Macromolecules
Article
1H NMR (DMSO-d
, 600 MHz): δ 7.36−7.18 (m, ∼5H), 4.47−3.80
scanning calorimetry (DSC), analytical ultracentrifugation
6
(AUC), and static light scattering (SLS).
(m, ∼182H), 3.40−3.00 (m, ∼177H), 3.00−2.65 (m, ∼70H), 1.65−
13
1
.25 (d, br, ∼144H), 0.95−0.68 (d, br, ∼216H) ppm. C NMR
(DMSO-d , 100 MHz): δ 169.2, 169.0, 48.9, 48.0, 20.3, 20.1, 11.1
6
EXPERIMENTAL SECTION
app
−1
app
■
ppm. SEC (NMP, PMMA calibration): M
̅
n
7.7 kg mol , M
̅
w
8.7
−
1
app
1
Materials. N-tert-Butyloxycarbonyl(Boc)-N-methylglycine (Boc-
Sar-OH, ≥99%, Sigma-Aldrich), phosphorous trichloride (PCl ,
kg mol , (M
̅
w
/M
̅
)
n
1.13. P70M
42: H NMR (DMSO-d , 600 MHz):
6
δ 7.36−7.18 (m, ∼5H), 4.47−3.80 (m, ∼221H), 3.40−3.00 (m,
3
9
9%), glyoxylic acid monohydrate (98%), n-propylamine (≥99%),
∼170H), 3.00−2.65 (m, ∼127H), 1.65−1.25 (d, br, ∼143H), 0.95−
app
and n-heptanes (≥99%) were purchased from Sigma-Aldrich and used
0.68 (d, br, ∼216H) ppm. SEC (NMP, PMMA calibration): M
̅
n
8.7
−
1
app
−1
app
1
as received. Ethyl acetate (EtOAc, 99.5%, Th. Geyer) and methanol
kg mol , M
̅
w
10.0 kg mol , (M
̅
w
/M
̅
)
n
1.15. P70M76. H NMR
(
MeOH, LiChrosolv, VWR) were used as received. Anhydrous N-
(DMSO-d , 600 MHz): δ 7.36−7.18 (m, ∼4H), 4.47−3.80 (m,
6
methyl-2-pyrrolidone (NMP, 99.5%) and benzonitrile (PhCN, 99%)
were purchased from Sigma-Aldrich in septum-sealed bottles over
∼287H), 3.40−3.00 (m, ∼173H), 3.00−2.65 (m, ∼230H), 1.65−1.25
(d, br, ∼144H), 0.95−0.68 (d, br, ∼216H) ppm. SEC (NMP, PMMA
app
−1
app
−1
app
molecular sieves. Benzylamine (BnNH , 99.5%), acetic anhydride
calibration): M
1.17. P70
̅
n
10.0 kg mol , M
153. H NMR (DMSO-d
6
̅
w
11.7 kg mol , (M
̅
w n
̅
/M )
2
1
(
(
Ac O, 99%), dichloromethane (DCM, ≥99.9%), and cyclohexane
M
, 600 MHz): δ 7.36−7.18 (m,
2
cHex, ≥99%), all from Sigma-Aldrich, were distilled from calcium
∼4H), 4.47−3.80 (m, ∼444H), 3.40−3.00 (m, ∼257H), 3.00−2.65
hydride and stored over activated molecular sieves (3 Å; 3−5 mm
beads) under argon (flowed through a CaCl2 drying tube). All
laboratory equipment was cleaned and flash dried prior to use with a
heat gun at reduced pressure (∼0.01 mbar).
