Synthesis and characterization of rigid functional anionic polyelectrolytes: Block copolymers and star homopolymers

Seven cyclolinear polymers bearing the tertiary‐butyl α‐(hydroxymethyl)acrylate (TBHMA) ether dimer were prepared using reversible addition–fragmentation chain transfer (RAFT) polymerization. Of the seven polymers, five were cyclolinear homopolymers of the TBHMA ether dimer with different degrees of polymerization, one was an “arm‐first” star homopolymer, and the other was an amphiphilic linear copolymer based on the positively ionizable hydrophilic 2‐(dimethylamino)ethyl methacrylate (DMAEMA) and the TBHMA ether dimer. For comparison, two more polymers were prepared using RAFT polymerization where the TBHMA ether dimer was replaced by tertiary‐butyl methacrylate (tBuMA). In particular, an amphiphilic linear DMAEMA–tBuMA diblock copolymer and a tBuMA arm‐first star homopolymer were also synthesized. All polymers were characterized in terms of their molecular weights and composition using gel permeation chromatography and ¹H NMR spectroscopy, respectively. Subsequently, the tertiary‐butyl groups of the TBHMA ether dimer units and those of the tBuMA units were cleaved by hydrolysis to yield carboxylic acid groups. The successful removal of the tertiary‐butyl groups was confirmed using ¹H and ¹³C NMR and attenuated total reflectance‐Fourier transform infrared spectroscopies. The hydrolyzed (co)polymers exhibited pK values of the carboxylic acid groups of around 4.5, and glass transition temperatures, T_g, of around 200 °C, which were 50 °C higher than those of their nonhydrolyzed precursors. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Dendrimers as scaffolds for multifunctional reversible addition–fragmentation chain transfer agents: Syntheses and polymerization

The synthesis and characterization of novel first‐ and second‐generation true dendritic reversible addition–fragmentation chain transfer (RAFT) agents carrying 6 or 12 pendant 3‐benzylsulfanylthiocarbonylsulfanylpropionic acid RAFT end groups with Z‐group architecture based on 1,1,1‐hydroxyphenyl ethane and trimethylolpropane cores are described in detail. The multifunctional dendritic RAFT agents have been used to prepare star polymers of poly(butyl acrylate) (PBA) and polystyrene (PS) of narrow polydispersities (1.4 < polydispersity index < 1.1 for PBA and 1.5 < polydispersity index < 1.3 for PS) via bulk free‐radical polymerization at 60 °C. The novel dendrimer‐based multifunctional RAFT agents effect an efficient living polymerization process, as evidenced by the linear evolution of the number‐average molecular weight (M_n) with the monomer–polymer conversion, yielding star polymers with molecular weights of up to M_n = 160,000 g mol^?1 for PBA (based on a linear PBA calibration) and up to M_n = 70,000 g mol^?1 for PS (based on a linear PS calibration). A structural change in the chemical nature of the dendritic core (i.e., 1,1,1‐hydroxyphenyl ethane vs trimethylolpropane) has no influence on the observed molecular weight distributions. The star‐shaped structure of the generated polymers has been confirmed through the cleavage of the pendant arms off the core of the star‐shaped polymeric materials. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5877–5890, 2004     

Synthesis and characterization of “Living” star‐shaped poly(N‐vinylcaprolactam) with four arms and carboxylic acid end groups

Poly(N‐vinylcaprolactam) (PNVCL) star‐shaped polymers with four arms and carboxyl end groups were synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization of N‐vinylcaprolactam (NVCL) employing a tetrafunctional trithiocarbonate as an R‐RAFT agent. The resulting star polymers were characterized using ¹H NMR, FT‐IR, gel permeation chromatography (GPC), and UV–vis. Molecular weight of star polymers were analyzed by GPC and UV–vis being observed that the values obtained were very similar. Furthermore, the thermosensitive behavior of the star polymers was studied in aqueous solution by measuring the lower critical solution temperature by dynamic light scattering. Star‐shaped PNVCL were chain extended with ethyl‐hexyl acrylate (EHA) to yield star PNVCL‐b‐PEHA copolymers with an EHA molar content between 4% and 6% proving the living character of the star‐shaped macroCTA. These star block copolymers form aggregates in aqueous solutions with a hydrodynamic diameter ranged from 170 to 225 nm. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2156–2165     

