Poly(ester amide)s derived from L-malic acid

Article abstract of DOI:10.1021/ma035108o

A series of aregic poly(ester amide)s (ar-PEALM) with ester to amide groups ratios (a:b) ranging from 1:50 up to 1:2 were prepared from O-methyl-L-malic acid, 1,6-hexanediol, and 1,6-hexanediamine. The ester linkage was incorporated in the poly(ester amid

Full text of DOI:10.1021/ma035108o

Macromolecules 2004, 37, 2067-2075
2067
Poly(ester amide)s Derived from L-Malic Acid
C. Rega n˜ o, A. Alla , A. Ma r tı´n ez d e Ila r d u ya , a n d S. Mu n˜ oz-Gu er r a *
Departament d’Enginyeria Qu´ımica, Universitat Polite`cnica de Catalunya, ETSEIB, Diagonal 647,
08028 Barcelona, Spain
Received J uly 30, 2003; Revised Manuscript Received December 11, 2003
ABSTRACT: A series of aregic poly(ester amide)s (ar-PEALM) with ester to amide groups ratios (a:b)
ranging from 1:50 up to 1:2 were prepared from O-methyl-L-malic acid, 1,6-hexanediol, and 1,6-
hexanediamine. The ester linkage was incorporated in the poly(ester amide) chain using 6-aminohexyl-
pentachlorophenyl O-methyl-L-malate as comonomer in the polycondensation of bis(pentachlorophenyl)
O-methyl-L-malate with 1,6-hexanediamine. The polycondensation of the amino ester alone afforded
isoregic ir-PEALM (1:1) with both the amino alcohol and the malic units oriented in a unique manner
along the polymer chain. The composition of ar-PEALM was found to be close to that of the feed used for
polycondensation, with the diamine units incorporated in slight excess. The molecular weights of PEALM
roughly oscillated between 10 000 and 50 000. All the poly(ester amide)s were semicrystalline with Tm
decreasing with the content in ester groups from 168 to 144 °C and Tg falling down in parallel from 60
to 10 °C. The thermal decomposition of PEALM initiated around 260 °C and proceeded through a
mechanism involving an intramolecular amidolysis reaction with generation of N-substituted cyclic
malimides. PEALM poly(ester amide)s were easily degraded in water at pH 7.4, 37 °C, at a rate that
increased with the content in ester groups. The hydrolytic process was found to occur preferentially on
the ester linkages and to involve also the occurrence of intramolecular amidolysis reactions.
Sch em e 1
In tr od u ction
Polymers that are sensitive to moisture have at-
tracted great attention due to the practical advantages
that can be taken of their degradability in water. Poly-
(ester amide)s are polycondensates combining the amide
and ester groups in their backbone. Such hybrid nature
is expected to render polymers susceptible to hydrolytic
and biological degradation but retaining the good me-
chanical properties and processing behavior that dis-
tinguish their parent polyamides. Since Carothers1
synthesized for the first time in 1932 poly(ester amide)s
from diacids, diols, and diamines, a good number of
these polymers covering a wide variety of constitutions
have been described.2 Among them, special interest
presently exists for poly(ester amide)s made from
naturally occurring compounds for their potential as
biomedical materials. Within this group, poly(ester
amide)s made from R-amino acids3 and from carbohy-
drate deriving monomers4,5 constitute the two main
families currently under investigation.
1). The presence of these two methoxy groups makes
PEAT very sensitive to water. The constitution of poly-
(malaester amide)s are at halfway between poly(ester
amide)s deriving from succinic and tartaric acid, and
they are expected to show therefore intermediate prop-
erties between them. PEALM are here examined in this
regards as well as to evaluate the potential of naturally
occurring L-malic acid as an easily accessible monomer
for the preparation of poly(ester amide)s. The use of
L-malic as a diacidic monomer for the preparation of
aregic polymalamides has been recently reported.7
In this work we want to present the synthesis,
characterization, and properties of a series of poly(ester
amide)s obtained from L-malic acid, 6-aminohexanol,
and 1,6-hexanediamine, in which the hydroxy side group
of malic acid is protected as methyl ether. These poly-
(ester amide)s are called PEALM (a:b), a and b being
the molar content in ester and amide groups, respec-
tively. Some years ago we reported extensively on poly-
(tartaraester amide)s (PEAT), a family of semicrystal-
line polyamides made from 2,3-di-O-methyltartaric
acid.5 PEAT were proved to undergo hydrolysis under
physiological conditions at a rate highly depending on
the microstructure of the polymer.6 Poly(tartaraester
amide)s can be envisaged as deriving from poly(suc-
cinester amide)s in which two vicinal methoxy side
groups have been inserted in the diacidic moiety (Scheme
Exp er im en ta l Section
Ma ter ia ls a n d Meth od s. All chemicals were obtained
commercially from either Aldrich or Merck. They were analyti-
cal grade or higher and used without further purification.
