for mimicking soft tissues, where polymer architecture allows tuning of matrix degradation. These matrices rapidly formed in the presence of sensitive breast cancer cells (MCF-7) for successful encapsulation with high cell viability, greatly improved relative to that observed with the more widely used radically-initiated thiol-ene crosslinking chemistry. Furthermore, controlled matrix degradation by both bulk and local mechanisms, ester hydrolysis of the polymer network and cell-driven enzymatic hydrolysis of cell-degradable peptide, allowed cell proliferation and the formation of cell clusters within these thiol-yne hydrogels. These studies demonstrate the importance of chemistry in ECM mimics and the potential thiol-yne chemistry has as a crosslinking reaction for the encapsulation and culture of cells, including those sensitive to radical crosslinking pathways.

Fabrication of Photoluminescent Quantum Dot Thiol-yne Nanocomposites via Thermal Curing or Photopolymerization.

Strong, flexible, and transparent materials have garnered tremendous interest in recent years as materials and electronics manufacturers pursue devices that are bright, flexible, durable, tailorable, and lightweight. Depending on the starting components, polymers fabricated using thiol–yne chemistry have been shown to be exceptionally strong and/or flexible, while also being amenable to modification by the incorporation of nanoparticles. In the present work, novel ligands were synthesized and used to functionalize quantum dots (QDs) of various diameters. The functionalized QDs were then incorporated into thiol–yne prepolymer matrices. These matrices were subsequently polymerized to form QD thiol–yne nanocomposite polymers. To demonstrate the versatility of the fabrication process, the prepolymers were either thermally cured or photopolymerized. The resulting transparent nanocomposites expressed the size-specific color of the QDs within them when exposed to ultraviolet irradiation, demonstrating that QDs can be incorporated into thiol–yne polymers without significantly altering QD expression. With the inclusion of QDs, thiol–yne nanocomposite polymers are promising candidates for use in numerous applications including as device display materials, optical lens materials, and/or sensor materials.

Fabrication of Luminescent Quantum Dot Thiol-yne Nanocomposites via UV Photopolymerization

Event Abstract Back to Event Fabrication of Luminescent Quantum Dot Thiol-yne Nanocomposites via UV Photopolymerization Darryl A. Boyd1*, Michael H. Stewart1, Kimihiro Susumu2, Eunkeu Oh2, Christopher G. Brown1, Collin C. McClain1 and Edward P. Gorzkowski1 1 United States Naval Research Laboratory, United States 2 Sotera Defense Solutions (United States), United States Polymers containing quantum dots are fabricated using thiol-yne chemistry in order to develop strong, flexible and luminescent materials. To accomplish this, novel ligands were synthesized and used to functionalize quantum dots (QDs) of various diameters. These functionalized QDs were then incorporated into thiol-yne prepolymer matrices. These matrices were subsequently polymerized to form QD thiol-yne nanocomposite polymers. The resulting transparent nanocomposites expressed the size-specific color of the QDs within them when exposed to UV irradiation, demonstrating that QDs can be incorporated into thiol-yne polymers without significantly altering QD expression. With the inclusion of QDs, thiol-yne nanocomposite polymers are promising candidates for use in numerous applications including as waveguides, optical lens materials, and sensor applications. Keywords: Thiol Click, quantum dot, nanocomposite, photopolymerization, Additive manufacturing Conference: National Organization for the Professional Advancement of Black Chemists and Chemical Engineers (NOBCChE) 45th Annual Conference , Orlando, Florida, United States, 17 Sep - 20 Sep, 2018. Presentation Type: Oral Presentation Topic: Nanochemistry Citation: Boyd DA, Stewart MH, Susumu K, Oh E, Brown CG, McClain CC and Gorzkowski EP (2019). Fabrication of Luminescent Quantum Dot Thiol-yne Nanocomposites via UV Photopolymerization. Front. Chem. Conference Abstract: National Organization for the Professional Advancement of Black Chemists and Chemical Engineers (NOBCChE) 45th Annual Conference . doi: 10.3389/conf.fchem.2018.01.00005 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Oct 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. Darryl A Boyd, United States Naval Research Laboratory, Washington D.C., United States, darryl.anthony@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Darryl A Boyd Michael H Stewart Kimihiro Susumu Eunkeu Oh Christopher G Brown Collin C McClain Edward P Gorzkowski Google Darryl A Boyd Michael H Stewart Kimihiro Susumu Eunkeu Oh Christopher G Brown Collin C McClain Edward P Gorzkowski Google Scholar Darryl A Boyd Michael H Stewart Kimihiro Susumu Eunkeu Oh Christopher G Brown Collin C McClain Edward P Gorzkowski PubMed Darryl A Boyd Michael H Stewart Kimihiro Susumu Eunkeu Oh Christopher G Brown Collin C McClain Edward P Gorzkowski Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Programmable Peptide-Cross-Linked Nucleic Acid Nanocapsules as a Modular Platform for Enzyme Specific Cargo Release.

