Amino acid and dipeptide functionalized polyolefins

Article abstract of DOI:10.1021/ma021668w

N-protected amino acid and dipeptide branched, chiral polyolefins have been prepared using acyclic diene metathesis polycondensation chemistry. The polymerizations were performed in THF using Grubbs' second-generation catalyst. The polymers bearing CBz-pr

Full text of DOI:10.1021/ma021668w

2206
Macromolecules 2003, 36, 2206-2214
Amino Acid and Dipeptide Functionalized Polyolefins
Tim oth y E. Hop k in s a n d Ken n eth B. Wa gen er *
The George and J osephine Butler Polymer Laboratory, Department of Chemistry, University of Florida,
P.O. Box 117200, Gainesville, Florida 32611-7200
Received November 8, 2002; Revised Manuscript Received J anuary 21, 2003
ABSTRACT: N-protected amino acid and dipeptide branched, chiral polyolefins have been prepared using
acyclic diene metathesis polycondensation chemistry. The polymerizations were performed in THF using
Grubbs’ second-generation catalyst. The polymers bearing CBz-protected amino acids and dipeptides are
semicrystalline with melt transitions of up to 150 °C, whereas the polymers bearing BOC-protected amino
acids and dipeptides are primarily amorphous with the exception of the di-BOC-protected lysine polymer,
which is semicrystalline.
In tr od u ction
bearing RGD with a norbornene bearing penta(ethylene
oxide) yielded a water-soluble polymer capable of bind-
ing to fibronectin; the RGD-based copolymer has poten-
tial for a variety of biomedical applications.11
The synthesis of polymers containing amino acid and
peptide moieties is a subject of much interest, since a
high degree of amino acid functionality and chirality can
lead to polymers with enhanced solubility and the
ability to form secondary structures such as R-helices
and â-sheets.1,2 Possible applications include drug-
delivery agents, chiral recognition stationary phases,
asymmetric catalysts, metal ion absorbents, and bio-
compatible materials.3,4 In the 1960s, Pino and co-
workers used amino acids to create chiral polymers;
however, the lack of readily available enantiopure amino
acids limited further enhancement of this initial re-
search.4 Recently, advances in the areas of chiral
separation and synthesis have produced a variety of
inexpensive and enantiopure protected amino acids and
small peptides.2 These advances have enabled the
preparation of a new generation of amino acid-based
biomaterials.2
We now describe the synthesis of amino acid and
peptide branched polymers using simple polycondensa-
tion chemistry, acyclic diene metathesis (ADMET).12
Previously, we reported that ADMET could be used to
synthesize linear amino alcohol containing polymers as
well as polymers containing branched amino acids.13
The polymers are strong, film-forming materials pos-
sessing moduli of up to 220 MPa with up to 260%
elongation. These polymers are intended to be durable
materials possessing hydrophilic surfaces, properties
that could prove useful for biomedical applications
where biologically compatible materials are desired, e.g.,
coatings for artificial implants. In addition, the attach-
ment of amino acids onto a polyolefin backbone could
be advantageous for biomaterial applications, since the
resulting polymer backbones are not biodegradable.
Endo and co-workers have synthesized a variety of
amino acid and peptide branched acrylamides via radi-
cal polymerizations.5,6 A peptide moiety composed of
L-leucine, L-alanine, and R-aminoisobutyric acid units,
which is known to form a helix, was coupled to meth-
acrylic acid and polymerized to yield a polymer dem-
onstrating the same CD spectrum as the monomer when
polymerized using dichlorobenzene as the solvent.1
Thus, Endo and co-workers reported the polymer main-
tained a linear backbone structure with R-helix-shaped
branches. Similar work by North et al. involved the
synthesis of a variety of serine-based amino acid
branched polymers by radical polymerization, which
differ from those of Endo and co-workers since the
amino acid functionality is attached to the acrylate
through the alcohol of the serine side chain.7 In addition,
monomers bearing dipeptides and tripeptides attached
through the acid and amine of the serine unit, respec-
tively, were prepared.8
Exp er im en ta l Section
Ch em ica ls. Chemicals were purchased from the Aldrich
Chemical Co., unless otherwise noted. Diethyl ether and THF
were used as received from Fisher Scientific, unless it is stated
that dry solvents were used, which were obtained from the
Aldrich keg system and dried over Al2O3 or by distillation of
the solvent over Na/K. 11-Bromo-1-undecene, which was
purchased from Fluorochem, 5-bromo-1-pentene, and ethyl
formate were refluxed over CaH for 12 h and distilled prior to
use. Methylene chloride and chloroform were used as pur-
chased from Fisher, unless it is noted that the solvent was
dry; then the solvents were refluxed and distilled over CaH.
Triethylamine was purchased from Aldrich and purified by
distillation over CaH. Methanol was used from Fisher as
received; however, when dry methanol was required, it was
used as purchased from an Aldrich sure seal bottle. Anhydrous
DMF (99.8%) was used as purchased in an Aldrich sure seal
container equipped with an Aldrich Schlenk cap. The second-
generation Grubbs’ Ru catalyst (tricyclohexylphosphine[1,3-
bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene][ben-
zylidene]ruthenium(IV) dichloride) was used exclusively and
was synthesized as described previously by Grubbs et al.14 The
protected amino acids and dipeptides were used as purchased
from Bachem, except CBz alanine-valine, di-CBz lysine, and
di-CBz cysteine, which were purchased from Sigma-Aldrich.
In str u m en ta tion . All 1H NMR (300 MHz) and 13C NMR
(75 MHz) spectra were recorded on a Varian Associates Gemini
300, Varian Associates VXR 300, or a Varian Associates
Mercury 300 spectrometer. All chemical shifts were referenced
Grubbs et al.9 and North et al.10 have used ring-
opening metathesis chemistry (ROMP) to make poly-
(norbornenes) bearing amino acid and peptide branched
polymers. The Grubbs group has extended this work to
include the synthesis of polymers bearing the biologi-
cally active peptide arginine-glycine-aspartic acid
(RGD).11 A simple copolymerization of a norbornene
* Corresponding author: e-mail wagener@chem.ufl.edu.
10.1021/ma021668w CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/13/2003

Macromolecules, Vol. 36, No. 7, 2003
Amino Acids and Polyolefins 2207
to TMS (0.00 ppm) for 1H NMR and to CDCl3 (77.23 ppm) or
DMSO-d6 (39.51 ppm) for 13C NMR.
acetate:methanol) mobile phase yielding the desired product
3a (9.28 g) for an overall yield of 73%. 1H NMR (300 MHz,
CDCl3, ppm): δ 1.15-1.70 (m, 8H), 2.01-2.15 (br, 4H), 2.65-
2.76 (br, 1H), 4.90-5.10 (m, 4H), 5.75-5.90 (m, 2H). 13C NMR
(75 MHz, CDCl3, ppm): δ 25.87, 34.29, 37.84, 51.45, 114.95,
139.19.
Gel permeation chromatography (GPC) of the unsaturated
ADMET polymers was performed using two 300 mm Polymer
Laboratories 5 µm mixed-C columns. The instrument consists
of a Rainin SD-300 pump, a Hewlett-Packard 1047-A RI
detector, a TC-45 Eppendorf column heater set to 35 °C, and
a Waters U6K injector. The solvent used was THF at a flow
rate of 1 mL/min, and the samples were dissolved in ACS grade
THF (5-8 mg/mL) and filtered before injection. Retention
times were calibrated to narrow polystyrene standards pur-
chased from Polymer Laboratories (Amherst, MA).
