Novel chiral poly(ester-imide)s with different natural amino acids in the main chain as well as in the side chain: synthesis and characterization

Several novel chiral and potentially biodegradable poly(ester-imide)s (PEI)s bearing natural amino acids in the main chain as well as in the side chain were synthesized via direct polyesterification of N,N'-(pyromellitoyl)-bis-(L-tyrosine dimethyl ester) as a biodegradable optically active phenolic diol and synthesized diacids containing different amino acids and phthalimide group in the side chain. With the aim of tosyl chloride/pyridine/N,N-dimethylformamide (DMF) system as a condensing agent under conventional heating condition, the new optically active PEIs were obtained in good yield and moderate inherent viscosity up to 0.35 dL/g. The obtained polymers were characterized with FT-IR, ¹H NMR, X-ray diffraction (XRD), elemental and thermogravimetric analysis (TGA) techniques. They are readily soluble in amide type solvents such as N,N-dimethylacetamide, DMF, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, and protic solvents such as sulfuric acid. TGA showed that the 10% weight loss temperature in argon atmosphere was around 350 °C, which indicates that the resulting PEIs have a good thermal stability. The presence of amino acid in the PEIs architecture, not only cause to be used as optically active materials but also makes them susceptible to be biocompatible and biodegradable compound.     

Studies on synthesis and in vitro biodegradability of novel optically active nanostructure poly(ester-imide)s containing <Emphasis Type="SmallCaps">l</Emphasis>-phenylalanine and <Emphasis Type="SmallCaps">l</Emphasis>-isoleucine linkages

A series of biodegradable functional amino-acid-based poly(ester-imide)s (PEI)s were designed and synthesized by the direct polycondensation reaction of chiral diacids composed of naturally occurring α-amino acids with 4,4′-thiobis(2-tert-butyl-5-methylphenol) in the presence of tosyl chloride, pyridine, and N,N-dimethylformamide as a condensing agent. These new chiral polymers were characterized with respect to chemical structure and purity using specific rotation experiments, FT-IR, ¹H-NMR, techniques, and elemental analysis. The surface morphology of these polymers was investigated by field emission scanning electron microscopy. The result indicated nanoscale morphology of the obtained polymers. Thermal stability and the weight loss behavior of the resulting PEIs were studied by TGA techniques. All PEIs showed no significant weight loss below 400 °C in a N₂ environment. The monomers and prepared polymers were co-cultivated with airborne fungal spores in culture media to study their biological activity. Soil burial test was also used for evaluation of their biodegradation behavior. The results showed that the synthesized monomers and their derived polymers are biologically active and that their degradation products are probably nontoxic to microbial growth.     

Sulfide and sulfoxide based poly(ether-amide)s: Synthesis and characterization

Two new diacid monomers, 2,2′-sulfide bis(4-methyl phenoxy acetic acid) and 2,2′-sulfoxide bis(4-methyl phenoxy acetic acid) were successfully synthesized by refluxing the 2,2′-sulfide bis(4-methyl phenol) and 2,2′-sulfoxide bis(4-methyl phenol) with chloroacetonitrile in the presence of potassium carbonate, and subsequent basic reduction. Two novel series of poly(sulfide-ether-amide)s and poly(sulfoxide-ether-amide)s with aliphatic units in the main chain were prepared from diacids with various diamines.The polyamides were obtained in quantitative yields and their inherent viscosities were in the range of 0.43-0.89 dl g⁻¹ at a concentration of 0.5 g dl⁻¹ in N,N-dimethylacetamide (DMAc) solvent at 25 °C. They showed good thermal stability. The temperature for 10% weight loss in argon atmosphere was in the range of 350-415 °C. The polymers showed glass transition temperatures between 228 and 261 °C. Almost all of the polyamides were readily soluble in a variety of polar solvents such as N-methyl-2-pyrrolidone (NMP) and dimethyl sulfoxide (DMSO).     

Pseudo-poly(amino acid)s: study on construction and characterization of novel chiral and thermally stable nanostructured poly(ester-imide)s containing different trimellitylimido-amino acid-based diacids and pyromellitoyl-tyrosine-based diol

