Versatile functionalization of aromatic polysulfones via thiol‐ene click chemistry

A facile, efficient approach for preparation of functionalized aromatic polysulfones by postpolymerization modification with thiol‐ene click chemistry is described. The key synthetic strategy is to incorporate a pendant vinyl ether group into polysulfones as a reactive precursor with controlled degrees of functionalization. Synthetic utility of the pendant alkenyl group is demonstrated by generating diverse polymer derivatives using thiol‐ene functionalization including glycosylated polysulfone. The highly reactive alkene platform in the polymer affords convenient, metal‐free, and azide‐free click transformations to create diverse ranges of new functionalized polysulfones that could be applied in various applications. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3237–3243     

Synthesis and functionalization of dendron‐polymer conjugate based hydrogels via sequential thiol‐ene “click” reactions

Fabrication and functionalization of hydrogels from well‐defined dendron‐polymer‐dendron conjugates is accomplished using sequential radical thiol‐ene “click” reactions. The dendron‐polymer conjugates were synthesized using an azide‐alkyne “click” reaction of alkene‐containing polyester dendrons bearing an alkyne group at their focal point with linear poly(ethylene glycol)‐bisazides. Thiol‐ene “click” reaction was used for crosslinking these alkene functionalized dendron‐polymer conjugates using a tetrathiol‐based crosslinker to provide clear and transparent hydrogels. Hydrogels with residual alkene groups at crosslinking sites were obtained by tuning the alkene‐thiol stoichiometry. The residual alkene groups allow efficient postfunctionalization of these hydrogel matrices with thiol‐containing molecules via a subsequent radical thiol‐ene reaction. The photochemical nature of radical thiol‐ene reaction was exploited to fabricate micropatterned hydrogels. Tunability of functionalization of these hydrogels, by varying dendron generation and polymer chain length was demonstrated by conjugation of a thiol‐containing fluorescent dye. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 926–934     

Photocatalyzed thiol–alkene coupling: Mechanistic study and polymer synthesis

Due to the “click” chemistry characteristics of the thiol–ene reaction, these transformations have been gaining an increasing amount of attention in current chemical research. The high efficiency and selectivity of these transformations have been useful for many areas of study, from small molecule organic synthesis, to polymer synthesis and functionalization, to bio‐conjugation reactions. In this work, a study of a novel method of photochemical thiol–ene reactions using alkyl halides and an tris[2‐phenylpyridinato‐C2,N]iridium(III) (Ir(ppy)₃) photocatalyst is investigated. This process is shown to progress rapidly and has the benefit of low catalyst and initiator concentrations relative to reagents as well as mild conditions associated with photochemical processes. To understand the mechanism of this process, catalyst and initiator concentrations and other reaction conditions are varied. To demonstrate the utility of this process, a step‐growth thiol–ene polymer is synthesized using dithiol and diene monomers and a crosslinked polymer network is synthesized as well. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1931–1937     

Orthogonal multifunctionalization of aliphatic polycarbonate via sequential Michael addition and radical‐thiol‐ene click reactions

Aliphatic polycarbonate (PC) copolymer is synthesized by ring opening copolymerization of acrylate‐ and allyl‐functional cyclic carbonate monomers. The post‐polymerization functionalization of the resulting copolymer is performed quantitatively using a variety of thiol compounds via sequential Michael addition and photo‐induced radical thiol‐ene click reactions within relatively short reaction time at ambient temperature. This metal‐free click chemistry methodology affords the synthesis of biocompatible PC copolymer with multifunctional groups. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1581–1587     

Tailored composite polymer–metal nanoparticles by miniemulsion polymerization and thiol‐ene functionalization

A simple and modular synthetic approach, based on miniemulsion polymerization, has been developed for the fabrication of composite polymer–metal nanoparticle materials. The procedure produces well‐defined composite structures consisting of gold, silver, or MnFe₂O₄ nanoparticles (～10 nm in diameter) encapsulated within larger spherical nanoparticles of poly(divinylbenzene) (～100 nm in diameter). This methodology readily permits the incorporation of multiple metal domains into a single polymeric particle, while still preserving the useful optical and magnetic properties of the metal nanoparticles. The morphology of the composite particles is retained upon increasing the inorganic content and also upon redispersion in organic solvents. Finally, the ability to tailor the surface chemistry of the composite nanoparticles and incorporate steric stabilizing groups using simple thiol‐ene chemistry is demonstrated. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1594–1606, 2010     