Fourier transform infrared (FT-IR) spectrometry was per-
formed using a Bio-Rad FTS-40A spectrometer. The polymers
were analyzed by dissolving a small amount of sample into
CH2Cl2 and allowing the solution to evaporate on a salt plate,
and the solid monomers were ground up with IR grade KBr
into a homogeneous mixture and analyzed using a KBr pellet
formed from the mixture.
Syn th esis of 1-Un dec-10-en yl-dodec-11-en ylam in e (3b).
3b was synthesized as described above using 11-bromo-1-
undecene (25.0 g, 0.106 mol) instead of 5-bromo-1-pentene.
When purified as above using flash column chromatography,
an overall yield of 48% (13.0 g) was obtained. However, it was
found that a quick purification of the product can be performed
by placing the crude amine on a plug of silica gel and washing
with 3:1 hexanes:ethyl acetate until the starting materials are
no longer present by TLC. Removal of the amine by washing
the plug of silica gel with methanol (∼1 L) gave 3b in similar
1
yields. H NMR (300 MHz, CDCl3, ppm): δ 1.15-1.45 (br, 32
H), 2.05 (q, br, 4H), 2.65-2.75 (br, 1H), 4.88-5.05 (m, 4H),
5.72-5.38 (m, 2H). 13C NMR (75 MHz, CDCl3, ppm): δ 26.39,
29.20, 29.41, 29.76, 29.84, 29.90, 30.07, 34.08, 38.02, 51.50,
114.36, 139.50.
Differential scanning calorimetry (DSC) was performed
using a Perkin-Elmer DSC 7 at a heating rate of 10 °C/min
using indium and n-octane as calibration standards. Heats of
fusion were referenced against indium. The samples were
scanned three times to remove recrystallization differences
between samples and the results reported came from the third
scan. The results are listed in tabular form as well as within
the text as Tm (melting peak) and Tg (glass transition).
Ch a r a cter iza tion . Strenuous purification was only per-
formed on the final monomers reported herein. Only 1H NMR
and 13C NMR spectra are reported for the precursors (3a , 3b,
and 3c) to these monomers. The alcohols (1a , 1b, and 1c) and
ketones (2a , 2b, and 2c) were only isolated in crude form, so
no characterization data is given. All of the monomers were
Syn th esis of 1-Dec-9-en yl-u n d ec-10-en yla m in e (3c).
Synthesis was performed using a modified procedure by
Zantour and co-workers.15 To a 500 mL three-neck round-
bottom flask equipped with a reflux condenser and an addition
funnel was added 10-undecenoyl chloride (0.100 mol, 20.27 g,
21.48 mL) and dry diethyl ether (150 mL). The solution was
cooled to 0 °C, and triethylamine (0.180 mol, 18.21 g, 25.09
mL) was added dropwise, instantly forming white triethylam-
monium chloride salts. The reaction mixture was warmed to
room temperature and stirred for 24 h, followed by Bu¨chner
filtration of the salts and evaporation to yield the liquid
intermediate lactone. Deionized water (100 mL) and NaOH
(2.10 mol, 8.80 g) were added, and the mixture was refluxed
for 6 h. The solution was acidified with 1 M HCl and extracted
with diethyl ether (3 × 40 mL), and the combined organic
layers were washed with 1 M HCl (2 × 20 mL), saturated
NaHCO3 (2 × 20 mL), and brine (2 × 20 mL). After drying
over MgSO4 and recrystallizing from MeOH, the pure ketone
1
fully characterized by H NMR, 13C NMR, IR, EI/HRMS, and
elemental analysis. The polymers were characterized by 1H
NMR, 13C NMR, IR, GPC, and DSC, and only the character-
ization for the high molecular weight polymers is reported.
Mon om er Syn th esis. Syn th esis of 1-P en t-4-en yl-h ex-
5-en yla m in e (3a ). Magnesium (4.89 g, 0.20 mol) was added
to a 500 mL three-neck flask equipped with a reflux condenser
and an addition funnel, and the reaction vessel was backfilled
three times with Ar and flamed out after the second backfill.
Dry ether (100 mL) was added, followed by the dropwise
addition of 5-bromo-1-pentene (25.0 g, 19.9 mL, 0.17 mol) in
60 mL of dry diethyl ether at such a rate as to maintain a
gentle reflux. After the addition was complete, a heating
mantle was placed under the reaction vessel, and the solution
was refluxed for 2 h. Ethyl formate (5.64 g, 0.076 mol) in 20
mL of dry diethyl ether was added dropwise to the cooled
reaction mixture (0 °C), and the solution was allowed to warm
slowly to room temperature and refluxed for an additional 12
h. Hydrochloric acid (1 M, 100 mL) was added, and the solution
was extracted with ether (3 × 25 mL), washed with 1 M HCl
(1 × 30 mL), and washed with brine (3 × 20 mL). The solution
was dried over MgSO4, followed by evaporation of the solvent
to yield 13.6 g of the crude alcohol (1a ).
1
(2c) (12.58 g, 82%) was obtained. The H NMR and 13C NMR
were in agreement with those reported previously.15,17
The ketone 2c (11.30 g, 36.9 mmol) was converted to the
amine 3c (8.00 g, 70%) using the same methodology as
described above. The overall yield for the two steps was 52%.
1H NMR (300 MHz, CDCl3, ppm): δ 1.18-1.62 (br, 28H), 2.04
(q, 4H), 2.80-2.94 (m, br, 1H), 4.03-4.54 (br, 2H), 4.88-5.07
(m, 4H), 5.71-5.91 (m, 2H). 13C NMR (75 MHz, CDCl3, ppm):
δ 26.52, 29.34, 29.54, 29.88, 30.01, 30.20, 34.21, 38.18, 51.61,
114.46, 139.48.
Gen er a l Cou p lin g P r oced u r e of th e Am in o Acid /
Dip ep tid es to 3a /3b/3c. The amino acid/ dipeptide and
1-hydroxybenzotriazole (HOBt) (2.5 equiv to amino acid) were
added to a 100 mL round-bottom flask. To the flask, equipped
with a septum, a stir bar, and under argon, was added 1,3-
diisopropylcarbodiimide (DIC) (1.2 equiv to amino acid) and
dry THF (just enough to dissolve the compounds). The reaction
vessel was equipped with a reflux condenser and stirred 1 h
at room temperature, followed by the addition of 3a /3b/3c (1.1
equiv to amino acid). The reaction mixture was then refluxed
for 12 h for the amino acids and 24 h for the dipeptides. The
insoluble urea was removed via gravity filtration, and THF
was evaporated to yield a crude white solid. The product was
purified with three successive recrystallizations using ethanol/
water or methanol/water (ethanol was used for the monomers
that melt above the boiling point of ethanol); the product was
dissolved in hot ethanol/ methanol, and water was added until
the solution became cloudy. The pure product was then
collected by vacuum filtration through a Kontes filtration
apparatus and dried under vacuum (10-2 mmHg) for 48 h.
Syn th esis of [(S)-3-Meth yl-1-(1-p en t-4-en yl-h ex-5-en yl-
ca r ba m oyl)bu tyl]ca r ba m ic Acid ter t-Bu tyl Ester (4a ).
