Thio‐bromo “Click,” post‐polymerization strategy for functionalizing ring opening metathesis polymerization (ROMP)‐derived materials

The use of a thio‐bromo click strategy as an efficient postpolymerization tool is described. Norbornene derivatives bearing an α‐bromo ester could be polymerized using Grubbs 2^nd generation initiator to provide α‐bromo ester‐containing homo‐and block copolymers that could be efficiently functionalized through reactions with various thiols. A one‐pot strategy was also used, in which up to four different thiols were reacted simultaneously. This chemistry could also be used as an efficient cross‐linking strategy to form ROMP‐based gels as well as a tool for terminal functionalization of polypropylene‐based oligomers. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 179–185     

A “click” approach to ROMP block copolymers

Amphiphilic block copolymers can be conveniently prepared via convergent syntheses, allowing each individual polymer block to be prepared via the polymerization technique that gives the best architectural control. The convergent “click‐chemistry” route presented here, gives access to amphiphilic diblock copolymers prepared from a ring opening metathesis polymer and polyethylene glycol. Because of the high functional group tolerance of ruthenium carbene initiators, highly functional ring opening metathesis polymerization (ROMP) polymer blocks can be prepared. The described synthetic route allows the conjugation of these polymer blocks with other end‐functional polymers to give well‐defined and highly functional amphiphilic diblock copolymers. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2913–2921, 2008     

Synthesis of dendritic macromolecules through divergent iterative thio‐bromo “Click” chemistry and SET‐LRP

The development of a novel nucleophilic thio‐bromo “Click” reaction, specifically base‐mediated thioetherification of thioglycerol with α‐bromoesters was reported in an earlier article. The combination of this thio‐bromo click reaction with subsequent acylation with 2‐bromopropionyl bromide provides an iterative two‐step divergent growth approach to the synthesis of a new class of poly(thioglycerol‐2‐ propionate) (PTP) dendrimers. In this article, the addition of a third step, the single‐electron transfer living radical polymerization (SET‐LRP) of methyl acrylate (MA), was shown to provides access to a three‐step “branch” and “grow” divergent approach to dendritic macromolecules wherein poly(methyl acrylate) (PMA) connects the branching subunits. This facile methodology can provide a diversity of dendritic macromolecular topologies and will ultimately provide the means to the development of self‐organizable dendritic macromolecules. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3940–3948, 2009     

Synthesis of dendrimers through divergent iterative thio‐bromo “Click” chemistry

The development of a novel nucleophilic thio‐bromo “Click” reaction, specifically base‐mediated thioetherification of thioglycerol with α‐bromoesters, is reported. Combination of this thio‐bromo click reaction with subsequent acylation with 2‐bromopropionyl bromide provides an iterative two‐step divergent growth approach to the synthesis of a new class of poly(thioglycerol‐2‐propionate) (PTP) dendrimers. This approach is demonstrated in the rapid preparation of four generation (G1–G4) of PTP dendrimers with high‐structural fidelity. The isolated G1–G4 bromide‐terminated dendrimers can be used directly as dendritic macroinitiators for the synthesis of star‐polymers via SET‐LRP. Additionally, the intermediate hydroxy‐terminated dendrimers are analogs of other water‐soluble polyester and polyether dendrimers. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3931–3939, 2009     

Synthesis of ABCD 4‐Miktoarm star‐shaped quarterpolymers by combination of the “click” chemistry with multiple polymerization mechanism

Well‐defined ABCD 4‐Miktoarm star‐shaped quarterpolymers of [poly(styrene)‐poly(tert‐butyl acrylate)‐poly(ethylene oxide)‐poly(isoprene)] [star(PS‐PtBA‐PEO‐PI)] were successfully synthesized by the combination of the “click” chemistry and multiple polymerization mechanism. First, the poly(styryl)lithium (PS^?Li⁺) and the poly(isoprene)lithium (PI^?Li⁺) were capped by ethoxyethyl glycidyl ether (EEGE) to form the PS and PI with both an active ω‐hydroxyl group and an ω′‐ethoxyethyl‐protected hydroxyl group, respectively. After these two hydroxyl groups were selectively modified to propargyl and 2‐bromoisobutyryl group for PS, the resulted PS was used as macroinitiator for ATRP of tBA monomer and the diblock copolymer PS‐b‐PtBA with a propargyl group at the junction point was achieved. Then, using the functionalized PI as macroinitiator for ROP of EO monomer and bromoethane as blocking agent, the diblock copolymer PI‐b‐PEO with a protected hydroxyl group at the conjunction point was synthesized. After the hydrolysis, the recovered hydroxyl group of PI‐b‐PEO was modified to bromoacetyl and then azide group successively. Finally, the “click” chemistry between them was proceeded smoothly. The obtained star‐shaped quarterpolymers and intermediates were characterized by ¹H NMR, FT‐IR, and SEC in detail. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2154–2166, 2008     

