Ethylmethacrylate

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 M_n: 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-CH₂CH₂ peak (δ=4.2) (DP_n: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-CH₂CH₂O-), 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-CH₂CH₂O-), 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-CH₂CH₂-), 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-CH₂CH₂-), 1.57 (2H, -O-CH₂CH₂-), 1.28 (18H, CH₂-(CH₂)₆-CH₃), 0.91 (3H, -C-CH₃), 0.80 (3H, -C-CH₃)