Preparation and characterization of the poly(2-hydroxyethyl methacrylate)–salicylic acid conjugate

A new polymeric system containing hydrolysable ester bond linked to salicylic acid to be used for controlled drug release was synthesized. Poly(2-hydroxyethyl methacrylate) (PHEMA) functionalized with chloroacetate groups was obtained by the reaction between PHEMA and chloroacetyl chloride using the N,N-dimethylacetamide/5% lithium chloride system as a solvent and pyridine as a catalyst. The degree of substitution was calculated from the chlorine content and ranged from 32.2 to 98.1 mol.% depending on the ratio of chloroacetyl chloride to PHEMA. The coupling of salicylic acid to PHEMA functionalized with chloroacetate groups was carried out by the reaction between PHEMA and the sodium salt of salicylic acid. The structures of chloroacetylated PHEMA and PHEMA–salicylic acid conjugates were determined by means of FTIR, ¹H-NMR and ¹³C-NMR spectra. The hydrolysis in the heterogeneous system of PHEMA–salicylic acid conjugates were performed in buffer solutions (pH 7.6 and 8.5) at 37 °C and showed that the release of the drug (sodium salicylate) from tablets was dependent on the hydrophilic character of conjugate as well as on the pH value of the medium.     

Synthesis,characterization, and in vitro drug‐release properties of 2‐hydroxyethyl methacrylate copolymers

2‐Hydroxyethyl methacrylate was copolymerized with acrylamide, N‐vinyl‐2‐pyrrolidone, and n‐butyl methacrylate by free‐radical solution polymerization with α,α′‐azobisisobutyronitrile as an initiator at 70 ± 1°C. The average molecular weights and molar compositions of the resultant copolymers were determined with gel permeation chromatography and ¹H‐NMR spectroscopy data, respectively. Diclofenac or 2‐[(2,6‐dichlorophenyl)amino]benzene acetic acid, a nonsteroidal anti‐inflammatory drug, was chemically attached to the copolymers by transesterification reaction in the presence of N,N′‐dicyclohexylcarbodiimide to give macromolecular prodrugs. All the synthesized polymers were characterized with Fourier transform infrared, ¹H‐, and ¹³C‐NMR spectroscopy techniques. The polymer–drug conjugates were hydrolyzed in cellophane member dialysis bags containing aqueous buffered solutions (pH 8) at 37°C, and the hydrolysis solutions were detected by UV spectrophotometer at selected intervals. The results showed that the drug could be released by selective hydrolysis of the ester bond from the side chain of the drug moiety. The release profiles of the drug indicated that the hydrolytic behavior of polymeric prodrugs strongly depends on the hydrophilicity of the polymer. The results suggest that the synthesized copolymers could be useful carriers for the release of diclofenac in controlled‐release systems. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 2403–2409, 2007     

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 Polymerization of a Four-Arm Star with Pendent Cyclopentadienyliron Moieties

The synthesis of the title complex was achieved via the reaction of a η⁶-p-dichlorobenzene-η⁵-cyclopentadienyliron cation with an organic four-arm core to produce the tetrairon complex. This tetrairon-containing core was subsequently polymerized via nucleophilic aromatic substitution with various dinucelophiles such as 4,4′-thiobenzenethiol, bisphenol-A, 4,4′-(1-phenylethylidene)bisphenol, 4,4′-biphenol, bis(4-hydroxyphenyl)methane, producing five different cross-linked cationic organoiron polymers. Another cross-linked polymer was produced via direct polymerization of the four-arm organic core with the η⁶-p-dichlorobenzene-η⁵-cyclopentadienyliron cation. Due to the poor solubility of these cross-linked polymers, solid-state ¹³C CPMAS NMR was performed in order to verify that polymerization was successful. Thermogravimetric analysis (TGA) revealed that following the decoordination of the cyclopentadienyliron moieties, the polymers were thermally stable. Differential scanning calorimetry (DSC) showed that the polymers exhibited glass transition temperatures (T _g’s) ranging from 104 to 146°C. This article is dedicated to Professor Ian Manners for his outstanding contribution to the field of metal-containing polymers.     