R‐RAFT approach for the polymerization of N‐isopropylacrylamide with a star poly(ε‐caprolactone) core

Reversible addition‐fragmentation chain transfer (RAFT) polymerization is a more robust and versatile approach than other living free radical polymerization methods, providing a reactive thiocarbonylthio end group. A series of well‐defined star diblock [poly(ε‐caprolactone)‐b‐poly(N‐isopropylacrylamide)]₄ (SPCLNIP) copolymers were synthesized by R‐RAFT polymerization of N‐isopropylacrylamide (NIPAAm) using [PCL‐DDAT]₄ (SPCL‐DDAT) as a star macro‐RAFT agent (DDAT: S‐1‐dodecyl‐S′‐(α, α′‐dimethyl‐α″‐acetic acid) trithiocarbonate). The R‐RAFT polymerization showed a controlled/“living” character, proceeding with pseudo‐first‐order kinetics. All these star polymers with different molecular weights exhibited narrow molecular weight distributions of less than 1.2. The effect of polymerization temperature and molecular weight of the star macro‐RAFT agent on the polymerization kinetics of NIPAAm monomers was also addressed. Hardly any radical–radical coupling by‐products were detected, while linear side products were kept to a minimum by careful control over polymerization conditions. The trithiocarbonate groups were transferred to polymer chain ends by R‐RAFT polymerization, providing potential possibility of further modification by thiocarbonylthio chemistry. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

A strategy for synthesis of ion‐bonded amphiphilic miktoarm star copolymers via supramolecular macro‐RAFT agent

Amphiphilic supramolecular miktoarm star copolymers linked by ionic bonds with controlled molecular weight and low polydispersity have been successfully synthesized via reversible addition‐fragmentation chain transfer (RAFT) polymerization using an ion‐bonded macromolecular RAFT agent (macro‐RAFT agent). Firstly, a new tetrafunctional initiator, dimethyl 4,6‐bis(bromomethyl)‐isophthalate, was synthesized and used as an initiator for atom transfer radical polymerization (ATRP) of styrene to form polystyrene (PSt) containing two ester groups at the middle of polymer chain. Then, the ester groups were converted into tertiary amino groups and the ion‐bonded supramolecular macro‐RAFT agent was obtained through the interaction between the tertiary amino group and 2‐dodecylsulfanylthiocarbonylsulfanyl‐2‐methyl propionic acid (DMP). Finally, ion‐bonded amphiphilic miktoarm star copolymer, (PSt)₂‐poly(N‐isopropyl‐acrylamide)₂, was prepared by RAFT polymerization of N‐isopropylacrylamide (NIPAM) in the presence of the supramolecular macro‐RAFT agent. The polymerization kinetics was investigated and the molecular weight and the architecture of the resulting star polymers were characterized by means of ¹H‐NMR, FTIR, and GPC techniques. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5805–5815, 2008     

Cationic star polymer siRNA transfectants interconnected with a piperazine-based cationic cross-linker

Cationic star polymers of 2-(dimethylamino)ethyl methacrylate (DMAEMA) were prepared via the “arm-first” method under group transfer polymerization (GTP) conditions, and were interconnected using a novel, hydrophilic, positively ionizable dimethacrylate cross-linker which is essentially the cyclic dimer of DMAEMA, thus ensuring that the building units of the arms and the core of the star polymers were identical. After their physicochemical characterization, these star-like polyamines were evaluated for their ability to transfer small interfering RNA (siRNA) to murine myoblast cells. Suppression efficiency was found to increase with polymer loading and star branch size, attaining sufficiently high values, comparable to that observed with standard non-viral siRNA transfection systems, while cytotoxicity was kept reasonably low.     

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     

Star polymers by cross‐linking of linear poly(benzyl‐L‐glutamate) macromonomers via free‐radical and RAFT polymerization. A simple route toward peptide‐stabilized nanoparticles

Poly(benzyl‐L ‐glutamate) (PBLG) macromonomers were synthesized by N‐carboxyanhydride (NCA) polymerization initiated with 4‐vinyl benzylamine. MALDI‐ToF analysis confirmed the presence of styrenic end‐groups in the PBLG. Free‐radical and RAFT polymerization of the macromonomer in the presence of divinyl benzene produced star polymers of various molecular weights, polydispersity, and yield depending on the reaction conditions applied. The highest molecular weight (M_w) of 10,170,000 g/mol was obtained in a free‐radical multibatch approach. It was shown that the PBLG star polymers can be deprotected to obtain poly(glutamic acid) star polymers, which form water soluble pH responsive nanoparticles. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Block and star block copolymers by mechanism transformation X. Synthesis of poly(ethylene oxide) methyl ether/polystyrene/poly(l-lactide) ABC miktoarm star copolymers by combination of RAFT and ROP

