Novel biodegradable polyphosphazenes containing glycine ethyl ester and benzyl ester of amino acethydroxamic acid as cosubstituents

Novel biodegradable polyphosphazenes containing glycine ethyl ester and benzyl ester of amino acethydroxamic acid as cosubstituents (PGBP) were synthesized by further modifying poly[bis(glycine ethyl ester)phosphazene] (PGP). The polymers were characterized by IR, ¹H‐NMR, DSC, and elemental analysis. Degradation experiments were conducted in vitro at varied pH conditions. The results indicated that the degradation of PGBP was pH‐sensitive. The sample dissoluted after 1.5 days under a physiological condition (pH 7.4) but took more than 20 days under an acidic condition (pH 5–6), which was related to the content of the benzyl ester of amino acethydroxamic acid in the polymer. The “two‐stage” degradation mechanism of PGBP was proposed: that the polymer first degraded to a water‐soluble polymeric product with the fast break of side groups, followed by the relatively slow scission of the backbone. This property of PGBP may be useful in controlled drug‐delivery systems. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 2987–2995, 2000     

Synthesis and characterization of tetrafluorophenyl phosphonic acid functionalized polyacrylates as potential proton conducting materials in fuel cells

Novel acrylate polymers functionalized with tetrafluorophenyl phosphonic acid groups were prepared by free radical polymerization of phosphonic ester acrylate monomers. Liberation of the free acid functions was realized by ester cleavage with Me₃SiBr and the subsequent hydrolysis with methanol. The obtained polymers were analyzed by NMR and IR spectroscopy. The ion exchange capacity of the phosphonic acid functionalized methacrylate polymer was determined to 2.8 mmol/g by titration with 0.1 M NaOH. The proton conductivity under anhydrous conditions was determined to 6.84 × 10⁻⁶ Scm⁻¹ at 120°C by electrochemical impedance spectroscopy.     

Synthesis and characterization of thermosensitive poly(organophosphazene) gels with an amino functional group

Thermosensitive poly(organophosphazene) gels have been synthesized with a host of side groups, including α‐amino‐ω‐methoxy‐poly(ethylene glycol), hydrophobic amino acid esters (PheOEt, LeuOEt, and IleuOEt), depsipeptide ethyl ester (GlyGlycOEt), and lysine ethyl ester (lysOEt). The fraction of the last side group, lysOEt, which possesses two amine functional groups, was designed to be in the range of 0.1–0.3 mol per polymer unit. The poly(organophosphazenes) have been characterized via ¹H‐ and ³¹P‐NMR spectroscopies, GPC, and elemental analysis. The phase transition behavior of the poly(organophosphazenes) in aqueous solution has been determined via viscometry. Some of the poly(organophosphazenes) with amino functional groups exhibit reversible sol–gel transitions at temperatures near those of the human body, when in aqueous solution. These polymers form a sol at lower temperatures, and become gels at higher temperatures. Also, these polymer solutions have been found to behave generally like Newtonian fluids in the sol state, but appear to exhibit pseudoplastic qualities in the gel state. The polymers possessing depsipeptide ethyl esters (ethyl‐2‐(O‐glycyl)glycolate) as a side group tend to exhibit much higher degradation rates under physiological conditions than do those which lack the depsipeptide ethyl ester group. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci 120:998–1005, 2011     

Esterification reactions on syndiotactic poly(methallylalcohol)

Summary Syndiotactic poly(methallyl alcohol) was esterified with selected carboxylic acids under complete conversion to the corresponding homopolymers. Reactions were carried out in HBr-acetic acid to yield acetate; with pivaloyl chloride or phthalic anhydride to obtain pivalate and acid phthalate, respectively, as well as with the N-protected amino acids, N-phthaloyl-glycine, N-phthaloyl-L-phenylalanine or N-carbobenzoxy-L-tryptophane in the presence of dicyclohexylcarbodiimide (DCC) or 1-ethoxycarbonyl-2-ethoxy-1.2-dihydroquinoline (EEDQ) to yield N-protected amino acid ester side chains. Conversion and structure of the polymers were confirmed by ¹H- and ¹³C-NMR spectra.     