The pure product 4a was obtained in 78% yield with a melting
To a 1 L round-bottom flask equipped with an addition
funnel was added pyridinium chlorochromate (PCC) (26.0 g,
0.12 mol), celite (26.0 g), and methylene chloride (100 mL)
followed by the addition of crude 1a (13.6 g, 0.080 mol) in
methylene chloride (20 mL). The reaction was stirred over 4
h, followed by the addition of diethyl ether (200 mL) and
filtering through a pad of silica gel. The solvent evaporation
yielded 13.0 g of the crude ketone (2a ).
To a 1 L round-bottom flask was added 2a (12.96 g, 0.078
mol), dry methanol (200 mL), ammonium acetate (60 g, 0.78
mol), NaCNBH3 (25 g, 0.40 mol), and crushed 4 Å molecular
sieves (one scoopula tip) under N2 and refluxed for 48 h. The
crushed molecular sieves were filtered via Bu¨chner filtration,
and deionized water (200 mL) was added to the filtrate,
followed by extraction with diethyl ether (3 × 50 mL). The
organic layer was washed with 1 M NaOH (2 × 50 mL) and
brine (2 × 30 mL) and dried over MgSO4. The solution was
concentrated to a viscous brown oil, which was purified by
flash column chromatography using a 3:1:1 (hexane:ethyl
1
point range of 117-119 °C. H NMR (300 MHz, CDCl3, ppm):
δ 0.85-0.95 (m, 6H), 1.27-1.55 (br, 18H), 1.58-1.72 (br, 2H),
2.05 (q, br, 4H), 3.82-3.92 (br, 1H), 3.95-4.06 (m, 1H), 4.86-

2208 Hopkins and Wagener
Macromolecules, Vol. 36, No. 7, 2003
5.03 (m, 5H), 5.65-5.83 (m, 2H), 5.88 (d, br, 1H).13C NMR (75
MHz, CDCl3, ppm): δ 22.51, 22.96, 24.99, 25.21, 25.28, 25.51,
28.51, 33.71, 33.76, 34.82, 34.88, 41.07, 49.09, 53.55, 114.91,
138.67, 138.70, 156.00, 172.27. FTIR (KBr pellet, cm-1): 3344,
3279, 3083, 2979, 2936, 2869, 1688, 1649, 1561, 1522, 1455,
1392, 1367, 1321, 1294, 1248, 1176, 1121, 1048, 1023, 995, 910,
875, 792, 753, 633. Anal. Calcd for C22H40N2O3: C, 69.43; H,
10.59; N, 7.36. Found: C, 69.38; H, 10.61; N, 7.49. EI/HRMS
[M + 1]: Calcd for C22H40N2O3: 380.3039 g/mol. Found:
380.3117 g/mol.
(75 MHz, CDCl3, ppm): δ 26.02, 28.53, 29.16, 29.34, 29.69,
29.77, 34.02, 35.49, 49.51, 114.31, 139.46, 172.16. FTIR (KBr
pellet, cm-1): 3332, 3295, 2924, 2854, 1690, 1656, 1549, 1526,
1468, 1391, 1369, 1325, 1248, 1174, 1070, 1054, 913. Anal.
Calcd for C31H58N2O3: C, 73.47; H, 11.54; N, 5.53. Found: C,
73.53; H, 11.60; N, 5.27. EI/HRMS [M + 1]: Calcd for
C
34H64N2O3: 506.4447 g/mol. Found: 506.4522 g/mol.
Syn th esis of [(S)-5-Ben zyloxyca r bon yla m in o-5-(1-u n -
d ec-10-en yl-d od ec-11-en ylca r b a m oyl)p en t yl]ca r b a m ic
Acid Ben zyl Ester (6a ). The pure product 6a was obtained
1
Syn th esis of [(S)-3-Meth yl-1-(1-u n d ec-10-en yl-d od ec-
11-en ylca r ba m oyl)bu tyl]ca r ba m ic Acid ter t-Bu tyl Ester
(4b). The pure product 4b was obtained in 39%16 yield with a
in 47%16 yield with a melting point range of 111-113 °C. H
NMR (300 MHz, CDCl3, ppm): δ 1.15-1.91 (br, 37H), 1.95-
2.13 (br, 1H), 2.23 (q, br, 4H), 3.25-3.44 (br, 2H), 3.96-4.12
(br, 1H), 4.18-4.33 (br, 1H), 4.91-5.07 (br, 1H), 5.08-5.24 (br,
4H), 5.30 (s, br, 4H), 5.56-5.71 (br, 1H), 5.89 (d, br, 1H), 5.93-
6.09 (m, 2H), 7.49-7.60 (br, 10H). 13C NMR (75 MHz, CDCl3,
ppm): δ 22.66, 25.97, 29 (m), 33.91, 34.12, 35.37, 40.41, 49.59,
55.00, 66.71, 114.29, 128 (m), 138.63, 156.49, 171.11. FTIR
(KBr pellet, cm-1): 3316, 3278, 2926, 2854, 1691, 1650, 1535,
1467, 1266, 1247, 1153, 1080, 1054, 1024, 911, 696. Anal. Calcd
for C45H69N3O5: C, 73.83; H, 9.50; N, 5.74. Found: C, 73.48;
H, 9.59; N, 5.65. EI/HRMS [M + 1]: Calcd for C34H64N2O3:
731.5237 g/mol. Found: 731.5315 g/mol.
1
melting point range of 75-76 °C. H NMR (300 MHz, DMSO-
d6, ppm): δ 0.84 (m, 6H), 1.05-1.43 (br, 42H), 1.46-1.64 (br,
2H), 1.98 (q, br, 4H), 3.56-3.71 (br, 1H), 3.88 (q, br, 1H), 4.87-
5.03 (br, 4H), 5.68-5.85 (m, 2H), 6.70 (d, br, 1H), 7.34 (d, br,
1H). 13C NMR (75 MHz, DMSO-d6, ppm): δ 25.23, 26.22, 26.27,
28.74, 29.39, 29.59, 29.82, 29.94, 30.02, 30.06, 30.08, 30.13,
30.18, 34.21, 34.27, 35.67, 35.73, 35.77, 35.80, 49.65, 114.51,
139.65, 172.17, 174.63. FTIR (KBr pellet, cm-1): 3336, 3291,
2924, 2854, 1690, 1654, 1526, 1468, 1391, 1368, 1326, 1246,
1175, 1055, 913. Anal. Calcd for C34H64N2O3: C, 69.43; H,
10.59; N, 7.36. Found: C, 69.38; H, 10.61; N, 7.49. EI/HRMS
Syn th esis of [(S)-5-ter t-Bu toxyca r bon yla m in o-5-(1-u n -
d ec-10-en yl-d od ec-11-en ylca r b a m oyl)p en t yl]ca r b a m ic
Acid ter t-Bu tyl Ester (6b). The pure product 6b was
obtained in 87% yield with a melting point range of 82-84
°C. 1H NMR (300 MHz, CDCl3, ppm): 1.17-1.68 (br, 50H),
1.74-1.92 (m, 2H), 2.05 (q, 4H), 3.10 (q, br, 2H), 3.78-3.91
(br, 1H), 3.97 (q, br, 1H), 4.55-4.66 (br, 1H), 4.86-5.05 (m,
4H), 5.06-5.18 (br, 1H), 5.72-5.89 (m, 3H). 13C NMR (75 MHz,
CDCl3, ppm): δ 22.91, 26.07, 28.53-29.92 (m), 32.05, 34.03,
35.39, 35.43, 49.53, 114.32, 139.45, 156.35, 172.38. FTIR (KBr
pellet, cm-1): 3375, 3342, 3302, 2981, 2926, 2855, 1690, 1653,
1530, 1450, 1391, 1367, 1279, 1250, 1176, 910, 637. Anal. Calcd
for C19H34N2O3: C, 70.54; H, 11.08; N, 6.33. Found: C, 70.57;
H, 11.16; N, 6.12. EI/HRMS [M + 1]: Calcd for C19H34N2O3:
663.5550 g/mol. Found: 663.5628 g/mol.
