New catalytic systems for the manufacture of poly(aspartic acid)

Aspartic acid (I), when heated to a temperature in excess of 180 °C, undergoes a solid-state condensation polymerization to afford the useful polymeric intermediate known as poly(succinimide) (II). Treatment of poly(succinimide) with aqueous base, such as sodium hydroxide, affords sodium poly(α,β-DL-aspartate) (III) also known as thermal poly(aspartate) (TPA). Acid catalysts, such as phosphoric acid have been added to the aspartic acid to afford higher-molecular-weight poly(succinimide) than is obtained in the non-catalyzed polymerization. Recently, new sulfur-based catalysts have been disclosed for the polymerization of aspartic acid. The sulfur-containing catalysts provide a route to highly biodegradable, low-color poly(aspartate)s in the molecular weight range of 2 000 to 20 000. A comparison of biodegradability, molecular weight, and spectral characteristics of the poly(succinimide)s and poly(aspartate)s derived from the catalyzed and non-catalyzed polymerizations is presented.     

Synthesis and characterization of poly(succinimide-co-6-aminocaproic acid) by acid-catalyzed polycondensation of L-aspartic acid and 6-aminocaproic acid

The polycondensation of L -aspartic acid ( ASP ) with 6-aminocaproic acid ( ACA ) using o-phosphoric acid produced poly(succinimide-co-6-aminocaproic acid). The yield of the MeOH-insoluble copolymer decreased from 99 to 52% and that of the MeOH-soluble one increased from 9 to 47%, with increasing molar ratio of ACA in the monomer feed. The compositions of the succinimide ( SCI ) unit in the MeOH -insoluble and -soluble copolymers tended to be higher than those of ASP in the monomer feed. The copolymers with the 35 mol % SCI units or above were soluble in DMSO , DMF , and conc- H₂SO₄ , but those with the 20 and 21 mol % SCI units were soluble only in conc-H₂SO₄. The melting temperature appeared for the copolymers with less than 76 mol % SCI units. Poly(succinimide-co-6-aminocaproic acid) was easily hydrolyzed to yield poly(aspartic acid-co-6-aminocaproic acid), and it exhibited biodegradability toward activated sludge. © 1997 John Wiley & Sons, Inc.     

Polycondensations of hydroxycarboxylic acids derived from optically active aminoalcohols and acid anhydrides—syntheses of functional poly(ester-amide)s

Syntheses and polycondensations of optically active hydroxycarboxylic acids prepared from acid anhydrides and aminoalcohols were carried out. Novel polymers with M̄_n 9900–27,200 were obtained by the polycondensations of hydroxycaboxylic acids derived from maleic or succinic acid using 1.2 eq. of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC · HCl) in DMF (2M) at room temperature for 8 h in satisfactory yields. Meanwhile, a hydroxycarboxylic acid obtained from phthalic acid afforded no polymer but a phthalimide derivative. The radical additions of ethanethiol or mercaptoethanol with the polymers derived from maleic anhydride proceeded smoothly in satisfactory incorporation ratios (65–98%), respectively. The polymer obtained from succinic anhydride and 2-aminoethanol showed hydrolytic degradability. © 1997 John Wiley & Sons, Inc.     

Kinetics of solid phase thermal polycondensation of aspartic acid in evacuated system

Solid phase thermal polycondensation of aspartic acid in evacuated system results in formation of poly(aspartic acid) at 190–207°C and in poly(succinimide) at 210–230°C. Kinetic parameters of formation of poly(aspartic acid) and poly(succinimide) have been determined. The aspartic acid → poly(aspartic acid) → poly(succinimide) polycondensation is accompanied by partial decarboxylation of the monomeric units.     