Thiol‐epoxy “click” chemistry: Application in preparation and postpolymerization modification of polymers

Base‐catalyzed reaction between a thiol and an epoxide group is a simple fusion process that leads to the formation of a β‐hydroxythio‐ether linkage. This reaction is efficient, regio‐selective, and fast. In addition, it produces a reactive hydroxyl group upon completion. Therefore, it is of considerable potential in synthesis of reactive and functional soft materials. Here, we discuss the fundamental aspects of this process, the so‐called thiol‐epoxy “click” reaction, and its utility in the preparation and post‐polymerization functionalization of polymers and crosslinked networks. Furthermore, its application in surface modification of solid substrates is also considered. Finally, utility of multifunctional materials created using the thiol‐epoxy reaction is discussed in the biomedical arena. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3057–3070     

Combining “click” chemistry and step‐growth polymerization for the generation of highly functionalized polyesters

Aliphatic polyesters bearing pendant alkyne groups were successfully prepared by step‐growth polymerization of different building blocks such as adipic acid and succinic acid in combination with an acetylene‐based diol, 2‐methyl‐2‐propargyl‐1,3‐propanediol, besides 1,4‐butanediol and ethylene glycol. It was demonstrated that the alkyne groups survive the high reaction temperatures (200 °C) in the presence of a radical inhibitor. The alkyne loading has been tuned by the ratio of the different monomers used, up to 25 mol % of alkyne groups. Subsequently, the alkyne groups have been reacted with azides by the copper‐catalyzed Huisgen 1,3‐dipolar cycloaddition reaction, a popular type of “click” chemistry. “Click” reactions have been performed quantitatively in the presence of benzyl azide and azide‐terminated poly(ethylene glycol), yielding brush copolymers in the latter case. Kinetic investigations about this click reaction have been performed by means of on‐line Fourier transform mid‐infrared spectroscopy, which was reported for the first time in the field of the click chemistry research. A whole range of functionalized polyesters, based on poly(ethylene succinate) and poly(butylene adipate), is available, the properties of which can be tailored by choosing the appropriate azide compound. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6552–6564, 2008     

Three‐arm star ring opening metathesis polymers via alkyne‐azide click reaction

The click chemistry strategy is successfully applied for the preparation of three‐arm star (A₃) ring opening metathesis polymers. A well‐defined monoazide end‐functionalized poly(N‐ethyl oxanorbornene) and a poly(N‐butyl oxanorbornene) obtained via ring opening metathesis polymerization using first generation Grubbs' catalyst are simply clicked with the trisalkyne core affording the synthesis of target star polymers. The obtained star polymers are characterized via nuclear magnetic resonance spectroscopy and gel permeation chromatography (GPC). The deconvolution analyses of GPC traces reveal that the click reaction efficiency for the star formation strongly depends on the chemical nature and the molecular weight of ROM polymers. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2344–2351, 2009     

Ring opening metathesis polymerization of triazole‐bearing cyclobutenes: Diblock copolymer synthesis and evaluation of the effect of side group size on polymerization kinetics

Cyclobutenes containing pendant groups of varying sizes were polymerized via ring opening metathesis polymerization using Grubbs catalyst 2nd generation (G2). The rate of polymerization depended on the size of the pendant groups attached to the cyclobutene rings, with longer side‐chains producing slower polymerization rates and narrower molecular weight distributions. The polymerization of these new molecules proceeded with first order kinetics, consistent with a living polymerization. Chain extension experiments produced cyclobutene‐based diblock copolymers with polydispersity indices below 1.33. The synthetic methods in this report will allow the use of G2 to access new complex polymeric architectures with a higher density of pendant groups than those derived from norbornene analogs and cyclooctene moieties. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1929–1939     

Synthesis of AB3‐type miktoarm star polymers with steroid core via a combination of “Click” chemistry and ring opening polymerization techniques

