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     

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     

Quadruple click reactions for the synthesis of cysteine‐terminated linear multiblock copolymers

Synthesis of cysteine‐terminated linear polystyrene (PS)‐b‐poly(ε‐caprolactone) (PCL)‐b‐poly(methyl methacrylate) (PMMA)/or poly(tert‐butyl acrylate)(PtBA)‐b‐poly(ethylene glycol) (PEG) copolymers was carried out using sequential quadruple click reactions including thiol‐ene, copper‐catalyzed azide–alkyne cycloaddition (CuAAC), Diels–Alder, and nitroxide radical coupling (NRC) reactions. N‐acetyl‐L ‐cysteine methyl ester was first clicked with α‐allyl‐ω‐azide‐terminated PS via thiol‐ene reaction to create α‐cysteine‐ω‐azide‐terminated PS. Subsequent CuAAC reaction with PCL, followed by the introduction of the PMMA/or PtBA and PEG blocks via Diels–Alder and NRC, respectively, yielded final cysteine‐terminated multiblock copolymers. By ¹H NMR spectroscopy, the DP_ns of the blocks in the final multiblock copolymers were found to be close to those of the related polymer precursors, indicating that highly efficient click reactions occurred for polymer–polymer coupling. Successful quadruple click reactions were also confirmed by gel permeation chromatography. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

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     

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     

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     

Alternating Copolymerization by Nitroxide‐Mediated Polymerization and Subsequent Orthogonal Functionalization

A novel method for the preparation of functionalized alternating copolymers is presented. Nitroxide‐mediated polymerization of hexafluoroisopropyl acrylate with 7‐octenyl vinyl ether provides the corresponding alternating polymer, which can be chemically modified using two orthogonal polymer‐analogous reactions. A thiol–ene click reaction followed by amidation provides dual‐functionalized alternating copolymers. The potential of this method is illustrated by the preparation of a small library (15 examples) of functionalized alternating copolymers.     

Maleimidophenyl isocyanates as postpolymerization modification agents and their applications in the synthesis of block copolymers

The maleimide structure is highly reactive, exemplified by thiol–ene click reactions with thiols and Diels–Alder reactions with furans. Although postpolymerization modifications and macromolecular conjugations involving maleimide units have been widely studied, mostly due to their selectivity and high reactivity, little has been reported on the one‐pot postpolymerization introduction of maleimides in polymer chains. Herein, we report p‐maleimidophenyl isocyanate and its derivatives as modification agents to introduce maleimide moieties by reaction with hydroxy groups into polymer chains. The high reactivity of the resulting modification agents and of the corresponding maleimide structures once inserted in the polymer chains was examined by studying their reaction kinetics. Furthermore, these modification agents were successfully applied to the synthesis of macromonomers for graft polymerization and various block copolymers, with, for example, AB‐type, star‐shaped, and H‐shaped architectures. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 2396–2406     

Facile and Efficient Synthesis of Carbosiloxane Dendrimers via Orthogonal Click Chemistry Between Thiol and Ene

A combination of a thiol‐Michael addition reaction and a free radical mediated thiol–ene reaction is employed as a facile and efficient approach to carbosiloxane dendrimer synthesis. For the first time, carbosiloxane dendrimers are constructed rapidly by an orthogonal click strategy without protection/deprotection procedures. The chemoselectivity of these two thiol–ene click reactions leads to a design of a new monomer containing both electron‐deficient carbon–carbon double bonds and unconjugated carbon–carbon double bonds. Siloxane bonds are introduced as the linker between these two kinds of carbon–carbon double bonds. Starting from a bifunctional thiol core, the dendrimers are constructed by iterative thiol–ene click reactions under different but both mild reaction conditions. After simple purification steps the fifth dendrimer with 54 peripheral functional groups is obtained with an excellent overall yield in a single day. Furthermore, a strong blue glow is observed when the dendrimer is excited by a UV lamp.

     

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     

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.     

Synthesis and nanoimprinting of high refractive index and highly transparent polythioethers based on thiol-ene click chemistry

This work demonstrates the UV nanoimprinting lithography (UV-NIL) of high refractive index and highly transparent polythioethers based on thiol-ene click chemistry. Herein, 9,9-bis(3-mercaptopropylphenylether)fluorene (BMPF) is designed as a new thiol monomer with a high refractive index, high transparency, and good processability for UV-NIL. Colorless polythioethers are synthesized from BMPF and ene monomers under mild thiol-ene click reaction conditions. Excellent transmittance (96%) of 400 nm light is observed in all the polymer films and high refractive index values of 1.5972–1.6382 are attained. UV-NIL using thiol-ene photopolymerization affords polymer nanoimprinting patterns with various features on the order of 100–500 nm without any fractures. To the best of our knowledge, this is the first report on UV-NIL of high refractive index and highly transparent polymers. Through proper monomer and polymer design, novel polythioethers with suitable glass transition temperature (T _g) values are developed with high refractive index, high transparency, and good UV-NIL processability. Furthermore, UV-NIL based on thiol-ene click chemistry is accomplished at the nanoscale. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2175–2182     