Synthesis and micellization of amphiphilic poly(sebacic anhydride)–poly(ethylene glycol)–poly(sebacic anhydride) block copolymers

Amphiphilic biodegradable block copolymers [poly(sebacic anhydride)–poly(ethylene glycol)–poly(sebacic anhydride)] were synthesized by the melt polycondensation of poly(ethylene glycol) and sebacic anhydride prepolymers. The chemical structure, crystalline nature, and phase behavior of the resulting copolymers were characterized with ¹H NMR, Fourier transform infrared, gel permeation chromatography, and differential scanning calorimetry. Microphase separation of the copolymers occurred, and the crystallinity of the poly(sebacic anhydride) (PSA) blocks diminished when the sebacic anhydride unit content in the copolymer was only 21.6%. ¹H NMR spectra carried out in CDCl₃ and D₂O were used to demonstrate the existence of hydrophobic PSA domains as the core of the micelle. In aqueous media, the copolymers formed micelles after precipitation from water‐miscible solvents. The effects on the micelle sizes due to the micelle preparation conditions, such as the organic phase, dropping rate of the polymer organic solution into the aqueous phase, and copolymer concentrations in the organic phase, were studied. There was an increase in the micelle size as the molecular weight of the PSA block was increased. The diameters of the copolymer micelles were also found to increase as the concentration of the copolymer dissolved in the organic phase was increased, and the dependence of the micelle diameters on the concentration of the copolymer varied with the copolymer composition. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1271–1278, 2006     

Biodegradation of poly(amino acid)s: Evaluation methods and structure-to-function relationships

Two poly(amino acid) systems were studied: (a) poly[N⁵-(2-hydroxyethyl)-L-glutamine] (PHEG) derivatives prepared by NCA polymerization; (b) poly-α,β-[N-(2-hydroxyethyl)-DL-aspartamide] (PHEA) derivatives prepared by thermal polycondensation of aspartic acid to racemic polysuccinimide followed by chemical modification reactions. The degradation of polymers by isolated enzymes and homogenate of kidney tissue was studied in vitro and the effect of polymer structure on the rate of degradation and the size of degradation products was evaluated. A PHEA derivative (modified by tyramine residues in 9.6 % of side chains) was accumulated in the lysosomes of kidney cells of rats and the molecular-weight distribution of the polymer retained inside the lysosomes of living cells and that of the polymer excreted into urine was analysed by a high-sensitivity size-exclusion chromatography using the fluorescence and radioactive labelling. While PHEG derivatives were degraded by isolated mammalian enzymes and a tissue homogenate, no significant degradation of PHEA and derivatives was observed, either in vitro, with isolated enzymes and homogenate or in vivo, under a long-term exposure to the lysosomal enzymes in living cells.     

Cope elimination and complexation of poly(dimethylaminoethyl methacrylate N-oxide)

Poly(dimethylaminoethyl methacrylate N-oxide) (poly(DMAEMNO)) was prepared by oxidation of poly(dimethylaminoethyl methacrylate) with hydrogen peroxide in methanol. From thermogravimetric and IR spectroscopic investigations Cope elimination of amine oxide group in poly(DMAENO) was found to occur at 120–150°C. The postpolymerization of partially pyrolyzed polymer carrying vinyl ester group as pendant was performed with azobisisobutyronitrile at 60°C in methanol to give cross-linked polymer that was found to form hydrogel. Poly(DMAEMNO) gave metal–polymer complexes with CuCl₂, ZnCl₂, and CoCl₂. Cobalt–polymer complex had a constitution of 1:2 of metal ion to amine oxide group, while copper– and zinc–polymer complexes seemed to have structures of 1:1 and 1:2 of metal ion to amine oxide group. Furthermore, polymer complexes of poly(DMAEMNO) with poly(methacrylic acid) and poly(acrylic acid) were found to be formed by mixing aqueous solutions of both polymers and also by radical polymerization of the acid monomers in the presence of poly(DMAEMNO). From elemental analysis, thermogravimetric investigation, and measurement of turbidity it was concluded that the resulting polymer–polymer complexes contained more than one acid monomer unit per one N-oxide unit.     

