Fabrication of biodegradable poly(ester-amide)s based on tyrosine natural amino acid

Article abstract of DOI:10.1007/s00726-011-0931-1

N,N'-Bis[2-(methyl-3-(4-hydroxyphenyl)propanoate)] isophthaldiamide (5), a novel diol monomer containing chiral group, was prepared by the reaction of S-tyrosine methyl ester (3) with isophthaloyl dichloride (4a). A new family of optically active and potentially biodegradable poly(ester-amide)s (PEAs) based on tyrosine amino acid were prepared by the polycondensation reaction of diol monomer 5 with several aromatic diacid chlorides. The resulting new polymers were obtained in good yields with inherent viscosities ranging between 0.25 and 0.42 dL/g and are soluble in polar aprotic solvents. They showed good thermal stability and high optical purity. The synthetic compounds were characterized and studied by FT-IR, ¹H-NMR, specific rotation, elemental and thermogravimetric analysis (TGA) techniques and typical ones by ¹³C-NMR, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-SEM) analysis. Soil burial test of the diphenolic monomer 5, and obtained PEA6a, and soil enzymatic assay showed that the synthesized diol and its polymer are biologically active and probably biodegradable in soil environment. Springer-Verlag 2011.

Full text of DOI:10.1007/s00726-011-0931-1

Amino Acids (2012) 42:1997–2007
DOI 10.1007/s00726-011-0931-1
ORIGINAL ARTICLE
Fabrication of biodegradable poly(ester-amide)s based on tyrosine
natural amino acid
•
Amir Abdolmaleki Shadpour Mallakpour
•
•
Sedigheh Borandeh Mohammad R. Sabzalian
Received: 3 January 2011 / Accepted: 29 April 2011 / Published online: 24 May 2011
Ó Springer-Verlag 2011
Abstract N,N0-Bis[2-(methyl-3-(4-hydroxyphenyl)pro-
panoate)]isophthaldiamide (5), a novel diol monomer
containing chiral group, was prepared by the reaction of
S-tyrosine methyl ester (3) with isophthaloyl dichloride
(4a). A new family of optically active and potentially
biodegradable poly(ester-amide)s (PEAs) based on tyrosine
amino acid were prepared by the polycondensation reaction
of diol monomer 5 with several aromatic diacid chlorides.
The resulting new polymers were obtained in good yields
with inherent viscosities ranging between 0.25 and
0.42 dL/g and are soluble in polar aprotic solvents. They
showed good thermal stability and high optical purity. The
synthetic compounds were characterized and studied by
microscopy (FE-SEM) analysis. Soil burial test of the di-
phenolic monomer 5, and obtained PEA6a, and soil
enzymatic assay showed that the synthesized diol and its
polymer are biologically active and probably biodegrad-
able in soil environment.
Keywords Optically active polymer ꢀ Tyrosine amino
acid ꢀ Biodegradable ꢀ Poly(ester-amide) ꢀ
Polycondensation
Introduction
1
FT-IR, H-NMR, specific rotation, elemental and thermo-
High-performance materials like polyamides and polyes-
ters attended lots of interest, and many works has been
focused on synthesis and study of their properties (Bani-
hashemi and Firoozifar 2003; Sheng et al. 2009; Tamami
et al. 2004; Tsai et al. 2008). Each group has its benefits
and disadvantages. For instance, polyamides show high
thermal stability, chemical resistance, low combustibility,
and incredible mechanical properties (Liaw et al. 2001;
Mehdipour-Ataei and Babanzadeh 2007); however, the
poor solubility and high melting temperatures caused by
the high crystallinity and high rigidity, and strong inter-
molecular interactions through hydrogen bonding of the
polymer backbone has lead to difficult processability of
these materials (San-Jose et al. 2007). To overcome some
disadvantages, a great interest has lately been focused on
the study of poly(ester-amide)s (PEA)s since they combine
properties of amide groups (high temperature stability,
excellent mechanical strength and good chemical resis-
tance) and polyesters (high degradability and flexibility)
(Okada 2002).
