JOURNAL OF POLYMER SCIENCE PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
phenylalanine, and tin(II) 2-ethyl hexanoate were purchased
from Aldrich and used as received. Methoxy-poly(ethylene
glycol)-amine (MW ¼ 5000) and D,L-lactide (3,6-dimethyl-
1,4-dioxane-2,5-dione) were purchased from SunBio and TCI,
respectively, and used as received. Tetrahydrofuran and tolu-
ene were dried over sodium metal and distilled. Other rea-
gent-grade solvents were used as received. 1H NMR spectra
were recorded on a Bruker Avance-300 spectrometer. 13C
NMR spectra were recorded on a Bruker Avance-500 spec-
trometer. Elemental analysis was performed using EA1110
(CE Instrument, Italy). FTIR measurements were recorded
on a PERKIN ELMER Spectrum GX I using KBr pellets. The
particle sizes and zeta potentials of the nanoparticles were
measured using an ELS-Z (Otsuka Electronics, Japan) spec-
trometer. A typical result was obtained based on the average
from 5 runs. SEM images were taken by a JEOL JSM6330F
microscope. UV–vis spectra were obtained with a SCINCO S-
3100 spectrometer.
mL) and further purified by reprecipitation of the polymer
solution in dichloromethane into diethyl ether.
1
Yield, 0.855 g. H NMR (DMSO-d6, 300 MHz): d ¼ 7.99 (NH),
4.0–4.5 (CH and CH2 of polyserine), 3.50 (OCH2CH2).
Synthesis of Poly(ethylene glycol)-b-[poly
(L-serine)-g-poly(D,L-lactide)]
Poly(ethylene glycol)-poly(L-serine) block copolymer (0.20 g)
and D,L-lactide (1.22 g) were dissolved in dry toluene (75
mL). To remove moisture in the monomer and the macroini-
tiator, the solution was further dried by azeotropic distilla-
tion for 1 day. The solution (50 mL) and tin(II) 2-ethylhexa-
noate (0.5 wt %) were put into a flame-dried polymerization
tube (100 mL). After three freeze-thaw cycles, the tube was
sealed under vacuum condition. The polymerization was car-
ꢁ
ried out at 110 C for 24 h. After evaporation of the solvent,
the solid residue was dissolved in dichloromethane. The
polymer was isolated by precipitation into an excess amount
of diethyl ether and further purified by reprecipitation from
the polymer solution in dichloromethane into diethyl ether
twice.
Synthesis of O-(tert-Butyl)-L-serine N-Carboxyanhydride
A solution of triphosgene (3.31 g, 11.2 mmol) in THF (10
mL) was added to a suspension of O-(tert-butyl)-L-serine
Yield, 0.23 g. 1H NMR (DMSO-d6, 300 MHz): d ¼ 8.20 (NH),
5.19 (CH of polylactide), 4.0–4.8 (CH and CH2 of polyserine),
3.50 (OCH2CH2), 1.46 (CH3 of polylactide); FTIR (KBr, cmꢀ1):
3300 (NAH), 2930–2870 (CAH), 1760 (C¼¼O), 1630 (amide
I), 1550 (amide II), 1190 (CAO).
ꢁ
(1.50 g, 9.31 mmol) in THF (20 mL) at 50 C, and the result-
ing solution was stirred for 2 h at the same temperature.21
After evaporation of the solvent, the crude product was iso-
lated by precipitation in n-hexane. The product was purified
by recrystallization from THF/n-hexane [yield: 1.33
g
(76.0%)].
