ATRP of tert-Butoxycarbonylaminomethyl acrylate (tBAMA): Well

Article pubs.acs.org/Macromolecules

ATRP of tert-Butoxycarbonylaminomethyl acrylate (tBAMA): WellDefined Precursors for Polyelectrolytes of Tunable Charge Mark Billing†,‡ and Felix H. Schacher*,†,‡ †

Laboratory of Organic and Macromolecular Chemistry, Friedrich-Schiller-University Jena, Humboldtstraße 10, D-07743 Jena, Germany ‡ Jena Center for Soft Matter (JCSM), Friedrich-Schiller-University Jena, Philosophenweg 7, D-07743 Jena, Germany S Supporting Information *

ABSTRACT: We present the controlled radical polymerization of homo and block copolymers containing tertbutoxycarbonylaminomethyl acrylate (tBAMA) via ATRP. By varying monomer concentration, solvent, reaction temperature, and ligand (PMDETA, HMTETA, TPMA, Me6TREN and dNbpy), suitable reaction conditions could be established. Moderate control over the polymerization was achieved when using Me6TREN as ligand, whereas this could be drastically improved in case of dNbpy. For block copolymerization, a variety of macroinitiators (polystyrene, poly(n-butyl acrylate), poly(ethylene oxide)) were prepared via ATRP or end group modification. Block extensions resulted in well-defined block copolymers with moderately low dispersity indices (Mw/Mn = 1.12−1.36). In addition, the use of a bromine-functionalized porp core as multifunctional initiator (n = 4) resulted in monomodal star-shaped PtBAMA. The applied homopolymers, macroinitiators, and diblock copolymers were characterized by 1H NMR, 13C NMR and SECas well as MALDI−ToF for one PtBAMA homopolymer. We have already shown for materials prepared using free radical polymerization that the presence of orthogonal protective groups for either −NH2 or −COOH moiety of PtBAMA allows for selective deprotection, thereby generating polyelectrolytes of different charge and charge density. The herein presented PtBAMA of moderate dispersity and different architecture will enable the preparation of similar albeit better defined materials in the near future.

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INTRODUCTION Since their introduction by Szwarc, living polymerizations, for example living anionic polymerization, have been used for the preparation of well-defined polymeric materials with controllable molecular weight or end groups.1,2 One clear disadvantage of these polymerization methods is that relatively strict polymerization conditions have to be applied and only a limited range of monomers is accessible. As an alternative, controlled radical polymerization techniques such as nitroxide− mediated polymerization (NMP)3 or reversible addition− fragmentation chain transfer (RAFT)4 polymerization have been developed and significant progress concerning end group fidelity, dispersity, and accessible molecular weight has been made during recent years. In addition, reversible deactivation radical polymerization methods (RDRP) have significantly influenced the synthesis of well-defined polymers. The most prominent example, atom transfer radical polymerization (ATRP), was first described by Matyjazweski and Sawamoto in 1995.5−7 For ATRP, control over the polymerization process is maintained by a redox reaction of a catalyst system formed by a transition metal and a corresponding ligand. During the activation process, the transition metal catalyst in the lower oxidation state (Mn) is converted to its higher oxidation state (Mn+1). This process activates either the initiator (initiation) or the growing polymer chain Pn• in its dormant state (chain © XXXX American Chemical Society

growth). Depending on the reaction conditions, after a defined time interval the catalyst is reduced and the chain end is converted to the dormant species Pn−X. Since its invention, a wide range of catalytic systems has been established for conducting ATRP processes. Although also Ru8 and Fe9−11 have been successfully applied, Cu-based systems are still most widely used.12,13 Various Cu precursors and a wide range of ligands have enabled a great variety of combinations, and allow fine-tuning of reactivity as well as polymerization control for the desired monomer or monomer combinations. Often this is realized by nitrogen-based ligands, thereby ranging from bidentate to tetradentate examples.14 Additionally, these ligands are able to control the catalyst activity by altering the underlying redox potential.15 One of the main perceived drawbacks of ATRP is the required amount of copper used for polymerization and thus contamination of the resulting materials. As potential alternatives, either alternative copper sources or strategies which minimize the required amount of catalyst by, e.g., the addition of regenerators have been investigated.14,16 Currently, ATRP is mainly applied for acrylonitrile, styrenes and derivatives, and (meth)acrylic esters.17 In contrast, reports on Received: January 30, 2016 Revised: April 22, 2016

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DOI: 10.1021/acs.macromol.6b00224 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

10AD pump, and a RID-10A refractive index detector using a solvent mixture containing chloroform (CHCl3), triethylamine (TEA), and iso-propanol (i-PrOH) (94:4:2) at a flow rate of 1 mL min−1 on a PSS SDV linear S 5-μm column at 40 °C. The system was calibrated with PMMA (410−88 000 g mol−1), PEO (440−44 700) and PS (310−128 000 g mol−1) standards. UV/Vis Spectroscopy. UV/vis absorption spectra were recorded with a Specord 250 spectrometer (Analytik Jena) in Suprasil quartz glass cuvettes 104-QS (Hellma Analytics) with a thickness of 10 mm. The temperature at the measurements was controlled by a Juno dTRON 08.1 (Analytik Jena). Matrix-Assisted Laser Desorption Ionization−Time-of-Flight Mass Spectrometry (MALDI−ToF MS). Spectra were recorded on a Bruker Autoflex III with an acceleration voltage of 20 kV and a neodymium-doped yttrium aluminum garnet (Nd:YAG) (tripled) 355 nm laser. The matrix material consisted of trans-2-[3-(4-tertbutylphenyl)-2-methyl-2-propenylidene]malonitrile (DCTB) dissolved in THF with a concentration of 20 g·L−1 and the samples dissolved in methanol with a concentration of 4 g·L−1 and crystallized in a ratio of 10:1 (matrix:sample). The time-of-flight mode was set to linear mode. Chain-End Modification of Monomethoxy−Poly(ethylene oxide) (2000 g mol−1) PEO44−OH with a Bromide Functionality. α-Bromoisobutyryl bromide (0.8 mL, 7.5 mmol) was added dropwise to a solution of PEO44−OH (3.0 g, 1.50 mmol; 2000 g mol−1) and trimethylamine (TEA, 1.05 mL, 7.5 mL) in THF (75 mL) at 0 °C. Afterward, the solution was stirred for 12 h at room temperature. The solvent was removed under reduced pressure, the residue dissolved in chloroform, and extracted with deionized water. After evaporation of chloroform, the concentrated solution was precipitated twice into cold diethyl ether. The white precipitate was dried under vacuum (2.21 g, 1.04 mmol, 69%). 1 H NMR (300 MHz, CDCl3, δ): 4.32 (m, −CH2OCO−), 3.87− 3.39 (m, −CH2−O−), 3.37 (s, −O−CH3), 1.94 (s, -C(CH3)2-Br) ppm. SEC (CHCl3/i-PrOH/TEA): Mn = 1900 g mol−1; PDI = 1.04 (PEO calibration). General Procedure for the Synthesis of Polystyrene (PS-Br). For the synthesis of PS30-Br (the subscript denotes the degree of polymerization) styrene, CuBr, PMDETA, and methyl α-bromoisobutyrate (MeBiB) were dissolved in 1,4-dioxane (9.6 M) degassed using four freeze−pump−thaw cycles ([Sty]/[CuBr]/[PMDETA]/ [MeBiB] = 100/1/1/1]). The polymerization was carried out at 90 °C for 2.5 h. Afterward, the reaction was terminated by cooling down in liquid nitrogen, followed by the addition of methanol. After removal of copper by AlOx column, the polymers were further purified via precipitation in methanol and the solvent was removed under reduced pressure. 1 H NMR (300 MHz, CD2Cl2, δ): 7.37−6.37 (m, −ArH−), 2.54− 1.23 (m, −CH2−CH−) ppm. SEC (CHCl3/i-PrOH/TEA): Mn = 2900 g mol−1; PDI = 1.08 (PS calibration). General Procedure for the Synthesis of Poly(n-butyl acrylate) (PnBA-Br). For the synthesis of PnBA25-Br, n-butyl acrylate, CuBr, PMDETA and MeBiB were dissolved in anisole (7.73 M) and degassed using four freeze−pump−thaw cycles ([nBA]/[CuBr]/ [PMDETA]/[MeBiB] = 70/1/1/1). The polymerization was carried out at 80 °C for 1.5 h. Afterward, the reaction was terminated by cooling down in liquid nitrogen, followed by the addition of methanol. After removal of copper by AlOx column, the polymers were further purified via dialysis against THF. After removal of the solvent under reduced pressure, the desired polymer was isolated. 1 H NMR (300 MHz, CD2Cl2, δ): 4.04 (m, −COO−CH2−), 2.28 (m, −CH−COO−CH2−), 1.88 (m, −CH2−CH−COO−CH2−), 1.60 (m, −COO−CH2−CH2−), 1.38 (m, −CH2−CH3), 0.92 (m, −CH3) ppm. SEC (CHCl3/i-PrOH/TEA): Mn = 3500 g mol−1; PDI = 1.10 (PMMA calibration). Synthesis of [TTP−Br]4. 5,10,15,20-Tetrakis(4-hydroxyphenyl)21H,23H-porphyrin ([TTP−OH]4, 300 mg, 0.442·mmol) was dissolved in THF (15 mL) and mixed with pyridine (0.699 g, 8.84 mmol) and α-bromoisobutyryl bromide (2.03 g, 8.84 mmol). The reaction was carried out at room temperature for 24 h under

