Synthesis, structural study and hydrolytic degradation of copolymer based on glycolic acid and bis-2-hydroxyethyl terephthalate

The current demand for environmentally degradable copolymers has initiated the use of novel degradable copolyesters. One of them is a copolyester based on poly(ethylene terephthalate-co-glycolic acid) (PET-GLA). The copolymer was synthesized by the melt reaction of bis-2-hydroxyethyl terephthalate (BHET) with glycolic acid (GLA) oligomers in the presence of Sb₂O₃ as a catalyst.Hydrolytic degradation of the copolymer was carried out in two buffered solutions at 45 °C: degradation was studied by incubating samples in powder form, in a concentrated solution from 30 to 150 days.The copolymer before and after degradation was characterized by means of different analytical techniques. ¹H and ¹³C NMR spectroscopy was used to confirm the incorporation of glycolide units in PET chains and to observe the structure and decomposition of the novel polyester. The thermal properties and morphology before and during the degradation were studied by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis for determining melting points as well as melting and decomposition temperatures of investigated copolyester.     

Synthesis and structural study of copolymers of l-lactic acid and bis(2-hydroxyethyl terephthalate)

Poly(ethylene terephthalate)-poly(lactic acid) (PET-PLLA) copolyesters were synthesized by the melt reaction of bis(2-hydroxyethyl terephthalate) (BHET) with l-lactic acid oligomers (OLLA) in the presence of SnCl₂, H₂O-p-toluene sulfonic acid, H₂O catalytic system. The ¹H and ¹³C NMR studies confirm the incorporation of lactate units in PET chains after reaction. Copolyesters containing nearly equimolar terephthalate/lactate ratio are not completely random and present some block-copolymer character, while the microstructure of PET-rich copolyesters is a random one. Due to a longer PET sequence length, the latter exhibit a melting point close to 210 °C while the other ones are amorphous. SEC/MALDI-TOF MS off-line coupling was used to obtain the absolute average molar masses of the copolyesters. The results indicate that the conventional polystyrene calibration method leads to a strong overestimation of PET-PLLA molar masses, while the determined by NMR is much closer to the SEC/MALDI value.     

Synthesis and characterization of amorphous poly(ethylene terephthalate) copolymers containing bis[4-(2-hydroxyethoxy)phenyl]sulfone

Poly(ethylene terephthalate) copolymers (abbreviated as PETS) that contain bis[4-(2-hydroxyethoxy)phenyl]sulfone (BHEPS) were prepared from dimethyl terephthalate (DMT), ethylene glycol (EG) (5-95%) and BHEPS (5-95%). The compositions and microstructures of the copolyesters were determined by ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy, respectively. The thermal behaviors were studied over the entire range of copolymer compositions, using X-ray analysis, differential scanning calorimeter (DSC) and thermogravimetric analysis (TGA). The molecular weights, optical characteristics and tensile properties of these polymers were also determined. Experimental results indicated that the copolymers had a random microstructure. The intrinsic viscosities of the copolymers ranged from 0.65 to 0.69 dL/g. The copolyesters with BHEPS of <10 mol% were crystallizable, whereas the copolyesters with BHEPS of ?10 mol% were amorphous. Incorporating BHEPS affected the glass-transition temperature (T_g) values of those polymers, from about 81 °C for PETS₅ to 126 °C for PETS₉₅. The optical transmissions exceeded 86% for λ = 400 nm for all of the amorphous polyesters. The tensile modulus and strength of the copolyesters increased with BHEPS. However, they also became brittle and their elongation at break decreased.     

Study on poly(oxybenzoate-p-trimethylene terephthalate) copolymer

This study examined copolymers synthesized from poly(trimethylene terephthalate) (PTT) and p-acetoxybenzoic acid using solution proton nuclear magnetic resonance (NMR) spectroscopy. Proton NMR spectra showed that these p-oxybenzoate (POB)/PTT copolyesters were almost random copolymers because the preference factor of POB bonded to another POB unit in these copolyesters is close to 1.0 with a POB content between 20 and 80 mol%.The melting and crystallization behaviors of these copolyesters were studied by differential scanning calorimetry (DSC). In the heating DSC scan of the POB rich composition, the endothermic peak is weaker because the enthalpy of fusion decreased due to a melting transition from a crystalline to anisotropy liquid state. Thermogravimetric analysis results indicated that the decomposition temperature (T_d) increased with POB content. The crystalline morphology of the copolyester was further investigated with a polarized optical microscope, indicating that the POB/PTT copolyesters with 60 mol% POB are highly anisotropic in the liquid state.     