Synthesis and Structural Characterization of Novel Nanostructured Aromatic Optically Active Poly(Ester–Amide)s Derived from S-tyrosine Containing Symmetric Diol and Aromatic Diacid Chlorides

In this study, at first N,N′-bis[2-(methyl-3-(4-hydroxyphenyl)propanoate)]terephthaldiamide, as a new chiral monomer based on tyrosine amino acid, was synthesized from the reaction of S-tyrosine methyl ester and terephthaloyl dichloride. Then novel nanostructured aromatic optically active and eco-friendly poly(ester–amide)s based on tyrosine amino acid were synthesized by the solution polycondensation of the new diol and a number of aromatic diacid chlorides. The resulting poly(ester–amide)s exhibited good yields, solubility, inherent viscosities, and thermal stability. All polymers were characterized by Fourier transform infrared, ¹H NMR, elemental analysis, and specific rotation. They were also studied by X-ray diffraction, thermogravimetric analysis, and field emission scanning electron microscopy.     

Synthesis and Characterizations of Triphenylamine End-Functionalized Polymers via Reversible Addition-Fragmentation Chain Transfer Polymerization

A novel reversible addition-fragmentation chain transfer (RAFT) reagent bearing triphenylamine (TPA) group, 4-diphenylamino-dithiobenzoic acid benzyl ester (DDABE), was designed and synthesized. It was used in the RAFT polymerizations of styrene (St) and methyl acrylate (MA) to prepare end-functionalized polymers. The results of the polymerization showed that the RAFT polymerizations could be well controlled using DDABE as the RAFT agent. Number-average molecular weight (M_n,GPC) increased linearly with monomer conversion, and molecular weight distributions were relatively narrow (PDI< 1.50). The results of chain-extension reaction, ¹H NMR spectra and UV/Vis spectra confirmed that most of the polymers chains were end-capped by the functional triphenylamine (TPA) groups. The effect of feed molar ratios of St/DDABE/AIBN on polymerization was investigated.     

Versuche zur chromatographischen racemattrennung an synthetischen asymmetrischen polymeren

Sulphochlorinated and chloromethylated polystyrene reacted with D-α-phenyl-ethylamine, D-ephedrine, D-alanine, L-alanine, L-alanine methyl ester, L-alanine benzyl ester, L-phenyl-alanine and D-α-aminophenylacetic acid yielding asymmetric polymers. These polymers were used as specific adsorbents for the chromatographic resolution of racemates. The influence of the different substituents in the asymmetric centre of the polymers and the racemates on the resolution was investigated. DL-Mandelic acid and DL-α-aminophenylacetic acid could be partially resolved, using different eluents, on the polymers, prepared from polystyrenesulphonyl chloride and optically active amino acids. Polymers prepared from polystyrenesulphonyl chloride and L-alanine esters showed stereoselective adsorption power only after the saponification of the ester groups to the free carboxyl groups. An exchange of the carboxyl group by a methyl group on the asymmetric C-atom of the polymers and also of the racemates leads to a loss of resolution activity, -respectively- separability. The replacement of the benzyl- or methyl-groups by a phenyl group showed a much greater influence on the resolution effect in the racemates than in the polymers. The presence of a (? SO₂? NH? )-bridge, in comparison to a (? CH₂-NH? )-bridge, between the matrix polymer and the optically active component increased the resolution activity. The difference in the firmness of the binding of the antipode over a hydrogen bridge linkage in the polymer was thought to be the reason for the partial resolution of the racemates.     

Application of 2-hydroxyethyl methacrylate polymers in controlled release of 5-aminosalicylic acid as a colon-specific drug

