Page 1 of 9
European Journal of Applied Sciences – Vol. 11, No. 2
Publication Date: April 25, 2023
DOI:10.14738/aivp.112.14193.
Matin, M. A., Chowdhury, M. N., Khatun, A. A., Nasrin, J., & Mahmud, A. (2023). Synthesis and Characterization of Stimuli- Responsive Poly (Maleic Acid-Co-Malic Acid-Co-Propane-1,2-Diol-Co-Adipic Acid). European Journal of Applied Sciences, Vol -
11(2). 482-490.
Services for Science and Education – United Kingdom
Synthesis and Characterization of Stimuli-Responsive Poly
(Maleic Acid-Co-Malic Acid-Co-Propane-1,2-Diol-Co-Adipic Acid)
Md. Abdul Matin
Department of Materials Science and Engineering,
University of Rajshahi, Rajshahi-6205, Bangladesh
Monishita Nuzhat Chowdhury
Department of Materials Science and Engineering,
University of Rajshahi, Rajshahi-6205, Bangladesh
Anjuman Ara Khatun
Department of Materials Science and Engineering,
University of Rajshahi, Rajshahi-6205, Bangladesh
Jahanara Nasrin
Department of Materials Science and Engineering,
University of Rajshahi, Rajshahi-6205, Bangladesh
Abu Mahmud
Department of Materials Science and Engineering,
University of Rajshahi, Rajshahi-6205, Bangladesh
ABSTRACT
Poly (Maleic acid-co-Malic acid-co-Propane-1,2-diol-co-Adipic acid) was
synthesized using the Dean-Stark apparatus. Stoichometric proportions of maleic
acid, malic acid, adipic acid and propane-1, 2-diol were taken in a round bottom
flask along with a trace amount of anhydrous ferric chloride which worked as
catalyst and o-xylene used as reaction medium. The total system was heated at
temp. 135-1400C for about 5 hours. Molecular weight, FTIR-spectra, thermo
gravimetric and elemental analysis, solubility tests in common organic solvents,
melting point and degradation tests were used for the characterization of the
synthesized co-polyester. At room temperature (300C) the hydrolytic degradation
study of the co-polyester in solutions of various pH values (pH=1.15-4.40) showed
that, there has no degradation of the co-polyester, but it gradually degraded in
solutions of pH values 6.50-8.99. This showed its stimuli-responsive characteristics.
The co-polyester almost 70% degraded in normal soil within 30 days indicating its
biodegradable nature. If satisfactory toxicity result of the synthesized co-polyester
is observed, it might be usable as an enteric coating material.
Keywords: Polymer, Stimuli-Responsive, Co-Polyester, Biodegradable, Enteric Coating.
Page 2 of 9
483
Matin, M. A., Chowdhury, M. N., Khatun, A. A., Nasrin, J., & Mahmud, A. (2023). Synthesis and Characterization of Stimuli-Responsive Poly (Maleic
Acid-Co-Malic Acid-Co-Propane-1,2-Diol-Co-Adipic Acid). European Journal of Applied Sciences, Vol - 11(2). 482-490.
URL: http://dx.doi.org/10.14738/aivp.112.14193.
INTRODUCTION
Stimuli-responsive polymers are special type of high-performance polymers that undergoes
conformational change in response to different pH, which can be used in drug delivery (Galev
& Mattiasson, 2010; Wolcott & Fischenich, 2014; Siniaguine & Kachiguina,2015). Such
materials can be sensitive to a number of factors such as humidity, pH, temperature, the
wavelength or an electrical or magnetic field and can respond in various ways, like altering
color or transparency, becoming conductive or permeable to water or changing shape (Muller
& Keck,2004;Saltzman & Torchilin,2008;Bertend & Leoux,2011).Usually, slight changes in the
environment are sufficient to induce large changes in the polymer’s behaviors (Bawa et
al.,2009). Currently, the most important use for Stimuli-responsive polymers in biomedicine is
for specifically site-targeted drug delivery, insecticides, pesticide and fertilizer carriers as well
as nontoxic surgical implant materials. As the advent of timed-release pharmaceuticals,
scientists have been faced with the problem of finding ways to deliver drugs to a particular site
in the body without having them first degrade in the highly acidic stomach environment.
Researchers have many paths to use smart polymers to control the release of drugs until the
delivery system has reached the desired target. In this respect different linear polyesters
(Heller,1980; Gliding &Reed,1979; Asano et al.,1985), such as poly (lactic acid), poly (glycolic
acid), co-polyesters of lactic acid and glycolic acid are being used for controlled drug
formulations (Rosenberg et al.,1983; Graham,1978;Devi et al.,1985). keeping the same view
ahead, we have attempted to synthesize a polymer from maleic acid, malic acid, adipic acid,
propane 1,2-diol. This paper we report its synthesis, characterization and hydrolytic
degradation.
MATERIALS AND METHODS
Materials
Maleic acid, malic acid,adipic acid propane-1,2-diol and were A.R. grade products from E.
Merck, Germany which were the monomers and all were used as such. Anhydrous ferric chloride
from E. Merck,India used as catalyst.