Synthesis, characterization and biodegradable studies of 1,3-propanediol based polyesters

A series of biodegradable polyesters were synthesized from dicarboxylic acids and 1,3-propanediol catalyzed by transestrification polycondensation reaction in the bulk. The structure, average molecular weights and physical properties of the resulting aliphatic polyesters were characterized by ¹H NMR, FT-IR, solution viscosity, GPC, DSC and TGA. Homopolyesters show higher degree of crystallinity, melting and thermal stability in comparison to copolyesters. The biodegradability of the polyesters was determined by monitoring the normalized weight loss of polyester films with time in phosphate buffer (pH 7.2) without and with Rhizopus delemar lipase at 37 °C. The rate of enzymatic degradation of homopolyesters follows the path PPSu > PPAd > PPSe. PPSe did not show significant weight loss in presence of enzyme which may be due to its highest degree of crystallinity and melting point compared to the PPSu, PPAd and copolyesters. In the soil burial degradation polyester sample showed severe surface degradation by the attack of microorganism.     

Poly(ethylene terephthalate) copolymers containing 5‐nitroisophthalic units. I. Synthesis and characterization

Poly(ethylene terephthalate‐co‐5‐nitroisophthalate) copolymers, abbreviated as PETNI, were synthesized via a two‐step melt copolycondensation of bis(2‐hydroxyethyl) terephthalate and bis(2‐hydroxyethyl) 5‐nitroisophthalate mixtures with molar ratios of these two comonomers varying from 95/5 to 50/50. Polymerization reactions were carried out at temperatures between 200 and 270 °C in the presence of tetrabutyl titanate as a catalyst. The copolyesters were characterized by solution viscosity, GPC, FTIR, and NMR spectroscopy. They were found to be random copolymers and to have a comonomer composition in accordance with that used in the corresponding feed. The copolyesters became less crystalline and showed a steady decay in the melting temperature as the content in 5‐nitroisophthalic units increased. They all showed glass‐transition temperatures superior to that of PET with the maximum value at 85 °C being observed for the 50/50 composition. PETNI copolyesters appeared stable up to 300 °C and thermal degradation was found to occur in two well‐differentiated steps. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1934–1942, 2000     

New polymer syntheses. CIX. Biodegradable,alternating copolyesters of terephthalic acid,aliphatic dicarboxylic acids,and alkane diols

Copolyesters with an alternating sequence of terephthalic acid and aliphatic dicarboxylic acids were prepared with three different methods. First, dicarboxylic acid dichlorides were reacted with bis(2‐hydroxyethyl)terephthalate (BHET) in refluxing 1,2‐dichlorobenzene. Second, the same monomers were polycondensed at 0–20 °C in the presence of pyridine. Third, dicarboxylic acid dichlorides and silylated BHET were polycondensed in bulk. Only this third method gave satisfactory molecular weights. Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry revealed that the copolyesters prepared by the pyridine and silyl methods might have contained considerable fractions of cyclic oligoesters and polyesters despite the absence of transesterification and backbiting processes. The alternating sequences and thermal properties were characterized with ¹H NMR spectroscopy and differential scanning calorimetry measurements, respectively. In agreement with the alternating sequence, all copolyesters proved to be crystalline, but the crystallization was extremely slow [slower than that of poly(ethylene terephthalate)]. A second series of alternating copolyesters was prepared by the polycondensation of silylated bis(4‐hydroxybut‐ yl)terephthalate with various aliphatic dicarboxylic acid dichlorides. The resulting copolyesters showed significantly higher rates of crystallization, and the melting temperatures were higher than those of the BHET‐based copolyesters. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3371–3382, 2001     