Monomer Synthesis. The N-methylglycine (sarcosine) N-
carboxyanhydride (MeGlyNCA) was obtained in a one-step synthesis
from N-Boc-N-methylglycine (dried under reduced pressure overnight,
(m, ∼459H), 1.65−1.25 (d, br, ∼145H), 0.95−0.68 (d, br, ∼216H)
app
−1
app
ppm. SEC (NMP, PMMA calibration): M
̅
12.7 kg mol , M
̅
n
w
−1
app
1
14.6 kg mol , (M
̅
/M
̅
)
n
1.15. P70M
290. H NMR (DMSO-d , 600
w
6
MHz): δ 7.36−7.18 (m, ∼9H), 4.47−3.80 (m, ∼741H), 3.40−3.00
(m, ∼347H), 3.00−2.65 (m, ∼871H), 1.65−1.25 (d, br, ∼148H),
0.95−0.68 (d, br, ∼216H) ppm. SEC (NMP, PMMA calibration):
app
−1
app
−1
app
M
̅
14.3 kg mol , M
̅
16.9 kg mol , (M
̅
/M
̅
)
n
1.18.
n
w
w
1
0.6 g, 0.056 mol) in anhydrous DCM (350 mL) with PCl (added via
Analytical Instrumentation and Methods. Melting points were
3
dropping funnel, 5.86 mL, 0.067 mol) at 0 °C for 6 h. Volatiles were
determined with a MEL-TEMP II apparatus (Laboratory Devices Inc.
(USA)) in open glass capillaries. Purity of low molecular weight
compounds and monomer conversion was examined with gas
chromatography−mass spectrometry (GC-MS) using an Agilent
removed by rotoevaporation, and final purification was obtained by
sublimation (65 °C, 0.012 mbar, 12 h), yielding a white crystalline
1
material (80−90%); mp 103.2 °C. H NMR (DMSO-d , 400 MHz) δ
6
4
.22 (s, 2H), 2.86 (s, 3H) ppm. GC-MS (MSD) R 10.8 min; (EI) m/z
15.0 (M , [C H NO] = 71.0). The N-(n-propyl)glycine N-
Technologies GC 6890N MS 5975. Aliquots of the polymerization
t
+
+
−1
1
solution were diluted with CHCl at concentrations of 1−10 mg mL
3
5
3
carboxyanhydride (PrGlyNCA) was synthesized in three steps, starting
and prepared in 2 mL septum-sealed vials. The Enhanced
ChemStation software was used to set following measurement
parameters: A sample volume of 1 μL was injected into the preheated
chamber (250 °C), split (10:1), and flowed (He; 0.76 bar) through the
1
0
from glyoxylic acid and n-propylamine, as described elsewhere. The
crude product was purified by distillation followed by filtering through
silica and washing with EtOAc. After rotoevaporation, the product was
redissolved in EtOAc, filtered, and concentrated afterward. cHex was
added to the oily product, stirred vigorously, and decanted, and the
procedure was repeated (3×) before final drying under reduced
−
1
heated (30−300 °C; 2 min hold, then 30 K min ) column. Data were
acquired after 3 min of solvent delay (duration of 11.33 min), and
subsequently the aforementioned software was used to analyze the
chromatogram. Nuclear magnetic resonance (NMR) spectroscopy was
conducted with a Bruker DPX-400 or Varian 600 MHz device at room
pressure (0.012 mbar), yielding a beige, waxy solid (67%); mp <20 °C.
1
H NMR (CDCl , 400 MHz): δ 4.10 (s, 2H), 3.38 (t, 2H), 1.65 (m,
3
−1
2
H), 0.97 (t, 3H) ppm. GC-MS (MSD) R 13.7 min; (EI) m/z 143.1
temperature. Samples of ∼5−25 mg mL concentrations were
prepared in CDCl or DMSO-d (Aldrich). Signals were referenced to
signals of residual protonated solvent: CDCl C
t
+
+
+
(
M , [C H NO] = 100.1, [C H NO] = 57.1).