Solvents to be used under anhydrous conditions were dried
by standard methods. Viscosities were measured in dichloro-
acetic acid at 25.0 ( 0.1 °C using an Ubbelohde microviscom-
eter. Infrared spectra were recorded on a FT-IR Perkin-Elmer
2000 instrument from films prepared by casting from trifluo-
roethanol (TFE). 1H and 13C NMR spectra were recorded at
room temperature on a Bruker AMX-300 spectrometer. Spec-
tra of intermediate compounds, monomers, and polymers were
taken in CDCl3, either pure or containing 10% of trifluoroacetic
acid (TFA) or in pure TFA-d1. Sample concentrations about 1
and 5% (w/v) were used for 1H and 13C analysis, respectively,
* Corresponding author: e-mail sebastian.munoz@upc.es.
10.1021/ma035108o CCC: $27.50 © 2004 American Chemical Society
Published on Web 02/25/2004

2068 Regan˜o et al.
Macromolecules, Vol. 37, No. 6, 2004
Sch em e 2
Compounds I, II, III, and VI were obtained as previously
described elsewhere. The synthesis of polyamide P6MLM was
performed as recently reported.7
O-Meth yl-L-m a lic An h yd r id e (IV). This compound was
obtained by treating O-methyl-L-malic acid (II) with Ac2O
following the method described in the literature for the
synthesis of 2,3-di-O-methyl-L-tartaric acid.10
IR (νmax, cm-1): 3006; 2942; 2840; 1872; 1796; 1465; 1410;
1
1235; 1134; 1078; 1037. H NMR (CDCl3): δ, ppm: 2.94 (dd,
CH2, 1H); 3.30 (dd, CH2, 1H); 3.63 (s, OCH3, 3H); 4.44 (dd,
CH, 1H). 13C NMR (CDCl3): δ, ppm: 35.76 (CH2); 59.09 (OCH3);
75.16 (CH); 167.55 (CH2COOCO); 169.57 (CHCOOCO).
N-ter t-Bu toxyca r bon yl-3-m eth oxy-4-oxo-5-oxy-11-a m i-
n ou n d eca n oic Acid (VII). Compounds VI (6.5 g, 0.030 mol)
and IV (3.9 g, 0.030 mol) were dissolved in dried THF (50 mL),
and the mixture was left under stirring at 60 °C for 6 h. The
residue left after rotavaporating the reaction mixture was
dissolved in AcOEt and washed with water. The organic layer
was dried on anhydrous Na2SO4 and evaporated to a slightly
yellowish oily, which crystallized in the freezer to afford
compound VII in 70% yield.
1H NMR (CDCl3): δ, ppm: 1.36 (m CH2CH2CH2CH2O, 4H);
1.44 (s, (CH3)3C, 9H); 1.48 (m, CH2CH2NH, 2H); 1.65 (m, CH2-
CH2O, 2H); 2.83 (m, CH2COOH, 2H); 3.11 (m, CH2NH, 2H);
3.50 (s, OCH3, 3H); 4.18 (m, CH2OCO, 2H); 4.21 (m, CH, 1H).
13C NMR (CDCl3): δ, ppm: 26.20, 25.31 (CH2CH2CH2CH2O);
28.43 (C(CH3)3); 28.14 (CH2CH2O); 29.80 (CH2CH2NH); 37.32
(CH2COOH); 39.97 (CH2NH); 59.10 (OCH3); 65.32 (CH2OCO);
75.20 (CH); 79.8 (C(CH3)3); 157 (OCONH); 167 (OCO); 171
(COOH).
P en ta ch lor oph en yl N-ter t-Bu toxyca r bon yl-3-m eth oxy-
4-oxo-5-oxy-11-a m i-n ou n d eca n oa te (VIII). To a solution of
compound VII (3 g, 0.0086 mol) and pentachlorophenol (2.75
g, 0.0103 mol) in AcOEt (40 mL), a solution (30 mL) of
dicyclohexylcarbodiimide (DCCI) (2.12 g, 0.0103 mol) in the
same solvent was added dropwise. The mixture was left under
stirring at room temperature for 5 days, filtered and concen-
trated to half volume, and left in the freezer. The precipitated
dicylcohexylurea was filtered out, and the operation was
repeated several times until complete removal of this com-
pound. The final solution was evaporated to render VIII in
nearly 100% yield.
1H NMR (CDCl3): δ, ppm: 1.38 (m, CH2CH2CH2CH2O, 4H);
1.45 (s, C(CH3)3, 9H); 1.50 (m, CH2CH2NH, 2H); 1.71 (m, CH2-
CH2O, 2H); 3.12 (m, CH2NH, 2H); 3.12 (m, CH2COOPcp, 2H);
3.51 (s, OCH3, 3H); 4.19 (m, CH2OCO, 2H); 4.3 (dd, CH, 1H).
