Facile and Efficient One‐Pot Transformation of RAFT Polymer End Groups via a Mild Aminolysis/Michael Addition Sequence

Summary: The trithiocarbonate end groups of polymers prepared by RAFT polymerization are converted into colorless and stable thioethers in a one‐pot process that combines aminolysis of the trithiocarbonate functions and Michael addition of the resulting thiols to α, β‐unsaturated carbonyl derivatives. This post polymerization procedure, which is carried out under mild conditions to near quantitative conversion, is described in the case of a telechelic poly(N‐isopropylacrylamide) sample bearing isobutylsulfanylthiocarbonylsulfanyl end groups. The chemical composition, purity, and molar masses of the modified polymers are assessed by GPC, ¹H NMR spectroscopy and UV‐vis spectroscopy, which together demonstrate the efficiency of the method and confirm that the molecular weight and polydispersity of the precursor RAFT polymer are not affected by the treatment.

The facile, one pot synthesis combines the reactions of trithiocarbonate aminolysis and Michael addition of a thiol to an α, β‐unsaturated ester to transform the labile, colored thiocarbonylthio moiety into a stable, colorless thioether.     

Synthesis and characterization of telechelic polymethacrylates via RAFT polymerization

The reversible addition–fragmentation chain transfer (RAFT) polymerization technique has been employed to synthesize linear α,ω ‐telechelic polymers with either hydroxyl or carboxyl end groups. Methyl methacrylate, butyl methacrylate, and butyl acrylate were polymerized with RAFT polymerization. The polymerizations exhibited the usual characteristics of living processes. Telechelic polymethacrylates were obtained from a hydroxyl monofunctional RAFT polymer with a two‐step chain‐end modification procedure of the dithioester end group. The procedure consisted of an aminolysis followed by a Michael addition on the resulting thiol. The different steps of the procedure were followed by detailed analysis. It was found that this route was always accompanied by side reactions, resulting in disulfides and hydrogen‐terminated polymer chains as side products next to the hydroxyl‐terminated telechelic polymers. Telechelic poly(butyl acrylates) with carboxyl end groups were produced in a single step procedure with difunctional trithiocarbonates as RAFT agents. The high yield in terms of end group functionality was confirmed by a new critical‐liquid‐chromatography method, in which the polymers were separated based on acid‐functionality and by mass spectrometry analysis. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 959–973, 2005     

Direct Synthesis of Pyridyl Disulfide‐Terminated Polymers by RAFT Polymerization

A trithiocarbonate RAFT agent was modified with a pyridyl disulfide group and used in the direct synthesis of endgroup pyridyl disulfide‐functionalized homo‐ and amphiphilic block copolymers of oligo(ethyleneglycol) acrylate (PEG‐A) and butyl acrylate (BA). Both the homo‐ and copolymerizations were found to be well controlled via the RAFT mechanism. The NMR analysis indicated that both the homopolymers of PEG‐A and the amphiphilic diblock copolymers of PEG‐A and BA possessed pyridyl disulfide terminal groups. A UV‐Vis absorption test revealed that the pyridyl disulfide endgroup of the polymer could be efficiently used to couple thiol‐bearing molecules to the polymer without the need for any post‐polymerization modification. This communication presents the first efficient direct synthesis of thiol‐reactive endgroup‐functionalized well‐defined polymers via the RAFT technique.

     

RAFT Polymerization and Thiol Chemistry: A Complementary Pairing for Implementing Modern Macromolecular Design

Reversible addition fragmentation chain transfer (RAFT) polymerization is one of the most extensively studied reversible deactivation radical polymerization methods for the production of well‐defined polymers. After polymerization, the RAFT agent end‐group can easily be converted into a thiol, opening manifold opportunities for thiol modification reactions. This review is focused both on the introduction of functional end‐groups using well‐established methods, such as thiol‐ene chemistry, as well as on creating bio‐cleavable disulfide linkages via disulfide exchange reactions. We demonstrate that thiol modification is a highly attractive and efficient chemistry for modifying RAFT polymers.