gravimetric analysis (TGA) techniques and typical ones by
13C-NMR, differential scanning calorimetry (DSC), X-ray
diffraction (XRD), and field emission scanning electron
A. Abdolmaleki (&) ꢀ S. Borandeh
Department of Chemistry, Isfahan University of Technology,
84156-83111 Isfahan, Iran
e-mail: abdolmeleki@cc.iut.ac.ir; amirabdolmaleki@yahoo.com
A. Abdolmaleki ꢀ S. Mallakpour
Nanotechnology and Advanced Materials Institute,
Isfahan University of Technology, 84156-83111 Isfahan, Iran
S. Mallakpour (&)
Organic Polymer Chemistry Research Laboratory,
Department of Chemistry, Isfahan University of Technology,
84156-83111 Isfahan, Iran
e-mail: mallak@cc.iut.ac.ir; mallak777@yahoo.com;
mallakpour84@alumni.ufl.edu
M. R. Sabzalian
Department of Agronomy and Plant Breeding,
College of Agriculture, Isfahan University of Technology,
84156-83111 Isfahan, Iran
Biocompatible equipments may be rewarded while
using multi-functional natural metabolites such as amino
123

1998
A. Abdolmaleki et al.
acids. These materials are naturally occurring compounds;
hence, polymers based on amino acids are expected to be
biodegradable and biocompatible (Sanda and Endo 1999;
Tsai et al. 2008; Wang et al. 2009). Consequently, among
different poly(ester-amide)s, amino acid-based PEAs have
attracted more considerable interests due to owing natural
resources, biocompatibility of the degradation products,
and biodegradability under certain enzymatically catalyzed
conditions (Okada 2002; Armelin et al. 2001; Guo and Chu
2007). In addition, it should be mentioned that amino acids
are not only biocompatible materials but also the practical
sources of chemically functional materials that have been
used in different areas like pharmaceuticals, food and feed
additives, dietary supplements, and neutraceuticals (Bon-
gaerts et al. 2001). These kinds of polymers are potentially
optically active (have a chiral group) with unique proper-
ties and show numerous applications in diverse areas
(Dardas and Kuczynski 2004; Hu et al. 2001; Okamoto and
Ikai 2008; Okamoto and Yashima 1998; Pu 1998). Syn-
thetic optically active polymers like their homologs, natu-
ral polymers, are biologically important. They could show
special chemical activities such as catalytic properties that
exist in genes, proteins, and enzymes.
tetrazolium chloride (TTC) to triphenyl formazan (TPF) in
the soil containing different compounds.
Experimental
Materials
S-Tyrosine was purchased from Merck Chemical Co. N-
methyl-2-pyrrolidinon (NMP, Merck Chemical Co.) and
triethylamine (TEA, Merck Chemical Co.) were dried over
BaO and then was distilled under reduced pressure and
˚
stored over 4 A molecular sieves. Isophthaloyl dichloride
(4a) (Merck chemical Co.) and other reagents and solvents
were obtained commercially and used as received. 4,40-
dicarbonyl chloride diphenyl sulfone (4b), 4,40-dicarbonyl
chloride diphenyl ether (4c), and benzofuro[2,3b]benzofu-
ran-2,9-dicarbonyl chloride (4d) were prepared based on
reported works (Abdolmaleki 2000).
Instrumentation
The 1H-NMR and 13C-NMR spectra were recorded on
Bruker Avance 400 and 500 MHz spectrometer operating
on monomers and polymers solution in DMSO-d6. Chem-
ical shifts are given in the d scale in parts per million
(ppm). Proton resonances are designated as singlet (s),
doublet (d), triplet (t), multiplet (m), and doublet of doublet
(dd). FT-IR spectra were recorded using a Jasco-680 FT-IR
spectrophotometer (Japan) with KBr pellet. Vibration
bands were reported as wave number (cm-1). The band
intensities were classified as weak (w), medium (m), strong
(s), broad (br), and shoulder (sh). Inherent viscosities of
polymer solution (0.5% w/v) in NMP were determined at
25°C by a standard procedure using a Cannon Fenske
Routine viscometer (Cannon, Mainz, Germany). The spe-
cific rotations were measured by a Jasco polarimeter
(Japan). Thermogravimetric analysis (TGA) data for the
polymers were taken on STA503 win TA instrument in
nitrogen atmosphere at a heating rate of 10°C/min. DSC
analysis was taken by Perkin-Elmer DSC-7 in nitrogen
atmosphere at a heating rate of 10°C/min. Elemental
analyses were performed with a CHNS-932, Leco. The
X-ray diffraction patterns were recorded by using a Philips
Xpert MPD diffractometer equipped with a Cu Ka anode
Recently Mallakpour and co-workers reported synthesis
and application of different kinds of optically active poly-
mers (Mallakpour et al. 2008; Mallakpour and Kolahdoozan
2007; Mallakpour and Taghavi 2009; Mallakpour and
Zadehnazari 2009). Based on in vitro toxicity, they sug-
gested that amino acid containing polymers are favorable
candidates as biodegradable and biologically active poly-
mers (Mallakpour et al. 2010a, b, c, 2011).
