Preparation and characterization of biodegradable condensation polyimide

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Preparation and characterization of biodegradable condensation polyimide

Rong-Hsien Lin

a,*

_{, Wei-Ming Wang}

a

_{, Yi-Hung Chen}

b

_{, Tzung-Han Ho}

a

a_{Department of Chemical and Material Engineering, National Kaohsiung University of Applied Sciences, Kaohsiung, Taiwan} b_{Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan}

a r t i c l e i n f o

Article history:

Received 17 February 2012 Received in revised form 17 April 2012

Accepted 23 April 2012 Available online 12 May 2012

Keywords: Polyimide Biodegradable Condensation Poly(propylene fumarate)

a b s t r a c t

Various biodegradable polyimides (bio-PI) were successfully synthesized and investigated in this study. First, biodegradable oligomer, amine terminated poly (propylene fumarate) (PPF-NH2), was preliminarily

synthesized from poly (propylene fumarate) oligomer (PPF) and 3-chloropropylamine hydrochloride. The resulting PPF-NH2was subsequently used to react with equal mole ratio of 3,30,4,40-biphenyl

tetra-carboxylic dianhydride (s-BPDA) in the solvent to generate biodegradable poly (amic acid) (bio-PAA) through condensation reaction. Aﬁnal product of biodegradable polyimide (bio-PI) was successfully obtained by immidization of bio-PAA at a low-temperature (120C) under the vacuum condition. A 3-component system of biodegradable polyimide (3C-bio-PI) was also synthesized by replacing different level of PPF-NH2by 4,40-oxydianiline (4,40-ODA) in previously mentioned bio-PI.

The biodegradation characterizations of the various bio-PIs (including 3C-bio-PI) were performed with phosphate buffer solution. Morphological changes for the biodegraded surface of the various bio-PIﬁlms were apparent after buffer solution test. Mechanism of morphological changes for the biodegraded surface is also proposed in this work. The bio-PIﬁlm synthesized from equal mole ratio of PPF-NH2and

s-BPDA was biodegraded more quickly than the 3-component system of biodegradable PIﬁlm incorporated with 4,40-ODA.

The thermal properties of various bio-PIs are slightly inferior to those of regular PI; however, it is comparable to those of regular PI. The mechanical property of various bio-PIs is a little worse than that of regular PI, but it’s still in the same order of magnitude.

1. Introduction

Polyimides were widely used in electron devices, anti-soldiering

ink, and ﬂexible printed circuit boards because of its excellent

thermal stability, low dielectric constant, and excellent mechanical properties. The recovery and treatment of waste polyimide is a considerable environmental problem because of the increase in the consumption of polyimide. We attempted to introduce a biodegradable polymer segment into polyimide chain to circumvent this problem. Poly (propylene fumarate) (PPF) is a

well-known biodegradable polymer [1e6]. It is a linear unsaturated

polyester, and may undergo a self-polymerization through its

unsaturated carbonecarbon double bond. In addition, it may

undergo crosslinking reaction to be a biodegradable network through the introduction of curing agent, such as N-vinyl pyrroli-dinone or PPF-diacrylate (PPF-DA). The cross-linked biodegradable network exhibited excellent mechanical properties and low water

uptake; its mechanical intensity and biodegradation ability can be

controlled by tuning the ratio of PPF/PPF-DA[7,8].

Elmalak et al.[5]produced a biomedical material in application

of bone-bonding, based on PPF and MMA as a matrix, and calcium

phosphate and calcium carbonate as ﬁllers by controlling its

crosslinking density and molecular weight. This literature also

reported that PPF can be biodegraded to non-poisonous

compounds of propylene glycol and fumaric acid. This literature suggested that the di-ol functional groups on PPF molecule can react with other compounds to yield a PPF derivative with amine

groups on both ends (PPF-NH2). Consequently, we attempted to

synthesize PPF-NH2using the suggested method, as described in

this literature, and performed a condensational polymerization of

PPF-NH2with di-anhydrides to yield biodegradable polyimide.

Mikos et al.[6]presented a number of synthesis methods for PPF

in his patent, and subsequently presented a series of methods for

modifying PPF toﬁt the application in biomedical category. This

patent illustrated that PPF may undergo crosslinking reaction with curing agents to yield a biodegradable network. We referred to the synthesis methods, as stated in the patent, to synthesize PPF oligomer.

* Corresponding author. Tel.: þ886 7 3814526x5118; fax: þ886 7 3830674. E-mail address:[email protected](R.-H. Lin).

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Several researchers focused on modiﬁcation and crosslinking of

PPF [9e13]. Among them, Gangula et al. [13] attempted to

synthesize amine terminated PPF (PPF-NH2).