sterically hindered monomers such as itaconates using ATRP protocols are scarce.18−20 Another example of sterically hindered monomers can be different derivatives of dehydroalanine, also known as amidoacrylates. Different substitution patterns have been reported and some of the corresponding polymers showed lower critical solution temperatures (LCST) in aqueous media.21 Specific examples include poly(methyl 2-propionamidoacrylate) (PMPA), poly(methyl 2-isobutyroamidoacrylate) (PMIBA), or PNPAM (poly(N-n-propylacrylamide)s).22,23 In that regard, another interesting monomer with (after deprotection) potential zwitterionic character is tert-butoxycarbonylaminomethyl acrylate (tBAMA), a derivative of dehydroalanine featuring orthogonal protective groups for the carboxylic acid (methyl ester) or the amino functionality (tertbutoxy carbonyl). Up to now, tBAMA has been polymerized using free radical polymerization21,24 or in first attempts using nitroxide-mediated polymerization, but with limited control over molar mass and dispersity.25 We could further show that both protective groups can be selectively removed, providing access to different polyelectrolytes, although the solubility of the materials after deprotection of the amino moiety has proven to be challenging so far. Nevertheless, both the polyanion and the polyampholytic polydehydroalanine (PDha) could already be used as coatings for superparamagnetic iron oxide nanoparticles26 and the resulting core−shell hybrid materials were investigated concerning charge and charge distribution effects during the formation of a protein corona in fetal calf serum.27,28 We herein present the synthesis and characterization of welldefined homopolymers, block copolymers, and star-shaped polymers of tBAMA by ATRP. For this, we identified two promising catalytic systems after extensive variation of the reaction conditions based on Cu(I) and either dNbpy or Me6TREN as ligand. Depending on the system used, different molar masses are accessible (dNbpy 6500 g mol−1, Me6TREN 20 000 g mol−1), different reaction times were observed, and the sensitivity of the overall reaction progress toward oxygen changes significantly. We are interested in the controlled radical polymerization of PtBAMA as well-defined samples with lower molecular weight might provide further insight into solution properties and give access to polyelectrolytes of tunable charge, charge density, and architecture.

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EXPERIMENTAL SECTION

All starting materials were purchased from Sigma-Aldrich, Merck, or Carbolution and were used as received if not mentioned otherwise. Tetrahydrofuran (THF) and dichloromethane (DCM) were purified using a PureSolv-EN Solvent purification System (Innovative Technology). Any glassware was cleaned in a KOH/isopropanol bath and dried at 110 °C. All deuterated solvents were obtained from Deutero. For dialysis, a Spectra/PorDialysis membrane with a MWCO of 1000 g·mol−1 was used. The used ligands, 1,1,4,7,10,10hexamethyltriethylenetetramine (HMTETA), 4,4′-dinonyl-2,2′-dipyridyl (dNbpy), N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDET A ) , T P M A ( t r i s ( 2 -p y r i dy l m e t h y l ) a m i n e , a n d t r i s [ 2 (dimethylamino)ethyl]amine (Me6TREN), were purchased from Sigma-Aldrich and used as received. Nuclear Magnetic Resonance Spectroscopy (NMR). 1H NMR and 13C NMR spectra were recorded in CDCl3 (or CD2Cl2) on a Bruker AC 300-MHz spectrometer at 298 K. Chemical shifts are given in parts per million (ppm, δ scale) relative to the residual signal of the deuterated solvent. Size-Exclusion Chromatography (SEC). SEC was performed on a Shimadzu system equipped with a SCL-10A system controller, a LCB