Biodegradable poly(sebacic anhydride-co-caprolactone) multi-block copolymers: Synthesis, characterization, crystallinity and crystalline morphology

Biodegradable poly(sebacic anhydride-co-caprolactone) (PSA-co-PCL) multi-block copolymers were prepared by condensation of acylated PSA and PCL prepolymers with different weight ratios. The homopolymer and copolymers were characterized by ¹H-NMR, gel permeation chromatography (GPC), differential scanning calorimeter (DSC) and atom force microscope (AFM). ¹H-NMR and GPC has indicated the formation of PSA-co-PCL multi-block copolymers, in which PSA and PCL segments are randomly distributed. The incorporation of PCL segments into the molecule chains even at a content of 20 wt% could significantly decrease the molecular weight distribution of the copolymer and increase its weight average molecular weight, as compared with PSA homopolymer. DSC has revealed that the melting temperature and degree of crystallinity for both SA and CL components are strongly composition dependent, implying the hindrance effect of the two components on crystallinity of each other. AFM observation has shown the difference in crystalline structures between PSA and PCL phases in the copolymers. In-vitro degradation tests performed at 37 °C in PBS buffer solution (pH 7.4, 0.1 M) have demonstrated the acceleration of degradation rate of the sample with increasing SA content in the copolymer.     

Synthesis and characterization of biodegradable aliphatic copolyesters with poly(ethylene oxide) soft segments

A series of multiblock poly(ether-ester)s based on poly(butylene succinate) (PBS) as the hard segments and hydrophilic poly(ethylene oxide) (PEO) as the soft segments was synthesized with the aim of developing degradable polymers which could combine the mechanical properties of high performance elastomers with those of flexible plastics. The aliphatic poly(ether-ester)s were synthesized by the catalyzed two-step transesterification reaction of dimethyl succinate, 1,4-butanediol and α,ω-hydroxyl terminated poly(ethylene oxide) (PEO, = 1000 g/mol) in bulk. The content of soft PEO segments in the polymer chains was varied from about 10 to 50 mass%. The effect of the introduction of the soft PEO segments on the structure, thermal and physical properties, as well as on the biodegradation properties was investigated. The composition and structure of these aliphatic segmented copolyesters were determined by ¹H NMR spectroscopy. The molecular weights of the polyesters were verified by gel permeation chromatography (GPC), as well as by viscometry of dilute solutions and polymer melts. The thermal properties were investigated using differential scanning calorimetry (DSC). The degree of crystallinity was determined by means of DSC and wide-angle X-ray scattering. A depression of melting temperature and a reduction of crystallinity of the hard segments with increasing content of PEO segments were observed. Biodegradation of the synthesized copolyesters, estimated in enzymatic degradation tests in phosphate buffer solution with Candida rugosa lipase at 37 °C was compared with hydrolytic degradation in the buffer solution. The weight losses of the samples were in the range from 2 to 10 mass%. GPC analysis confirmed that there were significant changes in molecular weight of copolyesters with higher content of PEO segments, up to 40% of initial values. This leads to conclusion that degradation mechanism of the poly(ether-ester)s based on PEO segments occurs through bulk degradation in addition to surface erosion.     

Influence of melting conditions on the thermal behaviour of poly(l-lactic acid)

The influence of melting temperature and time on the thermal behaviour of poly(l-lactic acid) (PLLA) was studied with differential scanning calorimetry (DSC). Different melting conditions were investigated at temperature ranging from 200 to 210 °C, and for time from 2 to 20 min. For lower-molecular-weight PLLA, a single exothermic peak could be observed at cooling rate of 2 °C/min, after melted at different conditions. The obtained peak temperature and degrees of crystallinity dramatically increased with an increase of melting temperature or time. During subsequent heating scans, double melting peaks could be observed, which were significantly affected by prior melting conditions. The degradation of this material in the melt and the melt/re-crystallization mechanism might be responsible for the observations above. Apart from double melting, double cold crystallization peaks were observed during heating traces for this material after fast cooling (20 °C/min) from the melt. Prior melting conditions could significantly influence the cold crystallization behaviour. The competition between the crystallization from the nuclei remained after cooling, and that from spontaneous nucleation might be responsible for the appearance of double peaks. Additionally, the influence of melting conditions on the thermal behaviour of PLLA was dependent on the initial molecular weight.     