3
6
5
9
2
2
1
13
Block Copolypeptoid Synthesis. A series of five poly(N-(n-
3
: δ H 7.26 ppm,
: δ H 2.50 ppm, C 39.5 ppm. Size exclusion
chromatography (SEC) was performed in NMP (+ 0.5 wt % LiBr) as
1
13
propyl)glycine) -block-poly(N-methylglycine) (P M ) (subscripts de-
77.0 ppm; DMSO-d
6
x
y
x
y
1
note the average number of repeat units, by H NMR) were
synthesized by sequential nucleophilic ring-opening polymerization of
the corresponding NCAs. A batch of poly(N-(n-propyl)glycine)70 (in
the following referred to as P ) macroinitiator was prepared by adding
−1
eluent at +70 °C, flow rate: 0.8 mL min , utilizing simultaneous UV
(λ = 270 nm) and RI detection. The stationary phase consisted of two
300 × 8 mm PSS-GRAM columns (7 μm spherical polyester
2
70
particles) columns with porosities of 10 and 103 Å. Solutions
containing ∼0.15 wt % polymer were filtered through 0.45 μm filters
(GF/F Whatman); the injected volume was 100 μL. Calibration curve
was recorded with poly(methyl methacrylate) (PMMA) standards.
Data analysis was done with the PSS WinGPC software (Polymer
Standards Service (PSS) GmbH, Mainz, Germany). Analytical
ultracentrifugation (AUC) measurements were conducted using an
Optima XL-I analytical ultracentrifuge (Beckman Coulter, Palo Alto,
CA) equipped with a Rayleigh interference optics. A four-hole
titanium rotor was operated at 25 °C and 1500/5000/20 000 and
60 000 rpm. The samples (0.15 wt % aqueous solutions) were filled in
12 mm double sector center pieces made from titanium (Nanolytics,
Potsdam, Germany). Sedimentation coefficient distributions were
evaluated by the least-squares g*(s) (ls g*(s)) evaluation using the
2
a 1 M BnNH /NMP stock solution to a solution of PrGlyNCA (3.79
2
g) in PhCN (38 mL) ([NCA] /[BnNH ] = 60); the mixture was
0
2 0
stirred at room temperature under an argon atmosphere and
frequently degassed over time. The conversion was monitored by
1
GC-MS and H NMR, and once all monomer was consumed (after
∼
48 h) the reaction volume was split into six portions: five for further
reactions and one for analysis (→ P70 homopolymer, terminated with
Ac O). Volatiles were evaporated, and the crude product was
2
redissolved in MeOH, precipitated in n-heptanes, and dialyzed against
MeOH (MWCO 3500 Da, regenerated cellulose). After drying, P70
1
was obtained as a white powder; gravimetric yield: 416 mg (95%). H
NMR (DMSO-d , 600 MHz): δ 7.36−7.18 (m, 5H), 4.47−3.80 (m,
6
∼
139H), 3.40−3.00 (m, ∼169H), 1.65−1.25 (d, br, ∼144H), 0.95−
13
0
.68 (d, br, ∼216H) ppm. C NMR (DMSO-d , 100 MHz): δ 169.2,
6
3
6
1
68.3, 128.2, 49.0, 48.0, 21.0, 20.2, 11.1 ppm. SEC (NMP, PMMA
SEDFIT software package. Turbidimetric measurements were
conducted with a turbidimetric photometer TP1 (Tepper Analytik,
Wiesbaden, Germany) operating at λ = 670 nm. Stirred samples were
app
−1
app
−1
app
calibration): M
̅
7.0 kg mol , M
̅
w
̅ ̅
7.4 kg mol , (M /Mn) 1.06.
n
w
The P70 macroinitiator (0.062 mmol) in PhCN (6.4 mL) was added
−1
to solutions of MeGlyNCA (1.23−17.3 mmol) in PhCN to obtain
and analyzed between 5 and 95 °C at a heating rate of 0.1 K min .
The sample chamber was purged with nitrogen to prevent
condensation onto the quartz cuvettes below room temperature.
Micro-differential scanning calorimetry (micro-DSC) was performed
using a MicroCal VP-DSC MicroCalorimeter (−10 to +130 °C, short-
∼
2.2−10 wt % monomer solutions. The mixtures were stirred for 48 h
at room temperature under an argon atmosphere and then quenched
with Ac O (3 mL). Polymers were purified and isolated (89−94%
2
1
yield) as described above and analyzed by H NMR (→ composition,
−1
y) and SEC (→ apparent molar mass averages and dispersity). P M :
term noise 0.5 μcal K ; MicroCal, GE Healthcare and Life Science,
70
23
B
Macromolecules XXXX, XXX, XXX−XXX