Monomers and polymers from plant oils via click chemistry reactions

As a consequence of the depleting of fossil reserves and environmental issues, today, plant oils and fatty acids derived therefrom have a respectable status within the polymer chemistry community. However, maximizing the benefits of these renewable feedstocks requires the utilization of sustainable and efficient chemical transformations. The emergence of click chemistry concept and especially the renaissance of thiol‐ene addition reaction have had an impact on the way to make plant oil‐derived polymers. This highlight discusses the applicability and success of thiol‐ene addition and other click reactions in the transformation of oleochemicals into monomers and polymers. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013     

L‐arabinitol‐based functional polyurethanes

Three new polymerizable diols, based on mono‐, di‐, and tri‐O‐allyl‐L ‐arabinitol derivatives, were prepared from L ‐arabinitol as versatile materials for the preparation of tailor‐made polyurethanes with varied degrees of functionalization. Their allyl functional groups can take part in thiol‐ene reactions, to obtain greatly diverse materials. This “click” reaction with 2‐mercaptoethanol was firstly studied on the highly hindered sugar precursor 2,3,4‐tri‐O‐allyl‐1,5‐di‐O‐trityl‐L ‐arabinitol, to apply it later to macromolecules. A polyurethane with multiple pendant allyl groups was synthesized by polyaddition reaction of 2,3,4‐tri‐O‐allyl‐L ‐arabinitol with 1,6‐hexamethylene diisocyanate, and then functionalized by thiol‐ene reaction. The coupling reaction took place in every allyl group, as confirmed by standard techniques. The thermal stability of the novel polyurethanes was investigated by thermogravimetric analysis and differential scanning calorimetry (DSC). This strategy provides a simple and versatile platform for the design of new materials whose functionality can be easily modified. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis and postfunctionalization of well‐defined star polymers via “double” click chemistry

In this article, the synthesis and the functionalization of well‐defined, narrow polydispersity (polydispersity index < 1.2) star polymers via reversible addition‐fragmentation chain transfer polymerization is detailed. In this arm first approach, the initial synthesis of a poly(pentafluorophenyl acrylate) polymer, and subsequent, cross‐linking using bis‐acrylamide to prepare star polymers, has been achieved by reversible addition fragmentation chain transfer polymerization. These star polymers were functionalized using a variety of amino functional groups via nucleophilic substitution of pentafluorophenyl activated ester to yield star polymers with predesigned chemical functionality. This approach has allowed the synthesis of star glycopolymer using a very simple approach. Finally, the core of the stars was modified via thiol‐ene click chemistry reaction using fluorescein‐o‐acrylate and DyLigh 633 Maleimide. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Cysteine‐Functional Polymers via Thiol‐ene Conjugation

A thiofunctional thiazolidine is introduced as a new low‐molar‐mass building block for the introduction of cysteine residues via a thiol‐ene reaction. Allyl‐functional polyglycidol (PG) is used as a model polymer to demonstrate polymer‐analogue functionalization through reaction with the unsaturated side‐chains. A modified trinitrobenzenesulfonic acid (TNBSA) assay is used for the redox‐insensitive quantification and a precise final cysteine content can be predetermined at the polymerization stage. Native chemical ligation at cysteine‐functional PG is performed as a model reaction for a chemoselective peptide modification of this polymer. The three‐step synthesis of the thiofunctional thiazolidine reactant, together with the standard thiol‐ene coupling and the robust quantification assay, broadens the toolbox for thiol‐ene chemistry and offers a generic and straightforward approach to cysteine‐functional materials.

     

Modification of polysaccharides via thiol‐ene chemistry: A versatile route to functional biomaterials

We present herein a mild and rapid method for the modular functionalization of polysaccharides. Several ene‐functional charged and neutral polysaccharides, that is, hyaluronic acid and dextran, were prepared by esterification of the hydroxyl groups with pentenoic anhydride. The modified polysaccharides were then reacted with six model mercaptans under UV light, leading to linear polymers modified with hydrophobic groups, peptides, or oligosaccharides as well as chemical hydrogels. The thiol‐ene coupling reactions were found to proceed with high efficiency in short reaction times and with nearly no degradation of the polysaccharide backbone. Moreover, they were carried out in aqueous media, without the use of any metal catalysts, enhancing the attractive nature of this process. Notably, we investigated whether it is feasible to prepare cell‐responsive hydrogels by sequential bioconjugation and cross‐linking of the polysaccharide backbone with a bioactive peptide and poly(ethylene glycol)‐dithiol, respectively. All together, these results highlight the potential of this coupling strategy for the modular functionalization of polysaccharides under click chemistry‐like conditions. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Postfunctionalization of polyoxanorbornene via sequential Michael addition and radical thiol‐ene click reactions