In 1999, Ueda and co-workers (Li et al. 1999) reported
the synthesis of ordered poly(amide-ester)s; which consti-
tutional regularity of the polymers strongly influenced the
physical properties. Herein, we wish to report the synthesis
and properties of new optically active ordered poly(ester-
amide)s by the polycondensation of different diacid
chlorides (4a–4d) with N,N0-Bis[2-(methyl-3-(4-hydroxy-
phenyl)propanoate)] isophthaldiamide (5). The introduc-
tion of ester side chains, aromatic rings, and optically
active groups into these polymer’s backbones is expected
to improve the solubility, thermal stability, and environ-
mentally friendly of the obtained polymers, respectively.
The structure of the resulting polymers was verified by FT-
IR, 1H-NMR, specific rotation, elemental and thermo-
gravimetric analysis (TGA) techniques and typical ones by
13C-NMR, differential scanning calorimetry (DSC), X-ray
diffraction (XRD) and field emission scanning electron
microscopy (FE-SEM) analysis. Soil burial test was
employed to examine biodegradability of synthetic diol 5
and one of the polymers (PEA6a). Also soil dehydrogenase
activity was calculated by the reduction of triphenyl
˚
(k = 1.51418 A). The field emission scanning electron
microscopy (FE-SEM) micrographs of polymer were taken
on a Hitachi (S-4160). Melting points were taken with a
Gallenkamp melting point apparatus. UV/vis spectra of
samples were measured on UV/Vis/NIR spectrophotome-
ter, Beckman 7200 in the spectral range between 200 and
800 nm.
123

Fabrication of biodegradable poly(ester-amide)s
1999
Synthesis of S-tyrosine methyl ester hydrochloride (2)
(0.5 g, 2.5 mmol) grain by grain (Scheme 1). After stirring
for 2 h, the mixture was poured into a mixture of cold
distilled water/HCl (diluted). The white precipitates was
collected by filtration and washed thoroughly with water
and dried at 80°C for 12 h: yield 0.98 g (75%), mp
118–120°C, [a]2D5 = -82° (c = 0.5 g/dL, NMP). FT-IR
(KBr, cm-1): m = 3,365 (OH, NH, s, br), 1,737 (C=O ester,
s), 1,646 (C=O amide, m), 1,515 (s, sh), 1,442 (m), 1,364
(C–N, w), 1,223 (C–O, m), 1,106 (w), 1,173 (w), 827 (w),
S-Tyrosine (9.06 g, 50 mmol) was added to a methanol
solution (50 mL) containing thionyl chloride (13 mL,
150 mmol) at -10°C, and the solution was stirred at room
temperature for 12 h. The solvent was removed under
reduced pressure, and the residual mass was washed with
ethyl ether (75 mL) several times to obtain white, powdery,
S-tyrosine methyl ester hydrochloride (2), which was used
for the next step without further purification: yield 10.95 g
(95%), mp 193°C (Lit. mp 194–195°C) (Nagai et al. 2004).
IR (KBr, cm-1): m = 3,341 (OH, m), 3,200–2,624
(NH3?, m, br), 1,743 (C=O ester, s), 1,614 (m), 1,591 (m),
1,514 (m, sh), 1,448 (w), 1,396 (w), 1,348 (w), 1,107 (m),
1,059 (m), 839 (m).
1
730 (w), 538 (w). H-NMR (400 MHz, DMSO-d6, ppm):
d = 2.96–3.10 (m, 4H), 3.64 (s, 6H), 4.57–4.63 (m, 2H,
chiral center), 6.65–6.67 (d, J = 8.4 Hz, 4H), 7.08–7.10 (d,
J = 8.4 Hz, 4H), 7.55–7.59 (t, J = 7.6 Hz, 1H), 7.93–7.95
(d, J = 8.0 Hz, 2H), 8.26 (s, 1H), 8.93–8.95 (NH, d,
J = 8.0 Hz, 2H), 9.21 (OH, s, 2H). 13C-NMR (400 MHz,
DMSO-d6, ppm): d = 35.98 (CH2), 52.36 (CH3–O), 55.25
(CH, chiral center), 115.54 (4CH, ArC), 127.23 (CH, ArC),
128.07 (4CH, ArC), 128.80 (2CH, ArC), 129.68 (CH,
ArC), 130.65 (2C, ArC), 134.42 (2C, ArC), 156.41 (2C,
ArC), 166.48 (2 C=O ester), 172.70 (2 C=O amide). Elem.
Anal. Calc for C28H28N2O8: C, 64.61; H, 5.42; N, 5.38.
Found: C, 64.38; H, 5.59; N, 5.21.