Synthesis of Polymer
Maleic acid, malic acid, adipic acid in mole combinations 1,1.25,1 respectively and 3 mole of
propane-1,2-diol alltogether with anhydrous FeCl3 as catalyst (approximately 0.4% of the total
weight) were taken in a 500ml round bottom flask which was connected to a dean & stark
apparatus for eliminating the byproduct water azeoteropically with O-xylne. Here malic acid
were taken greater than 1 mole which will discuss in result and discussion section.The reaction
mixture heated at 135-140°C for 4-5 hours. When elimination of water subsided, the reaction
mixture was heated for an additional 1 hours under the same condition. The polymer was sticky
at room temperature, which was stored in a vacuum desicator.
Characterization
Determination of Molecular Weight:
Molecular weights of polymer were determined by the following end group analysis and
viscosity method. End group analysis depends on the total number of molecules present in a
system hence; the number average molecular weight was obtained. Then this number average
molecular weight was applied to find out the values of ‘K’ and ‘a’ to determine the molecular
weight by viscosity method.
Page 3 of 9
Services for Science and Education – United Kingdom 484
European Journal of Applied Sciences (EJAS) Vol. 11, Issue 2, April-2023
A. End Group Analysis: Procedure: At first 1:3 mixture of toluene & ethanol was made. A
precisely’ weighed quantity (less than lgm) of the polyester sample was dissolve in
toluene & ethanol mixture. This was titrated against 0.1 N alcoholic potassium
hydroxide solution using phenolphthalein as indicator. The end point was the
appearance of a slightly pink color.
B. Viscosity Method: Different fractions of polymer sample were taken and for each
fraction, the molecular weight was determined by end group analysis. For each fraction,
a number of solutions of different known concentrations (gm/ml) of the polymer sample
were made. The solvent flow time t„ and the solution How time t for different
concentrations is measured using Oswald viscometer. For each concentration, the
corresponding reduced viscosity was calculated and graphed (reduced viscosity vs.
concentration) which was extrapolated to zero concentration. The common ordinate
intercept of their graph’s viscosity gave the intrinsic.
Finally, the logarithms of the intrinsic viscosities of these polymers were plotted against the
logarithms of their molecular weight and a linear curve was obtained. The ordinate intercept
and the slope of the curve gave the values of‘K’ and ‘a’ respectively.
Hydrolytic Test:
A. In Acid Medium: Hydrochloric acid was used for this purpose. Polyester sample was
cut in to suitable slices and were placed in solutions of different pH values of separate
conical flasks. Conical flasks were sealed with rubber cork. After suitable time interval
its pH was measured up to 10 hours with pH-meter Corning-700 at room temperature
(30°C). Results were plotted in graph and compared with blank acid solutions.
B. In Basic Medium: Sodium carbonate was used for this purpose. Polyester sample was
cut in to suitable slices and were placed in solutions of different pH values of separate
conical flasks. Conical flasks were sealed with rubber cork. After a suitable time interval
its pH was measured up to 10 hours with pH-meter Corning-700 at room temperature
(27°C). Results were plotted in graph and compared with blank sodium carbonate
solutions.
RESULT & DISCUSSION
Synthesis
The co-polyester was synthesized by di-carboxylic acid namely Maleic acid, Malic acid, adipic
acid and propane -1, 2-diol. The obtained sample was slightly transparent, light yellow color
and sticky at room temperature. The co-polyester is produced by poly-condensation reaction
among the monomers in the presence of anhydrous FeCl3.Synthesis and characterization of
malic acid-propane 1,2-diol copolyester have already been published and it has been reported
that about 20% carboxyl groups of malic acid react with its own hydroxyl groups. Theoretically
50% of the carboxyl groups should take part in the reaction, but it happens so probably because
of steric effect. For this reason, we took 1.25 mole of malic acid (Bakr et al.,2000). The reaction
equation and the expected structure of the co-polyester would be as shown below:
Page 4 of 9
485
Matin, M. A., Chowdhury, M. N., Khatun, A. A., Nasrin, J., & Mahmud, A. (2023). Synthesis and Characterization of Stimuli-Responsive Poly (Maleic
Acid-Co-Malic Acid-Co-Propane-1,2-Diol-Co-Adipic Acid). European Journal of Applied Sciences, Vol - 11(2). 482-490.
URL: http://dx.doi.org/10.14738/aivp.112.14193.
Characterization
Solubility:
Solubility of this co-polyester in various organic solvents at the ambient temperatures is
different. From the investigation it can be seen that acetone, ethyl acetate, mixed solvent
(toluene: ethanol, 1:3), are good solvents. Chloroform, acetic acid, benzene are poor solvents
and diethyl ether, xylene, toluene, ethyl alcohol, rectified (RS) carbon-di-sulphide, water,
phenol, carbontetra chloride are non-solvents for this co-polyester
Molecular Weight Determination:
A. By End Group Analysis: The molecular weights (Mn) of fractionated polymers were
determined by end group analysis and they were 18800,14700,12000, 9900 and 7400
respectively.