Article

Macromolecules

(−COO−CH3), 153.59 (−NH−COO−boc), 79.80 (−O−C(CH3)3), 60.21 (−CH2−CH−), 52.64 (−COO−CH3), 41.24 (−CH2−C−), 28.70 (−O−C(CH3)3) ppm; PEO44: 71.84 (−O−CH3), 70.59 (−CH2−CH2−O−) ppm. SEC (CHCl3/i-PrOH/TEA): Mn = 8600 g mol−1; PDI = 1.28 (PS-calibration). General Procedure for the Synthesis of PS30-b-PtBAMAx. For the synthesis of PS30-b-PtBAMAx, tBAMA, CuBr, dNbpy and PS44−Br were dissolved in anisole (14.45 M) and degassed using four freeze− pump−thaw cycles. ([tBAMA]/[CuBr]/[dNbpy]/[PS30-Br], 100/1/ 1/1). The polymerization was carried out at 50 °C for 24 h. Then, the reaction was terminated by cooling down in liquid nitrogen, followed by the addition of methanol. After removal of copper by an AlOx column, the block copolymer was further purified via dialysis against THF, the solvent was removed under reduced pressure, and the desired block copolymer was isolated. 1 H NMR (300 MHz, CD2Cl2, δ): PtBAMA, 6.06−5.00 (m, −NH−), 3.97−3.40 (m, −O−CH3), 3.36−1.92 (m, −C−CH2−), 1.74−1.03 (m, −COO−C(CH3)3) ppm; PS30, 7.2−6.3 (Ar−H), 2.1− 1.60 (−CH2−CH−), 1.60−1.2 (−CH2−CH−) ppm. 13C NMR (75 MHz, CDCl3, δ): PtBAMA, 173.93 (−COO−CH3), 156.16 (−COO− C(CH3)3), 81.59 (−COO−C(CH3)3), 61.66 (−CH2−C−), 55.56 (−COO−CH3), 42.34 (−CH2−C−), 30.15 (−COO−C(CH3)3) ppm; PS30, 147.28 (−CH−C(CH) (CH)−), 129.93 (m-position Ar−C), 127,55 (p-position Ar−C), 61.66 (−CH2−CH−), 42.34 (−CH2− CH−) ppm. SEC (CHCl3/i-PrOH/TEA): Mn = 8000 g mol−1; PDI = 1.38 (PS calibration). General Procedure for the Synthesis of PnBA25-b-PtBAMAx. For the synthesis of PnBA25-b-PtBAMAx, tBAMA, CuBr, dNbpy and PnBA25-Br were dissolved in anisole (12.95 M) and degassed using four freeze−pump−thaw cycles. ([tBAMA]/[CuBr]/[dNbpy]/ [PnBA25-Br], 100/1/1/1). The polymerization was carried out at 50 °C for 24 h. Then, the reaction was terminated by cooling down in liquid nitrogen, followed by the addition of methanol. After removal of copper by an AlOx column, the block copolymer was further purified via dialysis against THF. After removal of the solvent under reduced pressure, the desired block copolymer was isolated and dialyzed against THF. 1 H NMR (300 MHz, CD2Cl2, δ): PtBAMA, 6.06−5.00 (m, −NH−), 3.97−3.40 (m, −O−CH3), 3.36−1.92 (m, −C−CH2−), 1.74−1.03 (m, −COO−C(CH3)3) ppm; PnBA25, 4.2−3.9 (−COO− CH2−), 2.3 (−CH2−CH-), 1.95 (−CH2−CH−), 1.65 (−COO− CH2−CH2−), 1.40 (−CH2−CH3), 0.96 (−CH3) ppm. 13C NMR (75 MHz, CDCl3, δ): PtBAMA, 172.31 (−COO−CH3), 153.60 (−NH− COO−boc), 79.62 (−O−C(CH3)3), 59.90 (−CH2−C−), 52.36 (−O(CH3)), 41.33 (−CH2−C−), 28.57 (−COO−CH3) ppm; PnBA25, 72.31 (−COO−CH2−), 64.39 (−COO−CH2−), 41.33 (−CH2−CH−, −CH2−CH−), 30.74 (−COO−CH2−CH2−), 19.14 (−CH2−CH3), 13.63 (−CH2−CH3) ppm. SEC (CHCl3/i-PrOH/ TEA): Mn = 9700 g mol−1; PDI = 1.35 (PS calibration). General Procedure for the Synthesis of Star-Shaped [TTP− PtBAMAx]4. For the synthesis of [TTP−PtBAMAx]4, tBAMA, CuBr, dNbpy, and [TTP−Br]4 were dissolved in anisole (7.87 M) and degassed using four freeze−pump−thaw cycles ([tBAMA]/[CuBr]/ [dNbpy]/[TTP−Br]4], 400/5/5/1). The polymerization was carried out at 50 °C for 24 h. Then, the reaction was terminated by cooling down in liquid nitrogen, followed by the addition of methanol. After removal of copper by an AlOx column, the star-shaped polymer was further purified via dialysis against THF. After removal of the solvent under reduced pressure, the desired polymer was isolated and dialyzed against THF. 1 H NMR (300 MHz, CD2Cl2, δ): 8.8 (pyrrole −H), 8.1 (Ar−H), 7.4 (Ar−H), 6.06−5.00 (m, −NH−), 3.97−3.40 (m, −COO−CH3), 3.36−1.92 (m, −C−CH2−), 1.74−1.03 (m, −COO−C(CH3)3), −2.9 (−NH−) ppm. 13C NMR (75 MHz, CDCl3, δ): 172.16 (−COO− CH3), 153.89 (−COO−C(CH3)3), 80.20 (−COO−C(CH3)3), 59.90 (−CH2−C−), 53.08 (−COO−CH3), 41.62 (−CH2−C−), 28.57 (−COO−C(CH3)3) ppm. The signals for the C carbon atoms of the porphyrine could not be observed in 13C NMR spectrum, probably due to low signal intensity and potential overlap with the polymer-

continuous stirring. The solution was passed through a neutral alumina colum n to r emov e the quate rnary ammoniu m halide (CH3CH2)3NH+Cl−. The solvent was removed by rotary evaporation and the product was purified by column chromatography (dichloromethane as eluent). Porphyrin-(Br)4 ([TPP−Br]4) was obtained as a purple solid (154 mg, yield 28%). 1 H NMR (300 MHz, CDCl3, δ): 8.81 (d, 8H, pyrrole ring), 8.17 (d, 8H, benzene ring), 7.50 (d, 8H, benzene ring), 2.17 (s, 3H, −CH3), −2,88 (s, 2H, pyrrole NH) ppm. 13C NMR (75 MHz, CDCl3, δ): 170.49 (−COO−), 150.78 (ipso-C), 139.97 (ortho-C), 135.37 (paraC), 131.31 (meta-C), 119.17 (meso-C), 55.51 (−C(CH3)Br), 30.80 (−C(CH3)Br) ppm; the signals for the quarternary CN and pyrroleC carbon atoms could not be observed in the 13C NMR spectrum;29 SEC (CHCl3/i-PrOH/TEA): RI, Mn = 1240 g mol−1, PDI = 1.02 (PScalibration); UV/vis (420 nm), Mn = 1150 g mol−1, PDI = 1.05 (PS calibration). Synthesis of tert-Butoxycarbonylaminomethyl acrylate (tBAMA): 30 N-(tert-Butoxycarbonyl)-D-serine methyl ester (10 g, 45.6 mmol) was dissolved in dichloromethane (200 mL). Methanesulfonyl chloride (Ms−Cl; 6 mL, 77.5 mmol) was added to the solution under vigorous stirring. The reaction mixture was cooled to 0 °C and triethylamine (TEA, 23 mL, 165.9 mmol) was added dropwise. The solution was stirred at 0 °C for 1 h and for a further 2 h at room temperature. Then the reaction mixture was washed with a potassium bisulfate solution (1%) to neutrality. The organic phase was dried over Na2SO4, filtered, and the solvent removed under reduced pressure. The product was further purified via column chromatography with silica gel (hexane/ethyl acetate v/v 8/2). The product was dried under reduced pressure, obtaining a colorless oil in a yield of 87% (8 g, 39 mmol). 1 H NMR (300 MHz, CDCl3, δ): 7.00 (s, 1 H, −NH), 6.13 (s, 1 H, −CCH−), 5.70 (s, 1 H −CCH−), 3.8 (s, 3 H, −O−CH3), 1.46 (s, 9 H, −COO−C(CH3)3) ppm. 13C NMR (75 MHz, CDCl3, δ): 164.57 (−COO−CH3), 152.82 (−COO−C(CH3)3), 131.18 (CC), 105.28 (CH2C), 80.58 (−COO−C(CH3)3), 52.98 (−COO−CH3), 28.45 (−COO−C(CH3)3) ppm. General Procedure for the Synthesis of PtBAMA. For the synthesis of PtBAMA, tBAMA, CuBr, dNbpy, and MeBiB were dissolved in anisole (18.4 M) and degassed using four freeze−pump− thaw cycles. ([tBAMA]/[CuBr]/[dNbpy]/[MeBiB], 100/1/1/1). The polymerization was carried out at 50 °C for the desired time interval. Then, the reaction was terminated by cooling down in liquid nitrogen, followed by the addition of methanol. After removal of copper by an AlOx column, the polymers were further purified via dialysis in THF. Alternatively, precipitation in n-hexane can be performed as well. After removal of the solvent under reduced pressure, the desired polymer was isolated. 1 H NMR (300 MHz, CDCl3, δ): 6.06−5.00 (m, −NH−), 3.97− 3.40 (m, −O−CH3), 3.36−1.92 (m, −C−CH2−), 1.74−1.03 (m, COO−C(CH3)3) ppm. 13C NMR (75 MHz, CDCl3, δ): 172.14 (−COO−CH3), 153.59 (−COO−C(CH 3) 3 ), 79.80 (−COO− C(CH 3 )3 ), 60.21 (−CH 2 −C−), 52.64 (−COO−CH3 ), 41.24 (−CH2−C−), 28.70 (−COO−C(CH3)3) ppm. Exemplarily, SEC (CHCl3/i-PrOH/TEA): Mn = 4500 g mol−1; PDI = 1.31 (PS calibration). General Procedure for the Synthesis of PEO44-b-PtBAMAx. For the synthesis of PEO44-b-PtBAMAx, tBAMA, CuBr, dNbpy, and PEO44−Br were dissolved in anisole (12.5 M) and degassed using four freeze−pump−thaw cycles. ([tBAMA]/[CuBr]/[dNbpy]/[PEO44− Br], 100/1/1/1). The polymerization was carried out at 50 °C for 24 h. Then, the reaction was terminated by cooling down in liquid nitrogen, followed by the addition of methanol. After removal of copper by an AlOx column, the block copolymer was further purified via dialysis against THF. After removal of the solvent under reduced pressure, the desired block copolymer was isolated. 1 H NMR (300 MHz, CDCl3, δ): PtBAMA, 6.06−5.00 (m, −NH−), 3.97−3.40 (m, −O−CH3), 3.36−1.92 (m, −C−CH2−), 1.74−1.03 (m, −COO−C(CH 3 ) 3 ) ppm; PEO 44 , 4.32 (m, −CH 2 −O−, CH2OCO), 3.87−3.39 (m, −CH2−O−), 3.37 (s, −O−CH3), 1.94 (s, −C−CH3) ppm. 13C NMR (75 MHz, CDCl3, δ): PtBAMA, 172.14 C