[M + 1]: Calcd for
548.4995 g/mol.
C34H64N2O3: 548.4917 g/mol. Found:
Syn th esis of [(S)-1-(1-P en t-4-en yl-h ex-5-en ylca r ba m -
oyl)eth yl]ca r ba m ic Acid ter t-Bu tyl Ester (5a ). The pure
product 5a was obtained in 76% yield with a melting point
range of 77-78 °C. 1H NMR (300 MHz, CDCl3, ppm): δ 1.27-
1.69 (br, 20H), 2.05 (q, br, 4H), 3.82-3.95 (br, 1H), 3.99-4.14
(m, 1H), 4.86-5.03 (m, 5H), 5.65-5.83 (m, 2H), 5.88 (d, br,
1H).13C NMR (75 MHz, CDCl3, ppm): δ 25.26, 25.30, 28.53,
33.76, 33.78, 34.88, 34.90, 49.18, 114.95, 138.69, 172.38. FTIR
(KBr pellet, cm-1): 3340, 3306, 3076, 2981, 2938, 2859, 1688,
1654, 1542, 1522, 1459, 1391, 1370, 1323, 1250, 1167, 1071,
1052, 1031, 999, 910, 856, 754, 701, 674. Anal. Calcd for
C
19H34N2O3: C, 67.42; H, 10.12; N, 8.28. Found: C, 67.41; H,
10.17; N, 8.44. EI/HRMS [M + 1]: Calcd for C19H34N2O3:
Syn th esis of Th ioca r bon ic Acid O-Ben zyl Ester S-[2-
b en zyloxyca r b on yla m in o-2-(1-u n d ec-10-en yl-d od ec-11-
en ylca r ba m oyl)eth yl] Ester (7). The pure product 7 was
obtained in 29%16 yield with a melting point range of 129-
130 °C. 1H NMR (300 MHz, CDCl3, ppm): δ 1.15-1.54 (br,
32H), 2.07 (q, br, 4H), 3.13-3.38 (m, 2H), 3.79-3.91 (br, 1H),
4.40 (q, br, 1H), 4.88-5.05 (m, 4H), 5.06-5.18 (m, 2H), 5.18-
5.29 (m, 2H), 5.68 (d, br, 1H), 5.73-5.89 (m, 2H), 5.93 (d, br,
1H), 7.35 (s, 10H). 13C NMR (75 MHz, CDCl3, ppm): δ 26.06,
29 (m), 33.50, 34.04, 35.24, 49.96, 55.59, 67.46, 69.79, 114.35,
128 (m), 135.03, 136.33, 139.44, 156.52, 169.29, 171.72. FTIR
(KBr pellet, cm-1): 3278, 2923, 2853, 1712, 1693, 1650, 1561,
1534, 1276, 1241, 1159, 1047, 994, 908, 746, 697. Anal. Calcd
for C42H62N2O5S: C, 71.35; H, 8.84; N, 3.96. Found: C, 71.20;
H, 8.83; N, 3.90. EI/HRMS [M + 1]: Calcd for C42H62N2O5S:
706.4379 g/mol. Found: 706.4458 g/mol.
338.2569 g/mol. Found: 338.2648 g/mol.
Syn t h esis of [(S)-1-(1-Dec-9-en yl-u n d ec-10-en ylca r -
ba m oyl)eth yl]ca r ba m ic Acid ter t-Bu tyl Ester (5b). The
pure product 5b was obtained in 75% yield with a melting
1
point range of 68-69 °C. H NMR (300 MHz, CDCl3, ppm): δ
1.15-1.55 (br, 40H), 2.02 (q, br, 4H), 3.78-3.93 (br, 1H), 4.00-
4.18 (br, 1H), 4.88-5.08 (br, 5H), 5.70-5.92 (br, 3H). 13C NMR
(75 MHz, CDCl3, ppm): δ 26.02, 28.53, 29.13, 29.32, 29.65,
29.67, 29.71, 29.73, 29.77, 29.80, 34.03, 35.48, 49.50, 114.33,
139.45, 172.18. FTIR (KBr pellet, cm-1): 3333, 3301, 2983,
2925, 2854, 1691, 1656, 1549, 1526, 1468, 1391, 1369, 1325,
1268, 1251, 1174, 1069, 1055, 1031, 992, 908, 858, 792, 757,
721, 701, 654. Anal. Calcd for C29H54N2O3: C, 72.75; H, 11.37;
N, 5.85. Found: C, 72.80; H, 11.55; N, 5.85. EI/HRMS [M +
1]: Calcd for C29H54N2O3: 478.4134 g/mol. Found: 478.4134
g/mol.
Syn th esis of {(S)-1-[(S)-2-Meth yl-1-(1-u n d ec-10-en yl-
d o d e c -11-e n y lc a r b a m o y l)p r o p y lc a r b a m o y l]e t h y l }-
ca r ba m ic Acid Ben zyl Ester (8). The pure product 8 was
obtained in 46%16 yield with a melting point range of 135-
136 °C. 1H NMR (300 MHz, CDCl3, ppm): δ 0.912 (m, 6H),
1.06-1.55 (br, 33H), 2.02 (q, br, 4H), 2.31-2.57 (br, 2H), 3.47
(q, br, 2H), 3.75-3.93 (br, 1H), 4.15 (t, 1H), 4.86-5.15 (br, 6H),
5.45-5.57 (m, br, 1H), 5.67-5.89 (br, 3H), 6.46 (d, br, 1H),
7.33 (s, br, 5H). 13C NMR (75 MHz, CDCl3, ppm): δ 18.48,
19.50, 26.10, 29 (m), 31.32, 34.01, 35.13, 35.31, 36.23, 37.50,
49.77, 59.16, 66.18, 114.33, 128.19, 128.24, 128.68, 136.81,
139.40, 170.70. FTIR (KBr pellet, cm-1): 3280, 3080, 2926,
2854, 1690, 1638, 1542, 1468, 1386, 1272, 1151, 1024, 994, 911,
723, 696. Anal. Calcd for C36H67N3O4: C, 73.20; H, 10.24; N,
6.57. Found: C, 73.05; H, 10.28; N, 6.30. EI/HRMS [M + 1]:
Calcd for C39H65N3O4: 639.4975 g/mol. Found: 639.5053 g/mol.