     

Versatile ω‐end group functionalization of RAFT polymers using functional methane thiosulfonates

Five different polymers, poly[methyl methacrylate] (PMMA), poly[lauryl methacrylate] (PLMA), poly[diethylene glycol methacrylate] (PDEGMA), poly[N‐isopropylacrylamide] (PNIPA), and poly[styrene] (PS) prepared by the RAFT process and thus terminated with dithioesters were aminolyzed in the presence of S‐3‐butynyl methane thiosulfonate (MTS), which was synthesized in two steps. Analysis of the polymers by 2D NMR, UV–vis absorbance, and gel permeation chromatography revealed them to quantitatively carry acetylene end groups connected with disulfide bridges, indicating that functional MTS reagents can be employed for end group functionalization of RAFT polymers. This versatile method is of advantage compared with conjugations with functional maleimides, where isolation of terminal thiols is often required but inexpedient for poly[(meth)acrylates] because their terminal thiols may undergo backbiting and thus avoid conjugation. The acetylene‐terminated polymers were bound to an azide functionalized glass surface in a Cu(I) catalyzed cycloaddition. The modified surfaces exhibited water contact angles corresponding to the polarity of the attached polymers. In the case of the stimulus responsive polymers PNIPA and PDEGMA, the surfaces showed temperature‐dependent contact angles. The disulfide bond connecting the polymers to the surface could be selectively cleaved and resulted in all surfaces having the same contact angle, independent of the nature of the polymer prior attached to the surface. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3118–3130, 2009     

A Strategy for Synthesis of Ion‐Bonded Supramolecular Star Polymers by Reversible Addition‐Fragmentation Chain Transfer (RAFT) Polymerization

We have developed a novel strategy for the preparation of ion‐bonded supramolecular star polymers by RAFT polymerization. An ion‐bonded star supramolecule with six functional groups was prepared from a triphenylene derivative containing tertiary amino groups and trithiocarbonate carboxylic acid, and used as the RAFT agent in polymerizations of tert‐butyl acrylate (tBA) and styrene (St). Molecular weights and structures of the polymers were characterized by ¹H NMR and GPC. The results show that the polymerization possesses the character of living free‐radical polymerization and the ion‐bonded supramolecular star polymers PSt, PtBA, and PSt‐b‐PtBA, with six well‐defined arms, were successfully synthesized.

     

End group transformations of RAFT‐generated polymers with bismaleimides: Functional telechelics and modular block copolymers

End group activation of polymers prepared by reversible addition‐fragmentation chain transfer (RAFT) polymerization was accomplished by conversion of thiocarbonylthio end groups to thiols and subsequent reaction with excess of a bismaleimide. Poly(N‐isopropylacrylamide) (PNIPAM) was prepared by RAFT, and subsequent aminolysis led to sulfhydryl‐terminated polymers that reacted with an excess of 1,8‐bismaleimidodiethyleneglycol to yield maleimido‐terminated macromolecules. The maleimido end groups allowed near‐quantitative coupling with model low molecular weight thiols or dienes by Michael addition or Diels‐Alder reactions, respectively. Reaction of maleimide‐activated PNIPAM with another thiol‐terminated polymer proved an efficient means of preparing block copolymers by a modular coupling approach. Successful end group functionalization of the well‐defined polymers was confirmed by combination of UV–vis, FTIR, and NMR spectroscopy and gel permeation chromatography. The general strategy proved to be versatile for the preparation of functional telechelics and modular block copolymers from RAFT‐generated (co)polymers. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5093–5100, 2008     

Aqueous RAFT polymerization of 2‐aminoethyl methacrylate to produce well‐defined,primary amine functional homo‐ and copolymers