13C NMR (CDCl3): δ, ppm: 26.31, 25.55 (CH2CH2CH2CH2O);
28 (C(CH3)3); 28.5 (CH2CH2O); 29.91 (CH2CH2NH); 37.30
(CH2COOPcp); 40.38 (CH2NH); 59.20 (OCH3); 65.40 (CH2OCO);
75.60 (CH); 79.09 (C(CH3)3); 127.58; 131.91; 132.07; 143.58
(aromatics); 156.01 (OCONH); 166.22 (COOPcp); 170.84 (OCO).
P en ta ch lor oph en yl-3-m eth oxy-4-oxo-5-oxy-11-a m in ou n -
d eca n oa te Hyd r obr om id e (IX). To a stirred solution of
compound VIII (7.5 g, 0.013 mol) in AcOH (70 mL) at room
temperature was added 33% HBr-AcOH (36 mL). The excess
of acid was evaporated to a solid residue that was dispersed
in ethyl ether and recovered by filtration. Crystallization in
THF/AcOEt rendered compound IX in 60% yield.
and tetramethylsilane was used as an internal reference. 13C
NMR measurements were made under proton decoupling
1
conditions at 75.48 MHz. For typical H NMR and 13C NMR
spectra, the numbers of accumulated scans were 64 and 300-
1500, respectively.
Hygroscopicity was measured according to Mori et al.8 in a
100% relative humidity atmosphere at 18 °C using disks of
12 mm diameter. These disks were dye-cut from approximately
200 µm thick films, which were prepared by casting from TFE.
Solubility essays were made following the method reported by
Braun.9 Differential scanning calorimetry (DSC) was carried
out using a Perkin-Elmer Pyris 1 instrument calibrated with
indium. 2-5 mg samples placed under a nitrogen atmosphere
were heated at a rate of 10 °C min-1 and cooled at varying
rates in the 30-200 °C temperature range. Thermogravimetric
measurements (TGA) were performed under a nitrogen atmo-
sphere with a Perkin-Elmer TGA6 thermobalance at heating
rates of 10 or 20 °C min-1. Hydrolysis experiments were
carried out on 12 mm diameter and 250 µm thick disks, which
were prepared as before. DSC analysis showed that all samples
displayed a similar level of crystallinity. Disks were separately
incubated in 0.1 M Na2HPO4-NaH2PO4 buffer solution at pH
7.4, 37 °C. After the selected incubation period of time, the
remaining solid was recovered, rinsed with water, and dried
to constant weight under vacuum. Analysis of the residual
polymer was made by viscosimetry, FTIR, and 1H NMR
spectroscopy. The residue recovered from the incubating
solution upon evaporation was analyzed by spectroscopy.
1H NMR (CDCl3): δ, ppm: 1.48 (m, CH2CH2CH2CH2O, 4H);
1.80 (m, CH2CH2NH3, 2H); 1.85 (m, CH2CH2O, 2H); 3.11 (m,
CH2NH, 2H); 3.12 (m, CH2COOPcp, 2H); 3.52 (s, OCH3, 3H);
4.19 (m, CH2OCO, 2H); 4.3 (t, CH,1H); 7.97 (t, NH3, 3H). 13C
NMR (CDCl3): δ, ppm: 25.95, 25.11 (CH2CH2CH2CH2O); 27.22
(CH2CH2O); 28.16 (CH2CH2NH); 37.27 (CH2COOPcp); 39.98
(CH2NH3); 59.19 (OCH3); 65.35 (CH2OCO); 75.60 (CH); 127.58;
131.91; 132.07; 143.58 (aromatics); 166.22 (COOPcp); 170.84
(OCO). Elemental analysis (C17H21O5Cl5Br): Found: C, 35.19%;
H, 3.705%; Cl, 30.45%; Br, 14.49%. Calculated: C, 35.41%; H,
3.67%; Cl, 30.74%; Br, 13.86%.
Gen er a l P r oced u r e for P olym er iza tion . To a vigorously
stirring solution of compound X and Et3N in N,N′-dimethyl-
formamide (DMF), a mixture of compounds III and IX in the
selected ratio was slowly added. The reaction was left to
proceed at 60 °C for 1 week. The polymer was precipitated by
adding ethyl ether and recovered by filtration. Purification of
Syn th esis of Mon om er s a n d P olym er s. The route of
synthesis leading to PEALM is depicted in Schemes 2 and 3.

Macromolecules, Vol. 37, No. 6, 2004
Poly(ester amide)s 2069
Sch em e 3
ar-PEALM was performed by reprecipitation from TFE with
ether. For the preparation of ir-PEALM (1:1), compound IX
was added to a solution of Et3N in DMF, and the reaction
mixture was worked up as before.
arises from the two possible orientations that both the
amino alcohol, and the diacid units can take up in the
polymer chain. Conversely, polycondensation of com-
pound IX led to the isoregic poly(ester amide) ir-PEALM
showing an unique orientation for the chemical blocks.
