A Novel Macroinitiator for the Synthesis of Triblock Copolymers via Atom Transfer Radical Polymerization: Polystyrene‐block‐poly(bisphenol A carbonate)‐block‐polystyrene and Poly(methyl methacrylate)‐block‐poly(bisphenol A carbonate)‐block‐poly(methyl methacrylate)

Summary: Bis(hydroxy)telechelic bisphenol A polycarbonate (PC) was prepared via melt polycondensation of bisphenol A (BPA) and diphenyl carbonate (DPC) using lanthanum(III ) acetylacetonate as a catalyst for transesterification. Subsequently, the polycarbonate was converted to a bifunctional macroinitiator for atom transfer radical polymerization (ATRP) with the reagent, α‐chlorophenylacetyl chloride. The macroinitiator was used for the polymerization of styrene (S) and methyl methacrylate (MMA) to give PS‐block‐PC‐block‐PS and PMMA‐block‐PC‐block‐PMMA triblock copolymers. These block copolymers were characterized by NMR and GPC. When styrene and methyl methacrylate were used in large excess, significant shifts toward high molecular weights were observed with quantitative consumption of the macroinitiator. Several ligands were studied in combination with CuCl as the ATRP catalyst. Kinetic studies reveal the controlled nature of the polymerization reaction for all the ligands used.

Formation of a bifunctional ATRP macroinitiator by esterification of bis(hydroxy)telechelic PC with α‐chlorophenylacetyl chloride.     

Protein-Resistant Materials via Surface-Initiated Atom Transfer Radical Polymerization of 2-Methacryloyloxyethyl Phosphorylcholine

Poly(2-methacryloyloxyethyl phosphorylcholine) (poly(MPC)) was grafted from various polymeric substrates to prepare protein-resistant materials. The poly(MPC) chain length was adjusted via the ratio of monomer to sacrificial initiator in solution. The surfaces were characterized by water contact angle and X-ray photoelectron spectroscopy (XPS). The protein-resistant properties of the poly(MPC)-grafted surfaces were evaluated by single adsorption experiments with fibrinogen and lysozyme. It was shown that the simple three-step grafting method could be applied to modify various biomaterial surfaces including polyurethane and silicones. The adsorption of fibrinogen and lysozyme to the modified surfaces was greatly reduced compared to the unmodified surfaces, and adsorption decreased with increasing poly(MPC) chain length. On polyurethane film grafted with poly(MPC) of chain length 100, the reduction in adsorption was approx. 96% for lysozyme and approx. 99% for fibrinogen.     

Tailor‐Made Antimicrobial/Antiviral Star Polymer via ATRP of Cyclodextrin and Guanidine‐Based Macromonomer

Novel star‐like polymers are prepared via atom transfer radical polymerization (ATRP) of polyhexamethylene guanidine hydrochloride (PHMG) macromonomer and acrylamide (AM) using β‐cyclodextrin (CD) with 8‐active and 5‐active sites as a macroinitiator. The resulting star‐like polymers are characterized by gel permeation chromatography (GPC) and ¹H NMR and are used for deactivating bacteria and viruses. It is found that star polymers with comparable amounts of PHMG possess excellent antimicrobial activity, which, however, strongly depends on the topological structure (i.e., the arm number and the monomer ratio) of the composing copolymers. The in vitro antibacterial activities of the synthesized polymers are investigated against Escherichia coli in terms of the minimum inhibitory concentration (MIC), whereas the antiviral activity of star copolymers is assessed via a plaque assay against non‐enveloped adenovirus (ADV). The results show that the highest antimicrobial activity is achieved by the star‐like copolymer with the monomer ratio of 20:3 (AM:PHGM, mol/mol), while the number of functional arms is fixed at 8. The incorporation of PHMG also renders the star copolymer highly antiviral, thus permitting it to be used as an effective antibacterial/antiviral agent for various applications.

     

AGET ATRP of Methyl Methacrylate Based on Thermoregulated Phase Transfer Catalysis in Organic/Aqueous Biphasic System: Facile and Highly Efficient In Situ Catalyst/Ligand Separation and Recycling

A novel polymerization system with activators generated by electron transfer for atom transfer radical polymerization (ATRP) for sustainable catalyst/ligand separation and recycling in situ is developed based on thermoregulated phase transfer catalysis in organic/aqueous biphasic system. Herein, a typical iniferter agent 1‐cyano‐1‐methylethyldiethyldithiocarbamte is used as the initiator, and CuBr₂, monomethoxy poly(ethylene glycol)‐350‐supported substituted dipicolylamine (L₃₅₀), ascorbic acid, and methyl methacrylate are employed as the catalyst, thermoresponsive ligand, reducing agent, and the model monomer, respectively. The “living” nature of the system is confirmed by polymerization kinetics with recycled catalyst complex aqueous solution and chain‐extension experiments via iniferter and ATRP mechanism, respectively. In addition, the catalyst residue in polymers is less than 2 ppm and the recycling efficiency of catalyst complex in water kept more than 95% even after 5 times of recovery experiments while keeping narrow molecular weight distribution (M_w/M_n < 1.33).

