A series of poly(poly(ethylene glycol) methyl ether methacrylate-co-pyridyldisulfide ethylmethacrylate)-block-(lauryl methacrylate-co-methacrylic acid) (P(PEGMA-co-PDSM)-b-(LMA-co-MAA)) block copolymers with LMA content of 25, 50, and 75 mol% was synthesized via RAFT polymerization. PDSM monomer was synthesized according to the procedure reported in the literature with minor modifications (Scheme S1 and Figure S1, Supporting Information )48 (link)-49 (link) and commercial monomers (PEGMA Mn: 300 g/mol, LMA, tert-butyl methacrylate (t-BMA), Sigma-Aldrich) were purified via basic alumina gel column chromatography prior to use.
A P(PEGMA-co-PDSM) macroRAFT chain transfer agent (CTA) was synthesized at a molar ratio of 100:1:0.2 representing total monomer, CTA, and initiator ratios, respectively. In brief, 6.2 g PEGMA (20 mmol), 460 mg PDSM (1.8 mmol), 62 mg RAFT agent 4-(cyanopentanoic acid)-4-dithiobenzoate (CPADB; 0.22 mmol, Sigma-Aldrich), and 7.4 mg initiator 2,2-azobisisobutyronitrile (AIBN; 0.04 mmol, recrystallized twice from methanol prior to use, Sigma-Aldrich) were dissolved in 45 mL anhydrous toluene, sealed with a rubber septa and purged with N2(g) for 30 min on ice. The mixture was polymerized at 70 °C for 6 h. The crude mixture was analyzed by 1H NMR (CDCl3) to determine conversion from the monomeric vinyl peaks (-C=CH2 , δ=6.2-5.6) and the PEGMA O-CH2 CH2 peak (δ=4.2) (DPn:36). The polymer was purified by precipitating the crude product into cold pentane (4x) and vacuum drying overnight. The composition and molecular weight of the purified macroRAFT was obtained by 1H NMR (Figure S2, Supporting Information ) and gel permeation chromatography (GPC, Agilent; mobile phase HPLC-grade dimethyl formamide (DMF) containing 0.1% LiBr), respectively. Molecular weight and polydispersity indexes (PDI) were calculated using the ASTRA V Software (Wyatt Technology).
1 (link)H NMR (CDCl3, 400 MHz in ppm): 8.46 (1H, aromatic proton ortho-N), 7.68 (2H, aromatic proton meta-N and para-N), 7.12 (1H, aromatic proton, orthodisulfide linkage), 4.19 (2H, -S-S-CH2 CH2O-), 4.06 (2H, -O-CH2CH2 -), 3.63 (12H, -O-(CH2CH2 -O)n), 3.53 (2H, -O-CH2CH2 -), 3.36 (3H, CH2-O-CH3 -), 3.03 (2H, -S-S-CH2 CH2O-), 1.01 (3H, methyl proton of the methacryloyl group), 0.86 (3H, -C-CH3 )
The macroRAFT CTA was chain extended with LMA and t-BMA monomers followed by acid hydrolysis of the tert-butyl group to form fatty-acid mimetic block copolymers with varying LMA composition (25, 50, and 75 mol% LMA, described herein as LMA25, LMA50, and LMA75, respectively). A representative polymerization (LMA25) consisted of the dissolution of LMA (0.25 g, 1 mmol), t-BMA (0.42 g, 3 mmol), macroRAFT (440 mg, 0.04 mmol), and AIBN (1.32 mg, 0.008 mmol) in anhydrous toluene (2 mL). The mixture was purged with N2(g) for 30 min on ice and reacted for 9 h at 70 °C. The resultant diblock copolymer was purified by membrane dialysis (Snakeskin® dialysis tubing MWCO 3500, Thermo Scientific) against acetone:water (Ace:H2O 80:20 v/v, water ratio was increased each day) for 3 d followed by lyophilization and analyzed via 1H NMR (Figure S3, Supporting Information ) and GPC.