Well‐defined AB₃‐type miktoarm star‐shaped polymers with cholic acid (CA) core were fabricated with a combination of “click” chemistry and ring opening polymerization (ROP) methods. Firstly, azide end‐functional poly(ethylene glycol) (mPEG), poly(methyl methacrylate) (PMMA), polystyrene (PS), and poly(ε‐caprolactone) (PCL) polymers were prepared via controlled polymerization and chemical modification methods. Then, CA moieties containing three OH groups were introduced to these polymers as the end groups via Cu(I)‐catalyzed click reaction between azide end‐functional groups of the polymers ( mPEG‐N₃ , PMMA‐N₃ , PS‐N₃ , and PCL‐N₃ ) and ethynyl‐functional CA under ambient conditions, yielding CA end‐functional polymers ( mPEG‐Cholic , PMMA‐Cholic , PS‐Cholic , and PCL‐Cholic ). Finally, the obtained CA end‐capped polymers were employed as the macroinitiators in the ROP of ε‐caprolactone (ε‐CL) yielding AB₃‐type miktoarm star polymers ( mPEG‐Cholic‐PCL₃ , PMMA‐Cholic‐PCL₃ , and PS‐Cholic‐PCL₃ ) and asymmetric star polymer [ Cholic‐(PCL)₄ ]. The chemical structures of the obtained intermediates and polymers were confirmed via Fourier transform infrared and ¹H nuclear magnetic resonance spectroscopic techniques. Thermal decomposition behaviors and phase transitions were studied in detail using thermogravimetric analysis and differential scanning calorimetry experiments. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3390–3399     

Ring opening metathesis polymerization (ROMP) of five- to eight-membered cyclic olefins: Computational,thermodynamic, and experimental approach

Ring opening metathesis polymerization (ROMP) of a series of low-strain cyclic olefins and their hydroxyl derivatives using second generation Hoveyda–Grubbs catalyst has been investigated. Additionally, density functional theory (DFT) calculations were performed to evaluate the ring strain energies of the cyclic olefins and their hydroxyl derivatives, coupled with kinetic studies for the ROMP reactions. It was found that among different ring size monomers, Cy8 having a relatively moderate ring strain energy in comparison with the other cyclic olefins, exhibited the highest monomer conversion. The effect of temperature (0, 10, 15, and 25 °C) and monomer concentration (1 M; 2.5 M and 5 M for Cy5 ; and 1 M and 5 M for Cy7 ) for the cyclic olefins Cy5 and Cy7 were investigated. In general, the experimental results for the kinetic ROMP studies obtained using complex HG2 correlate really well with the DFT calculations determined for the ring strain energies of the cyclic olefins. For comparison, DFT calculations predicted the following trend for the ring strain energies Cy8 > Cy5 > Cy7 > Cy6 , and the polymerizations carried out experimentally followed the same trend in terms of monomer conversion, with the exception of Cy5 and Cy7 at lower concentrations, which followed this trend Cy8 > Cy7 > Cy5 > Cy6 . © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3137–3145     

Polymer end group modifications and polymer conjugations via “click” chemistry employing microreactor technology

This study presents the development of microreactor protocols for the successful continuous flow end group modification of atom transfer radical polymerization precursor polymers into azide end‐capped materials and the subsequent copper‐catalyzed azide alkyne click reactions with alkyne polymers, in flow. By using a microreactor, the reaction speed of the azidation of poly(butyl acrylate), poly(methyl acrylate), and polystyrene can be accelerated from hours to seconds and full end group conversion is obtained. Subsequently, copper‐catalyzed click reactions are executed in a flow reactor at 80 °C. Good coupling efficiencies are observed and various block copolymer combinations are prepared. Furthermore, the flow reaction can be carried out in only 40 min, while a batch procedure takes several hours to reach completion. The results indicate that the use of a continuous flow reactor for end group modifications as well as click reactions has clear benefits towards the development and improvement of well‐defined polymer materials. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1263–1274     

Computational design of S‐nitrosothiol “click” reactions

To address a long‐standing problem of finding efficient reactions for chemical labeling of protein‐based S‐nitrosothiols (RSNOs), we computationally explored hitherto unknown (3+2) cycloaddition RSNO reactions with alkynes and alkenes. Nonactivated RSNO cycloaddition reactions have high activation enthalpy (>20 kcal/mol at the CBS‐QB3 level) and compete with alternative S—N bond insertion pathway. However, the (3+2) cycloaddition reaction barriers can be dramatically lowered by coordination of a Lewis acid to the N atom of the —SNO group. To exploit this effect, we propose to use reagents with Lewis acid and a strain‐activated carbon–carbon multiple bond linked by a rigid scaffold, which can react with RSNOs with small activation enthalpies (～5 kcal/mol) and high reaction exothermicities (～40 kcal/mol). The proposed efficient RSNO cycloaddition reactions can be used for future development of practical RSNO labeling reactions. © 2013 Wiley Periodicals, Inc.     