We demonstrated the successful postfunctionalization of poly(oxanorbornene imide) (PONB) with two types of double bonds using sequential orthogonal reactions, nucleophilic thiol‐ene coupling via Michael addition and radical thiol‐ene click reactions. First, the synthesis of PONB with side chain acrylate groups is carried out via ring‐opening metathesis polymerization and nitroxide radical coupling reaction, respectively. Subsequently, the resulting polymer having two different orthogonal functionalities, main chain vinyl and side chain acrylate, is selectively modified via two sequential thiol‐ene click reactions, nucleophilic thiol‐ene coupling via Michael addition and photoinduced radical thiol‐ene. The orthogonal reactivity of two diverse double bonds, vinyl and acrylate functionalities, for the abovementioned consecutive thiol‐ene click reactions was first demonstrated on the model compound. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

A versatile synthetic path to thiol containing polysiloxanes

A synthetic strategy to polydimethylsiloxanes and polymethylsiloxanes containing thiol functions as end‐ or side‐groups, respectively, is presented. Such polymers are important starting materials for elastomeric networks and postpolymerization modifications. The synthesis starts either with vinyl end‐functionalized polydimethylsiloxanes or with polymethylvinylsiloxanes. The vinyl groups are reacted either with thioacetic acid or with a thioacetic acid/butanethiol mixture via a UV‐initiated thiol‐ene reaction to form the respective thioester quantitatively within few minutes. The thioesters are subsequently deprotected to the respective thiols by reduction with LiAlH₄. The resulting thiol containing polysiloxanes can be used for the formation of networks or another functionalization. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2940–2948     

Antimicrobial equipment of poly(isoprene) applying thiol‐ene chemistry

The functionalization of anionically polymerized isoprene with cysteamine applying the thiol‐ene reaction is reported. Antimicrobial activity is implemented by quaternization of the amino functionality by either alkylation or by protonation. The resulting polymers were tested against Gram‐positive as well as Gram‐negative bacteria strains according to the Japanese Industrial Standard Z2801:2000 protocol, partly revealing excellent biocidal performance. Thermal stability up to 200°C allows extrusion processing of the functionalized poly(isoprene)s. The best performing polymer, that is, bearing butylated ammonium‐groups, was compounded with the commodity material poly(propylene). The compound bearing 5 wt % of the biocidal polymer exhibited satisfactory biocidal properties. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Modular material system for the microfabrication of biocompatible hydrogels based on thiol–ene‐modified poly(vinyl alcohol)

Novel modifications of the synthetic polymer poly(vinyl alcohol) (PVA) were developed for application in the field of biomedical engineering. PVA was modified with allyl succinic anhydride, norbornene anhydride as well as with γ‐thiobutyrolactone to produce macromers with reactive ene and thiol groups, respectively. Cytotoxicity studies have shown that the material exhibits almost no cell‐toxicity, when used in concentrations of 1 and 0.1 wt % for 24 h. The obtained macromers were photocrosslinked via thiol–ene chemistry. Storage stability of the macromer mixtures with different concentrations of pyrogallol as stabilizer were investigated. Photorheometry was employed to optimize mixtures concerning reactivity based on their thiol‐to‐ene ratio, photoinitiator concentration, and macromer content. The crosslinked hydrogels were studied concerning their swellability. To form hydrogels with cellular structure two‐photon‐polymerization (2PP) was employed. Processing windows for 2PP of selected mixtures were determined. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2060–2070     