We report the direct homopolymerization and block copolymerization of 2‐aminoethyl methacrylate (AEMA) via aqueous reversible addition‐fragmentation chain transfer (RAFT) polymerization. The controlled “living” polymerization of AEMA was carried out directly in aqueous buffer using 4‐cyanopentanoic acid dithiobenzoate (CTP) as the chain transfer agent (CTA), and 2,2′‐azobis(2‐imidazolinylpropane) dihydrochloride (VA‐044) as the initiator at 50 °C. The controlled “living” character of the polymerization was verified with pseudo‐first order kinetic plots, a linear increase of the molecular weight with conversion, and low polydispersities (PDIs) (<1.2). In addition, well‐defined copolymers of poly(AEMA‐b‐HPMA) have been prepared through chain extension of poly(AEMA) macroCTA with N‐(2‐hydroxypropyl)methacrylamide (HPMA) in water. It is shown that the macroCTA can be extended in a controlled fashion resulting in near monodisperse block copolymers. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5405–5415, 2009     

Synthesis and characterization of block copolymers containing poly(di(ethylene glycol) 2‐ethylhexyl ether acrylate) by reversible addition–fragmentation chain transfer polymerization

Reversible addition–fragmentation chain transfer (RAFT) polymerization has emerged as one of the important living radical polymerization techniques. Herein, we report the polymerization of di(ethylene glycol) 2‐ethylhexyl ether acrylate (DEHEA), a commercially‐available monomer consisting of an amphiphilic side chain, via RAFT by using bis(2‐propionic acid) trithiocarbonate as the chain transfer agent (CTA) and AIBN as the radical initiator, at 70 °C. The kinetics of DEHEA polymerization was also evaluated. Synthesis of well‐defined ABA triblock copolymers consisting of poly(tert‐butyl acrylate) (PtBA) or poly(octadecyl acrylate) (PODA) middle blocks were prepared from a PDEHEA macroCTA. By starting from a PtBA macroCTA, a BAB triblock copolymer with PDEHEA as the middle block was also readily prepared. These amphiphilic block copolymers with PDEHEA segments bearing unique amphiphilic side chains could potentially be used as the precursor components for construction of self‐assembled nanostructures. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5420–5430, 2007     

Synthesis of Seven-Arm Poly(vinyl pyrrolidone) Star Polymers with Lysozyme Core Prepared by MADIX/RAFT Polymerization

A poly(vinyl pyrrolidone) (PVP) seven-arms star polymer with lysozyme core was synthesized by conjugating linear N-succinimidyl ester terminated PVP polymer to lysozyme. Reactive PVP polymers were synthesized using a MADIX/RAFT agent functionalized with N-succinimidyl ester. The polymerization of N-vinyl pyrrolidone proceeded in a living fashion up to more than 90% conversion reaching molecular weight of up to 33 000 g · mol⁻¹ with narrow molecular weight distributions. The PVP polymer was conjugated to lysozyme resulting in the attachment of seven PVP polymers to one lysozyme core. While the reaction was found to be complete when using low-molecular weight PVP, some by-products with less than seven arms were observed when using PVP with a molecular weight of 33 000 g · mol⁻¹.

     

Synthesis of homopolymers and copolymers containing an active ester of acrylic acid by RAFT: Scaffolds for controlling polyvalent ligand display

We describe the synthesis of activated homopolymers and copolymers of controlled molecular weight based on the controlled radical polymerization of N‐acryloyloxysuccinimide (NAS) by reversible addition fragmentation chain transfer (RAFT). We synthesized activated homopolymers in a range of molecular weights with polydispersities between 1 and 1.2. The attachment of an inhibitory peptide to the activated polymer backbone yielded a potent controlled molecular weight polyvalent inhibitor of anthrax toxin. To provide greater control over the placement of the peptides along the polymer backbone, we also used a semibatch copolymerization method to synthesize copolymers of NAS and acrylamide (AAm). This approach enabled the synthesis of copolymers with control over the placement of peptide‐reactive NAS monomers along an inert backbone; subsequent functionalization of NAS with peptide yielded well‐defined polyvalent anthrax toxin inhibitors that differed in their potencies. These strategies for controlling molecular weight, ligand density, and ligand placement will be broadly applicable for designing potent polyvalent inhibitors for a variety of pathogens and toxins and for elucidating structure–activity relationships in these systems. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7249–7257, 2008     

Stability and utility of pyridyl disulfide functionality in RAFT and conventional radical polymerizations