Article

Macromolecules Scheme 1. Polymerization of 2-tert-Butoxycarbonylaminoacrylic Acid Methyl Ester (tBAMA) Using ATRP

Table 1. Characteristics of PtBAMA Synthesized by ATRP under Different Experimental Conditions entry

[I]a

1 2 3 4 5 6 7 8 9 10

1 1 1 1 1 1 1 1 1 1

24 24 24 24 24 24 24 24 24 24

h h h h h h h h h h

1 1 1 1 1 1 2 1 1 1

− − − − − − − − − −

11 12 13c 14 15 16a 16b 17a 17b 18a 18b 19a 19b 20 20b

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

45 min 10 min 24 h 15 min 90 min 5 min 60 min 5 min 60 min. 5 min 24 h 5 min 90 min 5 min 90 min

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

− − − − − − − 0.5 0.5 − − − − − −

time (h)

[Cu(I)]

[Cu(II)]

[L] 1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 3 3 1 1 10 10 1 1 1 1

[tBAMA] dNbpy 100 100 100 100 100 200 100 100 100 100 Me6TREN 100 100 100 100 100 100 100 100 100 100 100 100 100 50 50

conc. (% v/v) 82 75 69 75 75 69 86 47 bulk 75 75 75 75 15 4 4 4 4 4 4 4 4 4 2.2 2.2

temp [°C]

Mn [g mol‑1]b

Đb

90 70 60 60 50 50 50 50 50 40

− 3400 1300 3900 4600 2700 3600 1600 6500 2000

− 1.35 1.7 1.28 1.40 1.27 1.23 1.12 1.35 1.64

50 50 50 40 30 30 30 30 30 30 30 30 30 30 30

121000 84400 1200 29200 7700 4600 10500 8100 16100 3100 37000 8900 14700 5700 8400

1.33 1.42 1.14 1.89 2.58 1.46 2.36 1.56 2.16 1.46 1.57 1.41 1.80 1.45 1.89

a

I, Cu(I), Cu(II), and L given in equivalents with respect to tBAMA. bDetermined by SEC [(CHCl3/TEA/i-PrOH. (94/2/4): PS calibration]. cIn MeCN.

signals; SEC (CHCl3/i-PrOH/TEA): Mn = 7 900 g mol−1; PDI = 1.30 (PS calibration).

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oil recovery, as well as thickeners, flocculants and emulsifiers.32,33 Nevertheless, it is desirable to control molecular weight of PtBAMA and related materials. We therefore aimed at an improvement of the polymerization procedure using ATRP first for homopolymers (Scheme 1) and later on using block extensions of suitable macroinitiators toward block copolymers or star-shaped polymers. The polymerization of polar monomers (e.g., (meth)acrylics, acrylamides, or vinylpyridines) often is more prone toward unwanted side reactions occurring, for example interaction with the catalyst thereby diminishing the overall reactivity.34 Hence, the number of such monomers for which ATRP with low dispersities (D < 1.3) and predictable molar masses in a convenient range has been reported is limited (mainly DMAEMA,35,36 HEMA, PEGMA, and OEGMA37).34 At first, different conditions for conducting the ATRP of tBAMA were tested: therefore, the Cu(I)/Cu(II) ratio was

RESULTS AND DISCUSSION

Herein, we focus on the synthesis of tBAMA containing homopolymers and block copolymers via copper-mediated atom transfer radical polymerization (ATRP). Our interest in PtBAMA and related materials is mainly due to the possibility to selectively deprotect either functional group and, ultimatively, reach a high charge density in polyampholytes such as polydehydroalanine (PDha). We also expect these to be interesting candidates for applications in the fields of biomaterials or biomedicine.31 In earlier studies it was shown, that polyelectrolytes with tunable charge based on polydehydroalanine could be obtained by free radical polymerization (FRP).25 Potentially, zwitterionic polymers are well-suited as pH-responsive materials, and can be used for water purification, D