Acrylic type polymeric systems having degradable ester bonds linked to 5-aminosalicylic acid were synthesized and evaluated as materials for drug delivery. 5-Aminosalicylic acid, as an important drug in the treatment of inflammatory bowel diseases, was linked to 2-hydroxyethyl methacrylate by activated ester methodology in two-step and one-pot procedures to obtain methacryloyloxyethyl 5-amino salicylate. The resulting methacrylic derivative of 5-aminosalicylic acid was copolymerized with methacrylamide, 2-hydroxyethyl methacrylate and methyl methacrylate (in 1:3 mole ratio) by free radical polymerization method in N,N-dimethylformamide solution, utilizing α,ά-azoisobutyronitrile as initiator at the temperature range of 65–70 °C. The obtained polymers were characterized by FT-IR, ¹H NMR, ¹³C NMR and elemental analysis. The average molecular weights of the polymers bearing drug units as side substituents of the acrylic backbone were determined by gel permeation chromatography and their polydispersity indices resulted in the range of 1.6–1.8. Release studies of 5-aminosalicylic acid were performed into dialysis bags by hydrolysis in buffered solutions (pH 1, 7 and 8) at 37 °C. Detection of hydrolysis by UV spectroscopy at selected intervals showed that the drug can be released by selective hydrolysis of the ester bond at the side of drug moiety. The release profiles indicated that the hydrolytic behavior of polymeric prodrugs is strongly based on the polymer hydrophilicity and the pH value of the hydrolysis solution. The results suggest that these systems could be useful for preparation of a controlled release formulation of 5-aminosalicylic acid in colon.     

Fluorescent labelled dual-stimuli (pH/thermo) responsive self-assembled side-chain amino acid based polymers

Pyrene labelled chain transfer agent, py-CTA, was synthesized and employed for the reversible addition-fragmentation chain transfer (RAFT) polymerization of Boc-phenylalanine/alanine methacryloyloxyethyl ester (Boc-F/A-EMA) based monomers, for obtaining α-pyrene labelled homopolymers, pyrene-poly(Boc-phenylalanine/alanine methacryloyloxyethyl ester) (py-P(Boc-F/A-EMA)), with controlled molecular weight, narrow polydispersity and precise chain-end functionality. Subsequent Boc-deprotection produced pH-responsive cationic homopolymers with side-chain primary amino groups. Furthermore, py-P(Boc-F/A-EMA) was utilized as macro-CTA for the polymerization of di(ethylene glycol) methyl ether methacrylate (DEGMA) to afford block copolymers, which upon Boc-deprotection provided dual pH- and thermo-responsive polymers. An interplay of hydrophobicity of the incorporated amino acid residue as well as pH value of the solution were determined as the tunable parameter for the alteration of lower critical solution temperature (LCST) of these block copolymers. Functionalization of carbon nanotube (CNT) via non-covalent interactions, and unique morphologies generated from the self-assembly of these synthetic macromolecules were also investigated.     

Synthesis and characterization of piperazine-derived poly(amido-amine)s with different distributions of amido- and amino-groups along the macromolecular chain

Four poly(amido-amine)s based on piperazine have been synthesized by poly(acylation-addition) reaction of piperazind with various activated derivatives of acrylic acid. In these polymers, amido-, and amino groups are randomly arranged along the macromolecular chain. These polymers have been fully characterized by hydrolytic analysis, ¹³C n.m.r., and potentiometric techniques.     

Synthesis of amino acid‐based polymers having metronidazole moiety and study of their controlled release in vitro

A new polymeric drug carrier system using amino acid‐based polymers was developed. Amino acid‐based polymers with controlled molar mass and narrow molecular weight distribution have been synthesized by reversible addition‐fragmentation chain transfer polymerization of four amino acid‐carrying monomers having different chirality and hydrophilicity. Metronidazole (MTZ) was immobilized onto the amino acid‐based polymers, and the release profiles of the polymer‐MTZ adducts were investigated in phosphate buffer solutions (pH = 2.0, 7.4, and 8.5). The model drug was released by the hydrolysis of the ester group, and the release rate and behavior of the polymeric prodrugs strongly depended on the configuration of the amino acid‐based polymers‐MTZ adducts and the pH of the release media. The release kinetics was determined using the Higuchi and Korsmeyer equations, which revealed the release mechanism of the polymeric prodrugs. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Poly(amide‐ester)s derived from dicarboxylic acid and aminoalcohol

A series of alternating aliphatic poly(amide‐ester)s, derived from dicarboxylic acid and aminoalcohols, were obtained by polycondensation in melt. All poly(amide‐ester)s were characterized by FTIR and ¹H/¹³C‐NMR spectroscopies. The synthesized polymers showed an inherent viscosity ranging from 0.4 to 1.0 dL g^?1. Thermal analysis showed melting points within the range 100–115°C and glass transition within the range 30–60°C. Decomposition temperatures were more than 200°C higher than the corresponding melting temperatures. The polymers can thus be processed from the melt. The processed polymers were partially crystalline with good thermal stability. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 362–368, 2005     