A new class of chiral and potentially biodegradable poly(ester-imide)s (PEI)s as pseudo-poly(amino acid)s (PAA)s bearing natural amino acids in the main chain was synthesized. In this investigation, N,N′-(pyromellitoyl)-bis-(L-tyrosine dimethyl ester) as a biodegradable optically active diphenol and synthesized trimellitic anhydride-derived dicarboxylic acids containing different natural amino acids such as S-valine, L-methionine, L-leucine, L-isoleucine, and L-phenylalanine were used for direct polyesterification. With the aim of tosyl chloride/pyridine/N,N′-dimethylformamide system as a condensing agent, the new optically active PEIs were obtained in good yields and moderate inherent viscosity up to 0.42 dL/g. The obtained polymers were characterized with FT-IR, ¹H-NMR, X-ray diffraction (XRD), field emission scanning electron microscopy, elemental, and thermogravimetric analysis techniques. These polymers show high solubility in organic solvents, such as N,N′-dimethyl acetamide, N-methyl-2-pyrrolidone, and sulfuric acid at room temperature, and are insoluble in solvents, such as methylene chloride, cyclohexane, and water. Morphology probes showed these pseudo-poly(amino acid)s were noncrystalline and nanostructured polymers. On the basis of thermogravimetric analysis data, such PAAs are thermally stable and can be classified as self-extinguishing polymers. In addition due to the existence of amino acids in the polymer backbones these pseudo-PAAs not only are optically active but also are expected to be biodegradable and therefore could be classified under eco-friendly polymers.     

Synthesis and characterization of optically active polymers containing azo groups and (l)-α-amino acid moieties

The paper discusses the synthesis of new optically active azo diacids starting from two activated azo diesters (diethyl azodicarboxylate and ethyl phenylazocarboxylate) and various (l)-α-amino acids as: (l)-alanine, (l)-leucine, (l)-cysteic acid monohydrate and (l)-cystine. New chiral polymers derived from some of synthesized monomers were obtained under mild reaction conditions by unconventional polycondensation methods. The structure of synthesized compounds has been spectroscopically confirmed and the solubility, optical activity and thermal properties of the obtained materials are reported. To estimate the molecular weights of new polymers the ¹H-NMR and viscometric data were used and obtained values were compared with those of the polymers with alike chain structure synthesized by similar procedures.     

In vitro and in vivo degradation behaviors of thermosensitive poly(organophosphazene) hydrogels

Biodegradable and thermosensitive poly(organophosphazenes) with various substituents were synthesized and their hydrolytic degradation properties were investigated in vitro and in vivo. The aqueous solutions of all polymers showed a sol-gel phase transition behavior depending on temperature changes. The side groups of polymers significantly affected the polymer degradation and accelerated hydrolysis of polymers in the order of carboxylic acid > depsipeptide > without carboxylic acid and depsipeptide. The increased gel strength led to the decreased hydrolysis rate. The polymer hydrogels with 750 Da of α-amino-ω-methoxy poly(ethylene glycol) were rapidly decreased by dissolution. The polymer degradation was also influenced by pH and temperature. The in vivo behaviors of mass decrease of the polymer hydrogels were similar with the in vitro results. These results suggest that the biodegradable and thermosensitive poly(organophosphazenes) hold great potentials as an injectable and biodegradable hydrogel for biomedical applications with controllable degradation rate.     

Synthesis of novel poly(ethylene glycol) based amphiphilic polymers

The synthesis of new amphiphilic polyesters based on poly(ethylene glycol) (PEGs) and studies on their solution properties are reported. Two novel monomers, dimethyl 5-n-butoxy isophthalate (2) and dimethyl 5-n-octoxy isophthalate (3) were synthesized. Three series of novel amphiphilic polyesters, i.e. poly(ethyleneoxy isophthalate)s (10-15), poly(ethyleneoxy n-butoxy isophthalate)s (16-21) and poly(ethyleneoxy n-octoxy isophthalate)s (22-27) have been synthesized from PEGs of different sizes and dimethyl isophthalates 1-3 via the transesterification-polycondensation using dibutyltin diacetate as a catalyst. The structures of the polyesters were established from a detailed analysis of their spectra, i.e. FTIR, ¹H-NMR (one- and two-dimensional) and ¹³C-NMR. By adjusting the ratio of hydrophobic (diesters) and hydrophilic (PEGs) segments in polymers, their main chain structures and solution properties could be changed. The viscosity molecular weights (M_v) of polymers, obtained from Mark-Houwink-Sakurada relationship having poly(ethylene terephthalate) as a model, were in the range of 4500-32,000 g/mol. Intrinsic viscosities were studied based on polymer backbone length (PEGs effect) and pendant group (diesters effect) and these were found to be dependent on molecular weights of the PEGs used.     