Synthesis of S-tyrosine methyl ester (3)
Triethylamine (10.5 mL, 75.6 mmol) was added slowly to
a suspension of S-tyrosine methyl ester hydrochloride 2
(10.9 g, 47 mmol) in dichloromethane (CH2Cl2, 121 mL),
and the suspension was stirred for 1 h at 0°C. The solvent
was removed under reduced pressure, and the residual mass
was washed with H2O (500 mL), followed by recrystalli-
zation from N,N-dimethylformamide to obtain a colorless
solid, S-tyrosine methyl ester 3: yield 4.86 g (53%), mp
135–137°C, [a]2D5 = 21.52° (c = 0.5 g/dL, CH3OH) {Lit
135–136°C, [a]2D5 = 26.1° (c = 2.4 g/dL, CH3OH)} (Na-
gai et al. 2004). IR (KBr, cm-1): m = 3,354 (OH, m), 3,300
(NH2, w), 1,744 (C=O ester, s), 1,597 (m), 1,516 (w), 1,480
(w), 1,257 (m), 1,178 (w), 1,020 (m), 838 (s), 573 (m), 512
(m).
Synthesis of polymers
The poly(ester-amide)s (PEA6a–PEA6d) have been pre-
pared from the reaction of diol 5 and different diacid
chlorides 4a–4d according to Scheme 2. The resulting
PEA6a–PEA6d were prepared by the following procedure
(using polymer PEA6a as an example): Diol 5 (0.26 g,
0.5 mmol) and TEA (0.4 mL, 3 mmol) were dissolved in
NMP (2 mL) at room temperature. To this solution,
isophthaloyl dichloride 4a (0.1 g, 0.5 mmol) was added in
one portion. Then the solution was stirred at this temper-
ature for 12 h. The solution was poured into methanol
(50 mL). The precipitate was filtered off, washed with
methanol. Powdered polymer was dried at 80°C for 12 h
under vacuum to leave 0.273 g (84%) of light yellow solid
PEA6a.
Synthesis of N,N0-Bis[2-(methyl 3-(4-hydroxyphenyl)
propanoate)] isophthaldiamide (diol 5)
To a solution of S-tyrosine methyl ester 3 (1.07 g,
5.5 mmol), TEA (0.7 mL, 5 mmol) and NMP (6 mL) at
-20°C, was slowly added isophthaloyl dichloride 4a
Scheme 1 Synthesis of diol 5
123

2000
A. Abdolmaleki et al.
Scheme 2 Polycondensation
reactions of diol 5 with different
diacid chlorides 4a–4d
PEA6a
(d, J = 6.8 Hz, 4H), 8.28 (s, 1H), 8.28–8.30 (d,
J = 8.0 Hz, 4H), 9.03–9.05 (NH, d, J = 6.8 Hz, 2H).
Light yellow solid; [a]2D5 = -83° (c = 0.5 g/dL, NMP).
FT-IR (KBr, cm-1): m = 3,408 (NH, m, br), 1,741 (C=O
ester, s), 1,663 (C=O amide, m), 1,508 (m, sh), 1,437 (w),
1,299 (C–N, w), 1,221 (C–O, w), 1,194 (w), 1,165 (w),
1,062 (w), 1,017 (w), 722 (m), 524 (w). 1H-NMR
(500 MHz, DMSO-d6, ppm): d = 3.09–3.28 (m, 4H), 3.61
(s, 6H), 4.66–4.68 (m, 2H, chiral center), 7.17–7.19 (d,
J = 7.2 Hz, 4H), 7.34–7.35 (d, J = 6.8 Hz, 4H), 7.51–7.54
(t, J = 7.6 Hz, 1H), 7.74–7.76 (t, J = 10.4 Hz, 1H),
7.90–7.92 (d, J = 7.5 Hz, 2H), 8.19 (s, 1H), 8.34–8.35 (d,
J = 8.0 Hz, 2H), 8.65 (s, 1H), 9.01–9.02 (NH, d,
J = 7.4 Hz, 2H). 13C-NMR (400 MHz, DMSO-d6, ppm):
d = 36.00 (CH2), 52.46 (CH3–O), 54.77 (CH, chiral cen-
ter), 115.52 (4CH, ArC), 122.07 (CH, ArC), 127.27 (4CH,
ArC), 128.86 (CH, ArC), 130.19 (CH, ArC), 130.42 (2C,
ArC), 130.65 (2CH, ArC), 131.04 (CH, ArC), 134.36 (2C,
ArC), 135.22 (2CH, ArC), 136.08 (2C, ArC), 149.54 (2C,
ArC), 164.15 (2 C=O ester), 166.50 (2 C=O ester), 172.46
(2 C=O amide).