Two RAFT agents, suitable for inducing living radical polymerization in water, have been synthesized. Both RAFT agents were shown to be effective over the temperature range 25–70 °C. One RAFT agent was functionalized with a pyridyl disulfide group. RAFT efficacy was demonstrated for the polymerizations of N‐isopropyl acrylamide (NIPAAM) and poly(ethylene oxide)‐acrylate (PEG‐A) in both water and acetonitrile. The kinetic data indicates that the pyridyl disulfide functionality is largely benign in free radical polymerizations, remaining intact for subsequent reaction with thiol groups. This result was confirmed by studying conventional radical polymerizations in the presence of hydroxyethyl pyridyl disulfide. The utility of the pyridyl disulfide functionality at the terminus of the polymers was demonstrated by synthesizing polymer‐BSA conjugates. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7207–7224, 2008     

Efficient Usage of Thiocarbonates for Both the Production and the Biofunctionalization of Polymers

End group modification of polymers prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization was accomplished by conversion of trithiocarbonate into reactive functions able to conjugate easily with biomolecules or bioactive functionality. Polymers were prepared by RAFT, and subsequent aminolysis led to sulfhydryl‐terminated polymers that reacted in situ with an excess of dithiopyridyl disulfide to yield pyridyl disulfide‐terminated macromolecules or in the presence of ene to yield functional polymers. In the first route, the pyridyl disulfide end groups allowed coupling with oligonucleotide and peptide. The second approach exploited thiol–ene chemistry to couple polymers and model compounds such as carbohydrate and biotin with high yield.

     

Facile synthesis of star‐shaped copolymers via combination of RAFT and ring opening polymerization

Reversible addition fragmentation chain transfer (RAFT) polymerization and bifunctional sparteine/thiourea organocatalyst‐mediated ring opening polymerization (ROP) were combined to produce poly(L ‐lactide) star polymers and poly(L ‐lactide‐co‐styrene) miktoarm star copolymers architecture following a facile experimental procedure, and without the need for specialist equipment. RAFT was used to copolymerize ethyl acrylate (EA) and hydroxyethyl acrylate (HEA) into poly(EA‐co‐HEA) co‐oligomers of degree of polymerization 10 with 2, 3, and 4 units of HEA, which were in turn used as multifunctional initiators for the ROP of L ‐lactide, using a bifunctional thiourea organocatalytic system. Furthermore, taking advantage of the living nature of RAFT polymerization, the multifunctional initiators were chain extended with styrene (poly((EA‐co‐HEA)‐b‐styrene) copolymers), and used as initiators for the ROP of L ‐lactide, to yield miktoarm star copolymers. The ROP reactions were allowed to proceed to high conversions (>95%) with good control over molecular weights (ca. 28,000‐230,000 g/mol) and polymer structures being observed, although the molecular weight distributions are generally broader (1.3–1.9) than those normally observed for ROP reactions. The orthogonality of both polymerization techniques, coupled with the ubiquity of HEA, which is used as a monomer for RAFT polymerization and as an initiator for ROP, offer a versatile approach to star‐shaped copolymers. Furthermore, this approach offers a practical approach to the synthesis of polylactide star polymers without a glove box or stringent reaction conditions. The phase separation properties of the miktoarm star copolymers were demonstrated via thermal analyses. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 6396–6408, 2009     

Thermally amendable tailor‐made functional polymer by RAFT polymerization and “click reaction”

This investigation reports the preparation and characterization of thermally amendable functional polymer bearing furfuryl functionality via reversible‐addition fragmentation and chain transfer (RAFT) polymerization and Diels‐Alder (DA) reaction. In this case, furfuryl methacrylate (FMA) was polymerized using 4‐cyano‐4‐[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid as RAFT reagent and 4,4′‐azobis(4‐cyanovaleric acid) as thermal initiator. ¹H NMR, ¹³C NMR, and matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry analysis showed that furfuryl group in poly(furfuryl methacrylate) (PFMA) was not affected during RAFT polymerization and the tailor‐made polymer had RAFT end group. The DA reaction was successfully carried out between the reactive furfuryl functionality of PFMA and different bismaleimides. The thermoreversible property of these DA polymers was characterized by FT‐IR and DSC analysis. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3365–3374     