Poly(ethylene oxide) methyl ether/polystyrene/poly(l-lactide) (MPEO/PSt/PLLA) ABC miktoarm star copolymers were synthesized by combination of reversible addition-fragmentation transfer (RAFT) polymerization and ring-opening polymerization (ROP) using bifunctional macro-transfer agent, MPEO with two terminal dithiobenzoate and hydroxyl groups. It was prepared by reaction of MPEO with maleic anhydride (MAh), subsequently reacted with dithiobenzoic acid and ethylene oxide. RAFT polymerization of St at 110 °C yielded block copolymer, MPEO-b-PSt [(MPEO)(PSt)CH₂OH], and then it was used to initiate the polymerization of l-lactide in the presence of Sn(OCt)₂ at 115 °C to produce ABC miktoarm star polymers, s-[(MPEO)(PSt)(PLLA)]. The structures of products obtained at each synthetic step were confirmed by NMR and gel permeation chromatography data.     

Synthesis of star‐shaped poly(vinyl ethers) with many arms by living cationic polymerization

Star‐shaped polymers of isobutyl vinyl ether (IBVE) with many arms (“crew cut” type) have been synthesized by living cationic polymerization using the HCl‐IBVE adduct/ZnCl₂ initiating system. A short living polymer (DP_n ⪇ 30) of IBVE is allowed to react with a large amount of divinyl ether ([divinyl ether]₀/[P*] = 10–15) to give soluble star polymers whose number of arms ranged from 40 to 120. The diameter of such “crew cut” star polymers reached ca. 20 nm.     

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.

     

Hyperbranched polymers as scaffolds for multifunctional reversible addition–fragmentation chain‐transfer agents: A route to polystyrene‐core‐polyesters and polystyrene‐block‐poly(butyl acrylate)‐core‐polyesters

Polydisperse hyperbranched polyesters were modified for use as novel multifunctional reversible addition–fragmentation chain‐transfer (RAFT) agents. The polyester‐core‐based RAFT agents were subsequently employed to synthesize star polymers of n‐butyl acrylate and styrene with low polydispersity (polydispersity index < 1.3) in a living free‐radical process. Although the polyester‐core‐based RAFT agent mediated polymerization of n‐butyl acrylate displayed a linear evolution of the number‐average molecular weight (M_n) up to high monomer conversions (>70%) and molecular weights [M_n > 140,000 g mol^?1, linear poly(methyl methacrylate) equivalents)], the corresponding styrene‐based system reached a maximum molecular weight at low conversions (≈30%, M_n = 45,500 g mol^?1, linear polystyrene equivalents). The resulting star polymers were subsequently used as platforms for the preparation of star block copolymers of styrene and n‐butyl acrylate with a polyester core with low polydispersities (polydispersity index < 1.25). The generated polystyrene‐based star polymers were successfully cast into highly regular honeycomb‐structured microarrays. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3847–3861, 2003     

Temperature- and pH-responsive star amphiphilic block copolymer prepared by a combining strategy of ring-opening polymerization and reversible addition-fragmentation transfer polymerization

The star-shaped poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (HPs-Star-PCL-b-PDMAEMA) was synthesized by ring-opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization. Star-shaped polycaprolactones (HPs-Star-PCL) were synthesized by the bulk polymerization of ε-caprolactone (CL) with a hyperbranched polyester initiator and tin 2-ethylhexanoate as a catalyst. The number-average molecular weight of these polymers linearly increased with the increase of the molar ratio of CL to hyperbranched initiator. HPs-Star-PCL was converted into a HPs-star-PCL-RAFT by an esterification of HPs-Star-PCL and 4-cyanopentanoic acid dithiobenzoate. Star amphiphilic block copolymer HPs-Star-PCL-b-PDMAEMA was obtained via RAFT polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA). The molecular weight distribution of HPs-Star-PCL-b-PDMAEMA was narrow. Furthermore, the micellar properties of HPs-Star-PCL-b-PDMAEMA in water were studied at various temperatures and pH values by means of dynamic light scattering (DLS). The results indicated that the star copolymers had the pH- and temperature-responsive properties. The release behaviors of model drug aspirin from the star polymer indicated that the rate of drug release could be effectively controlled by pH value and temperature.     