Herein we describe a modular assembly strategy for photo-cross-linking peptides into nucleic acid functionalized nanocapsules. The peptides embedded within the nanocapsules form discrete nanoscale populations capable of gating the release of molecular and nanoscale cargo using enzyme-substrate recognition as a triggered release mechanism. Using photocatalyzed thiol-yne chemistry, different peptide cross-linkers were effectively incorporated into the nanocapsules and screened against different proteases to test for degradation specificity both in vitro and in cell culture. By using a combination of fluorescence assays, confocal and TEM microscopy, the particles were shown to be highly specific for their enzyme targets, even between enzymes of similar protease classes. The rapid and modular nature of the assembly strategy has the potential to be applied to both intracellular and extracellular biosensing and drug delivery applications.

Nucleic Acid Nanocapsules for Enzyme-Triggered Drug Release.

Herein we describe a nucleic acid functionalized nanocapsule in which nucleic acid ligands are assembled and disassembled in the presence of enzymes. The particles are fully degradable in response to esterases due to an embedded ester cross-linker in the particle's core. During synthesis the nanocapsules can be loaded with hydrophobic small molecules and post self-assembly undergo covalent cross-linking using copper catalyzed click chemistry. They can then be functionalized with thiolated DNA through stepwise thiolyne chemistry using UV light irradiation. Additionally, the capsule is compatible with enzyme mediated functionalization of a therapeutic mRNA-cleaving DNAzyme at the particle's surface. The resulting particle is highly stable, monodisperse in size, and maximizes the therapeutic potential of both the particles interior and exterior.

Well-defined hyperstar copolymers based on a thiol–yne hyperbranched core and a poly(2-oxazoline) shell for biomedical applications

Well defined ‘hyperstar’ copolymers were synthesized by combining hyperbranched polymers produced by thiol–yne chemistry with poly(oxazoline)s.

An efficient approach to synthesize glycerol dendrimers via thiol–yne “click” chemistry and their application in stabilization of gold nanoparticles with X-ray attenuation properties

We report an efficient synthesis of glycerol dendrimers via thiol–yne chemistry for stabilization of AuNPs with X-ray attenuation properties.

Relative Contribution of Lateral Packing Density to Albumin Adsorption on Monolayers.

The effect of functional group density on protein adsorption is systematically studied to support ongoing efforts in molecular imprinting of surfaces and bulk materials. In these applications, functional commodity chemicals are molded to complement the shape and chemistry of the target molecule. Here, we study the relationship between bovine serum albumin adsorption and ligand density for carboxylate, alcohol, and alkyl terminal groups. Control surfaces consisting of densely packed self-assembled monolayers (SAMs) are contrasted with low-density SAMs formed through thiol-yne chemistry. Direct comparison consistently yielded greater protein adsorption on low-density SAMs than conventional pure component SAMs of the same functional group. Critically, the carboxylate and alcohol low-density SAMS are more hydrophobic than their analogous dense SAMs. Mixed functional group, dense SAMs were formed with alkyl diluents to match the hydrophobicity of the low-density SAMs. Once hydrophobicity is matched, the dense carboxylate and alcohol SAMs have higher adsorption than the low-density SAMs. We conclude (1) surface charge and hydrophobicity trends dominate over surface density contributions; (2) when hydrophobicity is matched, greater adsorption occurs on dense hydrophilic groups than on lower density hydrophilic groups; (3) when hydrophobicity is matched, greater adsorption occurs on lower density hydrophobic groups than on higher density hydrophobic groups.