1 (link)H NMR (CDCl3, 400 MHz in ppm): 3.93 (2H, -O-CH2 CH2-), 1.57 (2H, -O-CH2CH2 -), 1.41 (9H, -C-(CH3 )3), 1.25 (18H, CH2-(CH2 )6-CH3), 1.02 (3H, -C-CH3 ), 0.87 (3H, -C-CH3 )
P(PEGMA-co-PDSM)-b-(LMA25-co-t-BMA75) (370 mg, 1.96 mmol tert-butyl ester) was dissolved in dichloromethane (DCM; 4.1 mL). The diblock copolymer was dissolved for 10 min followed by drop-wise addition of trifluoro acetic acid (TFA; 0.747 mL, 9.77 mmol) under vigourous stirring. The reaction continued to stir for 30 h at RT. Excess TFA and DCM were removed via rotary evaporation and deprotected polymer was dried under vacuum overnight. Removal of tert-butyl group from the copolymer was verified by 1H NMR. After 3 d dialysis (MWCO: 3500) against Ace:H2O (80:20 v/v) mixture followed by lyophilization, the fatty acid-mimetic copolymers were further characterized by 1H NMR (Figure S4, Supporting Information ) and GPC (Figure S5, Supporting Information ).
1 (link)H NMR (DMSO-d6, 400 MHz in ppm): 12.32 (1H, O=C-OH ), 3.87 (2H, -O-CH2 CH2-), 1.57 (2H, -O-CH2CH2 -), 1.28 (18H, CH2-(CH2 )6-CH3), 0.91 (3H, -C-CH3 ), 0.80 (3H, -C-CH3 )
A P(PEGMA-co-PDSM) macroRAFT chain transfer agent (CTA) was synthesized at a molar ratio of 100:1:0.2 representing total monomer, CTA, and initiator ratios, respectively. In brief, 6.2 g PEGMA (20 mmol), 460 mg PDSM (1.8 mmol), 62 mg RAFT agent 4-(cyanopentanoic acid)-4-dithiobenzoate (CPADB; 0.22 mmol, Sigma-Aldrich), and 7.4 mg initiator 2,2-azobisisobutyronitrile (AIBN; 0.04 mmol, recrystallized twice from methanol prior to use, Sigma-Aldrich) were dissolved in 45 mL anhydrous toluene, sealed with a rubber septa and purged with N2(g) for 30 min on ice. The mixture was polymerized at 70 °C for 6 h. The crude mixture was analyzed by 1H NMR (CDCl3) to determine conversion from the monomeric vinyl peaks (-C=
1 (link)H NMR (CDCl3, 400 MHz in ppm): 8.46 (1H, aromatic proton ortho-N), 7.68 (2H, aromatic proton meta-N and para-N), 7.12 (1H, aromatic proton, orthodisulfide linkage), 4.19 (2H, -S-S
The macroRAFT CTA was chain extended with LMA and t-BMA monomers followed by acid hydrolysis of the tert-butyl group to form fatty-acid mimetic block copolymers with varying LMA composition (25, 50, and 75 mol% LMA, described herein as LMA25, LMA50, and LMA75, respectively). A representative polymerization (LMA25) consisted of the dissolution of LMA (0.25 g, 1 mmol), t-BMA (0.42 g, 3 mmol), macroRAFT (440 mg, 0.04 mmol), and AIBN (1.32 mg, 0.008 mmol) in anhydrous toluene (2 mL). The mixture was purged with N2(g) for 30 min on ice and reacted for 9 h at 70 °C. The resultant diblock copolymer was purified by membrane dialysis (Snakeskin® dialysis tubing MWCO 3500, Thermo Scientific) against acetone:water (Ace:H2O 80:20 v/v, water ratio was increased each day) for 3 d followed by lyophilization and analyzed via 1H NMR (
1 (link)H NMR (CDCl3, 400 MHz in ppm): 3.93 (2H, -O-
P(PEGMA-co-PDSM)-b-(LMA25-co-t-BMA75) (370 mg, 1.96 mmol tert-butyl ester) was dissolved in dichloromethane (DCM; 4.1 mL). The diblock copolymer was dissolved for 10 min followed by drop-wise addition of trifluoro acetic acid (TFA; 0.747 mL, 9.77 mmol) under vigourous stirring. The reaction continued to stir for 30 h at RT. Excess TFA and DCM were removed via rotary evaporation and deprotected polymer was dried under vacuum overnight. Removal of tert-butyl group from the copolymer was verified by 1H NMR. After 3 d dialysis (MWCO: 3500) against Ace:H2O (80:20 v/v) mixture followed by lyophilization, the fatty acid-mimetic copolymers were further characterized by 1H NMR (
1 (link)H NMR (DMSO-d6, 400 MHz in ppm): 12.32 (1H, O=C-