Synthesis and hydrolytic degradation of stereoregular aromatic poly(ester amide)s derived from D‐xylose

Stereoregular poly(ester amide)s (PEAs) were prepared by the polycondensation method using naturally occurring D ‐xylose and aromatic diacids as the starting materials. The polymers were characterized by elemental analysis, GPC, IR, and ¹H‐ and ¹³C NMR spectroscopies. Thermal and X‐ray diffraction studies revealed them to be mainly amorphous. The polymers are hydrophilic and their degradation studies were carried out at 37 and 80 °C in buffered salt solution at pH 8. The degradation study was monitored by mass loss, GPC, IR, and NMR spectroscopies. The hydrolytic degradation of these PEAs occurred rapidly by hydrolysis of the ester functions to a final compound, which maintained the amide functions. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Synthesis and properties of novel aliphatic poly(carbonate-ester)s

The biodegradable poly(5-methyl-5-methoxycarbonyl-1,3-dioxan-2-one-co-d,l-lactide) [poly(MMTC-co-d,l-LA)] copolymers were synthesized by the ring-opening copolymerization. The results show that the yield and molecular weight of copolymers are significantly influenced by reaction conditions. The chemical structure of the resultant copolymers was characterized by FTIR, ¹H NMR and ¹³C NMR methods. Their molecular weight was measured by gel permeation chromatography (GPC). Study of monomer coreactivity ratios indicates that d,l-LA reacts faster than MMTC in the copolymerization. The enzymatic degradation of the polymers with various compositions was studied at 37 °C in pH = 8.6 Tris-HCl buffer solution in the presence of proteinase K. Their mechanical properties were also preliminarily investigated.     

Synthesis and characterization of poly(ether-urethane)s derived from 3,6-diisobutyl-2,5-diketopiperazine and PTMG and study of their degradability in environment

3,6-diisobutyl-2,5-diketopiperazine (DIBDKP) was prepared from L-Leucine with good yield. Then a new class of biodegradable poly(ether-urethane)s (PEUs) was synthesized by the pre-polymerization reaction of DIBDKP with 4,4-methylene-bis-(4-phenylisocyanate) (MDI). Prepolymer reacted with poly(tetramethylene glycol) (PTMG) with molecular weight of 1000 (PTMG-1000) to obtain a series of new poly(ether-urethane-urea)s (PEUU)s. These multiblock copolymers are biodegradable and thermally stable. Some structural characterization and physical properties of these polymers before and after degradation in soil, river water and sludge are reported. The environmental degradation of the polymer films was investigated by SEM, FT-IR, TGA, DSC, GPC and XRD techniques. A significant rate of degradation was occurred in PEU samples under river water and sludge condition. The polymeric films were not toxic to Escherichia coli (Gram negative), Staphylococcus aureus and Micrococcus (Gram positive) bacteria and showed good biofilm formation on polymer surface. Our results show that hard segment degraded selectively as much as soft segment and these polymers are susceptible to degradation in soil and water.     

Synthesis and characterization of calcium containing poly(urethane-ether)s

Calcium containing poly(urethane-ether)s (PUEs) were synthesized by the reaction of hexamethylene diisocyanate or toluylene 2,4-diisocyanate (HMDI or TDI) with a mixture of calcium salt of mono(hydroxybutyl)phthalate [Ca(HBP)₂] and polyethylene glycol (PEG₂₀₀ or PEG₄₀₀). A series of calcium containing PUEs having different composition were synthesized by taking the mole ratio of Ca(HBP)₂:PEG₂₀₀ or PEG₄₀₀:diisocyanate (HMDI or TDI) as 3:1:4, 2:2:4 and 1:3:4 to study the effect of calcium content on the properties of the copolymer. The structure of the polymers were confirmed by IR, ¹H-NMR, ¹³C-NMR, and solid state ¹³C-CP-MAS NMR. The polymers were soluble in dimethyl sulfoxide and dimethyl formamide. The initial decomposition temperature of the polymers decreases with increase in calcium content. The T_g value of PUEs increases with increase in calcium content and decreases with increase in soft segment content and length. A single T_g value is observed for the calcium containing PUEs based on PEG₂₀₀ shows the presence of homogeneous phase. However, two T_g values for the PUEs based on PEG₄₀₀ for various composition of Ca(HBP)₂, PEG₄₀₀ and diisocyanate (HMDI or TDI) shows the presence of heterogeneous phase. The viscosity of the calcium containing PUEs increases with increase in the soft segment content as well as its length and decreases with increase in calcium content. X-ray diffraction patterns of the polymers show that the HMDI based polymers are partially crystalline and TDI based polymers are amorphous in nature. The dynamic mechanical analysis of the calcium containing PUEs based on HMDI shows that at any given temperature modulus (g^′ and g^″) increases with increase in the ionic content in the polymers.     