Syn th esis of {(S)-3-Meth yl-1-[(S)3-m eth yl-1-(1-u n d ec-
10-en yl-d od ec-11-en ylca r ba m oyl)bu tylca r ba m oyl]bu tyl}-
ca r ba m ic Acid Ben zyl Ester (9). The pure product 9 was
obtained in 95% yield with a melting point range of 68-71
°C. 1H NMR (300 MHz, CDCl3, ppm): δ 0.917 (m, 12H), 1.17-
Syn t h esis of [(S)-1-(1-Dec-9-en yl-u n d ec-10-en ylca r -
ba m oyl)eth yl]ca r ba m ic Acid Ben zyl Ester (5c). The pure
product 5c was obtained in 74% yield with a melting point
range equal of 83-84 °C. 1H NMR (300 MHz, CDCl3, ppm): δ
1.12-1.55 (br, 31H), 2.02 (q, br, 4H), 3.78-3.92 (br, 1H), 4.09-
4.25 (m, 1H), 4.84-5.05 (m, 4H), 5.10 (s, 2H), 5.29-5.42 (br,
1H), 5.66 (d, br, 1H), 5.72-5.89 (br, 2H).13C NMR (75 MHz,
CDCl3, ppm): δ 26.03, 29 (m), 34.03, 35.37, 35.41, 49.66, 50.88,
67.21, 114.35, 128.24, 128.45, 128.78, 139.44, 171.73. FTIR
(KBr pellet, cm-1): 32.82, 3081, 2982, 2925, 2854, 1696, 1653,
1557, 1536, 1467, 1323, 1261, 1169, 1072, 1057, 994, 909, 787,
734, 696. Anal. Calcd for C32H52N2O3: C, 74.95; H, 10.22; N,
5.46. Found: C, 74.91; H, 10.35; N, 5.46. EI/HRMS [M + 1]:
Calcd for C32H52N2O3: 512.3978 g/mol. Found: 512.3978 g/mol.
Syn th esis of [(S)-1-(1-Un d ec-10-en yl-d od ec-11-en ylca r -
ba m oyl)eth yl]ca r ba m ic Acid ter t-Bu tyl Ester (5d ). The
pure product 5d was obtained in 22%16 yield with a melting
point range of 80-81 °C.1H NMR (300 MHz, CDCl3, ppm): δ
1.15-1.55 (br, 44H), 2.03 (q, br, 4H), 3.77-3.92 (br, 1H), 4.00-
4.16 (br, 1H), 4.89-5.07 (br, 5H), 5.73-5.90 (br, 3H). 13C NMR

Macromolecules, Vol. 36, No. 7, 2003
Amino Acids and Polyolefins 2209
1.79 (br, 47H), 2.03 (q, 4H), 3.75-3.91 (br, 1H), 3.97-4.14 (br,
1H), 4.31-4.43 (m, 1H), 4.86-5.04 (br, 5H), 5.72-5.89 (m, 2H),
5.97-6.10 (br, 1H), 6.47-6.62 (br, 1H). 13C NMR (75 MHz,
CDCl3, ppm): δ 22.70, 23.14, 24.98, 26.03, 26.11, 28.49, 29 (m),
34.03, 35.18, 35.45, 41.07, 49.58, 52.22, 53.49, 114.31, 139.45,
171.24, 172.67. FTIR (KBr pellet, cm-1): 3290, 3080, 2926,
2854, 1693, 1646, 1532, 1468, 1438, 1391, 1368, 1324, 1292,
1270, 1241, 1175, 1121, 1052, 1021, 993, 966, 912, 875, 792,
747, 720, 667, 570. Anal. Calcd for C40H75N3O4: C, 72.57; H,
11.42; N, 6.35. Found: C, 72.30; H, 11.61; N, 6.02. EI/HRMS
7.31 (s, 10H). 13C NMR (75 MHz, CDCl3, ppm): δ 22.62, 26.12,
29 (m), 32.38, 32.82, 35.30, 40.53, 49.67, 55.16, 66.84, 67.20,
128.27, 128.72, 130.57, 136.41, 156.84, 171.33. FTIR (KBr
pellet, cm-1): 3423, 3314, 3057, 2989, 2930, 2856, 1719, 1685,
1648, 1519, 1456, 1423, 1266, 1137, 1028, 973, 897, 742, 704.
Ch a r a cter iza tion of 12b. 1H NMR (300 MHz, CDCl3,
ppm): δ 1.02-1.70 (br, 50H), 1.71-2.22 (m, 6H), 2.97-3.19
(br, 2H), 3.75-3.91 (br, 1H), 3.90-4.07 (br, 1H), 4.59-4.71 (br,
1H), 5.10-5.48 (br, 3H), 5.91-6.19 (br, 1H). 13C NMR (75 MHz,
CDCl3, ppm): δ 22.91, 26.09, 27.43, 28.53, 28.65, 29 (m), 32.06,
32.11, 32.81, 35.43, 40.06, 49.54, 79.30, 80.09, 130.07, 130.52,
156.00, 156.36, 171.77. FTIR (KBr pellet, cm-1): 3426, 3334,
3056, 2985, 2930, 2857, 1708, 1673, 1510, 1457, 1424, 1393,
1368, 1267, 1171, 1047, 1021, 971, 897, 864, 743, 705.
Ch a r a cter iza tion of 13. 1H NMR (300 MHz, CDCl3,
ppm): δ 1.00-1.91 (br, 32H), 2.01-2.36 (br, 4H), 3.27-3.66
(m, 2H), 3.93-4.18 (br, 1H), 4.48-4.77 (br, 1H), 5.30 (s, br,
2H), 5.42 (s, br, 2H), 5.50-5.71 (br, 2H), 5.97-6.23 (br, 1H),
6.25-6.59 (br, 1H), 7.53 (s, br, 10H). 13C NMR (75 MHz, CDCl3,
ppm): δ 26.09, 29 (m), 32.87, 35.27, 49.97, 67.45, 69.81, 128
(m), 130.57, 135.01, 136.28, 139.44, 169.28, 171.70. FTIR (KBr
pellet, cm-1): 3414, 2397, 3056, 2988, 2929, 2856, 1716, 1677,
1504, 1457, 1423, 1266, 1146, 1048, 971, 897, 740, 705.
Ch a r a cter iza tion of 14. 1H NMR (300 MHz, DMSO-d6,
140 °C, ppm): δ 0.78-0.98 (br, 6H), 1.13-1.54 (br, 33H), 2.83-
2.11 (br, 4H), 2.31-2.46 (br, 2H), 3.20-3.38 (br, 2H), 3.57-
3.81 (br, 1H), 4.06-4.23 (br, 1H), 5.04 (s, br, 2H), 5.27-5.47
(br, 2H), 6.46-6.66 (br, 1H), 7.01-7.13 (br, 1H), 7.33 (s, br,
5H). 13C NMR (75 MHz, DMSO-d6, ppm): No spectra were
obtained due to only partial solubility of the polymer in hot
DMSO-d6. FTIR (KBr pellet, cm-1): 3575, 3506, 3300, 2975,
2856, 1726, 1654, 1535, 1460, 1365, 1241, 1070, 911.
[M + 1]: Calcd for
661.5835 g/mol.
C40H75N3O4: 661.5758 g/mol. Found:
P olym er Syn th esis. Gen er a l Syn th esis. The monomer
was added to a 50 or 100 mL Schlenk tube equipped with a
stir bar and a glass stopcock and dried by heating the vessel
in an oil bath at 50 °C under full vacuum (10-3 mmHg) for 24
h. After 24 h the reaction vessel was backfilled with Ar, and
the second-generation Grubbs’ Ru catalyst (100:1/monomer:
catalyst) was added, while maintaining a positive Ar flow
throughout the system. A septum was placed in the top of the
vessel equipped with a syringe needle to allow the Ar to flow
through the system and out through a bubbler. A minimal
amount of dry THF, just enough to dissolve the polymer, was
added via syringe, and the reaction mixture was allowed to
stir for 120 h. Dry THF was added periodically, due to the
loss of THF by evaporation, as to keep the polymer in solution.