Synthesis of Poly(ethylene glycol)-b-Poly(D,L-lactide)
The linear poly(ethylene glycol)-b-Poly(D,L-lactide) (PEG-PLA)
diblock copolymer was synthesized by ring opening polymer-
ization of D,L-lactide using methoxy-poly(ethylene glycol)-OH
(MW ¼ 5000) as an initiator according to the literatures.4,22
Anal. Cald for C8H13NO4: C, 51.33; H, 7.00; N, 7.48; found: C,
51.36; H, 6.99; N, 7.44; 13C NMR (CDCl3, 125 MHz): d ¼
168.07, 152.68, 74.67, 60.98, 58.97, 27.44; 1H NMR (DMSO-
d6, 300 MHz): d ¼ 8.94 (s, NH, 1H), 4.56 (t, CH, 1H), 3.63–
3.46 (m, CH2, 2H), 1.09 (s, ACCH3, 9H); FTIR (KBr, cmꢀ1):
3311 (NAH), 2976 (CAH), 1851 (C¼¼O), 1787 (C¼¼O).
Synthesis of L-Phenylalanine N-Carboxyanhydride
This compound was prepared in the same manner as the
preparation of O-(tert-butyl)-L-serine N-carboxyanhydride.
From L-phenylalanine (2.0 g, 12.1 mmol) and triphosgene
(4.65 g, 15.7 mmol), the product (1.63 g, 8.52 mmol) was
obtained in 70.4% yield.
Synthesis of Poly(ethylene glycol)-b-poly
[O-(tert-butyl)-L-serine] Diblock Copolymer
To a solution of O-(tert-butyl)-L-serine N-carboxyanhydride
(1.33 g, 7.10 mmol) in DMF (30.0 mL), a solution of
methoxy-poly(ethylene glycol)-amine (1.41 g, 0.28 mmol,
MW ¼ 5000) was added in DMF (20.0 mL). The reaction
Anal. Cald for C10H9NO3: C, 62.82; H, 4.74; N, 7.33; found: C,
62.85; H, 4.74; N, 7.29; 13C NMR (CDCl3, 125 MHz): d ¼
168.92, 152.21, 134.05, 129.41, 128.19, 59.04, 37.96; 1H
NMR (DMSO-d6, 300 MHz): d ¼ 9.07 (s, NH, 1H), 7.17–7.35
(m, AC6H5, 5H), 4.78 (t, CH, 1H), 3.01 (d, CH2, 2H); FTIR
(KBr, cmꢀ1): 3301 (NAH), 3030 (CAH from phenyl), 2923
(CAH), 1836 (C¼¼O), 1777 (C¼¼O).
ꢁ
mixture was stirred for 2 days at 40 C. After evaporation of
the solvent, the solid was dissolved in chloroform (40.0 mL).
The polymer was isolated by precipitation into diethyl ether
(500 mL) and further purified by reprecipitation from the
polymer solution in chloroform into diethyl ether twice.
Yield, 0.87 g. 1H NMR (DMSO-d6, 300 MHz): d ¼ 7.82 (NH),
4.0–4.5 (CH and CH2 of polyserine), 3.50 (OCH2CH2), 1.10
(CCH3).
Synthesis of Poly(ethylene glycol)-b-poly(L-
phenylalanine)
To a solution of L-phenylalanine N-carboxyanhydride (0.4 g,
0.68 mmol) in DMF (10.0 mL), a solution of methoxy-poly(-
ethylene glycol)-amine (0.2 g, 0.04 mmol, MW ¼ 5000) was
added in DMF (10.0 mL). The reaction mixture was stirred
Deprotection of tert-Butyl Group
To a solution of poly(ethylene glycol)-poly[O-(tert-butyl)-L-
serine] (0.87 g, 0.15 mmol) in dichloromethane (50 mL), a
solution of hydrogen bromide in acetic acid (33 wt %, 0.26
g) was added slowly. The reaction mixture was refluxed for
24 h. After concentration by evaporation of the solvent, the
polymer was isolated by precipitation into diethyl ether (500
ꢁ
for 3 days at 50 C. After evaporation of the solvent, the resi-
due was dissolved in dichloromethane (10.0 mL). The poly-
mer was isolated by precipitation into diethyl ether (400
mL) and further purified by reprecipitation from the poly-
mer solution in dichloromethane into diethyl ether twice.
2860
WILEYONLINELIBRARY.COM/JOURNAL/JPOLA
Lee, Hyunpyo