Equilibrium study of polymer–polymer complexation of poly(methacrylic acid) and poly(acrylic acid) with complementary polymers through cooperative hydrogen bonding

The degree of linkage, θ, defined as the ratio of the binding groups to the total of potentially interacting groups and the stability constant K of the polymer–polymer complexes in the systems poly(methacrylic acid)–poly(ethylene glycol), poly(acrylic acid)–poly(ethylene glycol), and poly-(methacrylic acid)–poly(vinyl pyrrolidone) in aqueous and aqueous alcohol media were determined as a function of temperature by potentiometric titration. It was found that θ and K are strongly dependent on chain length, temperature, and medium and that hydrophobic interaction is a significant factor in the stabilization of the complexes. The enthalpy and entropy changes and the cooperativeness parameter of the systems were calculated. A mechanism for the complexation in terms of cooperative interaction was proposed.     

聚天冬氨酸硅质固定相的研制及应用

D，L-天冬氨酸在浓磷酸的存在下加热聚合生成聚琥珀酰亚胺，此产物能与氨丙基硅胶快速反应生成聚琥珀酰胺硅胶，然后再水解生成聚天冬氨酸硅质固定相．并对反应条件进行了优化、实验表明，聚天冬氨酸固定相对蛋白质有较好的分离能力和选择性．     

Synthesis and properties of new adamantane‐based poly(ether imide)s

A new adamantane‐based bis(ether anhydride), 2,2‐bis[4‐(3,4‐dicarboxyphenoxy)phenyl]adamantane dianhydride, was prepared in three steps starting from nitrodisplacement of 4‐nitrophthalonitrile with the potassium phenolate of 2,2‐bis(4‐hydroxyphenyl)adamantane. A series of adamantane‐containing poly(ether imide)s were prepared from the adamantane‐based bis(ether anhydride) and aromatic diamines by a conventional two‐stage synthesis in which the poly(ether amic acid)s obtained in the first stage were heated stage‐by‐stage at 150–270°C to give the poly(ether imide)s. The intermediate poly(ether amic acid)s had inherent viscosities between 0.56 and 1.92 dL/g. Except for those from p‐phenylenediamine, m‐phenylenediamine, and benzidine, all the poly(ether amic acid) films could be thermally converted into transparent, flexible, and tough poly(ether imide) films. All the poly(ether imide)s showed limited solubility in organic solvents, although they were amorphous in nature as evidenced by X‐ray diffractograms. Glass transition temperatures of these poly(ether imide)s were recorded in the range of 242–317°C by differential scanning calorimetry and of 270–322°C by dynamic mechanical analysis. They exhibited high resistance to thermal degrdation, with 10% weight loss temperatures being recorded between 514–538°C in nitrogen and 511–527°C in air. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1619–1628, 1999     

Acid-catalyzed copolymerization of aspartic acid with ω-amino acid. -Biodegradability and Ca2+ chelating ability of poly(aspartic acid -Co- ω-amino acid)-

The polycondensation of L-aspartic acid (1) with various ω-amino acids (2) using phosphoric acid catalyst produced poly(succinimide-co-ω-amino acid)s (3), which was followed by alkali hydrolysis to poly(aspartic acid-co-ω-amino acid) (4). The Ca²⁺ chelating abilities of 4 depended on the content of comonomer unit in the copolymer and on the kind of amino acids. For the copolymer using 11-aminoundecanoic acid (2d) as a comonomer, the Ca²⁺ chelating ability was higher than that of poly(sodium acrylate). For poly(aspartic acid-co-6-aminocaproic acid) (4c), there was a tendency to increase according to the increase of 6-aminocaproic acid (2c) unit in the copolymer. The biodegradability of the copolymer in the case of 2c as a comonomer, evaluated by TOC measurement, was 63%, which was the highest degradability among the copolymers having different methylen length. The biodegradability of 4c decreased with increasing the 2c unit in 4c.     