An Arm‐First Approach to Cleavable Mikto‐Arm Star Polymers by RAFT Polymerization

Redox‐cleavable mikto‐arm star polymers are prepared by an “arm‐first” approach involving copolymerization of a dimethacrylate mediated by a mixture of macroRAFT agents. Thus, RAFT copolymerization of the monomers BMA, DMAEMA, and OEGMA, with the disulfide dimethacrylate cross‐linker (DSDMA), bis(2‐methacryloyl)oxyethyl disulfide, mediated by a 1:1:1 mixture of three macroRAFT agents with markedly different properties [hydrophilic, poly[oligo(ethylene glycol) methacrylate]—P(OEGMA)_8–9; cationizable, poly[2‐(dimethylamino)ethyl methacrylate]—P(DMAEMA); hydrophobic, poly(n‐butyl methacrylate)—P(BMA)] provides low dispersity mikto‐arm star polymers. Good control (Đ < 1.3) is observed for the target P(DMAEMA)/P(OEGMA)/P(BMA) (3:3:1) mikto‐arm star, a double hydrophilic P(DMAEMA)/P(OEGMA) (3:3) mikto‐arm star and a hydrophobic P(BMA) homo‐arm star. However, Đ for the target mikto‐arm stars increases with an increase in either the ratio [DSDMA]:[total macroRAFT] or the fraction of hydrophobic P(BMA) macroRAFT agent. The quaternized mikto‐arm star in dilute aqueous solution shows a monomodal particle size distribution and an average size of ≈145 nm.

     

Advanced Computational Strategies for Modelling the Evolution of Full Molecular Weight Distributions Formed During Multiarmed (Star) Polymerisations

Summary: A novel computational strategy is described for the simulation of star polymerisations, allowing for the computation of full molecular weight distributions (MWDs). Whilst the strategy is applicable to a broad range of techniques for the synthesis of star polymers, the focus of the current study is the simulation of MWDs arising from a reversible addition fragmentation chain transfer (RAFT), R‐group approach star polymerisation. In this synthetic methodology, the arms of the star grow from a central, polyfunctional moiety, which is formed initially as the refragmenting R‐group of a polyfunctional RAFT agent. This synthetic methodology produces polymers with complex MWDs and the current simulation strategy is able to account for the features of such complex MWDs. The strategy involves a kinetic model which describes the reactions of a single arm of a star, the kinetics of which are implemented and simulated using the PREDICI® program package. The MWDs resulting from this simulation of single arms are then processed with an algorithm we describe, to generate a full MWD of stars. The algorithm is applicable to stars with an arbitrary number of arms. The kinetic model and subsequent algorithmic processing techniques are described in detail. A simulation has been parameterised using rate coefficients and densities for a 2,2′‐azoisobutyronitrile (AIBN) initiated, bulk polymerisation of styrene at 60 °C. A number of kinetic parameters have been varied over large ranges. Conversion normalised simulations were performed, leading to information regarding star arm length, polydispersity index (PDI) and the fraction of living arms. These screening processes provided a rigorous test for the kinetic model and also insight into the conditions, which lead to optimal star formation. Finally, full MWDs are simulated for several RAFT agent/initiator ratios as well as for stars with a varying number of arms.

Full MWDs from a star with 1, 2, 4, 6 and 8 arms.     

Synthesis of ultra‐high molecular weight polymers by controlled production of initiating radicals

This study demonstrates that the gradual and slow production of initiating radicals (i.e., hydroxyl radicals here) is the key point for the synthesis of ultra‐high molecular weight (UHMW) polymers via controlled radical polymerization. Hydrogen peroxide (H₂O₂) and ferrous iron (Fe²⁺) react via Fenton redox chemistry to initiate RAFT polymerization. This work presents two enzymatic‐mediated (i.e., Bio‐Fenton‐RAFT and Semi Bio‐Fenton‐RAFT) and one syringe pump‐driven Fenton‐RAFT polymerization processes in which the initiating radicals are carefully and gradually dosed into the reaction solution. The “livingness” of the synthesized UHMW polymers is demonstrated by chain extension and aminolysis experiments. Zimm plots obtained from static light scattering (SLS) technique are used to characterize the UHMW polymers. This Fenton‐RAFT polymerization provides access to polymers of unprecedented UHMW (M_w ~ 20 × 10⁶ g mol^?1) with potential in diverse applications. The UHMW polymers made via the controlled Fenton‐RAFT polymerization by using a syringe pump shows that it is possible to produce such materials through an easy‐to‐set up and scalable process. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1922–1930     