PEA6c
Cream solid; [a]2D5 = -81.78° (c = 0.5 g/dL, NMP). FT-
IR (KBr, cm-1): m = 3,410 (NH, m, br), 1,736 (C=O ester,
s), 1,663 (C=O amide, m), 1,593 (m), 1,507 (m), 1,438 (w),
1,246 (w), 1,199 (w), 1,162 (m), 1,071 (m), 1,012 (w), 879
1
(w), 760 (w), 519 (w). H-NMR (400 MHz, DMSO-d6,
ppm): d = 3.16–3.21 (m, 4H), 3.65 (s, 6H), 4.69–4.75 (dd,
chiral center, J1 = 7.6 Hz, J2 = 8.8 Hz, 2H), 7.18–7.19 (d,
J = 6.4 Hz, 4H), 7.24–7.26 (d, J = 6.8 Hz, 4H), 7.37–7.39
(d, J = 7.6 Hz, 4H), 7.56–7.59 (m, 1H), 7.95–7.97 (d,
J = 7.2 Hz, 2H), 8.14–8.16 (d, J = 8.0 Hz, 4H), 8.29 (s,
1H), 9.04–9.06 (NH, d, J = 7.2 Hz, 2H).
PEA6d
Cream solid; [a]2D5 = -57.4° (c = 0.5 g/dL, NMP). FT-IR
(KBr, cm-1): m = 3,420 (NH, m, br), 1,738 (C=O ester, s),
1,665 (C=O amide, m), 1,507 (m), 1,438 (w), 1,284 (w),
1,200 (w), 1,166 (w), 1,107 (m), 1,059 (w), 1,019 (w), 758
PEA6b
1
(w), 729 (w), 651 (w). H-NMR (400 MHz, DMSO-d6,
Cream solid; [a]2D5 = -59.26° (c = 0.5 g/dL, NMP). FT-
IR (KBr, cm-1): m = 3,419 (NH, m, br), 1,741 (C=O ester,
s), 1,663 (C=O amide, m), 1,507 (m), 1,400 (w), 1,299 (w),
1,264 (m), 1,199 (m), 1,162 (m), 1,075 (m), 1,014 (m), 739
(w), 687 (w), 618 (m), 579 (w). 1H-NMR (400 MHz,
DMSO-d6, ppm): d = 3.14–3.20 (m, 4H), 3.64 (s, 6H),
4.70–4.71 (m, 2H, chiral center), 7.18–7.20 (d, J = 6.4 Hz,
4H), 7.37–7.39 (d, J = 7.6 Hz, 4H), 7.54–7.58 (t,
J = 7.6 Hz, 1H), 7.93–7.95 (d, J = 8.4 Hz, 2H), 8.17–8.19
ppm): d = 3.17 (m, 4H), 3.63 (s, 6H), 4.72 (m, 2H, chiral
center), 7.17 (s, 4H), 7.22 (s, 2H), 7.37 (m, 4H), 7.56 (d,
J = 7.6 Hz, 2H), 7.95 (d, 2H), 8.06 (t, J = 7.1 Hz, 1H),
8.29 (s, 1H), 8.70 (s, 1H), 9.06 (s, 2H).
Soil biodegradability
Diphenolic monomer 5 and PEA6a (30 mg) were sepa-
rately mixed with clay-loam soil (1.5 g), and the mixture
123

Fabrication of biodegradable poly(ester-amide)s
2001
was transferred into 2-mL plastic vials in three replications.
Samples of soil containing bisphenol A (BPA) or without
any added compounds were also tested in these experi-
ments as positive and negative controls, respectively. Vials
were incubated at 23–25°C, with a saturated humidity at
dark for 3 months. Days to 50 and 100% disappearance of
materials were recorded. Then water extracts of soil sam-
ples were inoculated by streak culture on Potato Dextrose
Agar (PDA) as culture media. The number of bacterial and
fungal colonies formed on the media was counted and
noted as colony forming units (CFUs) per 100 lL of water
extract.
Dehydrogenase activity
Soil dehydrogenase activity was calculated by the reduc-
tion of triphenyl tetrazolium chloride (TTC) to triphenyl
formazan (TPF) in the soil containing different compounds.
For this purpose, each soil sample (1 g) was incubated for
24 h at 37°C in 1 mL of TTC solution (5 g/L in 0.2 mol/L
Tris–HCl buffer, pH 7.4). One drop of concentrated H2SO4
was added after incubation to stop the reaction. The sam-
ples was then blended with toluene (1 mL) to extract TPF
and shaken for 30 min at 250 rpm (25°C), followed by
centrifugation at 5,000 rpm for 5 min. The supernatant was
removed, and absorbance in this extract was measured at
492 nm. Soil dehydrogenase activity was then reported as
lg TPF g-1 dry soil.