Synthesis and characterization of poly(benzobisthiazole) with tetramethylbiphenyl moiety in the main chain

Poly(benzobisthiazole)s containing an ortho-tetramethyl substituted biphenyl moiety were synthesized via the polycondensation of 2,5-diamino-1,4-benzenedithiol dihydrochloride with 2,2′,6,6′-tetramethylbiphenyl-4,4′-dicarboxylic acid in poly(phosphoric acid) (PPA). The intrinsic viscosities of the tetramethylbiphenyl poly-(benzobisthiazole)s in chlorosulfonic acid at 30°C were in the range of 6.9–13.4 dL/g. Copolycondensation of 2,5-diamino-1,4-benzenedithiol dihydrochloride with terephthalic acid and 2,2′,6,6′-tetramethylbiphenyl-4,4′-dicarboxylic acid was carried out as well by varying the ratio of the two dicarboxylic acid monomers in the reactant mixture. The homopolymers and copolymers were characterized by Fourier transform infrared spectroscopy (FTIR) and ¹³C solid-state nuclear magnetic resonance spectroscopy (NMR). Thermal stability of the polymers was evaluated by thermogravimetric analysis (TGA) and thermogravimetric mass spectrum analysis (TG-MS). The tetramethylbiphenyl poly(benzobisthiazole)s were found to be more stable at elevated temperatures than the parent poly(p-phenylene benzobisthiazole) (PBZT). © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1407–1416, 1998     

Synthesis and photochemical properties of poly(ester–amide)s containing norbornadiene (NBD) residues

N,N′‐Bis[(3‐carboxynorbornadien‐2‐yl)carbonyl]‐N,N′‐diphenylethylenediamine (BNPE) was synthesized in 70% yield by the reaction of 2,5‐norbornadiene‐2,3‐dicarboxylic acid anhydride with N,N′‐diphenylethylenediamine. Other dicarboxylic acid derivatives containing norbornadiene (NBD) residues having N,N′‐disubstituted amide groups were also prepared by the reaction of 2,5‐NBD‐2,3‐dicarboxylic acid anhydride with certain secondary diamines. When the polyaddition of BNPE with bisphenol A diglycidyl ether (BPGE) was carried out using tetrabutylammonium bromide as a catalyst in N‐methyl‐2‐pyrrolidone at 100°C for 12 h, a polymer with number average molecular weight of 69,800 was obtained in 98% yield. Polyadditions of other NBD dicarboxylic acid derivatives containing N,N′‐disubstituted amide groups with BPGE were also performed under the same conditions. The reaction proceeded very smoothly to give the corresponding NBD poly(ester–amide)s in good yields. Photochemical reactions of the obtained polymers with N,N′‐disubstituted amide groups on the NBD residue were examined, and it was found that these polymers were effectively sensitized by adding appropriate photosensitizers such as 4‐(N,N‐dimethylamino)benzophenone and 4,4′‐bis(N,N‐diethylamino)benzophenone in the film state. The stored energies in the quadricyclane groups of the polymers were also evaluated to be about 94 kJ/mol by DSC measurement of the irradiated polymer films. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 917–926, 1999     

Synthesis and characterization of new fluorene‐based poly(ether imide)s

A novel bis(ether anhydride) monomer, 9,9‐bis[4‐(3,4‐dicarboxyphenoxy)phenyl]fluorene dianhydride (4), was synthesized from the nitrodisplacement of 4‐nitrophthalonitrile by the bisphenoxide ion of 9,9‐bis(4‐hydroxyphenyl)fluorene (1), followed by alkaline hydrolysis of the intermediate tetranitrile and dehydration of the resulting tetracarboxylic acid. A series of poly(ether imide)s bearing the fluorenylidene group were prepared from the bis(ether anhydride) 4 with various aromatic diamines 5a–i via a conventional two‐stage process that included ring‐opening polyaddition to form the poly(amic acid)s 6a–i followed by thermal cyclodehydration to the polyimides 7a–i. The intermediate poly(amic acid)s had inherent viscosities in the range of 0.39–1.57 dL/g and afforded flexible and tough films by solution‐casting. Except for those derived from p‐phenylenediamine, m‐phenylenediamine, and benzidine, all other poly(amic acid) films could be thermally transformed into flexible and tough polyimide films. The glass transition temperatures (T_g) of these poly(ether imide)s were recorded between 238–306°C with the help of differential scanning calorimetry (DSC), and the softening temperatures (T_s) determined by thermomechanical analysis (TMA) stayed in the range of 231–301°C. Decomposition temperatures for 10% weight loss all occurred above 540°C in an air or a nitrogen atmosphere. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1403–1412, 1999     