On the other hand, polycondensation of 1,6-hexane-
diamine (X) with the pentachlorophenyl-O-methyl L-
malate (III) produced the aregic polymalamide P6MLM
with the diacid units oriented at random. This poly-
amide was used in this work for only comparative
purposes. The synthesis, characterization, and proper-
ties of P6MLM have been previously described in full
detail.7
Resu lts a n d Discu ssion
Syn th esis a n d Ch a r a cter iza tion . It is well-known
that polycondensation of amino alcohols with diacids
usually fails to produce poly(ester amide)s with prede-
termined ester-to-amide ratios due to the much lower
reactivity of the hydroxyl group relative to the amine
group. To circumvent such shortcoming, we have de-
signed a synthesis strategy based on the use of the
activated amino acidic comonomer IX, in which the ester
linkage was previously inserted (Scheme 2). The start-
ing products for the preparation of compound IX were
L-malic acid (I) and 6-amine-1-hexanol (V). The synthe-
sis is based on the regiospecific reaction of N-tert-
butoxycarbonyl-6-aminohexanol (VI) with the O-methyl-
L-malic anhydride (IV), the latter compound being
obtained straightforwardly by dehydration of the O-
methyl-L-malic acid (II). The hydroxy side group of
L-malic acid was converted into methoxy in order to
prevent any undesirable side esterification reaction
leading to cross-linked polycondensates. The methyl
group was the preferred one for this purpose since its
small size is expected to cause moderate perturbation
in chain packing and therefore minimum depression in
crystallinity. This blocking method has proven to be
highly efficient previously in the preparation of a fair
number of polyamides derived from tartaric acid11 and
other higher aldaric acids.12
The results obtained in the polycondensations leading
to poly(ester amide)s are compared in Table 1. The
content in monomeric units of the resulting copolymers
1
was accurately determined by H NMR. It can be seen
that although the composition of the polymer is close
to that present in the feed from which they are formed,
some noticeable deviations arise due to a slight defi-
ciency in the incorporation of compound IX in the
growing chain. As a consequence, the ester:amide ratios
in the resulting poly(ester amide)s are in general lower
than expected. On the other hand, the elemental
compositions determined by combustion analysis were
generally in agreement with the chemical formula of the
poly(ester amide) with the composition in comonomers
adjusted according to NMR data and considering that
a certain amount of water was retained by the polymer.
Such absorbed water is difficult to remove by the
habitual drying methods, and its presence was assessed
by NMR spectroscopy. This situation is usually found
in methoxy-substituted polyamides and poly(ester
amide)s derived from carbohydrates. The polymerization
yields oscillated between 80 and 90%, and intrinsic
viscosities of the poly(ester amide)s ranged between 0.9
and 0.3 dL g-1, with the polymer size decreasing with
According to Scheme 3, the polycondensation of
mixtures of III, IX, and X led to aregic poly(ester
amide)s ar-PEALM, with ester-to-amide ratios (a:b)
which could be roughly adjusted by the diamine X to
compound IX ratio that is chosen for feeding the
reaction. The aregic nature of these (polyester amide)s

2070 Regan˜o et al.
Macromolecules, Vol. 37, No. 6, 2004
Ta ble 1. P olycon d en sa tion Da ta of P oly(ester a m id e)s P EALM (a :b)
feed composition
polymer compositiona elemental analysisb
poly(ester amide)
[IX]/[X]/[III]
(a:b)
[IX]/[X]/[III]
(a:b)
C (%)
H (%)
N (%)
yield (%)c
85
[η]d (dL g-1
)
ar-PEALM (1:50)
2.6/48.7/48.7
1:38
1:20
1:12
1:9
2/49/49
1:50
55.21
(55.69)
56.10
(55.68)
55.27
(55.67)
55.45
(55.66)
56.14
(55.61)
55.68
(55.50)
54.40
8.65
(8.60)
8.39
(8.58)
8.67
(8.56)
8.45
(8.55)
8.63
(8.47)
8.51
(8.35)
7.79
11.38
(11.57)
11.17
(11.35)
11.38
(11.14)
10.74
(10.94)
10.56
(9.76)
11.80
(8.30)
5.77
0.60
ar-PEALM (1:25)
ar-PEALM (1:17)
ar-PEALM (1:12)
ar-PEALM (1:5)
ar-PEALM (1:2)
ir-PEALM (1:1)
5.0/47.5/47.5
8.2/45.9/45.9
11.0/44.5/44.5
25.0/37.5/37.5
50.0/25.0/25.0
100/0/0
4/48/48
6/47/47
8/46/46
21/40/39
42/29/29
100/0/0
1:25
1:17
1:12
1:5
83
90
85
80
80
85
0.93
0.70
0.50
0.35
0.30
0.30
1:4
1:2
1:2.4
1:1
1:1
(55.46)
(8.17)
(5.88)
a
b
Determined by 1H NMR. In parentheses, values calculated for the polymer with the experimentally found compositions and with
0.5 mol of added water. c Polycondensation yields referred to the isolated and purified polymer. Intrinsic viscosities measured in
d
dichloroacetic acid at 25 ( 0.1 °C.
cm-1 with an intensity that increases proportional to
the a:b ratio. A detailed inspection of this peak reveals
the occurrence of a weak shoulder at 1710 cm-1 which
becomes most apparent for ar-PEALM (1:2) but that is
almost inappreciable for ir-PEALM. A similar observa-
tion was reported in the FTIR analysis of poly(ester
amide)s derived from tartaric acid5a and therein ex-
plained as due to the existence of a second minor
population of ester groups differing from the major one,
either in conformation or in the manner in which the
chains are associated with each other in the solid state.