Synthesis, crystallization and hydrolysis of aromatic-aliphatic copolyester: Poly(trimethylene terephthalate)-co-poly(l-lactic acid)

In this study, poly(trimethylene terephthalate)-co-poly(l-lactic acid) (PTT-co-PLLA) copolyesters with different compositions were synthesized by melt polycondensation. The crystal morphologies of PTT-co-PLLA copolyesters were investigated with polarized light microscope (PLM). It was found that PTT-co-PLLA copolyesters exhibited banded spherulites with smaller band spacing at the same degree of super-cooling compared with PTT homopolymer. The PLLA segments in those copolyesters ranged from 0 to 28.4 mol% and did not form crystals during crystallization. Hydrolysis study on PTT homopolymer and PTT-co-PLLA copolyesters was carried out in buffer solutions. PTT-co-PLLA copolyesters represented pronounced hydrolytic degradation, which increased with the content of lactyl units. And it was concluded that degradation of PTT-co-PLLA was mainly attributed to the scission of PLLA segments.     

Synthesis and degradation of novel photocrosslinkable aromatic copolyanhydrides

Novel photocrosslinkable degradable aromatic copolyanhydrides have been prepared by melt-polycondensation from 1,6-bis(p-carboxyphenoxy)hexane (CPH) and 4,4′-(sebacoyldioxy)dicinnamic acid (CSC) derived from 4-hydroxycinnamic acid and sebacoyl chloride. FT-IR and ¹H NMR confirmed the copolymer structures. These copolymers were subsequently irradiated with a 400 W high-pressure mercury lamp (λ > 28 nm) to produce crosslinked materials. The gel yields of copolymers increased with increasing irradiation time and/or CSC contents. The photocrosslinking significantly enhanced the tensile strength at break (σ_b) and tensile modulus (E), but decreased the elongation at break (ε_b). The crosslinked CPH/CSC(25/75) film with gel content of 90% showed the highest σ_b of 28 MPa and E of 742 MPa. The degradation characteristics of copolymer films was investigated in a phosphate buffer solution (pH 7.2 and 10.0) at 37 °C by mass loss, molecular weight reduction by GPC and contact angle measurement. The induction period was detected for all copolyanhydrides, and the rate of degradation of copolyanhydrides was much higher than that of PCPH.     

On the explosive properties of 1H-benzotriazole and 1H-1,2,3-triazole

For 1H-benzotriazole, no explosive properties are observable, but the relative high exothermic decomposition energy of 1590 J/g should be kept in mind. Nevertheless, an endothermic melting barrier at 100 °C ensures safe handling at lower temperatures. For 1H-1,2,3-triazole, the exothermic decomposition energy is as high as 2600 J/g, but explosive properties are also not detectable. Therefore, both reagents are hazardous with regard to the exothermic decomposition potential and can be handled safely with precautions.     

New unsaturated polyesters as injectable drug carriers

New unsaturated polyesters of poly(fumaric acid-glycol-sebacic acid) copolymers and poly(maleic anhydride-glycol-sebacic acid) copolymers were prepared by melt polycondensation of the corresponding mixed monomers: sebacic anhydride, fumaric acid or maleic anhydride and glycol. Methyl-methacrylate (MMA) was used as crosslinker and dimer acid was used as thinner.In vitro studies showed that those copolymers are degradable in phosphate buffer at 37 °C and poly(fumaric acid-glycol-sebacic acid) has proper drug release rate as drug carriers. The biocompatibility of poly(fumaric acid-glycol-sebacic acid) copolymers under mice skin was also evaluated; macroscopic observation and microscopic analysis demonstrated that the copolymer is biocompatible and well tolerated in vivo. The injected poly(fumaric acid-glycol-sebacic acid) [molar ratio M_{fumaric acid}:M_glycol:M_{sebacic acid} = 1.75:2.20:0.25] containing 5% adriamycin hydrochloride (ADM) in the mice bearing Sarcoma-180 tumor exhibited a good antitumor efficacy. The volume doubling time (VDT) (18 ± 2.5 days) of the tumor growth by this treatment was longer than that (7 ± 0.9 days) by the subcutaneous injection of ADM.     