Cyclopolycondensation. XIII. New synthetic route to fully aromatic poly(heterocyclic imides) with alternating repeating units

Fully aromatic poly(heterocyclic imides) of high molecular weight were prepared by the cyclopolycondensation reactions of aromatic diamines with new monomer adducts prepared by condensing orthodisubstituted aromatic diamines with chloroformyl phthalic anhydrides. The low-temperature solution polymerization techniques yielded tractable poly(amic acid), which was converted to poly(heterocyclic imides) by heat treatment to effect cyclodehydration at 250–400°C under reduced pressure. In this way, the polyaromatic imideheterocycles such as poly(benzoxazinone imides), poly(benzoxazole imides), poly(benzimidazole imides) and poly(benzothiazole imides) were prepared, which have excellent processability and thermal stability both in nitrogen and in air. The poly(amic acids) are soluble in such organic polar solvents as N,N-dimethyl-acetamide, N-methylpyrrolidone, and dimethyl sulfoxide, and the films can be cast from the polymer solution of poly(amic acids) (η_inh = 0.8–1.8). The film is made tough by being heated in nitrogen or under reduced pressure to effect cyclodehydration at 300–400°C. The polymerization was carried out by first isolating the monomer adducts, followed by polymerization with aromatic diamines. On subsequently being heated, the open-chain precursor, poly(amic acid), undergoes cyclodehydration along the polymer chain, giving the thermally stable ordered copolymers of the corresponding heterocyclic imide structure.     

Synthesis and characterization of biodegradable poly(L-aspartic acid-co-PEG)

The melt polycondensation reaction of the prepolymer prepared from N-(benzyloxycarbonyl)-L -aspartic acid anhydride (N-CBz-L -aspartic acid anhydride) and low molecular weight poly(ethylene glycol) (PEG) using titanium isopropoxide (TIP) as a catalyst produced the new biodegradable poly(L -aspartic acid-co-PEG). This new copolymer had pendant amine functional groups along the polymer backbone chain. The optimal reaction conditions for the preparation of the prepolymer were obtained by using a 0.12 mol % of p-toluenesulfonic acid with PEG 200 for 48 h. The weight-average molecular weight of the prepolymer increased from 1,290 to 31,700 upon melt polycondensation for 6 h at 130°C under vacuum using 0.5 wt % TIP as a catalyst. The synthesized monomer, prepolymer, and copolymer were characterized by FTIR, ¹H- and ¹³C-NMR, and UV spectrophotometers. Thermal properties of the prepolymer and the protected copolymer were measured by DSC. The glass transition temperature (T_g) of the prepolymer shifted to a significantly higher temperature with increasing molecular weight via melt polycondensation reaction, and no melting temperature was observed. The in vitro hydrolytic degradation of these poly(L -aspartic acid-co-PEG) was measured in terms of molecular weight loss at different times and pHs at 37°C. This pH-dependent molecular weight loss was due to a simple hydrolysis of the backbone ester linkages and was characterized by more rapid rates of hydrolysis at an alkaline pH. These new biodegradable poly(L -aspartic acid-co-PEG)s may have potential applications in the biomedical field. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 2949–2959, 1998     

Synthesis and properties of poly(ether imide)s derived from 2,6-bis(3,4-dicarboxyphenoxy)naphthalene dianhydride and aromatic diamines