The 1H and 13C NMR spectra of the poly(ester amide)s
and polyamide P6MLM are shown in parts a and b of
1
Figure 2, respectively. It should be noticed that H NMR
spectra of ar-PEALM increase in complexity with the
content of the polymer in ester groups. Four new signals
attributed to CH, COOCH2, OCH3, and OCH2CH2
protons are seeing with increasing intensity although
they do not show splitting due to orientation effects.
Apparently, the length of the hexamethylene segment
mitigates any possible magnetic influence between
neighboring malic moieties. This means that the de-
scription of the microstructure of these poly(ester
amide)s in terms of dyads defined by the relative
orientation of either two consecutive diacid units or two
consecutive oxyaminohexamethylene units is not achiev-
able. It can be reasonably assumed, however, that these
poly(ester amide)s are essentially aregic polymers, since
this is the microstructure reported to be present in the
polymalamides obtained by condensation of III with X.
F igu r e 1. Compared FTIR spectra of poly(ester amide)s
PEALM and polyamide P6MLM.
The thermal behavior of PEALM has been character-
ized by DSC. In Figure 3a the heating and cooling DSC
traces obtained from PEALM (1:12) are reproduced for
the content in ester groups. This range of viscosities
would roughly correspond to number-average molecular
weights between 50 000 and 7000 if comparison with
data reported for poly(ester amide)s obtained from
6-aminohexanol and di-O-methyl-L-tartaric acid was
made.5b
The chemical constitution of PEALM was confirmed
by both FTIR and NMR spectroscopy. The FTIR spectra
of the poly(ester amide)s are compared in Figure 1
where the spectrum of the aregic poly(hexamethylene
L-O-methylmalamide) has been included for comparison.
As expected, the spectra of PEALM are similar, all
showing absorption bands consistent with the chemical
formula of the polymer. The presence of the ester
linkage is brought out by the peak appearing at 1740
illustration. All PEALM show melting and crystalliza-
tion peaks at heating and cooling, respectively, as well
as sharp Tg inflection points at the second heating
traces. The thermal data afforded by the DSC analysis
are listed in Table 2. In Figure 3b, the Tg and Tm values
for the whole series are plotted against the percentage
of the polymer in ester groups, illustrating the trend
followed by the two transition temperatures with com-
position. Both temperatures were observed to decrease
with the content in ester groups. It is worthy to mention
that, as represented in Figure 3b, PEALM (1:2) showed
two endothermic peaks which could be interpreted to
correspond to the melting of two populations of crystals
differing in size. Since no similar effects were observed
for other compositions, comparison of PEALM (1:2) to

Macromolecules, Vol. 37, No. 6, 2004
Poly(ester amide)s 2071
F igu r e 3. (a) DSC of ar-PEALM (1:12). (b) Variation of Tg
and Tm in PEALM as a function of the content in ester groups.
associated with the presence of the methoxy side group.
Such a group not only constitutes an anchoring point
for water molecules but also hinders the close packing
of the polymer chains, making the material more
accessible to water diffusion. This would explain that,
for the same ester:amide ratio, PEAT (with two methoxy
groups in the diacid unit) are more hygroscopic than
PEALM (with only one methoxy group per repeating
unit).
Th er m a l Degr a d a tion . The thermal stability of both
aregic and isoregic PEALM has been examined by
thermogravimetry by means of both dynamical and
isothermal experiments. The TGA traces of ir-PEALM
(1:1) and ar-PEALM (1:25) representing the remaining
weight as a function of temperature at a heating rate
of 10 °C min-1 and as a function of time under heating
at 250 °C are shown in Figure 5. The thermal decom-
position parameters evaluated for the whole set of poly-
(ester amide)s studied in this work as well as for the
polyamide P6MLM are given in Table 2.
The onset of decomposition of ar-PEALM was ob-
served in the dynamical traces between 275 and 280
°C, the upper limit being very close to the onset
temperature of polymalamide P6MLM, which is 284 °C.
In all cases decomposition was found to occur in two
stages, the first one taking place above 300 °C and the
second one above 460 °C with weight losses of 40-60%
in both of them. The isothermal treatment at 250 °C
initially produced an abrupt loss of weight in the
polymer, which after a few minutes stabilized in a
plateau for an approximately constant value of about
70% of the initial mass. The steady state was found to
be achieved faster as the content of the polymer in ester
F igu r e 2. 1H NMR (a) and 13C NMR (b) spectra of PEALM.