Article

Macromolecules varied from 1/0.25 to1/0, different solvents (DMF, anisole, 1,4dioxane, MeOH, i-PrOH), reaction temperatures (30−120 °C), monomer concentrations (4% v/v to bulk conditions), and ligands (PMDETA, HMTETA, TPMA, dNbpy, Me6TREN) were used. Thereby no polymer could be isolated for reactions using PMDETA and HMTETA, and up to now no control over the polymerization could be obtained when using TPMA as ligand. Nevertheless, two suitable systems could be identified: CuIBr/dNbpy and CuIBr/Me6TREN. The polymerizations were carried out in anisole, whereby CuIBr/dNbpy was conducted at high concentrations (∼47% v/v up to bulk conditions), whereas CuIBr/Me6TREN operated under more dilute conditions (usually ∼4% v/v). PtBAMA homopolymers were synthesized by using the initial feed ratio: ([tBAMA]/[Cu(I)]/[dNbpy]/[MeBiB] = 100/1/1/ 1) both in the bulk as well as in anisole at 50 °C. Thereby, PtBAMA with apparent molar masses from 1 600 to 6 500 g mol−1 could be synthesized according to SEC (PS calibration, Table 1, entries 8 and 9, exemplary yields for homopolymers and block copolymers are provided in Table S1). Hereby, the first attempt was carried out at 60 °C (entry 3) and reached a molar mass of 1 300 g mol−1. By increasing the monomer concentration, this increased to 3900 g mol−1 (entry 4). Higher temperatures led to lower molar mass polymers or no reaction at all (entries 1 and 2). Therefore, the following reactions were carried out at 50 °C at different concentrations and monomer to initiator ratios (entries 5−7), and polymers with a molar mass of up to 4600 g mol−1 could be isolated. Neither a higher amount of the catalytic system or more equivalents of monomer could increase the molar mass. A further decrease of the reaction temperature to 40 °C (entry 10) did not lead to any improvement, whereas carrying out the reaction under bulk conditions at 50 °C produced the highest molar mass (Mn, 6 500 g mol −1; Mp, 8800 g mol−1; Đ = 1.35) with acceptable dispersity so far (entry 9, Figure 1A). A kinetic study under typical reaction conditions using dNbpy as ligand (entry 5) revealed a near linear dependence of conversion vs molar mass (Figure 1B), indicating a controlled character of the polymerization. In addition, block extension of PtBAMA macroinitiators using styrene as monomer was possible (data not shown here). Unfortunately, absolute molar masses could not be obtained using 1H NMR as the initiator signal is included within the polymer backbone. Conversions up to 53% were reached with an almost linear increase in molar mass (Figures 1 and S1) and that within 6 min. No further propagation was observed afterward, and also an increase in reaction time up to 48 h did not lead to further monomer consumption. After purification of PtBAMA via an aluminum oxide column and subsequent precipitation in hexane, 1H NMR showed the signals for the polymer backbone (3.36−1.92 ppm), the methyl ester (3.97− 3.40 ppm, −O−CH3), and the boc-group (1.74−1.03 ppm, −CH−NH−COO−C(CH3)3) as well as for the protected amino moiety (6.06−5.00 ppm, −NH−). For one example, we determined the absolute molar mass using matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI−ToF MS) experiments using DCTB as matrix (Figure 2). As can be seen, a Mn of 3 285 g mol−1 is obtained, lower than the value determined from SEC using a PS calibration (4000 g mol−1, cf. Table S1, entry 1). In this case, polymerization conditions were chosen similar to entry 5, Table 1. As an alternative, we also used a combination of Me6TREN and CuIBr ([tBAMA]/[Cu(I)]/[Me6TREN]/[MeBiB] = 100/

Figure 1. (A) SEC elution trace of PtBAMA (6 500 g mol−1); SEC: CHCl3/TEA/i-PrOH (94/4/2). (B) Plot of conversion vs Mn and Mw/Mn for the ATRP of tBAMA in anisole at 50 °C (entry 5).

Figure 2. MALDI−ToF MS spectrum of PtBAMA.

1/1/1). In this case, molar masses of up to 20 000 g mol−1 according to PS calibration and with moderate dispersities could be achieved. In contrast to Cu(I)/dNbpy, the polymerizations were typically carried out under dilute conditions. However, higher dispersities of up to 2.68 were found for higher conversions (entries 14 and 18b). First attempts were carried out under similar conditions as described above for the dNbpy system, resulting in an uncontrolled polymerization process. Following that, the reaction conditions (temperature, time, concentration) were stepwise changed (entries 11−15). Decreasing the reaction temperature to 30 °C and lowering the concentration to 4% v/v led to partially improved control over the polymerization process (entries 16−20, a moderate dispersity of Đ = 1.56 was found upon addition of 0.5 equiv of Cu(II), entry 18). The use of 3 and 10 equiv of ligand (entries 16 and 18) to prevent eventual copper complexation by the polymer itself did not lead to increased reaction control. Nevertheless, changes in the monomer to initiator ratio (entries E


Article

Macromolecules Scheme 2. End-Group Modification of PEO44−OH to PEO44−Br and Block Extension with tBAMA via ATRP

Scheme 3. Synthesis of PS-b-PtBAMA and PnBA-b-PtBAMA via ATRP

19 and 20, Figure S2−S3) were directly reflected in the (apparent) molar mass of the resulting polymers, indicating an at least partially controlled polymerization process. Further, we observed a loss of control during the polymerization, indicated by increasing dispersity values after longer reaction times (Table 1, entries 16a,b to 20a,b). Direct comparison of both catalytic systems under the same reaction conditions (50 °C, anisole, 75% v/v, entries 5, 12) revealed that with Me6TREN as ligand higher molar masses are obtained (84 400 g mol−1 vs 4 600 g mol−1), but at the cost of higher dispersity values and loss of control. We also found that the Cu(I)/dNbpy combination is very sensitive toward air and moisture exposure, whereas CuIBr/Me6TREN seems to be more robust. This might be an explanation for the observation that the reactions often stopped at a conversion of approximately 27% during kinetic studies. Concerning reaction conditions, Cu(I)/dNbpy is suitable for reactions at high concentrations or under bulk conditions whereas more diluted conditions are favorable in case of CuIBr/Me6TREN. Synthesis of Block Copolymers Containing a PtBAMA Segment. We were also interested in the synthesis of block copolymers with a PtBAMA segment, i.e., to use ATRP for block extension with suitable macroinitiators (MI). The respective synthetic procedures are depicted in Scheme 2 and 3. All block extensions were carried out in anisole at 50 °C for 24 h, using the feed ratio: [tBAMA]/[Cu(I)]/[dNbpy]/[MI] = 100/1/1/1 (Table 2). We used the dNbpy/Cu(I) system as this has provided better control over the polymerization in case of PtBAMA homopolymers (see above). After 24 h, copper was removed by an AlOx column and the resulting block copolymer was purified by dialysis against THF (Spectra/PorDialysis Membrane, MWCO 1000 g mol−1). In

Table 2. Characterization Data for ATRP Macroinitiators and the Corresponding PtBAMA-Based Diblock Copolymers sampleb

Mna [g mol−1]

Mwa [g mol−1]

Da

PEO44−Br PEO44-b-PtBAMA30 PnBA25−Br PnBA25-b-PtBAMA50 PS30−Br PS30-b-PtBAMA40

1900 6000 3600 8100 3400 7900

2000 6800 4100 9500 3700 11000

1.03 1.12 1.13 1.18 1.10 1.38

a

Determined by SEC [(CHCl3/TEA/i-PrOH (94/4/2): PEO or PMMA calibration], bcomposition determined by 1H-NMR in CDCl3.

case of PEO44-b-PtBAMA30, commercially available PEO44− OH (2 000 g mol−1) was first converted into an ATRP macroinitiator via end group functionalization using triethylamine and 2-bromo-2-methyl-propionyl bromide in THF38 (Scheme S1, Figure S4). In size exclusion chromatography (Figure 3), a slight shift for PEO44−Br to lower elution volume was observed if compared to the pristine PEO44−OH (Figure S7, Table 2). Besides the expected signals for the PEO backbone (4.32, 3.87−3.39 and 3.37 ppm) a new signal at 1.94 ppm can be detected in the 1H NMR of PEO44−Br and, according to the integrals, a conversion of >98% can be calculated. Subsequent block extension using ATRP yielded a further shift to lower elution volume in SEC (Figure 3A). A slight tailing can be observed in case of PEO44-b-PtBAMA30, and the shift of the elution trace is not parallel. Hence, we cannot exclude the presence of traces of unreacted PEO macroinitiator. In both 1H NMR and 13C NMR, the successful block extension can be monitored by the appearance of the signals corresponding to PtBAMA (Figure S7 F