A new naphthalene unit-containing bis(ether anhydride), 2,6-bis(3,4-dicarboxyphenoxy)naphthalene dianhydride, was synthesized in three steps starting from the nucleophilic nitrodisplacement reaction of 2,6-dihydroxynaphthalene and 4-nitrophthalonitrile in N,N-dimethylformamide (DMF) solution in the presence of potassium carbonate, followed by alkaline hydrolysis of the intermediate bis(ether dinitrile) and subsequent dehydration of the resulting bis(ether diacid). High-molar-mass aromatic poly(ether imide)s were prepared using a conventional two-step polymerization process from the bis(ether anhydride) and various aromatic diamines. The intermediate poly(ether amic acid)s had inherent viscosities of 0.65–2.03 dL/g. The films of poly(ether imide)s derived from two rigid diamines, i.e. p-phenylenediamine and benzidine, crystallized during the thermal imidization process. The other poly(ether imide)s belonged to amorphous materials and could be fabricated into transparent, flexible, and tough films. These aromatic poly(ether imide) films had yield strengths of 104–131 MPa, tensile strengths of 102–153 MPa, elongation to break of 8–87%, and initial moduli of 1.6–3.2 GPa. The glass transition temperatures (T_g's) of poly(ether imide)s were recorded in the range of 220–277°C depending on the nature of the diamine moiety. All polymers were stable up to 500°C, with 10% weight loss being recorded above 550°C in both air and nitrogen atmospheres. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1657–1665, 1998     

Synthesis of poly(succinimide) by bulk polycondensation of L‐aspartic acid with an acid catalyst

The bulk polycondensation of L ‐aspartic acid (ASP) with an acid catalyst under batch and continuous conditions was established as a preparative method for producing poly(succinimide) (PSI). Although sulfuric acid, p‐toluenesulfonic acid, and methanesulfonic acid were effective at producing PSI in a high conversion of ASP, o‐phosphoric acid was the most suitable catalyst for yielding PSI with a high weight‐average molecular weight (M_w) in a quantitative conversion; that is, the M_w value was 24,000. For the continuous process using a twin‐screw extruder at 3.0 kg · h⁻¹ of the ASP feed rate, the conversion was greater than 99%, and the M_w value was 23,000 for the polycondensation with 10 wt % o‐phosphoric acid at 260°C. Sodium polyaspartate (PASP‐Na) originating from the acid‐catalyzed polycondensation exhibited high biodegradability and calcium‐ion‐chelating ability. The total organic carbon value was 86 ∼ 88%, and 100 g of PASP‐Na chelated with 5.5 ∼ 5.6 g of calcium ion, which was similar to the value for PASP‐Na from the acid‐catalyzed polycondensation with a mixed solvent © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 117–122, 2000     

Electron transfer reactions of V(IV) with Cl(I), Br(I) and I(I). A kinetic study

A kinetic study on the oxidation of V(IV) by chloramine-T (CAT) at pH 6.85 by N-bromo succinimide (NBS) in aqueous acetic acid–perchloric acid media and by N-iodo succinimide (NIS) in aqueous perchloric acid medium has been carried out. In all the systems studied the order with respect to the oxidant is unity. NBS and CAT oxidation reactions exhibited Michaelis–Menten type kinetics, and the NIS study indicated unit dependence on [substrate]. Independence on acidity has been observed in the case of CAT and NBS reactions, but NIS reactions exhibited inverse unit dependence on [acid]. Novel solvent influences have been noticed in the case of CAT reactions, but with NIS and NBS reactions retardation in the rate has been observed with an increase in the percentage of acetic acid. Plausible mechanisms consistent with the results have been postulated, and suitable rate laws in consonance with the postulated mechanisms have been derived.     

Molar Mass and Structural Characteristics of Poly[(lactide-co-(aspartic acid)] Block Copolymers

Summary: We report on various synthetic procedures for the preparation of biodegradable and biocompatible poly(lactide-co-aspartic acid) block copolymers based on natural monomeric units – lactic acid and aspartic acid. Multiblock poly(lactide-co-aspartic acid) copolymers of different comonomer composition were synthesized by heating a mixture of L-aspartic acid and L,L-lactide in melt without the addition of any catalyst or solvent and with further alkaline hydrolysis of the cyclic succinimide rings to aspartic acid units. Diblock poly(lactide-co-aspartic acid) copolymers with different block lengths were prepared by copolymerization of amino terminated poly(β-benzyl-L-aspartate) homopolymer and L,L-lactide with subsequent deprotection of the benzyl protected carboxyl group by hydrogenolysis. The differences in the structure, composition, molar mass characteristics, and water-solubility of the synthesized multiblock and diblock poly(lactide-co-aspartic acid) copolymers are discussed.