Dendrimer‐star polymer and block copolymer prepared by reversible addition‐fragmentation chain transfer (RAFT) polymerization with dendritic chain transfer agent

A new reversible addition‐fragmentation chain transfer (RAFT) agent, dendritic polyester with 16 dithiobenzoate terminal groups, was prepared and used in the RAFT polymerization of styrene (St) to produce star polystyrene (PSt) with a dendrimer core. It was found that this polymerization was of living characters, the molecular weight of the dendrimer‐star polymers could be controlled and the polydispersities were narrow. The dendrimer‐star block copolymers of St and methyl acrylate (MA) were also prepared by the successive RAFT polymerization using the dendrimer‐star PSt as macro chain transfer agent. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 6379–6393, 2005     

Amphiphilic AxBy mikto-arm star copolymers with PLMA and POEGMA arms: Self-assembly and drug encapsulation

We report on the synthesis and self-assembly of amphiphilic mikto-arm star copolymers of the A_xB_y type with mixed arms of poly(lauryl methacrylate) and poly(oligo ethylene glycol methacrylate). Two star copolymers with different hydrophobic-to-hydrophilic ratios are prepared in order to study their self-assembly in aqueous media. Both stars organize in structures with dimensions in the nanoscale. The star with the lower hydrophobic content forms aggregates of lower size and molar mass and it has a higher critical aggregation concentration. The synthesized mikto-arm stars are able to encapsulate curcumin (CUR) and preserve its fluorescence properties while their self-organization is affected by the incorporation of the hydrophobic drug compound. Interestingly, the more hydrophilic star is more strongly affected by the presence of CUR in terms of aggregate size and mass. In phosphate buffered saline (PBS) and fetal bovine serum-PBS solutions the star with higher hydrophobic content appears to better preserve its monomodal size distribution in comparison to the star with lower hydrophobic content either with or without encapsulated CUR. This work opens possibilities for using the new star copolymers in the solubilization of hydrophobic compounds and the delivery of hydrophobic drugs for pharmaceutical and bioimaging applications.     

Combining Steric and Electrostatic Stabilization Using Hydrophilic MacroRAFT Agents in an Ab Initio Emulsion Polymerization of Styrene

Hydrophilic (co)polymers carrying a thiocarbonyl thio end group such as poly(dimethylaminoethyl methacrylate), poly(ethylene oxide), and poly(ethylene oxide)‐block‐poly(dimethylaminoethyl methacrylate) have been evaluated as precursors of stabilizers in batch ab initio emulsion polymerization of styrene under acidic conditions to form electrosterically stabilized polystyrene latex particles. As a mixture of P(DMAEMA/H⁺Cl⁻)‐RAFT and PEO‐RAFT failed to give satisfactory results, PEO‐RAFT was used as a control agent for the RAFT polymerization of DMAEMA, and the resulting block copolymer was successfully used in ab initio styrene emulsion polymerization.

     

Synthesis and characterization of polystyrene-b-tetraaniline stars from polystyrene stars with surface reactive groups prepared by RAFT polymerization

Functionalized star polymers with tetraaniline on their surface have been successfully prepared by substitution reaction of N-succinimidyl-terminated star polymers with tetraaniline. A novel functional RAFT agent bearing N-succinimidyl group was used in the RAFT polymerization of styrene, and N-succinimidyl groups-terminated polystyrenes with narrow molecular weight distribution were obtained. The star polymers with reactive N-succinimidyl groups on their surface were synthesized via RAFT polymerization of DVB. Polymerization mechanism study by gel permeation chromatography displayed that complete disappearance of linear polymers in the products is difficult. The N-succinimidyl-terminated PSt, polymer stars with surface N-succinimidyl groups and the PSt-b-tetraaniline stars were characterized by ¹H NMR spectroscopy, FT-IR and GPC.