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Macromolecules

[PMDETA]/[MeBiB] = 100/1/1/1) targeting a DP of ∼30 styrene units. After 2.5h, PS with a molar mass of about 3 400 g mol−1 was isolated (Table 2, Figure S5, and Scheme S2). The subsequent block extension using tBAMA resulted in a welldefined block copolymer, characterized by a clear shift in SEC and a monomodal SEC (Figure 3B). A closer look to the SEC traces unveils a slight tailing of the block copolymers, also here hinting toward the presence of some unreacted macroinitiator. 1 H NMR confirmed the presence of both segments and comparison of the integrals of the aromatic region for PS and the methyl ester for PtBAMA resulted in a composition of PS30b-PtBAMA40 (Figure S8). Additionally, we also synthesized a PnBA-b-PtBAMA diblock copolymer, starting by preparing the PnBA macroinitiator in anisole at 80 °C with an initial feed ratio of ([nBA]/[CuBr]/ [PMDETA][MeBiB] = 70/1/1/1, Scheme 3, Table 2, Figure S6, Scheme S3). After 1.5 h, PnBA-Br with 3600 g mol−1 was yielded and used for block extension with tBAMA. As already noted for the block extension of the PS block, the shape of the block copolymer elution trace indicates the presence of some unreacted starting material. Again, a clear shift in SEC and complete reactivation of the macroinitiator could be shown by SEC (Figure 3C). Here, the calculation of the final block length ratio using 1H NMR is not as straightforward as shown for the other block copolymers. By comparing the integrals of the methylene group next to the ester (4.1 ppm) of nBA and the methyl ester for PtBAMA (3.7 ppm), a composition of PnBA25b-PtBAMA50 was calculated (Figure S9, eq S1. Synthesis of Star-Shaped PtBAMA. We were also interested in expanding the range of polymer architectures, in this case the synthesis of star-shaped PtBAMA featuring a porphyrin core and four arms (Scheme 4). Such materials might be of interest as unimolecular sensors through metal complexation by the prophyrin core or as supramolecular building blocks. For the synthesis of star-shaped polymers with a defined arm number either the arm-first strategy, where presynthesized polymer chains are attached to a functionalized core in macromolecular conjugation reactions, or the core-first approach starting from a multifunctional initiator are typically reported.14,39 We herein employed the core-first approach starting from commercially available [TTP−OH]4 for the preparation of [TTP−Br]4 by esterification using pyridine and α-bromoisobutyryl bromide at room temperature for 24 h.40 After purification via column chromatography the isolated product was investigated by 1H NMR confirming the desired pyrrole signals in the aromatic region (8.8, 8.1, and 7.5 ppm). The pyrrole NH signal of the porphyrin appeared at −2.97 ppm. New signals at 2.16 ppm appear for the methyl groups of the α-bromoisopropanoyl moiety. By comparing the integrals of the aromatic region of the Porphyrin and the methyl ester for α-bromoisobutyryl bromide, a conversion of >95% could be calculated from 1H NMR. The polymerization of tBAMA using [TTP−Br]4 as macroinitiator was carried out at 50 °C in anisole with an initial feed ratio of: ([[tBAMA]/[Cu(I)]/[dNbpy]/[TPP-Br]4] = 400/5/5/1). The reaction was terminated after 24 h by the addition of methanol and subsequent cooling with liquid nitrogen. As the porphyrin core can efficiently complex copper, 5 equiv Cu(I) instead of 4 were used for the polymerization, as well as 5 equiv of dNbpy. After 24 h, the purple material was purified by a short AlOx column to remove copper. After removal of the solvent, the product was analyzed by SEC,

Figure 3. SEC elution traces for PEO44−Br (black line) and PEO44-bPtBAMA30 (red line, A); PS30-Br (black line) and PS30-b-PtBAMA40 (red line, B); and PnBA25-Br (black line) and PnBA25-b-PtBAMA50 (red line, B).

and experimental part). The length of the PtBAMA block was calculated via NMR by comparing the signals of the PEO backbone and the boc-group of tBAMA, yielding PEO44-bPtBAMA30. We also prepared a PS-b-PtBAMA diblock copolymer (Scheme 3). Therefore, a PS macroinitiator was synthesized in anisole at 90 °C with an initial feed ratio of ([Sty]/[CuBr]/ G


Article

Macromolecules Scheme 4. Synthesis of Star-Shaped PtBAMA with 4 Arms Using a Modified Porphyrin Core ([TTP−Br]4) by ATRP

NMR, and UV/vis. In SEC a clear shift to lower elution volume if compared to the starting material can be observed (Figure 4).

Figure 5. UV/vis spectra of [TTP−Br]4 and [TTP−PtBAMA50]4.

implicates that no Cu was complexed by the porphyrin cavity during the ATRP as previously observed via the collapse of the individual signals at 519 and 554 nm [TTP−Br]4 into one broad signal (542 nm).41,42 Furthermore, the aromatic signals of the porphyrin core could be detected in 1H NMR measurements (Figure S10). Upon copper complexation, these signals usually vanish due to the ferromagnetic character of copper.41,43 This is quite remarkable, as in other studies copper complexation occurred even at room temperature.41 Often, additional steps have to be carried out to remove copper, e.g., the addition of neat sulfuric acid.41,44 The absence of complexed copper by the porphyrin ring can be explained by the excess of the used ligand dNbpy.41 Hence, the ATRP of tBAMA starting from [TTP−Br]4 might represent an elegant way to produce metal free star-shaped polymers with a porphyrin core.41,45,46

Figure 4. SEC elution traces of [TTB−Br]4 (solid black line) and [TTP−PtBAMA30]4 (solid red line). CHCl3/TEA/i-PrOH; 94/4/2 was used as eluent.

The approximate length of the PtBAMA arms was calculated by 1H NMR (Figure S10) by comparing the signals of the porphyrin core with the methyl ester or the boc protective group of PtBAMA, resulting in [TTP−PtBAMA13−50]4. By evaluating the 1H NMR of the star shaped polymer, the signals of the PtBAMA part, as well as the aromatic signals of the porphyrine ring can be detected. Unfortunately, we have not been able to analyze [TTP−PtBAMA13]4 by MALDI−TOF mass spectrometry so far, and therefore the arm length is based on the assumption that all four initiation sites reacted during the ATRP. Additionally, we were able to extend the range of synthesized star-shaped polymers by higher conversions to 30 and 50 repetition units (Table 3). The solution properties of [TTP−Br]4 were investigated via UV/vis in THF. According to the UV/vis spectra in Figure 5, the distribution and shape of the absorption maxima remains constant both for [TTP−Br]4 and [TTP−PtBAMA13]4. Besides the typical intensive Soret band at 421 nm, further bands at 549, 554, 595, and 653 nm were detected. These observation supports the integrity of the functionalized porphyrin and

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CONCLUSION We have demonstrated the controlled radical polymerization of tBAMA by ATRP at moderate temperatures of 50 °C in anisole by using CuBr and either dNbpy or Me6TREN as ligand. Homopolymers of different dispersity and molecular weight as well as block copolymers featuring PS, PnBA, and PEO as second segment could be prepared and characterized. Further, star-shaped [TTP−PtBAMA]4 with four arms and DPs of 13−