Copolymer compositions indicated in (a).
the other PEALMs in this regard is uncertain. The trend
curve for Tm shown in Figure 3b was drawn for the
higher Tm value found for PEALM (1:2); a minimum
would result instead for this polymer if the lower had
been chosen. On the other hand, the crystallinity of
PEALM, estimated by the melting enthalpy, follows the
same trend as the melting temperature.
The solubility of PEALM has been evaluated in a
series of solvents of different nature, and the results
are compared in Table 2. It appears that all of them
are insoluble in water but soluble in hydrogen bond
breaking solvents as TFE, TFA, and formic acid. The
solubility in nonacidic organic solvents depends on both
the polarity of the solvent and the amide:ester ratio of
the poly(ester amide). Thus, they are soluble in chloro-
form and dimethyl sulfoxide for ester contents higher
than 20% whereas they remain insoluble in ethanol for
the whole range of compositions. These poly(ester
amide)s are highly hydrophilic polymers as it is reflected
in their sorption of moisture (Figure 4), which arrives
to be more than 20% for PEALM (1:2). The water uptake
increases with the content in ester groups which could
be due in part to the fact that both Tg and crystallinity
diminish in that sense. However, the high affinity for
water displayed by these polymers should be directly

2072 Regan˜o et al.
Macromolecules, Vol. 37, No. 6, 2004
Ta ble 2. Th er m a l P r op er ties a n d Solu bilities of P oly(ester a m id e)s P EALM (a :b)
thermal properties
solubilityc
a
a
b
b
b
poly(ester amide) Tg
Tm
0Td
ITd
IITd
∆Wc H2O
EtOH
CHCl3 DMSO
HCOOH
TFE
TFA
P6MLM
68
179 (59)
166 (32)
167 (24)
159 (18)
158 (19)
150 (14)
145 (13)
144 (43)
284
280
280
279
272
269
275
261
316 (69) 466 (19)
315 (95) 474 (5)
311 (65) 466 (13)
312 (62) 473 (8)
311 (63) 464 (13)
303 (65) 462 (15)
301 (40) 475 (0)
286 (25) 458 (8)
92
ar-PEALM (1:50)
ar-PEALM (1:25)
ar-PEALM (1:17)
ar-PEALM (1:12)
ar-PEALM (1:5)
ar-PEALM (1:2)d
ir-PEALM (1:1)
58
52
51
38
43
26
10
86
86
86
81
81
81
47
-
-
-
-
-
-
-
-
-
-
-
-
(
(
-
+
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
(
+
(
+
+
+ +
+ +
+ +
(
+
+ +
+ +
a
b
Glass (Tg) and melting temperatures measured by DSC in °C; In parentheses, the melting enthalpy in J g-1
.
Onset (0Td) and first
(ITd) and second (IITd) stage decomposition temperatures measured by TGA in °C; in parentheses, the % remaining weight of the initial
mass at each decomposition stage. c (++) soluble at room temperature; (+) soluble on warning; (+-) slightly soluble; (-) insoluble.
c Remaining weight upon heating at 250 °C for 10 min. This PEALM showed another melting peak at 112 °C.
d
F igu r e 4. Absorbed moisture as a function of exposure time
for aregic poly(ester amide)s ar-PEALM, aregic poly(taraester
amide) PEAT (1:2) (data taken from reference), and aregic
polymalamide P6MLM.
groups increased. The regioregular poly(ester amide) ir-
PEALM (1:1) displayed the same pattern of behavior
as the aregic ones with changes taking place at signifi-
cantly lower temperatures and entailing larger weight
losses, indicative of its lower thermal stability.
Decomposition at higher temperatures (above 450 °C)
is known to happen by extensive scission of main chain
C-C bonds to produce volatile compounds and carbon-
aceous residues and ashes. On the other hand, the
changes taking place around 300 °C are usually associ-
ated with specific reactions between functional groups.
To get insight into the molecular mechanism operating
in the decomposition of these poly(ester amide)s at the
lower temperature decomposition stage, the products
resulting upon heating at 250 °C the poly(ester amide)s
ar-PEALM and ir-PEALM (1:1) were analyzed by both
FTIR and NMR spectroscopy. In Figure 6, the IR spectra
of the residual polymer and the released gases resulting
in the degradation of ir-PEALM (1:1) are compared to
that registered from the original polymer. The most
apparent changes are those perceived in the carbonyl
region, where the ester band initially present at 1740
cm-1 completely disappeared, and a new intense peak
F igu r e 5. TGA traces of ir-PEALM (1:1) (top) and ar-PEALM
(1:25) (bottom). The isothermal traces were recorded at 250
°C.