Functionalized poly(oxanorbornene)‐block‐copolymers: Preparation via ROMP/click‐methodology

Block copolymers on basis of poly(oxanorbornenes) bearing functional moieties in their side‐chains are prepared via a combination of ROMP‐methods and 1,3‐dipolar‐“click”‐reactions. Starting from N‐substituted‐ω‐bromoalkyl‐oxanorbornenes and alkyl‐/perfluoroalkyl‐oxanorbornenes, block copolymers with molecular weights up to 25,000 g mol^?1 were generated. Subsequent nucleophilic exchange‐reactions yielded the block‐copolymers functionalized with ω‐azidoalkyl‐moieties in one block. The 1,3‐azide/alkine‐“click” reactions with a variety of terminal alkynes in the presence of a catalyst system consisting of tetrakis(acetonitrile)hexafluorophosphate copper(I) and tris(1‐benzyl‐5‐methyl‐1H‐ [1,2,3]triazol‐4‐ylmethyl)‐amine furnished the substituted block copolymers in high yields, as proven by NMR‐spectroscopy. The resulting polymers were investigated via temperature‐dependent SAXS‐methods, revealing their microphase separated structure as well as their temperature‐dependent behavior. The presented method offers the generation of a large set of different block‐copolymers from only a small set of starting materials because of the high versatility of the “click” reaction, thus enabling a simple and complete functionalization after the initial polymerization reaction. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 485–499, 2007     

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     

ABC‐type hetero‐arm star terpolymers through “Click” chemistry

Hetero‐arm star ABC‐type terpolymers, poly(methyl methacrylate)‐polystyrene‐poly(tert‐butyl acrylate) (PMMA‐PS‐PtBA) and PMMA‐PS‐poly(ethylene glycol) (PEG), were prepared by using “Click” chemistry strategy. For this, first, PMMA‐b‐PS with alkyne functional group at the junction point was obtained from successive atom transfer radical polymerization (ATRP) and nitroxide‐mediated radical polymerization (NMP) routes. Furthermore, PtBA obtained from ATRP of tBA and commercially available monohydroxyl PEG were efficiently converted to the azide end‐functionalized polymers. As a second step, the alkyne and azide functional polymers were reacted to give the hetero‐arm star polymers in the presence of CuBr/N,N,N′,N″,N″‐pentamethyldiethylenetriamine ( PMDETA) in DMF at room temperature for 24 h. The hetero‐arm star polymers were characterized by ¹H NMR, GPC, and DSC. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5699–5707, 2006     

Synthesis of well‐defined star‐shaped poly(ε‐caprolactone)/poly(ethylbene glycol) amphiphilic conetworks by combination of ring opening polymerization and “click” chemistry

Well‐defined star‐shaped hydrophobic poly(ε‐caprolactone) (PCL) and hydrophilic poly(ethylene glycol) (PEG) amphiphilic conetworks (APCNs) have been synthesized via the combination of ring opening polymerization (ROP) and click chemistry. Alkyne‐terminated six arm star‐shaped PCL (6‐s‐PCLx‐C?CH) and azido‐terminated PEG (N₃‐PEG‐N₃) are characterized by ¹H NMR and FT‐IR. The swelling degree of the APCNs is determined both in water and organic solvent. This unique property of the conetworks is dependent on the nanophase separation of hydrophilic and hydrophobic phases. The morphology and thermal behaviors of the APCNs are investigated by SEM and DSC respectively. The biocompatibility is determined by water soluble tetrazolium salt reagents (WST‐1) assay, which shows the new polymer networks had good biocompatibility. Through in vitro release of paclitaxel (PTX) and doxorubicin (DOX), the APCNs is confirmed to be promising drug depot materials for sustained hydrophobic and hydrophilic drugs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 407–417     

Metal‐free synthesis of responsive polymers: Cloud point tuning by controlled “click” reaction

Nitroxide‐mediated radical polymerization has been used for the preparation of pentafluorostyrene (PFS) homopolymers and random copolymers of PFS and oligo(ethyleneglycol) methacrylate (OEGMA_8.5). The poly(pentafluorostyrene) homopolymers were reacted with thiophenol at different ratios at room temperature in the presence of triethylamine. The “clicked” polymers were characterized by ¹H and ¹⁹F NMR spectroscopy and size exclusion chromatography. Moreover, the copolymerization kinetics of the PFS and OEGMA_8.5 copolymers was followed, and the phase transition behavior of random copolymers with different compositions was discussed. Furthermore, copolymers of PFS and 2‐(dimethylamino) ethyl methacrylate (DMAEMA) were prepared at various mole ratios, and the copolymer with a 10:90 ratio, respectively, was soluble in water at room temperature. Turbidimetry measurements were performed for PFS and OEGMA_8.5 or DMAEMA copolymers to determine their cloud points. Finally, the PFS and OEGMA_8.5 copolymer with a mole ratio of 60:40 was reacted further with thiophenol to increase the hydrophobic part in the copolymer. The cloud points of the obtained copolymers could be tuned from 87 to 33 °C by using not only the controlled radical polymerization but also the “click” reaction in a controlled fashion. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1278–1286, 2010