Lipase-catalyzed synthesis of biodegradable copolymer containing malic acid units in solvent-free system

This work is to explore a new route to synthesize functional polyesters bearing pendant hydroxyl groups. The approach is via biocatalyzed direct polycondensation. l-Malic acid, adipic acid and 1,8-octanediol were used as comonomers and lipase Novozym 435 as a biocatalyst. ¹H NMR studies on the structure of the products indicated that Novozym 435 was strictly selective for esterification of l-malic acid carboxyl groups while leaving the hydroxyl groups unchanged. The influences of the monomer feeding ratio, reaction temperature, and reaction time on the molecular weight of the products were investigated. By varying l-malic acid feed ratio in the total monomers from 0 to 20 mol%, the molecular weight (M_W) of the product changed from 9.5 kilo Dalton (kD) to 4.7 kD while reaction was held at 70 °C for 48 h. The maximum M_W could reach 7.4 kD at 80 °C when varying temperature between 70 and 90 °C if l-malic acid is 20 mol% and reaction time is 48 h. At 75 °C the M_W increased from 5.2 kD to 6.6 kD when reaction time was elongated from 48 h to 72 h. However, little change in M_W was observed at 80 and 85 °C when the reaction time was above 48 h. Thermal property of the copolyesters was studied by differential scanning calorimetry (DSC). Increasing the l-malic acid content in copolyesters resulted in melting temperature depression.     

Thermal degradation kinetics of the biodegradable aliphatic polyester, poly(propylene succinate)

The preparation of the biodegradable aliphatic polyester poly(propylene succinate) (PPSu) using 1,3-propanediol and succinic acid is presented. Its synthesis was performed by two-stage melt polycondensation in a glass batch reactor. The polyester was characterized by gel permeation chromatography, ¹H NMR spectroscopy and differential scanning calorimetry (DSC). It has a number average molecular weight 6880 g/mol, peak temperature of melting at 44 °C for heating rate 20 °C/min and glass transition temperature at −36 °C. After melt quenching it can be made completely amorphous due to its low crystallization rate. According to thermogravimetric measurements, PPSu shows a very high thermal stability as its major decomposition rate is at 404 °C (heating rate 10 °C/min). This is very high compared with aliphatic polyesters and can be compared to the decomposition temperature of aromatic polyesters. TG and Differential TG (DTG) thermograms revealed that PPSu degradation takes place in two stages, the first being at low temperatures that corresponds to a very small mass loss of about 7%, the second at elevated temperatures being the main degradation stage. Both stages are attributed to different decomposition mechanisms as is verified from activation energy determined with isoconversional methods of Ozawa, Flyn, Wall and Friedman. The first mechanism that takes place at low temperatures is auto-catalysis with activation energy E = 157 kJ/mol while the second mechanism is a first-order reaction with E = 221 kJ/mol, as calculated by the fitting of experimental measurements.     

Preparation, characterization, swelling and in vitro drug release behaviour of poly[N-acryloylglycine-chitosan] interpolymeric pH and thermally-responsive hydrogels

Novel biodegradable pH- and thermal-responsive interpenetrating polymer network (IPN) hydrogels were prepared for controlled drug delivery studies. The IPN hydrogels were obtained in mild aqueous acid media by irradiation of solutions of N-acryloylglycine (NAGly) mixed with chitosan, in the presence of glutaraldehyde as a crosslinking agent and using 2,2-dimethoxy-2-phenyl acetophenone as photoinitiator. These hydrogels were subjected to equilibrium swelling studies at different temperatures (25 °C, 37 °C and 45 °C) in buffer solutions of pH 2.1 and 7.4 (similar to that of gastric and intestinal fluids respectively). 5-Fluorouracil (5-FU) was entrapped in the hydrogels, and drug release studies carried out at 37 °C in buffer solutions at pH 2.1 and 7.4.     