Ultrathin gradient films using thiol‐ene polymerizations

The application of surface‐attached, thiol‐ene polymer films for controlling material properties in a gradient fashion across a surface was investigated. Thiol‐ene films were attached to the surface by first depositing a thiol‐terminated self‐assembled monolayer and performing a thiol‐ene photopolymerization reaction on the surface. Property gradients were created either by creating and modifying a gradient in the surface thiol density in the SAM or by changing the polymerization conditions or both. Film thickness was modified across the substrate by changing either the density of the anchoring thiol functional groups or by changing the reaction conditions such as exposure time. Thicker films (1–11 nm) were obtained by polymerizing acrylate polymer brushes from the surface with varying exposure time (0–60 s). The two factors, that is, the surface thiol density and the exposure time, were combined in orthogonal directions to obtain thiol‐ene films with a two‐dimensional thickness gradient with the maximum thickness being 4 nm. Finally, a thiol‐acrylate Michael type addition reaction was used to modify the surface thiol density gradient with the cell‐adhesive ligand, Arg‐Gly‐Asp‐Ser (RGDS), which subsequently yielded a gradient in osteoblast density on the surface. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 7027–7039, 2006     

New photo‐induced thiol‐ene crosslinked films based on linear methacrylate copolymer polythiols

Thiol‐ene radical addition by photolysis is a highly efficient click reaction of sufhydryl groups with reactive enes that has been extensively explored as a promising means to construct multifunctional materials. Here, photo‐induced thiol‐ene crosslinked films composed of linear methacrylate copolymer polythiols (MCPsh) are reported. Well‐defined MCPsh copolymers were prepared by thiol‐responsive cleavage of pendant disulfide linkages positioned in the corresponding methacrylate copolymers with narrow molecular weight distribution which were synthesized by a controlled radical polymerization method. With a commercially available multifunctional acrylate as a model ene, photo‐induced thiol‐ene radical polyaddition of these polythiols is competitive to free‐radical homopolymerization of acrylates, yielding crosslinked films exhibiting rapid cure, uniform network, and enhanced mechanical properties; these properties are required for high performance coating materials. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2860–2868.     

Sequential thiol‐ene/thiol‐ene and thiol‐ene/thiol‐yne reactions as a route to well‐defined mono and bis end‐functionalized poly(N‐isopropylacrylamide)

Sequential thiol‐ene/thiol‐ene and thiol‐ene/thiol‐yne reactions have been used as a facile and quantitative method for modifying end‐groups on an N‐isopropylacrylamide (NIPAm) homopolymer. A well‐defined precursor of polyNIPAm (PNIPAm) was prepared via reversible addition‐fragmentation chain transfer (RAFT) polymerization in DMF at 70 °C using the 1‐cyano‐1‐methylethyl dithiobenzoate/2,2′‐azobis(2‐methylpropionitrile) chain transfer agent/initiator combination yielding a homopolymer with an absolute molecular weight of 5880 and polydispersity index of 1.18. The dithiobenzoate end‐groups were modified in a one‐pot process via primary amine cleavage followed by phosphine‐mediated nucleophilic thiol‐ene click reactions with either allyl methacrylate or propargyl acrylate yielding ene and yne terminal PNIPAm homopolymers quantitatively. The ene and yne groups were then modified, quantitatively as determined by ¹H NMR spectroscopy, via radical thiol‐ene and radical thiol‐yne reactions with three representative commercially available thiols yielding the mono and bis end functional NIPAm homopolymers. This is the first time such sequential thiol‐ene/thiol‐ene and thiol‐ene/thiol‐yne reactions have been used in polymer synthesis/end‐group modification. The lower critical solution temperatures (LCST) were then determined for all PNIPAm homopolymers using a combination of optical measurements and dynamic light scattering. It is shown that the LCST varies depending on the chemical nature of the end‐groups with measured values lying in the range 26–35 °C. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3544–3557, 2009     

From NMP to RAFT and Thiol‐Ene Chemistry by In Situ Functionalization of Nitroxide Chain Ends

A straightforward, novel strategy based on the in situ functionalization of polymers prepared by nitroxide‐mediated polymerization (NMP), for the use as an extension toward block copolymers and post‐polymerization modifications, has been investigated. The nitroxide end group is exchanged for a thiocarbonylthio end group by a rapid transfer reaction with bis(thiobenzoyl) disulfide to generate in situ reversible addition–fragmentation chain transfer (RAFT) macroinitiators. Moreover, not only have these macroinitiators been used in chain extension and block copolymerization experiments by the RAFT process but also a thiol‐terminated polymer is synthesized by aminolysis of the RAFT end group and subsequently reacted with dodecyl vinyl ether by thiol‐ene chemistry.