Solution ADMET is difficult to monitor because the ethylene
released is not as easily observed as in the case for bulk
ADMET polymerizations. After 120 h, the reaction was
1
sampled and tested for total conversion by H NMR (monitor-
ing terminal olefin disappearance). If incomplete conversion
was observed, the mixture was stirred for an additional 48 h.
Once it was evident that the polymerization had reached high
conversion, the mixture was dissolved in THF or CHCl3 and
precipitated into cold methanol, unless otherwise noted. The
polymers were then dissolved and solvent cast onto a Teflon
plate to yield a thin film.
Ch a r a cter iza tion of 15. 1H NMR (300 MHz, CDCl3,
ppm): δ 0.75-1.02 (br, 12H), 1.03-1.77 (br, 47H), 1.84-2.06
(br, 4H), 3.73-3.91 (br, 1H), 3.98-4.24 (br, 1H), 4.28-4.53 (m,
1H), 4.98-5.53 (br, 3H), 6.08-6.58 (br, 2H), 6.66-7.14 (br, 1H).
13C NMR (75 MHz, CDCl3, ppm): δ 18.15, 22.45, 23.08, 23.16,
24.98, 26.07, 27.04, 27.43, 28.53, 29 (m), 30.54, 32.83, 35.14,
35.45, 41.25, 49.58, 52.27, 53.44, 80.27, 124.73, 125.74, 130.10,
130.55, 155.98, 171.39, 172.80. FTIR (KBr pellet, cm-1): 3422,
2397, 3056, 2928, 2857, 1694, 1645, 1521, 1465, 1441, 1391,
1368, 1266, 1169, 1120, 1047, 1023, 970, 897, 874, 743, 706.
Ch a r a cter iza tion of 10b. 1H NMR (300 MHz, CDCl3,
ppm): δ 0.77-0.95 (br, 6H), 1.03-1.50 (br, 42H), 1.51-1.69
(br, 2H), 1.80-2.01 (br, 4H), 3.71-3.87 (br, 1H), 3.88-4.05 (br,
1H), 4.79-5.10 (br, 1H), 5.19-5.30 (br, 2H), 5.72-6.06 (br, 1H).
13C NMR (75 MHz, CDCl3, ppm): δ 22.48, 23.05, 24.88, 28.43,
28.88-31.88 (m), 32.87, 35.48, 41.27, 49.36, 49.57, 130.55,
155.99, 172.11. FTIR (KBr pellet, cm-1): 3285, 2976, 2955,
2854, 1689, 1649, 1526, 1465, 1456, 1437, 1391, 1366, 1320,
1289, 1249, 1174, 1119, 1046, 1023, 967, 921, 875, 800, 721.
Ch a r a cter iza tion of 11b. 1H NMR (300 MHz, CDCl3,
ppm): δ 1.09-1.58 (br, 40H), 1.84-2.07 (br, 4H), 3.78-3.94
(br, 1H), 4.06-4.26 (br, 1H), 5.25-5.52 (br, 3H), 6.06-6.34 (br,
1H). 13C NMR (75 MHz, CDCl3, ppm): δ 18.74, 26.07, 27.40,
28.53, 29 (m), 32.78, 35.14, 35.50, 49.46, 50.36, 79.95, 130.53,
155.75, 172.33. FTIR (KBr pellet, cm-1): 3424, 3328, 3055,
2984, 2931, 2856, 1705, 1669, 1519, 1497, 1455, 1425, 1392,
1368, 1324, 1266, 1167, 1094, 1067, 1027, 971, 897, 855, 744,
705.
Resu lts a n d Discu ssion
Mon om er Syn th esis. The synthesis of the amino
acid and dipeptide branched dienes needed for this
research is easily accomplished using standard peptide
coupling chemistry to attach amino acid or peptide
functionality to amine branched dienes. The amine
branched dienes 3a and 3b were prepared in three
steps, giving an overall yield of up to 73% (Figure 1).
The synthesis was achieved without strenuous purifica-
tion of the intermediatessonly simple acid/base extrac-
tions were performed. Alcohols 1a and 1b were prepared
by the Grignard reaction of 5-bromo-1-pentene and 11-
bromo-1-undecene, respectively, with ethyl formate.
Oxidation of 1a and 1b with pyridinium chlorochro-
mate (PCC) gives the ketones 2a and 2b, respectively,
in nearly quantitative yields, which can be subjected to
reductive amination using ammonium acetate as the
amine source, sodium cyanoborohydride as the reducing
agent, and crushed molecular sieves to help drive the
reaction to completion to give 3a and 3b. Purification
by flash chromatography using a 3:1:1 ethyl acetate:
hexanes:methanol mobile phase yielded the pure amines.
An alternative and faster purification was achieved by
placing the crude amine on a silica gel plug, followed
by successive washing with 3:1 hexane:ethyl acetate
until no starting materials were detected by TLC.
Methanol was then used to remove the pure amines 3a
and 3b from the silica gel, and the structures were
Ch a r a cter iza tion of 11c. 1H NMR (300 MHz, CDCl3,
ppm): δ 0.96-1.61 (br, 31H), 1.81-2.09 (br, 4H), 3.70-3.95
(br, 1H), 4.12-4.40 (br, 1H), 5.09 (s, br, 2H), 5.25-5.45 (br,
2H), 5.65-5.92 (br, 1H), 6.08-6.44 (br, 1H), 7.34 (br, 1H). 13
C
NMR (75 MHz, CDCl3, ppm): δ 19.38, 26.11, 29 (m), 32.84,
35.33, 35.45, 49.62, 50.84, 67.03, 128.11, 128.37, 128.74,
130.13, 130.59, 136.46, 156.20, 172.06. FTIR (KBr pellet, cm-1):
3422, 3341, 3056, 2988, 2930, 2857, 1718, 1673, 1503, 1454,
1423, 1266, 1068, 972, 897, 743, 705.
Ch a r a cter iza tion of 11d . 1H NMR (300 MHz, CDCl3,
ppm): δ 0.99-1.61 (br, 44H), 1.48-2.07 (br, 4H), 3.72-3.91
(br, 1H), 3.98-4.19 (br, 1H), 5.02-5.25 (br, 1H), 5.26-5.43 (br,
2H), 5.84-6.13 (br, 1H). 13C NMR (75 MHz, CDCl3, ppm): δ
18.70, 26.07, 28.54, 29 (m), 32.81, 35.49, 49.51, 130.55, 172.33.
FTIR (KBr pellet, cm-1): 3425, 3056, 2986, 2930, 2857, 1707,
1673, 1497, 1456, 1423, 1369, 1265, 1167, 1024, 897, 740, 705.
Ch a r a cter iza tion of 12a . 1H NMR (300 MHz, CDCl3,
ppm): δ 0.96-1.71 (br, 37H), 1.73-2.05 (br, 5H), 3.01-3.23
(br, 2H), 3.72-3.93 (br, 1H), 3.99-4.19 (br, 1H), 4.79-5.17 (br,
5H), 5.22-5.44 (br, 2H), 5.47-5.75 (br, 1H), 5.78-6.15 (br, 1H),

2210 Hopkins and Wagener
Macromolecules, Vol. 36, No. 7, 2003
F igu r e 1. Synthesis of the amine branched dienes 3a and 3b.