Enzymatically degradable prodrugs: A novel methodology for drug linkage

We have synthesized a novel enzymatically degradable prodrug system based on poly(ethylene glycol) (PEG) and tyrosine units by employing a synthetic methodology which eliminated the use of conventional blocking and deblocking methodology used for chemical linkage of drug molecule to the pendant ? NH₂ group of amino acid. A diester of PEG (6 kDa) and tyrosine hydrochloride was synthesized by dicyclohexyl carbodiimide (DCC)‐mediated condensation. In the second stage, oligomers were prepared by condensing phenolic ? OH groups of tyrosine in the diester with sebacic acid, using DCC. Finally, the hydrochloride salt of tyrosine in the oligomer was treated with triethylamine to activate ? NH₂ groups, which were reacted with benzoyl chloride to obtain a model prodrug system. The products synthesized were characterized by IR, ¹H‐NMR, and GPC. The spectral data were in accordance with the proposed structures of products. Chymotrypsin‐catalyzed degradation of the oligomers was characterized by both MW measurements and Ninhydrin assay for free tyrosine. Degradation studies indicated that the rate of main‐chain degradation (ester hydrolysis) is higher than that of the side chain (amide hydrolysis). This new, simple methodology should be useful for conjugating a variety of bioactive molecules to enzymatically degradable PEG–amino acid based polymers. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2108–2118, 2002     

“Living”/controlled polymerization of methyl acrylate mediated by dithiocarbamates under γ‐ray irradiation

γ‐Ray initiated reversible addition–fragmentation chain transfer (RAFT) polymerizations of methyl acrylate (MA) were investigated in bulk using five different dithiocarbamate structures, 2‐phenyl‐benzoimidazole‐1‐carbodithioic acid benzyl ester ( 1b ), 2‐methyl‐benzoimidazole‐1‐carbodithioic acid benzyl ester ( 1c ), 2‐pheny‐indole‐1‐cardithioic acid benzyl ester ( 1d ), 2‐(carbazole‐9‐carbothioylsulfanyl)‐2‐methyl‐propionic acid ester ( 1e ), and carbazole‐9‐carbodithioic acid naphthalene‐1‐ylmethyl ester ( 1f ), as RAFT agents. The experiment results showed that MA polymerized in a controlled way under a low irradiation dose rate, i.e., first‐order kinetic plots, the experimental molecular weights increased linearly with monomer conversions. The polydispersity indices of polymers generally remained at a relatively low value (lower than 1.4). The effect of irradiation dose on the polymerization results was investigated. The obtained polymers were characterized with ¹H NMR and GPC. Chain‐extension reaction was also successfully carried out using the obtained polymer as the macro‐RAFT agent and styrene as the second monomer. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1769–1775, 2007     

Synthesis of biodegradable amino‐acid‐based poly(ester amide)s and poly(ether ester amide)s with pendant functional groups

A new family of biodegradable amino‐acid‐based poly(ester amide)s (AA–PEAs) and amino‐acid‐based poly(ether ester amide)s (AA–PEEAs) consisting of reactive pendant functional groups (? COOH or ? NH₂) were synthesized from unsaturated AA–PEAs and AA–PEEAs via a thiol–ene reaction in the presence of a radical initiator (2,2′‐azobisisobutyronitrile). The synthetic method was a one‐step reaction with near 100% yields under mild reaction conditions. The resulting functional AA–PEA and AA–PEEA polymers were characterized by Fourier transform infrared spectroscopy, NMR, and differential scanning calorimetry. These new functional AA–PEA and AA–PEEA derivatives had lower glass‐transition temperatures than the original unsaturated AA–PEA and AA–PEEA polymers, and their solubility in some organic solvents also improved. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Phosphonic acid‐containing polysulfones as anticorrosive layers