     

Thermosensitive PHEMA microcarriers: ATRP synthesis,characterization, and usabilities in cell cultures

In this study, we developed a novel microcarrier to enhance the production of anchorage-dependent mammalian cells in large scale by preserving them from the effects of shear forces and to enhance their removal from the surface without using proteolytic enzymes and chelating agents. This ‘thermosensitive microcarrier’ was synthesized by the grafting thermoresponsive molecule, N-isopropylacrylamide (NIPAAm), to the crosslinked poly(2-hydroxyethyl methacrylate) (PHEMA) beads by surface-initiated atom transfer radical polymerization. NIPAAm was polymerized on bromine-activated beads’ surfaces to prepare PHEMA-g-PNIPAAm microcarriers. Then, they were chemically characterized by attenuated total reflectance Fourier transform infrared and electron spectroscopy for chemical analysis. Surface morphologies were further investigated by scanning electron microscope and atomic force microscopy techniques. The results of characterization studies confirmed that PNIPAAm was successfully grafted onto PHEMA beads by the means of atom transfer radical polymerization reaction. The cellular activities of PHEMA-g-PNIPAAm microcarriers were evaluated at static and dynamic culture conditions by using two types of cell lines with different morphology, i.e. L929 mouse fibroblasts and HS2 epithelial human keratinocytes. The microcarriers exhibited better cell adhesion and proliferation characteristics for both cell lines. Although their thermally induced cell detachment efficiencies are lower than that of trypsinization, thermally harvested cells preserved their surface morphologies and proliferation characteristics.     

Facile Synthesis of Well‐Defined Telechelic Alkyne‐Terminated Polystyrene in Polar Media Using ATRP With Mixed Fe/Cu Transition Metal Catalyst

The synthesis of polystyrene (PS) by atom transfer radical polymerization using the Fe(0)/CuBr₂ catalytic system in dimethylformamide is reported. The effects of temperature, ligand, initiator structure, and monomer to solvent ratio on the polymerization kinetics are evaluated. PS with high molecular weight, low polydispersity, and telechelic structure are achieved and successfully used for further reinitiation or the copper(I)‐catalyzed Huisgen 1,3‐dipolar cycloaddition click reaction between alkyne‐ and azide‐terminated PS. For the first time, suitable styrene polymerization rates are achieved using this cost‐effective and environmentally attractive catalytic system. This method can be very useful in macromolecular engineering to afford PS‐based materials with well‐controlled structure.     

Reaction Kinetics and Thermodynamic Aspects of Thermoreversibly Cross‐Linked Polymer Networks

The Diels–Alder reaction of furan and maleimide is used to prepare reversibly cross‐linking polymer gels consisting of furan‐bearing polymer chains and bismaleimides. The roles of chain length, stoichiometry, and concentration on gelation kinetics and other properties are evaluated. Additionally, kinetics of the Diels–Alder reactions in the gelling system are compared with the kinetics of small molecule systems. By combining spectroscopic and rheological techniques, a mechanochemical analysis is performed.

     

Synthesis of Hyperbranched Polymers via Metal‐Free ATRP in Solution and Microemulsion

Atom transfer radical polymerization (ATRP), as one of the most successful controlled radical polymerization techniques, has been broadly used by polymer chemists and nonspecialists for synthesis of various functional materials, although the use of copper as traditional catalyst often results in undesired color or properties. The first homopolymerization of an initiable monomer, that is, inimer, is reported via metal‐free ATRP using 10‐phenylphenothiazine (Ph‐PTH) as photocatalyst in both solution and microemulsion media. Although polymerizations of inimers in both media can be carried out, only the microemulsion polymerization of methacrylate‐based inimer 1 effectively confines the random bimolecular reaction within each segregated latex and produces hyperbranched polymers with high molecular weight and low polydispersity. Several experimental parameters in the microemulsion polymerization of inimer 1 are subsequently studied, including the Ph‐PTH amount, the solids content of microemulsion, and the light source of irradiation. The results not only provide an effective method to tune the structure and molecular weights of hyperbranched polymers in confined‐space polymerization, but also expand the toolbox of using metal‐free ATRP method for synthesizing highly branched polymers in controlled manner.     

Engineering of cell membranes with a bisphosphonate-containing polymer using ATRP synthesis for bone targeting

The field of polymer-based membrane engineering has expanded since we first demonstrated the reaction of N-hydroxysuccinimide ester-terminated polymers with cells and tissues almost two decades ago. One remaining obstacle, especially for conjugation of polymers to cells, has been that exquisite control over polymer structure and functionality has not been used to influence the behavior of cells. Herein, we describe a multifunctional atom transfer radical polymerization initiator and its use to synthesize water-soluble polymers that are modified with bisphosphonate side chains and then covalently bound to the surface of live cells. The polymers contained between 1.7 and 3.1 bisphosphonates per chain and were shown to bind to hydroxyapatite crystals with kinetics similar to free bisphosphonate binding. We engineered the membranes of both HL-60 cells and mesenchymal stem cells in order to impart polymer-guided bone adhesion properties on the cells. Covalent coupling of the polymer to the non-adherent HL-60 cell line or mesenchymal stem cells was non-toxic by proliferation assays and enhanced the binding of these cells to bone.     

Kinetic Investigations of Cu‐Mediated ATRP in Aqueous Solution

Cu‐mediated atom‐transfer radical polymerization (ATRP) is studied via on‐line vis/NIR spectroscopy in an aqueous solution of a monomer‐free model system, with CuBr/2,2′‐bipyridine acting as the catalyst, and 2‐hydroxyethyl 2‐bromoisobutyrate as the initiator, at a pressure of up to 2000 bar. Excess NaBr is added to avoid the water‐assisted dissociation of the Br–Cu(II)/L bond. The activation–deactivation equilibrium constant, K_model, is measured at different compositions of the water–poly(ethylene glycol) dimethylether (PEO) solvent mixture, in which PEO mimics a water‐soluble monomer. K_model increases by about three orders of magnitude in passing from a PEO to a water environment. The change in K_model is essentially due to the effect on the activation rate coefficient. Kinetic analysis of the model system upon variation of NaBr concentration in conjunction with predici simulations shows that the NaBr content has no significant impact on the activation and deactivation rate coefficients and thus on K_model, but on dispersity and on the degree of chain‐end functionality.