Table 3. Characterization Data for [TTP−Br]4 and [TTP−PtBAMA50]4 by SEC (RI and UV/Vis Detector)

a

sample

Mna [g mol‑1]RI

Mwa [g mol‑1]

Da

Mna [g mol‑1]UV

Mwa [g mol‑1]

Da

[TTP−Br]4 [TTP−PtBAMA13]4 [TTP−PtBAMA30]4 [TTP−PtBAMA50]4b

1240 6800 7800 10900

1150 7500 10300 12400

1.02 1.10 1.30 1.15

1270 6100 7900 10200

1200 8000 10700 11700

1.05 1.3 1.36 1.15

Determined by SEC [(CHCl3/ i-PrOH/TEA. (94/2/4): PS-calibration], UV/vis 420 nm, b50 °C, 24 h, anisole. H


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of transition-metal complexes. J. Am. Chem. Soc. 1995, 117 (20), 5614−5615. (7) Wang, J.-S.; Matyjaszewski, K. Controlled/″Living″ Radical Polymerization. Halogen Atom Transfer Radical Polymerization Promoted by a Cu(I)/Cu(II) Redox Process. Macromolecules 1995, 28 (23), 7901−7910. (8) Kamigaito, M.; Ando, T.; Sawamoto, M. Metal-Catalyzed Living Radical Polymerization. Chem. Rev. 2001, 101 (12), 3689−3746. (9) Fujimura, K.; Ouchi, M.; Sawamoto, M. Ferrocene Cocatalysis for Iron-Catalyzed Living Radical Polymerization: Active, Robust, and Sustainable System under Concerted Catalysis by Two Iron Complexes. Macromolecules 2015, 48 (13), 4294−4300. (10) Matyjaszewski, K.; Wei, M.; Xia, J.; McDermott, N. E. Controlled/“Living” Radical Polymerization of Styrene and Methyl Methacrylate Catalyzed by Iron Complexes. Macromolecules 1997, 30 (26), 8161−8164. (11) Poli, R.; Allan, L. E. N.; Shaver, M. P. Iron-mediated reversible deactivation controlled radical polymerization. Prog. Polym. Sci. 2014, 39 (10), 1827−1845. (12) Brandts, J. A. M.; van de Geijn, P.; van Faassen, E. E.; Boersma, J.; van Koten, G. Controlled radical polymerization of styrene in the presence of lithium molybdate(V) complexes and benzylic halides. J. Organomet. Chem. 1999, 584 (2), 246−253. (13) Matyjaszewski, K.; Xia, J. Atom Transfer Radical Polymerization. Chem. Rev. 2001, 101 (9), 2921−2990. (14) Pintauer, T.; Matyjaszewski, K. Atom transfer radical addition and polymerization reactions catalyzed by ppm amounts of copper complexes. Chem. Soc. Rev. 2008, 37 (6), 1087−1097. (15) Tang, W.; Matyjaszewski, K. Effect of Ligand Structure on Activation Rate Constants in ATRP. Macromolecules 2006, 39 (15), 4953−4959. (16) Nikolaou, V.; Anastasaki, A.; Alsubaie, F.; Simula, A.; Fox, D. J.; Haddleton, D. M. Copper(ii) gluconate (a non-toxic food supplement/dietary aid) as a precursor catalyst for effective photo-induced living radical polymerisation of acrylates. Polym. Chem. 2015, 6 (19), 3581−3585. (17) Ayres, N. Atom Transfer Radical Polymerization: A Robust and Versatile Route for Polymer Synthesis. Polym. Rev. 2011, 51 (2), 138− 162. (18) Okada, S.; Matyjaszewski, K. Synthesis of bio-based poly(Nphenylitaconimide) by atom transfer radical polymerization. J. Polym. Sci., Part A: Polym. Chem. 2015, 53 (6), 822−827. (19) Szablan, Z.; Toy, A. A.; Terrenoire, A.; Davis, T. P.; Stenzel, M. H.; Müller, A. H. E.; Barner-Kowollik, C. Living free-radical polymerization of sterically hindered monomers: Improving the understanding of 1,1-disubstituted monomer systems. J. Polym. Sci., Part A: Polym. Chem. 2006, 44 (11), 3692−3710. (20) Eyiler, E.; Walters, K. B. Magnetic iron oxide nanoparticles grafted with poly(itaconic acid)-block-poly(N-isopropylacrylamide). Colloids Surf., A 2014, 444, 321−325. (21) Mathias, L. J.; Hermes, R. E. Polymers from captodative dehydroalanine monomers: 2-alkanamide derivatives of methyl propenoate. Macromolecules 1988, 21 (1), 11−13. (22) Mori, T.; Hamada, M.; Kobayashi, T.; Okamura, H.; Minagawa, K.; Masuda, S.; Tanaka, M. Effect of alkyl substituents structures and added ions on the phase transition of polymers and gels prepared from methyl 2-alkylamidoacrylates. J. Polym. Sci., Part A: Polym. Chem. 2005, 43 (20), 4942−4952. (23) Okamura, H.; Mori, T.; Minagawa, K.; Masuda, S.; Tanaka, M. A novel thermosensitive polymer, poly(methyl 2-propionamidoacrylate), with geminal substituents. Polymer 2002, 43 (13), 3825−3828. (24) Isaacs, E.; Gudgeon, H. Great Britain Patent Specification 577771, 1946. (25) Günther, U.; Sigolaeva, L. V.; Pergushov, D. V.; Schacher, F. H. Polyelectrolytes with Tunable Charge Based on Polydehydroalanine: Synthesis and Solution Properties. Macromol. Chem. Phys. 2013, 214 (19), 2202−2212.

50 could be generated. Unlike in previous investigations, we found no indication of complexed copper within the porphyrin cavity. These homopolymers and block copolymers represent interesting starting materials for the preparation of polyelectrolytes with tunable charge and charge density as we have already shown that both the −NH2 and the −COOH moieties can be selectively deprotected in case of PtBAMA prepared using free radical polymerization.25 Future work using welldefined materials will contribute to a profound understanding of the solution properties, charge characteristics, and potential applications of polydehydroalanine and derivatives. In our opinion, these materials represent polyampholytes with rather high charge density per segment and, thus, interesting candidates for protein-repellant coatings, selective layers in membranes, and coatings for theranostic nanoparticles or as building blocks for interpolyelectrolyte complexes with invertable charge stoichiometry.47

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.6b00224. Additional kinetic studies, synthesis of macroinitiators, NMR data, and composition of block copolymers (PDF)

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AUTHOR INFORMATION

Corresponding Author

*(F.H.S.) E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS F.H.S. is grateful to the Thuringian Ministry of Science, Education, and Culture (TMBWK; Grant No. B515-10065, ChaPoNano, and No. B514-09051, NanoConSens) and Ulrich S. Schubert for continuous support. Tobias Rudolph is acknowledged for helpful discussions. We are further grateful to the NMR-platform at the Friedrich-Schiller-University Jena for support in NMR spectroscopy and to Dr. Steffen Weidner (Bundesanstalt für Materialforschung und Prüfung, BAM) for providing MALDI−MS data.