Fig. 1 FT-IR spectra of a diacid chloride 4a, b diol 5, and c PEA6a
resonance of C–H chiral center multiplet at
4.57–4.62 ppm; peak at 2.96–3.08 ppm is assigned to
diastereotopic CH2 protons bonded to chiral center. Singlet
peak at 3.64 ppm was assigned to the CH3 protons of
methoxy group; N–H amide group and phenolic O–H were
seen at 8.93–8.95 and 9.21 ppm, respectively. Moreover,
13C-NMR spectrum of monomer 5 (Fig. 3) shows CH
chiral center carbon at 55.25 ppm. In addition, the presence
of eight types of different aromatic carbons and two car-
bons for carbonyl groups in this spectrum confirm the
structure of monomer 5. The chemical structure of diol 5 is
also verified from the elemental analysis result, and the
data corresponded well with the calculated values.
Results and discussion
Monomer synthesis and characterization
A new optically active diol 5 was synthesized according to
the procedure depicted in Scheme 1. More particularly,
S-tyrosine 1 was added to a methanol solution containing
thionyl chloride to obtain white, powdery, S-tyrosine
methyl ester hydrochloride 2 which was deprotected with
triethylamine to obtain S-tyrosine methyl ester 3. The
symmetrical diol compound 5 was synthesized by reaction
of S-tyrosine methyl ester and diacid chloride 4a in NMP at
-20°C.
Polymer synthesis and characterization
PEA6a–PEA6d were synthesized by solution polycon-
densation reaction of diol 5 with various aromatic diacid
chlorides 4a–4d in NMP at room temperature (Scheme 2).
The reaction conditions were optimized, and the influence
of the time of reaction on the inherent viscosity and the
yield of the PEA6a were examined. For this purpose,
diacid chloride 4a with one equimolar diol 5 was reacted at
different reaction times. Figure 4 exhibits that 12 h is the
best time for the polymerization reaction which provided
maximum inherent viscosity of 0.35 dL/g and good yield of
84%. According to these results, the optimum condition
was selected for the synthesis of the other PEAs. Thus, one
equimolar of diol 5 with one equimolar of diacid chlorides
4b–4d were reacted for 12 h, and the resulting mixture was
The resulting symmetric diol 5 was characterized using
1
elemental analysis, FT-IR, H-NMR and 13C-NMR spec-
troscopic techniques and specific rotation measurement.
FT-IR spectrum of compound 5 shows a broad and strong
peak at 3,365 cm-1, which was assigned to the OH group
of phenolic diol and NH group of amide and two absorp-
tion bands at 1,737 and 1,646 cm-1 due to ester and amide
carbonyl stretching vibrations, respectively (Fig. 1b).
1H-NMR spectrum of compound 5 is shown in Fig. 2.
The 1H-NMR of this diol shows the characteristic
123

2002
A. Abdolmaleki et al.
Fig. 2 1H-NMR (400 MHz)
spectrum of diol 5 in DMSO-d6
Fig. 3 13C-NMR (400 MHz)
spectrum of diol 5 in DMSO-d6
precipitated in methanol to obtain polymers with high
yields.
readily soluble in polar solvents as NMP, DMAc, DMF,
and DMSO at room temperature. The relatively higher
solubility associated with these polymers is believed to be
related to the presence of chiral center and aliphatic side
chain, which prevents the close packing of chain and
decrease interchain interaction.
The synthesis and some physical properties of these
novel optically active PEAs are listed in Table 1. The
inherent viscosities of the resulting polymers under opti-
mized condition were in the range of 0.25–0.42 dL/g, and
the yields were between 70 and 91%. The incorporation of
a chiral unit into the polymer backbone was confirmed by
measuring the specific rotations of the obtained polymers
(Table 1). The specific rotation of polymers based on dif-
ferent diacid chlorides showed random changes. These
observations are the result of different polymer structures
and inherent viscosities. As shown in Table 1, all of the
polymers show optical rotation and therefore are optically
active. All polymers showed excellent solubility and were
FT-IR study
The structures of these polymers were confirmed as PEAs
by means of FT-IR spectroscopy. The FT-IR spectra of all
polymers showed absorptions around 3,408–3,420 cm-1
(N–H), carbonyl absorption at 1,736–1,741 cm-1 (ester
C=O) and 1,663–1,665 cm-1 (amide C=O). All of
these PEAs exhibited absorption at 1,246–1,299 and
123

Fabrication of biodegradable poly(ester-amide)s
2003
peak groups, the splitting patterns, the area under any peak,
and values of the coupling constants are thoroughly in
agreement with the proposed chemical structures. Fig-
1
ures 5 and 6 show H-NMR spectra of polymers PEA6a
and PEA6c. In 1H-NMR spectra of these two polymers, the
appearance of the N–H proton of amide groups around
9.01–9.05 ppm indicates the amide group in the polymer’s
chain. The absorption of aromatic protons appeared in the
range of 7.17–8.65 ppm. The proton of the chiral center
appeared at 4.66–4.68 ppm.