3000 cm-1 broadened and intensified at the same time
as it shifted to higher wavenumber values, indicating
that hydroxyl groups should have been formed in the
thermal decomposition. Similar changes were observed
for ar-PEALM (1:5) although in this case the disappear-
ance of the ester band was not complete.
at 1705 cm-1 together with a weak one at 1780 cm-1
,
both of them indicative of the presence of cyclic imide
structures, are brought out. The intensity of the amide
bands also diminished in the spectrum of the residual
polymer and became almost vanished in the spectrum
of the gases. On the other hand, the absorption above
The NMR analysis confirmed the results of the IR
analysis and provided further information to support
unambiguously the interpretation of the decomposition
mechanism. The 1H NMR spectra of the initial ir-
PEALM (1:1), the residual polymer after heating at 250

Macromolecules, Vol. 37, No. 6, 2004
Poly(ester amide)s 2073
F igu r e 6. FTIR of ir-PEALM (1:1): (a) pristine sample, (b)
residue after heating at 250 °C for 1 h, and (c) released gases.
°C for 60 min, and the gases released at increasing times
of heating are compared in Figure 7. The presence of
imide units and CH2OH end groups in the degraded
polymer (Figure 7a) is evidenced by signals appearing
at 4.81 ppm (two doublets, CHimide), 3.82 ppm (singlet,
OCH3 imide), 3.10-3.50 ppm (two doublets, CH2 imide), and
4.10 ppm (end CH2OH).
F igu r e 7. 1H NMR spectra of ir-PEALM (1:1): (a) original
and residual disk; (b) released gases at increasing heating
times, as indicated.
The spectra of the gases (Figure 7b) are all the same
regardless of the heating time, and they correspond to
almost pure N-(6-hydroxyethyl)-2-methoxy-L-malimide.
The decomposition reaction compatible with spectros-
copy data is depicted in Scheme 4. The process can be
reasonably described as consisting of an intramolecular
amidolysis of the ester group which is favored by the
formation of stable cyclic N-substituted malimide. It
should be noticed that a similar reaction could also be
feasible for diamide sequences with formation in this
case of N-(6-aminoethyl)-2-methoxy-L-malimide. Such
reaction has been reported to occur in the degradation
of polytartaramides5c and polymalamides.7 The fact that
the stability of PEALM is observed to decrease with the
content in ester groups is consistent with the higher
reluctance of the amide linkage to the nucleophilic
attack.
Sch em e 4
mides, and it has been also shown that their degrada-
tion in water is depending on the regicity of the
poly(ester amide) chain.6 The effect of inserting ester
linkages into the backbone of P6MLM is expected to
have a similar effect on hydrodegradability of these
polyamides. The changes taking place in PEALM and
P6MLM with time by effect of water pH 7.4 at 37 °C
are shown in Figure 8 for a variety of ester:amide ratios.
The enhancing effect of the ester group on the
hydrodegradability of PEALM is made apparent by
comparing the plots among them and to those obtained
for polyamide P6MLM. Both the viscosity and the
Hyd r olytic Degr a d a tion . It has been recently re-
ported that polyamides derived from L-malic acid and
aliphatic diamines are scarcely degraded by water.7
Despite the favorable effects exerted by the hydrophilic
electron-withdrawing methoxy side group, the polya-
mide chain continues to be too resistant to water attack.
The same occurs for polytartaramides in spite that they
have two methoxy groups per repeating unit.13 On the
contrary, poly(tartaraester amide)s are much more
susceptible to hydrolysis than their parent polytartara-

2074 Regan˜o et al.
Macromolecules, Vol. 37, No. 6, 2004
F igu r e 9. FT-IR of ir-PEALM subjected to hydrolytic degra-
dation at 70 °C for 6 days: (a) pristine sample, (b) residual
disk, and (c) residue from the incubating solution.
F igu r e 8. Decay of viscosity and remaining weight of poly-
(ester amide)s ar-PEALM and polymalamide P6MLM with
incubation time.
remaining weight of the initial polymer were found to
decrease for all PEALM with the time of incubation, a
trend that appeared to be more pronounced as the
content in ester groups increased. After 20-30 days of
incubation both magnitudes became stable, indicating
that degradation apparently ceased. The fact that the
decay in remaining weight is slightly more pronounced
than in viscosity is probably due to leaching of degraded
fragments of large size. FTIR and NMR spectroscopies
were used to explain these observations and to disclose
the degradation mechanism operating in the presence
of water. Figure 9 shows the FTIR spectra of the original
ir-PEALM (1:1), the residual polymer disk, and the
residue recovered from the incubating solution. For this
study, the temperature was risen to 70 °C in order to
enhance the degradation rate and facilitate the analysis
of the degradation products without lengthening exces-
sively the incubation time. Whereas almost insignificant
changes are detected in the degraded polymer, the
degradation products transferred to the solution contain
a considerable amount of imide groups. Furthermore,
the broad band appearing at 3200-3400 cm-1 indicates
F igu r e 10. 1H NMR spectra of ir-PEALM after incubation
for 6 days at 70 °C: (a) original disk, (b) residual polymer,
and (c) residue left by the incubating solution upon evapora-
tion.