As a part of research work to elaborate polymeric materials for metal corrosion protection, we have developed a new family of phosphonic acid‐containing polymers. The synthesis and the characterization of polysulfones bearing alkyl phosphonate ester side groups are first described. These polymers are synthesized by direct polycondensation of a phosphonate ester‐containing bisphenol by aromatic nucleophilic substitution. The physicochemical properties of the resulting polymers are described. Acidic hydrolysis of phosphonate esters results in the formation of phosphonic acid groups. A series of phosphonic acid‐containing polysulfones is therefore obtained and characterized. A preliminary evaluation of the anticorrosive properties of these polymers is described. In 0.25M Na₂SO₄ solution, the corrosion rate of a polymer‐coated mild steel sample is much lower than of the free metal substrate. These results suggest that phosphonic acid‐containing polysulfones might be interesting as anticorrosive coatings. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41890.     

Interfacial Polymerization of Linear Aromatic Poly(ester amide)s

Linear aromatic poly(ester amide)s (PEAs) have been synthesized by interfacial polycondensation (IPC) of aromatic diamidoacid chloride: 2-{[4-({[2-(chlorocarbonyl) phenyl]amino} carbonyl) benzoyl]amino} benzoyl chloride (2CCBC), with ethylene glycol, bisphenol A, resorcinol, 4,4′-bis(4-hydroxybenzilidine)diaminobenzanilide and 4,4′-bis(4-hydroxy benzilidine)-m-phenylenediamine in chloroform/water system employing phase-transfer-catalyst. The aromatic diamidoacid chloride has been prepared by condensation of terephthaloyl chloride with anthranilic acid. These polymers were characterized by elemental analysis, FTIR, ¹H-NMR, solubility studies, intrinsic viscosity and TGA analysis. The polyester-amides so obtained show good thermal stability.     

Stereo‐Controlled Asymmetric Bioreduction of α,β‐Dehydroamino Acid Derivatives

α,β‐Dehydroamino acid derivatives proved to be a novel substrate class for ene‐reductases from the ‘old yellow enzyme’ (OYE) family. Whereas N‐acylamino substituents were tolerated in the α‐position, β‐analogues were generally unreactive. For aspartic acid derivatives, the stereochemical outcome of the bioreduction using OYE3 could be controlled by variation of the N‐acyl protective group to furnish the corresponding (S)‐ or (R)‐amino acid derivatives. This switch of stereopreference was explained by a change in the substrate binding, by exchange of the activating ester group, which was proven by ²H‐labelling experiments.     

Liquid crystal polymers. III. Preparation and properties of poly(ester amides) from p-aminobenzoic acid and poly(ethylene terephthalate)

Poly(ester amides) with physical properties similar to those of liquid crystalline polyesters were prepared by acidolysis of poly(ethylene terephthalate) with p-acetamidobenzoic acid and then polycondensation through the acetamido and carboxyl groups. The ester amide polymers had a random sequence distribution, contained some branching, and at low frequencies had relaxation times appreciably longer than those of poly(ethylene terephthalate). Because of the extended chain orientation of the polymer segments that contained p-aminobenzoic acid (PAB) units, the mechanical properties of injection-molded polymers containing 20–30 mole % PAB were anisotropic. The liquid crystalline characteristics and mechanical properties were further increased by incorporating p-hydroxybenzoic acid units into the polymers.     

Controlled synthesis of thermoresponsive polymer via RAFT polymerization of an acrylamide containing l-proline moiety

Reversible addition–fragmentation chain transfer (RAFT) polymerization of N-acryloyl-l-proline methyl ester (A-Pro-OMe) was investigated in order to find suitable conditions to achieve controlled synthesis of amino acid-based polymers with pre-determined molecular weight, narrow polydispersity, well-defined chain end structure, and characteristic thermoresponsive property. The effect of various parameters, such as chain transfer agent (CTA)/initiator ratio, solvent, and temperature, on RAFT polymerization of A-Pro-OMe was examined using benzyl dithiobenzoate as a CTA. Chain-end structure of the resulting poly(A-Pro-OMe) was confirmed by ¹H NMR analysis, MALDI-TOF mass spectroscopy, and chain extension experiment. Thermally induced phase separation behaviors of poly(A-Pro-OMe)s prepared by RAFT and conventional free radical polymerizations were also studied in aqueous solution.