In addition, most studies related to biodegradable polyimide focused on bio-absorbable materials, such as poly (anhydride-co-imides). Among these materials, polyanhydride has a hydrophobic main chain and an easily hydrolyzed anhydride linkage, resulting in a number of characteristics with favorable biocompatibility and

obvious biodegradability. However, its relatively inferior

mechanical strength limits its applications. Consequently, Langer

et al. [14e16] developed a biodegradable polymer comprising

polyanhydrides and polyimides. Because most polyimides have the advantages of excellent mechanical properties and thermal stability, a biodegradable copolymer with high performance may be obtained by incorporating biodegradable polyanhydride with polyimide (referred to as poly (anhydride-co-imides)). They per-formed the degradation test for various constitutes of poly (anhydride-co-imides) at varying pH values to investigate the

effect of pH value on the degradation. Langer et al.[17]also found

that degradation of polyanhydride was attributed to surface-eroding.

Laurencin et al.[18e20]conducted a series of studies on poly

(anhydride-co-imides), such as performing in vitro biolysis test for the decomposed products of poly (anhydride-co-imides). Situa-tions of decomposed products of those copolymer were in situ observed by an environmental scanning electron microscopy (ESEM) during the period of degradation of poly (anhydride-co-imides); the cell growth situation was also observed when the cells

were exposed to the decomposed products of those copolymer[18].

In addition, in vivo biolysis test for poly (anhydride-co-imides) was

also presented[19]. The biocompatibility between poly

(anhydride-co-imides) and bone cells was further investigated. Subsequently, they presented the effect of decomposed products of previously stated copolymer on the bone cells, such as growth rate and

geomorphology of the bone cells[20].

To obtain various mechanical properties, Gopferich et al.[21]

copolymerized PEG with PLA to obtain a biodegradable copol-ymer, followed by tethering various imide moieties on the ends of copolymer chains. Based on a series of biolysis tests, these copolymers were applicable to tissue engineering.

Biodegradable polymers consisting of polyimide were subjected

to application in biomedical category[14e21]; few investigations of

biodegradable polyimide containing PPF with high mechanical performance were reported. Consequently, we attempted to incorporate biodegradable segment of poly (propylene fumarate) (PPF) into polyimide main chain. First, PPF oligomer was

synthe-sized. Subsequently, PPF-NH2 was synthesized by converting

di-functional group ofeOH on PPF oligomer to another di-functional

group ofeNH2. Finally, biodegradable polyimide was synthesized

using the synthesized PPF-NH2 to undergo condensational

poly-merization with di-anhydrides. Furthermore, the mechanical properties, thermal stability, and degradation phenomena of these biogradable polyimides (bio-PI) were investigated.

In addition, it is well-known that an aromatic polyimide can be produced by successively conducting an operation for poly-condensing an aromatic tetracarboxylic acid with an aromatic diamine, and another operation for converting the resulting poly-condensation product, that is, a polyamic acid (PAA), into the cor-responding polyimide resin. The converting process, that is, an imidization reaction, was performed by a dehydration procedure at

an elevated temperature of approximately 250e310 _C _[22,23]_.

However, polyimide containing PPF segments (bio-PI) cannot be prepared under such elevated temperatures; otherwise, PPF segment in PI chain will undergo thermal decomposition. This problem was also addressed in this work.

2. Experimental 2.1. Materials

The main chemical compounds used are fumaryl chloride

(Acros, U.S.A.), propylene glycol (Aldrich, Germany),

3-chloropropylamine hydrochloride (Aldrich, U.S.A.), 3,30,4,40

-biphe-nyltetracarboxylic dianhydride (s-BPDA; Chriskev, U.S.A.), and 4,40

-oxydianiline (4,40-ODA; Aldrich, U.S.A.). These chemical

compounds were used as purchased without further puriﬁcation;

and were used to synthesize PPF, PPF-NH2 and biodegradable

condensation PI (bio-PI). In addition, phosphate buffered saline

(SigmaeAldrich, U.S.A.) was used for the degradation test.