F igu r e 2. Previously published mechanism of ketone 2c15 and synthesis of the amine branched diene 3c.
1
verified by H NMR and 13C NMR. This quick purifica-
tion technique was possible because of the vast differ-
ences in polarity between the starting materials and the
final product. Similar yields were achieved for both
methods; however, lower yields were achieved for 3b
than for 3a , which could be attributed to steric differ-
ences.
easy purification (Figure 2).15 The ketone 2c is then
converted to the amine 3c using the same methodology
employed for the synthesis of amines 3a and 3b for an
overall yield of 52%.
All of the amino acid branched dienes were prepared
using simple textbook peptide coupling chemistry (Fig-
ure 3). The three-spacer BOC-L-leucine branched diene
(4a ) and the three-spacer BOC-L-alanine branched diene
(5a ) were synthesized by coupling 3a with the corre-
sponding BOC-protected amino acids by the standard
peptide coupling method using the 1-hydroxybenzatria-
zole (HOBt)/1,3-diisopropylcarbodiimide (DIC) method.
Purification was achieved by three successive recrys-
tallizations from CH3OH/water, yielding the pure prod-
ucts 4a and 5a in 78% and 76%, respectively.
The nine-spacer di-CBz-L-lysine branched diene (6a )
and the nine-spacer di-CBz-L-cysteine branched diene
(7) were prepared by coupling 3b with the corresponding
CBz-protected amino acid using the HOBt/DIC method
and purified by the recrystallization method described
above to yield 6 in 47% and 7 in 29%. The nine-spacer
BOC-L-alanine branched diene (5b), nine-spacer BOC-
L-leucine branched diene (4b), and nine-spacer BOC-L-
The amine 3c was not synthesized by the method
described for 3a and 3b due to the lack of readily
available starting material 10-bromo-1-decene. For this
reason Watson et al.17 and Zantour et al.15 have
published different syntheses for the ketone 2c from
derivatives of the inexpensive starting material 10-
undecenoic acid. Watson’s method involves the Claisen
condensation reaction of ethyl 10-undecenoate, followed
by dealkoxycarbonylation to give 2c in moderate yields
with difficult purification.17 In Zantour’s method, 10-
undecenoyl chloride is reacted with 1.8 equiv of triethyl-
amine to form a ketene, followed by the ketene coupling
reaction to form the intermediate â-lactone (Figure 2).
Refluxing the intermediate in a sodium hydroxide
solution opens the lactone, allowing decarboxylation to
occur forming the ketone 2c in high yields (82%) with

Macromolecules, Vol. 36, No. 7, 2003
Amino Acids and Polyolefins 2211
F igu r e 3. Synthesis and polymerization of the amino acid
branched dienes.
F igu r e 4. Synthesis and polymerization of the dipeptide
branched dienes.
a
lysine branched diene (6b) were prepared by coupling
the BOC-protected amino acids with 3b using the HOBt/
DIC method and purified as described above to give the
pure dienes in 22% for 5d , 39% for 4b, and 87% for 6b.
The BOC- and CBz-protected eight-spacer L-alanine
branched dienes (5b and 5c) were prepared by reacting
the corresponding protected amino acids with 3c using
the above methodology to yield the pure monomers 5b
and 5c in 75% and 74%, respectively. The dipeptide
branched dienes 8 and 9 were prepared by coupling the
protected dipeptides with 3b using the HOBt/DIC
coupling method and purified as described above, yield-
ing 46% and 95% for 8 and 9, respectively (Figure 4).
Ta ble 1.
polymer
Mh na (g/mol)
PDIa
Tmb (°C)
Tgb (°C)
10b
11b
11c
11d
12a
12b
13
20 000
37 000
21 000
13 000
25 000
11 000
14 000
12 000
7 500
1.96
1.85
1.89
2.11
1.92
1.92
1.76
2.61
1.78
c
c
34
7
d
18
d
d
d
d
40
46e
c
96
60
110
150
c
14
15
a
Mh n values were calculated by GPC vs polystyrene standards.
Data obtained using a Perkin-Elmer DSC 7. c No Tm observed
b
d
over the scanned range of -80 to 190 °C. No Tg observed over
the scanned range of -80 to 190 °C. e The Tm reported is that of
the solvent crystallized sample; no Tm was observed from the melt
crystallized sample.
Some observations were made during the synthesis
of the monomers. It appears that a longer reaction time
(up to 48 h for the protected dipeptides), performing the
reaction at THF reflux conditions, and using 2.5 equiv
of HOBt gave the best reaction yields. Also, CH2Cl2,
CHCl3, and THF were used as solvents for the amino
acid synthesis, but the latter was used preferably due
to the ease of availability of the pure dry solvent in our
laboratory,18 the high yields obtained, and the increased
solubility of the HOBT and amino acids/dipeptides in
this solvent. Purification was best achieved by filtration
of the insoluble urea and evaporation of the solvent,
followed by three recrystallizations from ethanol/water
or methanol/water depending on the mp of the mono-
mers. It was found that three recrystallizations resulted
in pure compounds by elemental analysis, NMR, and
HRMS; moreover, the yields were improved if extrac-
tions were not performed to remove the HOBt and
soluble urea due to emulsions that formed during the
extraction process.
P olym er Syn th esis. ADMET is a simple condensa-
tion polymerization that allows for precise branch and/
or functionality placement along the polymer backbone
by monomer design. ADMET is commonly performed in
the bulk; however, since the monomers were all solids,
the polymerization methodology chosen was that previ-
ously published using a small amount of solvent with
an argon purge to aid in the removal of ethylene.13
There appears to be a solvent effect associated with
this chemistry. For instance, when monomer 6a was
polymerized using CHCl3 as the solvent only oligomeric
products were observed, whereas the monomer was
successfully polymerized to 12a (Mh n of 25 000 g/mol)
using THF as the solvent (Table 1). The low conversion
in CHCl3 is likely due to complexation of the catalyst
to the amino acid functionality of the dienes;13,19 there-

2212 Hopkins and Wagener
Macromolecules, Vol. 36, No. 7, 2003
F igu r e 5. Synthesis of the previously published polymer 16.13
F igu r e 6. Comparison of the melt transitions of polymers 12a and 12b.
fore, THF appears to prevent complexation between the
monomer and catalyst. This is the first known example
of THF being used as a solvent for ADMET polymeri-
zation. As shown in Table 1, monomers 4b, 5b, 5c, 5d ,
and 6b were successfully polymerized using this meth-
odology to form polymers 10b, 11b, 11c, 11d , and 12b
with Mh n’s equal to 21 000, 37 000, 21 000, 13 000, and
11 000, respectively (Table 1). Further, no terminal
olefin resonances were observed in the 1H NMR for
these polymers, which is a phenomenon observed for
high molecular weight ADMET polymers.
To compare these polymers with those reported in a
previous communication,13 monomers 4a and 5a with
three methylene spacers between the olefin and the
amino acid branch were synthesized. The three-spacer-
L-leucine methyl ester branched diene 16, which was
reported previously, was successfully polymerized using
CHCl3 as the solvent (Figure 5); however, the polym-
erization of 4a in THF and 5a in THF or CHCl3 resulted
in only oligomer formation in all cases. One major
difference is evident when comparing these monomers:
the location of the amine and carbonyl group relative
to the diene. We reported previously that the amide
carbonyl prevented or limited the polymerization of
linear amino alcohol containing dienes when the car-
bonyl was two or three carbons from the diene, which
was due to intermolecular complexation of the nucleo-
philic amide carbonyl with the catalyst.13 In this case,
we believe the molecular orientation of monomers 4a
and 5a also allows for complexation to occur between
the monomer functionality and catalyst, resulting in
only oligomer formation.