B. By Viscosity Method: By calculating k and a value from intrinsic viscosity whose
magnitude are 4.3x10-3 &.75 respectively,we obtained molecular weight by viscosity
method were 19920,16932,13657,11084,&7750. . Molecular weight obtained by end
group analysis and viscosity method of different fractions of polymer are given in
following table which show that molecular weight obtained by viscosity method (Mv) is
greater than that end group analysis (Mn).
Page 5 of 9
Services for Science and Education – United Kingdom 486
European Journal of Applied Sciences (EJAS) Vol. 11, Issue 2, April-2023
Table: Characterization of synthesized co-polyester molecular weight by end group
analysis & viscosity method.
Polymer
sample
Maleic acid Malic acid Adipic acid Propane- 1,2-diol
Mol. wt. by end
group analysis, Mn
Mol. wt.by viscosity
method,
Mv
I
II
III
IV
V
1
1.25 1 3
18800
14700
12000
9900
7400
19920
16932
13657
11084
7750
IR Spectra:
The band representing the -OH group at the region 3100-3200 cm-1 in the spectrum of the diol
is almost absent in the spectrum of the polymer. The band representing the >C=0 group at the
1725-1735 cm-1 region of the spectrum of the di-acid shifted to 1710-1740 cm-1 and a new band
representing the ester linkage appeared at the 1263.37 cm-1 region of the spectrum of the
polymer (Bakr et al.,2006). All these indicate the reaction between -OH and -COOH groups
forming ester linkages.
Fig-1.:IR-spectra of Poly (Maleic acid-co-Malic acid-co-Propane-1,2-diol- co- Adipic acid ).
Hydrolytic Test:
In acid and base: Fig-2 shows that this co-polyester is intact in acid solutions (1.15-4.10 pH)
and degraded in basic solutions (6.50-8.99 pH).
Page 8 of 9
489
Matin, M. A., Chowdhury, M. N., Khatun, A. A., Nasrin, J., & Mahmud, A. (2023). Synthesis and Characterization of Stimuli-Responsive Poly (Maleic
Acid-Co-Malic Acid-Co-Propane-1,2-Diol-Co-Adipic Acid). European Journal of Applied Sciences, Vol - 11(2). 482-490.
URL: http://dx.doi.org/10.14738/aivp.112.14193.
sensitive’ or ‘smart’, these polymers experience rapid changes in their microstructure from a
hydrophilic to a hydrophobic state triggered by small changes in the environment. The changes
are reversible; therefore, the polymer is capable of returning to its initial state as soon as the
trigger is removed. Stimuli may occur internally (e.g., a change in pH in certain organs or
diseased states, a change in temperature or the presence of specific enzymes or antigens).
External stimuli include magnetic or electric fields, light, ultrasound etc. The co-polyester is
expected to be usable as enteric coating material on tablets for controlled and sustained release
of drugs.
So, this polyester might be tried as an enteric coating materials on the tablets containing
medicine.From the soil degradation study the polymer loses weights gradually after 56 days of
it mixes with the soil indicating the total soil degradation of the polymer under investigation.So
it may be use for coating material on insecticide as this polyester is biodegradable,have no
harmful effect on environment. This process is a trial and error method so long term research
needed.Due to short time I cannot carry the full process.But this process is continue in our lab
for its betterment.
Acknowledgement
The authors would like to thanks University of Rajshahi,Bangladesh for providing facilities to
carry out the research and the Ministry of National Science and Technology,Bangladesh for
their financial support. They also thank the BCSIR, Dhaka and Centre for Advanced Research in
Sciences (CARS), University of Dhaka, Bangladesh for supporting characterization of the
samples.
References
Asano, M., Yoshida, M., Maetsu, I.,Imai,K.,Tooru,M.,Yuasa,H.,Yamanaka,H.&Suzuki,K.(1985).Macromol.Chem.Rapid
Commun.6, 509.
Bakr, M.A., Hasan, K.,Islam,M.A.,Khatun,S.,Mannan,M.A.andAra,K.S.(2006) .J.Polym.Mater.23 ,217-222.
Bakr, M.A., Islam, M.A., Karim, M.A. and Ahmed,M.. (2000) .J.Polym.Mater.17 ,467-472.
Bawa,P., Pillay1,V., Choonara ,Yahya E. and Toit, Lisa C du. (2009) “Stimuli-responsive polymers and their
applications in drug delivery”1-2
Bertrand N, Leroux JC.; Leroux (2011). "The journey of a drug carrier in the body: an anatomo-physiological
perspective". Journal of Controlled Release. 161 (2): 152–63.
Devi,K.S. and Vasudevan,P.(1985).JMS.Rev.Macromol.Chem.Phys.C 25(3),315.
Galaev, Igor; Mattiasson, Bo, eds. (2010). Smart Polymers: Applications in Biotechnology and Biomedicine. CRC
Press. ISBN 1439858160. Retrieved 2013-03-20.
Gliding,D.K. & Reed,A.M.(1979).Polymer 20, 1459.
Grsham,N.B.(1978).J.British Polym. 10,260.
Heller,J.(1980). Biomaterials 1, 50.