Hyperbranched Polymers with High Degrees of Branching and Low Dispersity Values: Pushing the Limits of Thiol–Yne Chemistry

We propose a versatile approach to the production of hyperbranched polymers with high degrees of branching and low dispersity values (Đ), involving slow monomer addition of a thiol/yne monomer to multifunctional core molecules in the presence of photoinitiator and under UV irradiation. The small thiol/yne monomer was synthesized via 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloride (EDC·HCl) esterification, and batch polymerizations were performed at varying concentrations. The batch thiol–yne polymerizations had fast reaction kinetics and large dispersity values that increased with increasing concentration. Introduction of monomer by slow addition to a multifunctional alkyne core (tri(prop-2-yn-1-yl) 1,3,5-benzenetricarboxylate) or alkene core (triallyl 1,3,5-benzenetricarboxylate) was found to lower dispersity at monomer concentrations of 0.5–2.0 M. Degrees of branching were determined by 1H NMR spectroscopy to be greater than 0.8 in most cases. Increasing the fraction of core molecule was f...

Photopatterning of stable, low-density, self-assembled monolayers on gold.

Photoinitiated thiol-yne chemistry is utilized as a click reaction for grafting of acid-terminated alkynes to thiol-terminated monolayers on a gold substrate to create stable, low-density monolayers. The resulting monolayers are compared with a well-packed 11-mercaptoundecanoic acid monolayer and the analogous low-density monolayers prepared through a solution phase synthetic approach. The overall structuring of the monolayer prepared by solid-phase grafting is characterized by contact angle goniometry and Fourier transform infrared spectroscopy. The results show that the product monolayer has an intermediate surface energy and a more disordered chemical structuring compared to a traditional well-packed self-assembled monolayer, showing a low-packing density of the chains at the monolayer surface. The monolayer's structure and electrochemical stability were studied by reductive desorption of the thiolates. The prepared low-density monolayers have a higher electrochemical stability than traditional well-packed monolayers, which results from the crystalline structure at the gold interface. This technique allows for simple, fast preparation of low-density monolayers of higher stability than well-packed monolayers. The use of a photomask to restrict light access to the substrate yielded these low-density monolayers in patterned regions defined by light exposure. This general thiol-yne approach is adaptable to a variety of analogous low-density monolayers with diverse chemical functionalities.

Rapid access to phospholipid analogs using thiol-yne chemistry.

Phospholipids and glycolipids constitute an essential part of biological membranes, and are of tremendous fundamental and practical interest. Unfortunately, the preparation of functional phospholipids, or synthetic analogs, is often synthetically challenging. Here we utilize thiol-yne click chemistry methodology to gain access to phospho- and glycolipid analogs. Alkynyl hydrophilic head groups readily photoreact with numerous thiol modified lipid tails to yield the appropriate dithioether phospho- or glycolipids. The resulting structures closely resemble the structure and function of native diacylglycerolipids. Dithioether phosphatidylcholines (PCs) are suitable for forming giant unilamellar vesicles (GUV), which can be used as vessels for cell-free expression systems. The unnatural thioether linkages render the lipids resistant to phospholipase A2 hydrolysis. We utilize the improved stability of these lipids to control the shrinkage of GUVs composed of a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and dioleyl-dithioether PC, concentrating encapsulated nanoparticles. We imagine that these readily accessible lipids could find a number of applications as natural lipid substitutes.