Thermotropic liquid-crystalline copolyesters containing substituted phenylene terephthalate and ethylene terephthalate units

Three series of aromatic, thermotropic copolyesters, based on terephthalic acid (TA), ethylene glycol (EG), and another diol were prepared. The third monomer was selected from three different hydroquinones including, ethoxyhydroquinone (EHQ), phenylhydroquinone (PHQ), and hydroquinone itself (HQ). The amounts of the different hydroquinone terephthalate units were varied while the amounts of ethylene terephthalate units remained constant. The copolymers and terpolymers were characterized for solubility, for morphology by polarized light microscopy (PLM), for molecular weight by solution viscometry, and by NMR, DSC, and TGA. At elevated temperatures all samples, when observed by PLM, displayed the characteristic texture of a nematic phase. The melting transition temperatures, T_m, were found to vary from 255 to 325°C, while the 5 wt % loss temperatures, T_d, were found to vary from 330 to 440°C. The inherent viscosities varied from 0.6 to 1.9 dL/g. Increases in the HQ monomer content caused a decreased solubility and an increase in melting point. Copolymer compositions determined by NMR showed that only about one-half of the EG added was incorporated into the copolymers. © 1997 John Wiley & Sons, Inc.     

Wholly aromatic thermotropic liquid crystalline polyesters of 2-(α-phenylisopropyl)hydroquinone; copolymers with 1,1′-biphenyl-4,4′-diol and 2,6-dihydroxynaphthalene

Two series of new aromatic copolyesters have been synthesized and their properties including liquid crystallinity have been studied. The first series was synthesized by polymerizing mixtures of diacetates of 2-(α-phenylisopropyl)hydroquinone and 1,1′-biphenyl-4,4′-diol with terephthalic acid, and the second by polymerizing mixtures of diacetates of 2-(α-phenylisopropyl)hydroquinone and 2,6-dihydroxynaphthalene with terephthalic acid. These polyesters were characterized by differential scanning calorimetry, thermogravimetric analysis, wide-angle X-ray diffractomerty, and optical microscopy. The glass transition temperatures of the first series decrease from 167 to 138°C as one increases the content of the 1,1′-biphenyl-4,4′-diol unit to 50 mol %. The T_g values of the second series are slightly higher than those of the first series, and appear to be less dependent on their composition. The degree of crystallinity of the first series decreases rapidly by copolymerization, much faster than that of the second series. The melting points of the first series copolymers are significantly lower than those of the second series. All of the copolyesters reported in this investigation form nematic melts. The initial decomposition temperatures of the copolymers were higher than 450°C. It was confirmed that thermal stability of the homopolyester, PIBPL-1.00, containing the isopropylidene units is significantly improved when compared with that carrying benzylic hydrogens. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 2777–2786, 1997     

Synthesis and characterization of biodegradable poly(butylene succinate-co-butylene fumarate)s

A series of aliphatic biodegradable polyesters modified with fumaric residues was synthesized by transesterification in the melt of dimethyl succinate, dimethyl fumarate and 1,4-butanediol. The amount of unsaturation, originating from the fumaric acid residues in the polyesters chains was varied from 5 to 20 mol%. The molecular structure and composition of the polyesters were determined by ¹H NMR spectroscopy. The effects of the content of fumaric residues on the thermal and thermo-oxidative properties of the synthesized polyesters were investigated using differential scanning calorimetry (DSC) and thermogravimetric analysis. The degree of crystallinity was determined by DSC and wide angle X-ray scattering. The degrees of crystallinity of the unsaturated copolyesters were reduced, while the melting temperatures were higher in comparison to poly(butylene succinate). Biodegradation of the synthesized copolyesters was estimated in enzymatic degradation tests using a buffer solution with Rhizopus arrhizus lipase at 37 °C. Although the degree of crystallinity of the copolyesters decreases slightly with increasing unsaturation, the biodegradation is not enhanced suggesting that not only the chemical structure and molecular stiffness but also the morphology of the spherulites has an influence on the biodegradation properties. The highest biodegradability was observed for the copolyesters containing 5 and 10 mol% of fumarate units.