Synthesis, characterization and properties of naphthoxazine-functional poly(propyleneoxide)s

Thermally curable naphthoxazine-functionalized polymers were synthesized by the reaction of linear (diamines) and branched (triamines) poly(propyleneoxide)s (Jeffamine series) having various molecular weights, with p-formaldehyde, and 2-naphthol. The structures of the resulting polymers were characterized by using FT-IR and ¹H-NMR. In addition, curing behavior of these polymers was studied using differential scanning calorimeter (DSC). Hydrophilicity of these polymers, both in cured and non-cured states, was investigated by water contact angle measurements. The surface topographies of the polymers were also examined by atomic force microscope (AFM).     

Synthesis, characterization and biodegradation of butanediamine-grafted poly(dl-lactic acid)

Novel butanediamine-grafted poly(dl-lactic acid) polymers (BDPLAs) were synthesized via a series of chemical bulk modifications in this study. Briefly, maleic anhydride (MAH) was first grafted onto the side chain of poly(dl-lactic acid) (PDLLA) molecules via melt free radical copolymerization using benzoyl peroxide (BPO) as initiator to get maleic anhydride-grafted PDLLA polymers (MPLAs); thereafter butanediamine (BDA) was immobilized onto grafted anhydride groups in MPLAs via N-acylation reaction to obtain the desired BDPLAs. Gel permeation chromatography with multi-angle laser light scattering (GPC-MALLS), FT-IR, ¹³C NMR and XPS were employed to qualitatively characterize these synthesized polymers. Rhodamine-carboxyl interaction method and ninhydrin reaction were further used to quantitatively determine the graft ratio of MAH (MAH%) in MPLAs and the graft ratio of BDA (BDA%) in BDPLAs, respectively. The degradations of BDPLAs, PDLLA and MPLAs were investigated by observation of the changes of the pH value of incubation medium, molecular weight and weight loss ratio for a time interval of 12 weeks in vitro, respectively. The results revealed that grafting butanediamine onto PDLLA has weakened or neutralized the acidity of PDLLA degradation products. A uniform degradation of BDPLAs was observed in comparison with an acidity-induced auto-accelerating degradation featured by PDLLA and MPLAs. The biodegradation behaviors of BDPLAs are tunable by controlling the content of BDA. BDPLAs might be a new derivative of PDLLA-based biodegradable materials for medical applications without acidity-caused irritations and acidity-induced auto-accelerating degradation behavior as that of PDLLA.     

Synthesis of hyperbranched poly(ester urethane isocyanates) and their derivatives

Hyperbranched poly(ester urethanes) containing end isocyanate groups have been synthesized via the reaction of hyperbranched aliphatic polyesterpolydiols of three generations with tolylene diisocyanate. The interaction of these compounds with N,N-dimethylaminoethanol yields their functional derivatives. The polymers are characterized by functional analysis, ¹H NMR and IR spectroscopy, and DSC. It has been demonstrated that the incorporation of urethane moieties leads to development of the microheterogeneous structure of hyperbranched polymers.     

聚酯酸酐的合成与表征

聚酸酐具有优良的表面溶蚀性能，作为药物控释体系材料得到广泛的应用．以对（２ 羟基 乙氧基）苯甲酸和对（２ 甲基 ２羟基 乙氧基）苯甲酸分别与丁二酸酐，顺丁烯二酸酐和丁二酰氯反应得到六个含有酯基的新型二元酸单体，经熔融聚合得到聚酯酸酐．单体和聚合物经ＩＲ，１Ｈ ＮＭＲ和元素分析等表征．研究了催化剂对聚合物结构的影响．     

Synthesis and characterization of poly-α,β-[N-(2-hydroxyethyl)-L-aspartamide]-g-poly(glycolide) amphiphilic graft copolymers as potential drug carriers

A series of biodegradable amphiphilic graft polymers were successfully synthesized by grafting poly(glycolide) (PGA) sequences onto a water-soluble poly-α,β-[N-(2-hydroxyethyl)-_L-aspartamide] (PHEA) backbone. These novel graft polymers were synthesized by the ring-opening polymerization initiated by the macroinitiator PHEA bearing hydroxyl groups without adding any catalyst. The graft polymers were characterized by Fourier transform infrared spectroscopy (FTIR), ¹H nuclear magnetic resonance spectroscopy (¹H NMR), combined size-exclusion chromatography (SEC) and multiangle laser light scattering (MALLS) analysis, and differential scanning calorimetry (DSC). By controlling the feed ratio of the macroinitiator to the monomer, graft polymers with different branch lengths can be obtained. The degradation behaviors of the copolymers were studied. Based on the amphiphilicity of the graft copolymers, nanoparticle drug delivery systems were prepared by the direct dissolution method and the dialysis method, and the in vitro drug release behavior was investigated. Transmission electron microscopy (TEM) images demonstrated that these nanoparticles were regularly spherical in shape. The particle size and distribution of the nanoparticles were measured.     