1
the extensive presence of hydroxyl end groups. The H
NMR spectra of the same samples are compared in
Figure 10, which corroborated the conclusions drawn
from the IR analysis. Similar results were obtained in
the degradation study of ar-PEALM (1:5).
It seems therefore that degradation of PEALM in
water involves mainly the splitting of the ester groups
with formation of hydroxyl-ended fragments and cyclic
imide groups. The generation of such structures may
occur by intramolecular cyclic amidolysis, as it happens

Macromolecules, Vol. 37, No. 6, 2004
Poly(ester amide)s 2075
in the thermal degradation, or it can be the result of
the dehydration of carboxylic-ended fragments that were
previously generated by hydrolysis. These two possibili-
ties are depicted in Scheme 4.
Refer en ces a n d Notes
(1) Carothers, W. H.; Hill, J . V. J . Am. Chem. Soc. 1932, 54, 1566.
(2) Timmermann, R. Polyesteramides. In Biopolymers; Doi, Y.,
Steinbuechel, A., Eds.; Wiley-VCH: New York, 2003; Vol. 4,
pp 315-328.
(3) (a) Paredes, N.; Rodr´ıguez-Gala´n, A.; Puiggal´ı, J .; Peraire,
C. J . Appl. Polym. Sci. 1998, 69, 1537. (b) Rodr´ıguez-Gala´n,
A.; Paredes, N.; Puiggal´ı, J . Curr. Trends Polym. Sci. 2000,
5, 41.
(4) (a) Molina, I.; Bueno, M.; Galbis, J . A. Macromolecules 1995,
28, 3766. (b) Molina, I.; Bueno, M.; Zamora, F.; Galbis, J . J .
Polym. Sci., Polym. Chem Ed. 1998, 36, 67.
(5) (a) Alla, A.; Rodr´ıguez-Gala´n, A.; Mart´ınez de Ilarduya, A.;
Mun˜oz-Guerra, S. Polymer 1997, 38, 4935. (b) Villuendas, I.;
Iribarren, J . I.; Mun˜oz-Guerra, S. Macromolecules 1999, 32,
8015. (c) Regan˜o, C.; Mart´ınez de ilarduya, A.; Iribarren, J .
I.; Mun˜oz-Guerra, S. J . Polym. Sci., Polym. Chem. Ed. 2000,
38, 2687.
(6) Villuendas, I.; Molina, I.; Regan˜o, C.; Bueno, M.; Mart´ınez
de Ilarduya, A.; Galbis, J . A.; Mun˜oz-Guerra, S. Macromol-
ecules 1999, 32, 8033.
(7) Regan˜o, C.; Alla, A.; Mart´ınez de Ilarduya, A.; Mun˜oz-Guerra,
A. J . Polym. Sci., Polym. Chem. Ed. 2004, 42, 1566.
(8) Mori, T.; Tanaka, R.; Tanaka, T. J . Polym. Sci., Polym. Phys.
Ed. 1975, 13, 1633.
(9) Braun, D.; Chedron, H.; Keren, W. Praktikum der Makro-
molekularen Organishen Chemie; Alfred Huthig Verlag:
Heidelberg, 1966.
(10) Felner, I.; Schenker, K. Helv. Chim. Acta 1970, 53, 754.
(11) Bou, J . J .; Rodr´ıguez-Gala´n, A.; Mun˜oz-Guerra, S. Biodegrad-
able Optically Active Polyamides. In Polymeric Materials
Encyclopedia; Salomone, J . C., Ed.; CRC Press: Boca Raton,
FL, 1996; Vol. 1, p 561.
(12) Varela, O.; Orgueira, H. A. Adv. Carbohydr. Chem. Biochem.
1999, 55, 137.
Con clu d in g Rem a r k s
L-Malic acid has been used for the first time to
produce poly(ester amide)s.The method designed for this
synthesis has proven to be useful for obtaining both
aregic and isoregic polymers. As expected from their
intermediate constitution, thermal properties, water
affinity, and solubility of these poly(ester amide)s are
in between polymalamides and poly(tartarester amide)s.
Although PEALM are well stable to heating, they
degrade hydrolytically much faster than both tartaric
acid and malic acid deriving polyamides. The molecular
mechanism operating in the degradation process seems
to be the same as for poly(tartaraester amide)s with
ester hydrolysis and cyclic imide formation being in-
volved in both cases. The access to these novel poly(ester
amide)s fills the gap existing between unsubstituted
poly(succinester amide)s and double substituted poly-
(tartarester amide)s and contributes to enrich the
assortment of methoxy-substituted polyamides and
poly(ester amide)s that can be produced from aldaric
acids deriving monomers.
(13) Ruiz-Donaire, P.; Bou, J . J .; Mun˜oz-Guerra, S.; Rodr´ıguez-
Gala´n, A. J . Polym. Sci. 1995, 58, 41.
Ack n ow led gm en t. Financial support for this work
was provided by MCYT with Grants MAT99-0578-CO2-
02 and MAT02-04600-CO2-02.
MA035108O