Computational Studies of RAFT Polymerization–Mechanistic Insights and Practical Applications

Summary: Computational chemistry is a valuable complement to experiments in the study of polymerization processes. This article reviews the contribution of computational chemistry to understanding the kinetics and mechanism of reversible addition fragmentation chain transfer (RAFT) polymerization. Current computational techniques are appraised, showing that barriers and enthalpies can now be calculated with kcal accuracy. The utility of computational data is then demonstrated by showing how the calculated barriers and enthalpies enable appropriate kinetic models to be chosen for RAFT. Further insights are provided by a systematic analysis of structure‐reactivity trends. The development of the first computer‐designed RAFT agent illustrates the practical utility of these investigations.

     

Functionalization of multiwalled carbon nanotube via surface reversible addition fragmentation chain transfer polymerization and as lubricant additives

Polymer‐grafted multiwalled carbon nanotube (MWCNT) hybrid composite which possess a hard backbone of MWCNT and a soft shell of brush‐like polystyrene (PSt) were synthesized. The reversible addition fragmentation chain transfer (RAFT) agents were successfully immobilized onto the surface of MWCNT first, and PSt chains were subsequently grafted from sidewall of MWCNT via RAFT polymerization. Chemical structure of resulting product and the quantities of grafted polymer were determined by Fourier transform infrared, thermal gravimetric analysis, nuclear magnetic resonance, and X‐ray photoelectron spectra. Transmission electron microscopy and field emission scanning electron microscopy images clearly indicate that the nanotubes were coated with a polymer layer. Furthermore, the functionalized MWCNT as additives was added to base lubricant and the tribological property of resultant MWCNT lubricant was investigated with four‐ball machines. The results indicate that the functionalization led to an improvement in the dispersion of MWCNT and as additives it amended the tribological property of base lubricant. The mechanism of the significant improvements on the tribological properties of the functionalized MWCNT as additives was discussed. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3014–3023, 2008     

RAFT kinetics revisited: Revival of the RAFT debate

Recently, two electron spin resonance (ESR)‐based methods for the determination of addition and fragmentation rate coefficients in dithiobenzoate‐mediated reversible addition fragmentation transfer (RAFT) polymerization were introduced, one being based on a spin‐trapping method and the other on single‐laser pulse initiation in conjunction with ESR detection at microsecond time resolution. For the RAFT‐intermediate radical fragmentation rate, coefficient data differing by six orders of magnitude were obtained, which cannot be explained by the usual model dependencies, that is the so‐called cross‐termination versus stable intermediate model. Even under consideration of fast cross‐termination in both cases, the large difference persists. Both the experimental designs are thus critically reviewed to identify potential error sources and to explain the vast difference in the individual results. Both techniques appear to be robust and only small interferences could be identified. Finally, recommendations for the refinement of the individual techniques are given to achieve a consistent kinetic picture of the underpinning reaction equilibria. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Kinetic investigation of the RAFT polymerization of p‐acetoxystyrene

The kinetics of the RAFT polymerization of p‐acetoxystyrene using a trithiocarbonate chain transfer agent, S‐1‐dodecyl‐S′‐(α,α′‐dimethyl‐α″‐acetic acid)trithiocarbonate, DDMAT, was investigated. Parameters including temperature, percentage initiator, concentration, monomer‐to‐chain transfer agent ratio, and solvent were varied and their impact on the rate of polymerization and quality of the final polymer examined. Linear kinetic plots, linear increase of M_n with monomer conversion, and low final molecular weight dispersities were used as criteria for the selection of optimized polymerization conditions, which included a temperature of 70 or 80 °C with 10 mol % AIBN initiator in bulk for low conversions or in 1,4‐dioxane at a monomer‐to‐solvent volume ratio of 1:1 for higher conversions This study opens the way for the use of DDMAT as a chain transfer agent for RAFT polymerization to incorporate p‐acetoxystyrene together with other functional monomers into well‐defined copolymers, block copolymers, and nanostructures. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2517–2524, 2010