Figure 7 shows 13C-NMR spectrum of PEA6a. In the
13C-NMR spectrum of this polymer, the appearance of
amide carbonyl group at 172.46 ppm, ester carbonyl
groups at 164.15 and 166.50 ppm indicate the amide and
ester groups in the polymer’s chain. The chiral center
carbon appears at 54.77 ppm, and the presence of 12 aro-
matic carbons in the range of 115.52–149.54 ppm confirms
the structure of PEA6a.
Fig. 4 Time of reaction dependence of inherent viscosity and yield
Table 1 Synthesis and some physical properties of PEA6a–PEA6d
Elemental analysis values of the resulting polymers are
listed in Table 2.
Diacid
chloride
Polymer
Yield
(%)
ginh
[a]2D5 a
Color
(dL/g)a
4a
4b
4c
4d
a
PEA6a
PEA6b
PEA6c
PEA6d
84
72
91
70
0.35
0.25
0.34
0.42
-83
Light yellow
Cream
Thermal properties (TGA and DSC analysis)
-59.26
-81.78
-57.4
Cream
The thermal properties of PEA6a–PEA6d were evaluated
by means of TGA in a nitrogen atmosphere at a heating rate
of 10°C/min (Fig. 8). The relevant results are reported in
Table 3. The temperature of 5 and 10% weight loss toge-
ther with char yield at 800°C has been calculated by means
of thermograms and used as a criterion for the evaluation of
thermal stability of the polymers. The 10% weight loss
temperatures of the aromatic PEAs were recorded between
296 and 309°C. The amount of residue (char yield) of these
polymers in N2 atmosphere ranged from 43 to 49% at
800°C. TGA thermograms of above polymers reveal that
Cream
Measured at a concentration of 0.5 g/dL in NMP at 25°C
722–760 cm-1 that show the presence of the amide group
in these polymers (Fig. 1c).
1H-NMR, 13C-NMR study and elemental analysis
From the data obtained by 1H-NMR spectra of polymers, it
is clear that the values of chemical shifts, the number of
Fig. 5 1H-NMR (500 MHz)
spectrum of a PEA6a in
DMSO-d6
123

2004
A. Abdolmaleki et al.
Fig. 6 1H-NMR (400 MHz)
spectrum of PEA6c in
DMSO-d6
Fig. 7 13C-NMR (400 MHz)
spectrum of PEA6a in
DMSO-d6
Table 2 Elemental analysis of PEA6a–PEA6d
Polymer Formula
Elemental analysis (%)
C
H
N
S
PEA6a
PEA6b
PEA6c
PEA6d
(C36H30N2O10
MW (650.19)
(C42H34N2O12S) Calc.
)
Calc.
66.46 4.65 4.31
–
–
Found 66.02 4.77 4.16
63.79 4.33 3.54 4.05
Found 63.36 4.45 3.29 3.87
MW (790.18)
(C42H34N2O11
MW (742.22)
(C44H32N2O12
MW (780.73)
)
)
Calc.
Found 67.49 4.37 3.41
Calc. 67.69 4.13 3.59
Found 66.78 3.86 3.08
67.92 4.61 3.77
–
–
–
–
Fig. 8 TGA thermograms of PEA6a–PEA6d under N2 atmosphere
and heating rate of 10°C/min
Furthermore, DSC measurement of PEA6a was con-
ducted with a heating rate of 10°C/min under nitrogen
atmosphere. The glass transition temperature (Tg) value of
this polymer was at 146.75°C.
they are thermally stable, and this is in convenience with
aromatic polymers backbone which increases the stability
of the polymers toward heating.
123

Fabrication of biodegradable poly(ester-amide)s
2005
Table 3 Thermal properties of PEA6a–PEA6d
Polymer
Decomposition temperature (°C)
Char yield (%)b
a
a
T5
T10
PEA6a
PEA6b
PEA6c
PEA6d
a
300
295
302
276
305
306
309
296
44
46
43
49
Temperature at which 5 and 10% weight loss were recorded by
TGA at heating rate of 10°C min-1 in N2 atmosphere
b
Weight percent of the material left undecomposed after TGA at
maximum temperature 800°C in N2 atmosphere
Fig. 10 FE-SEM micrographs of PEA6a
Fig. 9 X-ray diffraction patterns of PEA6a
colonies was counted from water extracts of soil containing
diol 5 and PEA6a than control treatments (Table 4). Based
on these results, it could be concluded that these com-
pounds are biologically active in soil environment.
