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were purchased from commercial suppliers unless otherwise
specified.
the residue was purified using a flash column (silica gel,
mobile phase: petroleum ether/EtOAc, v/v, 3.5/1.5,
Rf 5 0.2 cm) to produce the product as a pale pink solid
with a yield of 68%. 1H NMR spectral characteristics (400
MHz, CDCl3 d): 5.08 (1H, ANH), 6.67 (1H, NH), 7.93, 7.52,
7.37 (5H, ph-group), 3.55 (4H, NHACH2A), 2.85 (4H,
CH2ASSACH2), 2.56 (2H, CH2), 1.95 (3H, CH3), 1.41 (9H,
(CH3)3 ppm. 13C NMR spectral characteristics (100 MHz,
CDCl3 d): 222.32, 171.1, 156.01, 144.2, 133.3, 128.9, 127.23,
80.01, 46.23, 38.23, 33.32, 32.18, 18.23, 24.42 ppm. The
mass spectra of the CTA-2 are shown Figure S2 Supporting
Information. It shows that the m/z of the CTA-2 is perfectly
matching MS [fast atom bombardment, m/z] [M 1 H]1 calcu-
lated for C22H32N3O3S4, 514,1319, found 514.1319.
Instruments and Measurements
The proton nuclear magnetic resonance [1H NMR, 400 MHz,
and 13C NMR (100 MHz)] spectra were recorded using a Var-
ian INOVA 400 NMR spectrometer. The chemical shifts were
presented as parts per million (ppm) relative to the residual
solvent peaks of the internal standard. The peak singlet, dou-
blet, triplet, multiplet, and broad multiplicities in the 1H
NMR spectra were abbreviated as s, d, t, m, and br, respec-
tively. The Fourier transform infrared (FTIR) spectra were
recorded using a Shimadzu IR Prestige 21 spectrometer. The
spectra were acquired using potassium bromide discs in the
range 4000–600 cm21. The dynamic light scattering (DLS)
measurements were performed using a Nano ZS90 zeta
potential analyzer (Malvern Instruments, UK) with a He-Ne
laser (633 nm), 908 collecting optics, and a thermoelectric
Peltier temperature controller. The block copolymer solu-
tions (2 mg/mL) were filtered through a 0.5-lM filter prior
to use. The particle morphology was analyzed using trans-
mission electron microscopy (TEM) using a JEOL-1299EX
electron microscope with an accelerating voltage of 80 keV.
The TEM samples were prepared in grids with formvar film
and treated with oxygen plasma (from a Harrick plasma
cleaner/sterilizer) for 15 s to render the surface hydrophilic.
Then, the TEM grid was floated on top of the bead with the
hydrophilic surface in contact with the solution. The aqueous
solution was blotted away with a strip of filter paper, and
the samples were dried overnight at room temperature.
Synthesis of Block Copolymers
Polymerization of MPC from CTA-2
MPC (0.73 g, 2.5 mmol), CTA-2 (0.05 mg, 0.1 mmol), 2,20-
azobis(2-methylpropionitrile) (AIBN, 4 mg, 0.025 mmol), and
methanol (5 mL) were added to a 10-mL Schlenk tube
equipped with
a magnetic stir bar. The [monomer]:[-
CTA]:[AIBN] ratio was 50:0.1:0.025. The solution was then
degassed via three freeze-vacuum-thaw cycles and placed in
an oil bath at 70 8C for 12 h. The Boc protected p(MPC) was
obtained by precipitation in excess acetone with yield 72%
(0.53 g). The Boc-protected p(MPC) (500 mg, Mn 5 7000)
was dissolved in 3 mL TFA/methanol v/v (2:1) and kept for
6 h at 50 8C. The NH2-terminated p(MPC) was isolated by
lyophilization and was used as the macroinitiator (0.44 g,
60% related to the initial feed of MPC) for further ROP. 1H
NMR spectral characteristics (400 MHz, CDCl3 d): 5.08 (1H,
ANH), 6.67 (1H, NH), 7.93, 7.52, 7.37 (5H, ph-group), 3.55
(4H, NHACH2A), 2.85 (4H, CH2ASASACH2), 2.56 (2H,
CH2), 1.95 (3H, CH3), and 1.41 (9H, (CH3)3) ppm
Synthesis of Chain Transfer Agent
Synthesis of Mono-Boc-Cystamine
Di-tert-butyldicarbonate (1.92 g, 8.8 mmol) and TEA
(3.64 mL, 3 Eq) were added to a methanolic solution
(25 mL) of cystamine bis(dihydrochloride) (0.5 g, 8.8 mmol).
After 30 min, the solvent was evaporated, and 1 M monoso-
dium phosphate (NaH2PO4) was added (50 mL, pH 4.2). The
aqueous solution was extracted with ether to separate the
di-t-Boc-cystamine. Then, the aqueous solution was basified
to pH 9 with 1 M sodium hydroxide (NaOH, 50 mL), and
extracted six times with ethyl acetate (EtOAc, 5 mL). The
combined organic phases were dried over magnesium sul-
fate, and the solvents evaporated to yield the product
(0.24 g, 48%). 1H NMR spectral characteristics (400 MHz,
CDCl3 d): 5.05 (2H, ANH2), 1.42 (1H, NH), 3.39 (2H,
ACH2A), 2.93 (4H, NH2ACH2A), 2.74 (4H, CH2ASASACH2),
1.39 (9H, (CH3)3 ppm. 13C NMR spectral characteristics (100
MHz, CDCl3 d): 29.04, 36.2, 37.4, 38.8, 39.6, 79.3, 155.4
ppm.
Synthesis of p(MPC)25-b-p(His)n
The Boc-L-His-(Bn)-OH (2.5 g) was suspended in anhydrous
1,4-dioxane (10 mL) and a solution of phosphorus penta-
chloride [1.8 g in 1,4-dioxane (20 mL)] was added while stir-
ring at 25 8C to form Bn-His-NCA. Within a few minutes, a
clear solution was obtained and filtered through a glass filter.
The filtrate was then added to an excess of diethyl ether to
precipitate the Bn-His-NCA crystals. The product was washed
and vacuum-dried. For the ROP of Bn-His-NCA, a macroinitia-
tor, p(MPC)ANH2 (0.7 g, 0.10 mmol) and a predetermined
amount of Bn-His-NCA were dissolved in methanol/DMF
(3:2) in two separate Schlenk flasks and subsequently mixed
under a stream of nitrogen gas using a transfer needle. The
reaction mixture was stirred for 72 h at room temperature
under an atmosphere of nitrogen gas. After polymerization,
the solution was vacuum-concentrated. The concentrated
DMF solution was then precipitated in anhydrous diethyl
ether and vacuum-dried to yield the p(MPC)25-b-p(Bn-His)n
(n 5 25, 35, 50, and 75).
Synthesis of Mono-Boc-Cystamine-Conjugated CTA (CTA-2)
A dry solution of CTA-1 (0.280 g, 1 mmol) and mono-boc-
cystamine (0.254 g, 1 mmol) in dichloromethane (CH2Cl2,
10 mL) was cooled in an ice bath. Then, DMAP (0.025 g, 0.2
mmol) and EDC (0.21 g, 1.1 mmol) were added after 30 min,
and the mixture was stirred at room temperature for 48 h.
The resultant reaction mixture was washed with water, and
To deprotect the benzyl groups a round-bottomed flask was
charged with a solution of p(MPC)25-b-p(Bn-His) in TFA
n
(100 mg, 3 mL). Then, a 2-fold molar excess of a 33 wt %
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JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY 2017, 00, 000–000
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John, Johnson V.