Studies on hydrolytic degradation of poly(ester-anhydride)s based on oligosuccinate and aliphatic diacids

This paper describes synthesis, characteristics and hydrolytic degradation of functional poly(ester-anhydride)s based on oligo(3-allyloxy-1,2-propylene succinate) (OSAGE) and aliphatic diacids (DA). The polymers were obtained by polycondensation of OSAGE with adipic (ADP), sebacic (SBA) or dodecanedicarboxylic acid (DDC). The carboxyl groups in OSAGE and in diacids were converted to mixed anhydride groups by acetylation with acetic anhydride. After that, prepolymers thus obtained were condensed in vacuum to yield poly(ester-anhydride)s. The structure of copolymers was confirmed by NMR spectroscopy. Influence of the kind of diacid and the OSAGE to diacid ratio on selected properties of poly(ester-anhydride)s were examined. Poly(ester-anhydride)s were subjected to hydrolytic degradation at 37 °C, in aqueous phosphate buffer solution of pH 7.41 (PBS). The course of degradation was monitored by determination of weight loss of samples, ¹H NMR and DSC. Fracture surfaces of samples during degradation were examined by scanning electron microscopy.     

New amino acid based biodegradable poly(ester amide)s via bis-azlactone chemistry

Abstract

Three new classes of the amino acid based biodegradable (AABB) polymers were synthesized via step growth polymerization of bis-azlactones and amino acid based diamine-diesters with activated fatty diester and alkylenediamine: a) poly(ester amide)s (PEAs) were obtained by polymerization of bis-azlactones with diamine-diesters, b) hydrophobically modified co-poly(ester amide)s (co-PEAs) were synthesized by copolymerization of activated fatty diacid diester and bis-azlactones with diamine-diesters, and c) poly(ester amide-co-amide)s (PEA-co-PAs) were obtained by copolymerization of alkylene diamine and diamine-diesters with bis-azlactones. The new poly(ester amide)s showed relatively low-molecular-weights (M_w within 2,800–19,600?Da, GPC in DMF), whereas the new co-poly(ester amide)s and poly(ester amide-co-amide)s exhibited high-molecular-weights (M_w within 40–100?kDa) leading to good mechanical properties. Incorporation of the bis-azlactone fragments into the poly(ester amide)s backbone increased hydrophobicity and thermal stability, whereas incorporation of diamine-diester units into the backbone of the bis-azlactone based polyamides rendered them biodegradable. Synthesized AABB polymers are potential candidates for constructing resorbable surgical and pharmaceutical devices.     

Synthesis and Characterization of Novel Surfactant Molecules Based on Amphiphilic Polymers

Twelve amphiphilic polymers were synthesized using poly(ethylene glycols) (PEGs) of different molecular weights, viz. 300, 600 and1000 as hydrophilic block and aliphatic diacids namely glutaric acid, adipic acid, pimelic acid and suberic acid as hydrophobic block in presence of catalyst Conc. H₂SO₄. Synthesized polyesters were characterized by using ¹H-NMR, ¹³C-NMR and IR spectroscopy. Micellar sizes of the polymers were determined using Dynamic Light Scattering (DLS) which ranged from 127.5–354 nm. Transmission Electron Microscope (TEM) results confirm the findings of DLS. Critical Micelle Concentrations (CMC) of the synthesized polymers were determined using electrical conductivity meter which ranged from 112 to 155 mg L^?1.     

Synthesis and characteristics of the poly(carboxybetaine)s and the corresponding cationic polymers

Two types of carboxybetaines and their corresponding cationic monomers and polymers are synthesized in this study. Comparing the chemical shifts of the methylene groups in the cationic monomers and carboxybetaines in both ¹H- and ¹³C-NMR spectra reveal that the respective methylene groups are clearly distinguished from their chemical shifts in ¹H- and ¹³C-NMR spectra. The solubilities, moisture regain properties, and solution properties of the poly(carboxybetaine)s and cationic polymers are investigated in relation to their molecular structures. Because the cationic polymers were ionized in an aqueous solution, the cationic polymers were more soluble than the poly(carboxybetaine). For the various functional groups of poly(carboxybetaine)s and cationic polymers, the order of tendency for moisture regain is  COO >  CONH . Results obtained from the reduced viscosity for cationic poly(TMMPAMS) are reversed from that for zwitterionic poly(DMAEAPL). © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 3527–3536, 1997