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REFERENCES

(1) Szwarc, M.; Levy, M.; Milkovich, R. Polymerization Initiated by Electron Transfer to Monomer. A new Method of Formation of Block Polymers. J. Am. Chem. Soc. 1956, 78 (11), 2656−2657. (2) WEBSTER, O. W. Living Polymerization Methods. Science 1991, 251 (4996), 887−893. (3) Hawker, C. J.; Bosman, A. W.; Harth, E. New Polymer Synthesis by Nitroxide Mediated Living Radical Polymerizations. Chem. Rev. 2001, 101 (12), 3661−3688. (4) Moad, G.; Rizzardo, E.; Thang, S. H. Living Radical Polymerization by the RAFT Process − A Third Update. Aust. J. Chem. 2012, 65 (8), 985−1076. (5) Kato, M.; Kamigaito, M.; Sawamoto, M.; Higashimura, T. Polymerization of Methyl Methacrylate with the Carbon Tetrachloride/Dichlorotris- (triphenylphosphine)ruthenium(II)/Methylaluminum Bis(2,6-di-tert-butylphenoxide) Initiating System: Possibility of Living Radical Polymerization. Macromolecules 1995, 28 (5), 1721− 1723. (6) Wang, J.-S.; Matyjaszewski, K. Controlled/″living″ radical polymerization. atom transfer radical polymerization in the presence I


Article

Macromolecules

Mixed-Metal Multiporphyrin Arrays. Inorg. Chem. 2003, 42 (14), 4322−4337. (45) Kumar, A.; Maji, S.; Dubey, P.; Abhilash, G. J.; Pandey, S.; Sarkar, S. One-pot general synthesis of metalloporphyrins. Tetrahedron Lett. 2007, 48 (41), 7287−7290. (46) Lemon, C. M.; Brothers, P. J.; Boitrel, B. Porphyrin complexes of the period 6 main group and late transition metals. Dalton Trans. 2011, 40 (25), 6591−6609. (47) Pergushov, D. V.; Müller, A. H. E.; Schacher, F. H. Micellar interpolyelectrolyte complexes. Chem. Soc. Rev. 2012, 41 (21), 6888− 6901.

(26) von der Lühe, M.; Günther, U.; Weidner, A.; Gräfe, C.; Clement, J. H.; Dutz, S.; Schacher, F. H. SPION@polydehydroalanine hybrid particles. RSC Adv. 2015, 5 (40), 31920−31929. (27) Gräfe, C.; Weidner, A.; Lühe, M. v. d.; Bergemann, C.; Schacher, F. H.; Clement, J. H.; Dutz, S. Intentional formation of a protein corona on nanoparticles: Serum concentration affects protein corona mass, surface charge, and nanoparticle−cell interaction. Int. J. Biochem. Cell Biol. 2015, DOI: 10.1016/j.biocel.2015.11.005. (28) Weidner, A.; Gräfe, C.; von der Lühe, M.; Remmer, H.; Clement, J.; Eberbeck, D.; Ludwig, F.; Müller, R.; Schacher, F. H.; Dutz, S. Preparation of Core-Shell Hybrid Materials by Producing a Protein Corona Around Magnetic Nanoparticles. Nanoscale Res. Lett. 2015, 10 (1), 282. (29) Manke, A.-M.; Geisel, K.; Fetzer, A.; Kurz, P. A water-soluble tin(iv) porphyrin as a bioinspired photosensitiser for light-driven proton-reduction. Phys. Chem. Chem. Phys. 2014, 16 (24), 12029− 12042. (30) Tullberg, E.; Schacher, F.; Peters, D.; Frejd, T. Solvent-Free Heck-Jeffery Reactions under Ball-Milling Conditions Applied to the Synthesis of Unnatural Amino Acids Precursors and Indoles. Synthesis 2006, 7, 1183−1189. (31) Siegwart, D. J.; Oh, J. K.; Matyjaszewski, K. ATRP in the design of functional materials for biomedical applications. Prog. Polym. Sci. 2012, 37 (1), 18−37. (32) Dobrynin, A. V.; Rubinstein, M. Theory of polyelectrolytes in solutions and at surfaces. Prog. Polym. Sci. 2005, 30 (11), 1049−1118. (33) Bertrand, P.; Jonas, A.; Laschewsky, A.; Legras, R. Ultrathin polymer coatings by complexation of polyelectrolytes at interfaces: suitable materials, structure and properties. Macromol. Rapid Commun. 2000, 21 (7), 319−348. (34) He, W.; Jiang, H.; Zhang, L.; Cheng, Z.; Zhu, X. Atom transfer radical polymerization of hydrophilic monomers and its applications. Polym. Chem. 2013, 4 (10), 2919−2938. (35) Billing, M.; Rudolph, T.; Täuscher, E.; Beckert, R.; Schacher, F. H. Synthesis and Complexation of Well-Defined Labeled Poly(N,Ndimethylaminoethyl methacrylate)s (PDMAEMA). Polymers 2015, 7 (12), 2478−2493. (36) Plamper, F. A.; Synatschke, C. V.; Majewski, A. P.; Schmalz, A.; Schmalz, H.; Müller, A. H. E. Polimery 2014, 59 (01), 66−73. (37) Miao, J.; He, W.; Zhang, L.; Wang, Y.; Cheng, Z.; Zhu, X. AGET ATRP of water-soluble PEGMA: Fast living radical polymerization mediated by iron catalyst. J. Polym. Sci., Part A: Polym. Chem. 2012, 50 (11), 2194−2200. (38) Hasneen, A.; Cho, I.-s.; Kim, K.-W.; Paik, H.-j. Synthesis of poly(ethylene glycol)-b-poly(mercapto ethylacrylamide) diblock copolymer via atom transfer radical polymerization. Polym. Bull. 2012, 68 (3), 681−691. (39) Braunecker, W. A.; Matyjaszewski, K. Controlled/living radical polymerization: Features, developments, and perspectives. Prog. Polym. Sci. 2007, 32 (1), 93−146. (40) Zhang, B.; Wang, D.; Li, M.; Li, Y.; Chen, X. Synthesis of star− comb-shaped polymer with porphyrin-core and its self-assembly behavior study. J. Appl. Polym. Sci. 2012, 126 (6), 2067−2076. (41) Rudolph, T.; Crotty, S.; Schubert, U. S.; Schacher, F. H. Starshaped poly(2-ethyl-2-oxazoline) featuring a porphyrin core: synthesis and metal complexation. e-Polym. 2015, 15, 227. (42) Dinçer, H.; Mert, H.; Şen, B. N.; Dağ, A.; Bayraktar, S. Synthesis and characterization of novel tetra terminal alkynyl-substituted phthalocyanines and their star polymers via click reaction. Dyes Pigm. 2013, 98 (2), 246−254. (43) Gárate-Morales, J.; Reyes-Ortega, Y.; Alvarez-Toledano, C.; Gutiérrez-Pérez, R.; Ramírez-Rosales, D.; Zamorano-Ulloa, R.; Basurto-Uribe, E.; Hernández-Díaz, J.; Contreras, R. Spectroscopic studies of novel porphyrin-copper(II) and zinc(II) complexes that share the pinch-porphyrin family structure of iron(III) complex models of peroxidases. Transition Met. Chem. 2002, 27 (8), 906−917. (44) Speckbacher, M.; Yu, L.; Lindsey, J. S. Formation of Porphyrins in the Presence of Acid-Labile Metalloporphyrins: A New Route to J


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