X-ray diffraction analysis
The X-ray diffraction patterns of PEA6a over the 2h range
of 10°–80° is shown in Fig. 9. Based on the XRD data,
PEA6a is totally amorphous in nature, which dose not
show any sharp diffraction peaks. The amorphous nature of
these polymers was also reflected in their good solubility.
Dehydrogenase activity
After 100 days of soil burial test, the dehydrogenase
activity was 26.60 and 20.03 lg TPF g-1 dry soil in soil
containing diol 5 and PEA6a, respectively (Table 4). The
dehydrogenase activities of treated soils were three times
higher than control soil and the soil containing BPA as a
reference, indicating that the abundance and activities of
the microbial communities in the treated soils were
enhanced by the presence of monomer and obtained
polymer (Table 4). This may indicate that our synthetic
polymer and their intermediates might serve as a carbon
source for microbial growth, and this will result in biode-
gradability of polymers and higher dehydrogenase activity.
Field emission scanning electron microscopy
Figure 10 shows the FE-SEM images of PEA6a. The
morphology of this polymer seems to be amorphous and
consisting of micro and nano spherical-shaped spheres. The
average mean diameter of PEA6a is as low as 79 nm up to
500 nm as depicted in Fig. 10.
Soil biodegradability
Diphenolic monomer 5 was disappeared to 50% after
1 month, and it was almost disappeared under experimental
condition after 2 months. In contrast, PEA6a was not
completely disappeared in the soil. This observation shows
that diol 5 is biologically active and biodegradable under
soil burial more than PEA6a. PDA Petri plates containing
bacterial and fungal colonies grown from different soil
water extract are shown in Fig. 11. Results of counting
fungal and bacterial colonies showed that higher number of
Conclusion
In this study, a novel chiral aromatic diol 5, containing
S-tyrosine amino acid as a biodegradable material, was
synthesized. A new series of novel PEAs-bearing chiral
center were successfully prepared from diol 5 with several
diacid chlorides 4a–4d via the low temperature solution
polycondensation. All polymers were amorphous and had
123

2006
A. Abdolmaleki et al.
Fig. 11 Fungal and bacterial
colonies grown from soil water
extract, 6 days after inoculation
on PDA Petri plates: a PEA6a,
b diol, and c control
Table 4 Microbial CFUs and
Dehydrogenase activities in soil
containing different compounds
after 100 days of soil burial test
(lg TPF g-1 dry soil)
Treatment
Dehydrogenase
activity
Bacterial CFUs
Fungal CFUs
Diol 5
26.60a
20.03b,*
8.52c
180.0 15.4
173.3 8.7
76.7 7.6
0.0 0.0
133.3 3.3
91.7 4.1
42.3 6.5
2.3 1.5
PEA6a
Control (negative)
BPA (positive control)
* Means with the same letters
are not significantly different
7.43c
Hu Q-S, Sun C, Monaghan CE (2001) Synthesis of optically active
polymers with chiral units attached to rigid backbones and their
application for asymmetric catalysis. Tetrahedron Lett
42(44):7725–7728
Li L, Seino H, Yonetake K, Ueda M (1999) Synthesis and
characterization of ordered poly(amide-ester)s from isophthaloyl
high solubility in various polar solvents while maintaining
good thermal stability. From the chemical point of view,
the ester group which imparts to the polymer’s main chain
increased sensibility to hydrolysis can cause chain break-
ing. In addition, because of the existence of amino acid in
the polymer backbone, these polymers are expected to be
biodegradable, and soil burial test and dehydrogenase
activity assay also confirmed their biodegradability.
Therefore, these materials could be classified under envi-
ronmentally friendly polymers.
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32(12):3851–3858
4-(2-aminoethyl)phenol.
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of new soluble cardo aromatic polyamides bearing diphenylm-
ethylene linkage and norbornyl group. Macromol Chem Phys
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polyesters containing a chiral pendent group. Eur Polym J
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Acknowledgments We wish to express our gratitude to the
Research Affairs Division, Isfahan University of Technology (IUT)
for financial support. Further financial support from National Elite
Foundation (NEF), Iran Nanotechnology Initiative Council (INIC),
and Center of Excellency in Sensors and Green Chemistry Research
(IUT) is gratefully acknowledged.
Mallakpour S, Zadehnazari A (2009) Fast synthesis, using microwave
induction heating in ionic liquid and characterization of optically
active aromatic polyamides. J Macromol Sci Pure Appl Chem
46(8):783–789
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