Monomer 7, bearing a cysteine branch, has a CBz
protected sulfursa functional group never before po-
lymerized by ADMET. This amino acid was of particular
interest since the unprotected sulfur could be used to

Macromolecules, Vol. 36, No. 7, 2003
Amino Acids and Polyolefins 2213
F igu r e 7. DSC trace of polymer 14.
make cross-linked materials.20 The monomer was suc-
cessfully polymerized to yield 13 with a Mh n of 14 000
g/mol.
hydrogen-bonding sites per repeat unit. Figure 6 com-
pares the DSC spectra for polymers 12a and 12b, which
differ only in protecting group strategy. These DSC
spectra demonstrate that although the BOC protecting
groups do not prevent crystallization, they do affect the
thermal properties of the resulting polymers. The pos-
sibility that polarity of the side branch has an impact
on the semicrystalline nature of the polymer is further
supported by the analysis of the cysteine branched
polymer 13, which is semicrystalline with a Tm of 110
°C.
The dipeptide branched polymers 14 and 15, having
a CBz-protected alanine-valine branch and a BOC-
protected leucine-leucine branch, respectively, were
also analyzed. Polymer 14 is semicrystalline with a Tm
value of 150 °C (Figure 7), whereas polymer 15 is
amorphous with a Tg of 40 °C. Interestingly, the Tg
found for polymer 15 is similar to that found for the
single BOC-protected leucine branched polymer 10b.
The differences in crystallinity can be explained not only
by the difference in protecting groups but also by the
relatively small alkyl branches, methyl and isopropyl,
on the dipeptide of polymer 14, which should have a
smaller effect on the crystallization than the two isobu-
tyl branches on the leucine moieties of polymer 15.
As is evident by the DSC study, both the nature of
the protecting group and the polarity of the amino acid
or peptide functionality appear to influence the crystal-
linity and the Tm of the resulting polymers. The differ-
ences in the percentage of mass composition of the
amino acid vs polymer backbone, as well as the high
Tm values obtained for some of the polymers, demon-
strate that it is indeed the amino acid or peptide
functionality that is responsible for the semicrystallinity
we observe.
The successful polymerization of dipeptide branched
monomers will lead toward the synthesis of monomers
bearing longer peptides, which could have specific
biological properties. Therefore, we attempted to poly-
merize the dipeptide monomer 8 to polymer 14 using
THF as the solvent. The polymer was relatively in-
soluble in THF; however, stirring 10 mg in 2 mL of THF
overnight allowed for successful GPC molecular weight
determination (12 000 g/mol).21 Polymerization of the
dipeptide monomer 9 yielded 15, which was shown to
be a high polymer by the lack of terminal olefin
resonances in the 1H NMR spectrum and had a GPC
molecular weight of 7500 g/mol.22 Polymer 15 could not
be purified by precipitation in cold methanol, since it
was slightly soluble in methanol and could not be
precipitated even with the addition of water. Purifica-
tion was achieved instead by dissolving the polymer in
CH2Cl2 and adding 25 equiv of 1 M tris(hydroxymethyl)-
phophine (THP) in isopropyl alcohol, a procedure which
removes catalyst residues.23
Th er m a l Ch a r a cter iza tion . Differential scanning
calorimetry (DSC) measurements were completed to
determine whether the samples were amorphous or
semicrystalline in nature. The BOC-protected polymers
10b, 11b, and 11d are amorphous with glass transitions
at 34, 7, and 18 °C, respectively, where the lack of
crystallinity likely is due to the presence of the bulky
BOC protecting groups. Polymers 11c and 12a each
possess CBz protecting groups and are semicrystalline
with melting points of 46 and 96 °C, respectively.
Surprisingly, polymer 12b, which has two BOC protect-
ing groups per repeat unit, also is semicrystalline with
a Tm of 60 °C. Why is polymer 12b semicrystalline? We
expected an amorphous polymer, as is the case for the
analogous polymers 10b, 11b, and 11d , since the
presence of two BOC protecting groups per repeat unit
in 12b should inhibit crystallization. This unexpected
crystallinity could be explained by the added polarity
of the amino acid branch in polymer 12b, which has two
Con clu sion s
Amino acid and dipeptide funtionalized polyolefins
have been prepared by ADMET polymerization from
monomers synthesized in high yields using simple
peptide coupling chemistry. The resulting polymers
have Tm values of up to 150 °C, which could lend them

2214 Hopkins and Wagener
Macromolecules, Vol. 36, No. 7, 2003
Kudo, H.; Sanda, F.; Endo, T. Macromol. Chem. Phys. 1999,
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useful for possible biomedical applications, and the
crystallinity of the polymers is due to the amino acid or
peptide functionality and not the polyolefin backbone.
Also, the polarity of the amino acid or peptide branch
appears to greatly affect the crystallinity of the sample
as well as the Tm values; the higher the polarity of the
amino acid or peptide branch, the higher the crystal-
linity and the higher the Tm.
We believe the ability to use ADMET to polymerize
amino acid and peptide containing monomers could lead
toward the synthesis of designer biomaterials for specific
biological applications. This methodology has the ad-
vantage that the amount of functionality as well as the
placement of the branch can be completely controlled
by either monomer synthesis or simple copolymeriza-
tion.
Ack n ow led gm en t. We thank the National Science
Foundation, Division of Materials Research, and the
Army Research Office for financial support of this work.
We would like to thank Dr. Ravi Orugunty, Mr. Claud
Robotham, Prof. J ean M. J . Fre´chet, Prof. Dennis
Wright, Prof. Eric Enholm, and Dr. J ames H. Pawlow
for helpful comments and discussions during the course
of this work. We acknowledge Mr. Brian Cuevas, Mr.
Clay Bohn, Prof. Anthony Brennan, and Prof. Eugene
Goldberg for help in obtaining initial material property
data. We acknowledge Dr. J ason Smith for his help in
obtaining thermoanalysis data for the polymers dis-
cussed and Mr. J ohn Sworen for his help in the
preparation of this manuscript and for helpful discus-
sions during the course of this work. Finally, we are
grateful to Dr. Richard Pederson of Materia, Inc., for
providing the THP solution required for removal of the
catalyst from polymer 15.
(15) Zantour, H.; Pousse, A.; Brini, M. Bull. Chim. Fr. 1972, 12,
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(16) The reaction conditions were not optimized to obtain the best
yield for this reaction, i.e., longer reaction times and reflux
temperatures.
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3196.
(18) The THF was used directly from the Aldrich Keg system.
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Refer en ces a n d Notes
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(21) Since the polymer was insoluble in CHCl3 and THF, we were
unable to perform molecular weight determination by GPC
analysis.
(22) GPC data gave a Mh n of 6500 g/mol; however, initial studies
using light scattering on polymer 11c suggest that this
number was off by a factor of 3. Therefore, we believe GPC
is not an accurate measure of molecular weight for these
systems including polymer 15.
(4) Pino, P. Adv. Polym. Sci. 1965, 4, 393.
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Inc.
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