2.2. Instrumentation

The instruments and their operation conditions are as follows:

(1) Fourier Transform Infrared Spectrometer (FTIR; PerkineElmer

Spectrum ONE): FTIR spectrum was obtained on FTIR

spectrom-eter in an optical range of 400e4000 cm1by averaging 32 scans at

a resolution of 8 cm1, the sample of which was mixed with dried

KBr powder, and pressed into a pellet; (2) 1H NMR (Nuclear

Magnetic Resonance) spectra were obtained using an

Inova-500 MHz highﬁeld FT NMR spectrometer. Samples were dissolved

in DMSO-d6. Chemical shifts (

d

) in ppm are reported relative to

TMS; (3) the storage modulus (E0) was measured in DMA (Dynamic

Mechanical Analysis; Perkin_{eElmer, Pyris Diamond) over the}

temperature range of 25e460_{C at a heating rate of 10}_{C/min, and}

ﬁlm size 40 20 mm with a thickness of approximately 30

m

m were

used for measurement. The frequency and amplitude were set to 1 Hz and 0.2 mm, respectively; (4) thermal stability and the weight loss were measured by TGA (Thermal Gravimetric Analysis;

PerkineElmer, Diamond TG/DTA). Samples of approximately

5e10 mg in weight were placed in platinum pans and scanned in

a TGA at a heating rate of 20C/min. A stream of nitrogen at aﬂow

rate of 100 ml/min1was used to purge the TGA chamber; (5) the

morphology changes of samples before and after degradation were observed in SEM (Scanning Electron Microscopy; JEOL-5610); (6)

the reaction results were justiﬁed by thin layer chromatography

(TLC) with acetate/hexane (1/3 v/v%) as an eluent, and (7) the number average molecular weights were measured by GPC (Gel Permeation Chromatography; Waters 717 plus) with 3 columns of

7.8 _{300 mm Styragel HR 2-4 THF in series and waters 2414}

Refractive index detector. The sample of polymer was dissolved at

0.05e0.1 wt.% in THF. After sonication, the completely dissolved

solution wasﬁltered with a 0.45

m

m pore-sizedﬁlter and injected

into GPC, performed at aﬂow rate of 1 ml/min.

2.3. Synthesis and structure identiﬁcation of Poly(propylene

fumarate) (PPF)[6]

A three-neck reactor was charged with 8.88 g potassium

carbonate (K2CO3), 27 mL of ethyl acetate (EA), and 9.12 g propylene

glycol (PG) in a completely dissolved situation, and controlled at

0C under a nitrogen atmosphere. Another completely dissolved

solution of 6.12 g fumaryl chloride in 8 mL of EA solvent (mole ratio

of fumaryl chloride/propylene glycol/K2CO3¼ 1/3/1.5) was slowly

added into the reactor over a period of 2 h by means of a dropping

funnel. Subsequently, the resultant mixture was raised to 25C and

stirred further for another 5 h to a complete reaction situation at this temperature. The reacted mixture was slowly poured into a separation funnel, and washed sequentially with a large amount of cold de-ionic water and saline several times to remove the

un-reacted reagents (PG, K2CO3). An appropriate amount of

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(organic layer) to remove residual water, followed byﬁltration of magnesium sulfate from organic layer. Furthermore, EA was evap-orated by a rotary vacuum operation, and a pale-yellow liquid product, that is, di-(2-hydroxypropyl) fumarate (DHPF), was

obtained. Finally, DHPF was subjected to inter-esteriﬁcation for 1 h

at 160C under a reduced atmosphere of 2 cm Hg. A pale-yellow

viscous liquid of oligomer was subsequently obtained, that is, poly (propylene fumarate) (PPF). The overall reaction paths are

illustrated inScheme 1.

The synthesized PPF was characterized by its FTIR spectrum and

1_{H NMR spectrum. Shown in}_{Fig. 1}_{are some corresponding FTIR}

spectra of (a) propylene glycol, (b) fumaryl chloride, and (c) PPF

oligomer. Fig. 1 (c) indicates the characteristic absorptions at

3340 cm1 (_{OH), 1730 cm}1(C_{]O in ester linkage), 1640 cm}1

(C]C), and 1260 cm1₍_{O in ester linkage). These characteristic}

absorptions, nearly the same as those in patent[6], demonstrate

the structure of PPF. In addition, these stated characteristic absorptions result from cure (a) and cure (b), respectively, indi-cating that PPF oligomer was successfully synthesized from propylene glycol and fumaryl chloride.

The PPF oligomer was further veriﬁed by the1_{H NMR spectrum.}

An analysis of the1H NMR spectrum was conducted to identify the

structure of the PPF oligomer, as shown inFig. 2. Each chemical shift

was individually assigned and associated with the identiﬁed

hydrogen atoms in the PPF oligomer, the structure of which was inserted above the spectrum. It should be mentioned that

1.207_{e1.244 ppm are attributed to the hydrogen atoms of the}

methyl groups (indicated as a) within repeat unit (inner site);

however, 1.063e1.075 ppm are attributed to the hydrogen atoms of

the methyl groups (indicated as h) on both ends of oligomer (outer

side). Chemical shifts of 4.285e4.298 ppm and 3.990e3.997 ppm

are attributed to the hydrogen atoms of the methylene groups (indicated as f and g) on both ends of oligomer. Because PPF is an oligomer with various degrees of polymerization, hydrogen atoms on methyl group or on methylene group have various positions in PPF main chain, resulting in a small shift of a number of hydrogen peaks for the same group. Those chemical shifts demonstrate that PPF oligomer was successfully synthesized from propylene glycol and fumaryl chloride.