Photo‐initiated thiol–ene “click” hydrogels from RAFT‐synthesized poly(N‐isopropylacrylamide)

Despite the efficiency and robustness of the widely used copper‐catalyzed 1,3‐dipolar cycloaddition reaction, the use of copper as a catalyst is often not attractive, particularly for materials intended for biological systems. The use of photo‐initiated thiol‐ene as an alternative “click” reaction to synthesize “model networks” is investigated here. Poly(N‐isopropylacrylamide) precursors were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization and were designed to have trithiocarbonate moieties as end groups. This structure design provides opportunity for subsequent end‐group modifications in preparation for thiol‐ene “click.” Two reaction routes have been proposed and studied to yield thiol and ene moieties. The advantages and disadvantages of each reaction path were investigated to propose a simple but efficient route to prepare copper‐free “click” hydrogels. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 4626–4636     

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     

Optical diffusers based on uniform nano-sized polymer balls/nematic liquid crystals composite films

ABSTRACT

Optical diffusers are promising diffusing materials in the optical devices such as monitors, projectors, fibre optics, light-emitting diode (LED) systems and liquid crystal displays (LCDs). We report optical diffusers comprising uniformly distributed nano-sized polymer balls/nematic liquid crystals (LCs) by ultraviolet (UV) click reaction of ene monomer and thiol monomer. By optimising the mass ratio 1:1 of ene and thiol, of which the average diameter of the corresponding nano-sized polymer balls is about 900 nm, relatively high optical transmission and haze with 88.99% and 94.49% are yielded, respectively. Furthermore, by controlling the curing time, the average diameter of nano-sized polymer balls can be reduced to 810 nm, and the developed film exhibits high transmission (98.49%) without sacrificing the high haze (91.77%). This paper demonstrates that UV click reaction is an economical approach to fabricate optical diffusers in a controllable manner.     

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.     

ABC type miktoarm star copolymers through combination of controlled polymerization techniques with thiol‐ene and azide‐alkyne click reactions

ABC type miktoarm star copolymer with polystyrene (PS), poly(ε‐caprolactone) (PCL) and poly(ethylene glycol) (PEG) arms was synthesized using controlled polymerization techniques in combination with thiol‐ene and copper catalyzed azide‐alyne “click” reactions (CuAAC) and characterized. For this purpose, 1‐(allyloxy)‐3‐azidopropan‐2‐ol was synthesized as the core component in a one‐step reaction with high yields (96%). Independently, ω‐thiol functionalized polystyrene (PS‐SH) was synthesized in a two‐step protocol with a very narrow molecular weight distribution. The bromo end function of PS obtained by atom transfer radical polymerization was first converted to xanthate function and then reacted with 1, 2‐ethandithiol to yield desired thiol functional polymer (PS‐SH). The obtained polymer was grafted onto the core by thiol‐ene click chemistry. In the following stage, ε‐caprolactone monomer was polymerized from the core by ring opening polymerization (ROP) using tin octoate as catalyst through hydroxyl groups to form the second arm. Finally, PEG‐acetylene, which was simply synthesized by the esterification of Me‐PEG and 5‐pentynoic acid, was clicked onto the core through azide groups present in the structure. The intermediates at various stages and the final miktoarm star copolymer were characterized by ¹H NMR, FTIR, and GPC measurements. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Functional aliphatic polyesters and nanoparticles prepared by organocatalysis and orthogonal grafting chemistry

We describe the use of organic catalysis for the ring‐opening polymerization of functionalized lactones and conversion of the resulting aliphatic polyesters into crosslinked nanoparticles that carry additional functional groups amenable to further modification. Specifically, highly functional aliphatic polyester homopolymers, as well as random and block copolymers, were prepared by 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene catalysis, giving polyesters with pendent alkene and alkyne groups. Azide‐alkyne click and thiol‐ene chemistries were used for postpolymerization modification of diblock copolymers possessing alkene groups on one block and alkyne groups on the other block. The polyesters were crosslinked using azide/alkyne cycloaddition, by reaction of α,ω‐diazides with the pendent alkynes on the polyester backbone. This gave polyester nanoparticles possessing alkene functionality, which were subjected to further modification using thiol‐ene reactions to introduce additional functionality. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Click Chemistry in Functional Aliphatic Polycarbonates

Click chemistry, one of the most important methods in conjugation, plays an extremely significant role in the synthesis of functional aliphatic polycarbonates, which are a group of biodegradable polymers containing carbonate bonds in their main chains. To date, more than 75 articles have been reported on the topic of click chemistry in functional aliphatic polycarbonates. However, these efforts have not yet been highlighted. Six categories of click reactions (alkyne‐azide reaction, thiol‐ene reaction, Michael addition, epoxy‐amine/thiol reaction, Diels‐Alder reaction, and imine formation) that have been afforded for further post‐polymerization modification of polycarbonates are reviewed. Through this review, a comprehensive understanding of functional aliphatic polycarbonates aims to afford insight on the design of polycarbonates for further post‐polymerization modification via click chemistry and the expectation of the practical application.