In addition, molecular weight of the synthesized PPF oligomer

was measured by GPC, as shown inFig. 3. A number of separated

peaks were observed, resulting from various degrees of polymeri-zation in the same pot of PPF oligomer. Each peak was individually

assigned and associated with the identiﬁed degree of

polymeriza-tion in the PPF oligomer. Degree of polymerizapolymeriza-tion was 1e4. The

average number molecular weight was calculated from the GPC spectrum as 347 g/mol, that is, average degree of polymerization was 1.7.

2.4. Synthesis and structure identiﬁcation of amine terminated PPF

(PPF-NH2)

A three-neck reactor was charged with 3.25 g of 3-chloropropylamine hydrochlorid (CPH), 1.518 g of triethyl amine (TEA), and 25 mL of DMSO in a completely dissolved situation, and controlled at ambient temperature under a nitrogen atmosphere. Another completely dissolved solution of 2.34 g of previously synthesized PPF in 15 mL of DMSO solvent (mole ratio of PPF/CPH/

TEA¼ 1/2.5/1.5) was slowly added into the reactor over a period of

2 h using a dropping funnel. Subsequently, the resultant mixture was further stirred for another 24 h to a complete reaction situation at ambient temperature.

The reacted mixture was slowly poured into a separation funnel, and washed with a homogenously mixed solution of

Scheme 1. Synthesis paths of poly (propylene fumarate) (PPF).

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dichloromethane and de-ionic water (with 1:1 v/v%) several times. The upper layer containing DMSO, water, and un-reacted reagents (CPH, PPF, TEA) was discarded. An appropriate amount of magne-sium sulfate anhydrous was added in the collected lower layer

containing PPF-NH2 and dichloromethane to remove residual

water, followed by ﬁltration of magnesium sulfate from the

mixture. Furthermore, dichloromethane was evaporated by a rotary vacuum operation, and a yellow liquid product, that is, amine

terminated PPF (PPF-NH2) oligomer, was obtained. Structure of

PPF-NH2oligomer is shown asFig. 4.

The synthesized PPF-NH2was characterized by its FTIR

spec-trum and 1H NMR spectrum. Fig. 5 shows corresponding FTIR

spectra of (a) PPF, (b) 3-chloropropylamine hydrochloride, and (c)

PPF-NH2oligomer.Fig. 5(c) shows the characteristic absorptions at

3424 cm1(NH), 1730 cm1(C]O in ester linkage), 1642 cm1

(C]C), 1260 cm1 (O in ester linkage), and 1024 cm1 for

primary amine group, preliminarily demonstrating the structure of

PPF-NH2 oligomer. These stated characteristic absorptions result

from cure (a) and cure (b). In addition, a comparison ofFig. 5(b) and

Fig. 5(c) revealed that disappearing absorption bands ofeNH3þCl

at 3014 cm1were accompanied by the emerging absorptions of

primary amine group at 1024 cm1. This suggests that PPF-NH2

oligomer was successfully synthesized from PPF and

3-chloropropylamine hydrochloride. However, chemical structures

of PPF and PPF-NH2 are not easily discerned from FIIR spectra

because of their similar characteristic absorptions. Therefore, thin layer chromatography (TLC) was used to discern these structures. Results of TLC comparison revealed that the disappearing site of

PPF was accompanied by the emerging site for PPF-NH2, further

demonstrating that PPF-NH2 oligomer was successfully

synthe-sized from PPF and 3-chloropropylamine hydrochloride.

The synthesized PPF-NH2 was ﬁnally characterized by its 1H

NMR spectrum (not shown here). Chemical shifts of this

Fig. 2.1_{H NMR spectrum of poly (propylene fumarate) (PPF) oligomer.}

Fig. 3. GPC spectrum of synthesized poly (propylene fumarate) (PPF) oligomer.

Fig. 4. Structure of amine terminated PPF (PPF-NH2) oligomer.

Fig. 5. FTIR spectra of (a) PPF oligomer, (b) 3-chloropropylamine hydrochloride, and (c) PPF-NH2oligomer.

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