Synthesis of amphiphilic network copolymers based on poly(ester dimethacrylates)

Poly(ester dimethacrylate) has been synthesized by condensation of the ɛ-caprolactone-based macromonomer and 2-hydroxyethyl methacrylate with dicyclohexylmethane diisocyanate. Network copolymers of different compositions capable of swelling in water, THF, and toluene are obtained by the free-radical copolymerization of poly(ester dimethacrylate) with N-isopropylacrylamide or 2-hydroxyethyl methacrylate. The rate constants and equilibrium swelling indices of network copolymers in these solvents are measured. The amphiphilic properties of the network copolymers can vary in a wide range depending on the composition of copolymers and the nature of a hydrophilic monomer. The copolymers of poly(ester dimethacrylate) with N-isopropylacrylamide are characterized by pronounced thermal sensitivity.     

Synthesis of water-soluble homo- and block-copolymers by RAFT polymerization under γ-irradiation in aqueous media

The ambient temperature (20 °C) reversible addition fragmentation chain transfer (RAFT) polymerization of several water-soluble monomers conducted directly in aqueous media under γ-initiation (at dose rates of 30 Gy h⁻¹) proceeds in a controlled fashion. Using functional trithiocarbonates, i.e., S,S-bis(α,α′-dimethyl-α″-acetic acid) trithiocarbonate (TRITT), 3-benzylsulfanyl thiocarbonylsulfanyl propionic acid (BPATT), and dithioester, i.e., 4-cyanopentanoic acid dithiobenzoate (CPADB), as chain transfer agents, fully water-soluble polymers of monomers such as N,N-dimethylacrylamide, 2-hydroxyethyl acrylate, acrylamide or oligo(ethylene glycol) methacrylate and stimuli-responsive polymers of monomers such as acrylic acid, N-isopropylacrylamide, 2-(dimethylamino)ethyl methacrylate or 2-acrylamido-2-methylpropane sulfonic acid can be obtained over a wide range of degrees of polymerization up to 10,000 with low polydispersity (typically ) to near quantitative conversions. Well-defined block copolymers between these monomers, based on several asymmetric macro-RAFT agents, can be obtained, suggesting that the RAFT agents are stable throughout the polymerization process so that complex and well-defined architectures can be obtained.     

Network characteristics of homopolymer and some copolymers of poly(2-hydroxyethyl methacrylate)

Soluble poly(2-hydroxyethyl methacrylate) and copolymers of 2-hydroxyethyl methacrylate with n-butyl acrylate and 2-hydroxypropyl acrylate of varying compositions were synthesised by solution polymerisation. The polymers were characterised by dilute solution viscometry and shear viscosity. Crosslinked membranes were prepared from these polymers by introducing crosslinks in solution state through the reaction with 1,6-hexamethylene diisocyanate at a number of different crosslinker concentrations. The membranes swollen in dimethylformamide and water were characterised by performing equilibirium swelling measurements and calculating polymer volume fraction, the molecular mass between crosslinks (M?^c) and equilibrium water content (EWC) at 25°C. The calculation of M?^c used an expression developed by Peppas & Lucht for equilibrium swelling. This is a modified equation of the original Flory–Rehner expression, that allows non-Gaussian distribution of chain lengths. The variation of M?^c with crosslinker concentration and copolymer composition is discussed in terms of structural and molecular characteristics of these highly crosslinked networks.     

Biologically active polymers. IV. Synthesis and antimicrobial activity of polymers containing 8‐hydroxyquinoline moiety

Polymers containing 8‐hydroxyquinoline moiety were prepared. Modifications of the base polymer of glycidyl methacrylate were carried out in order to introduce chloromethyl groups, either by the hydrolysis of the poly(glycidyl methacrylate) and the chloroacetylation of the hydrolyzed polymer by the reaction with chloroacetyl chloride or by aminating the poly(glycidyl methacrylate) either with ethylenediamine or with hexamethylenediamine, followed by reacting the aminated polymers with chloroacetyl chloride. The polymers containing 8‐hydroxyquinoline moiety were prepared by reacting the chloromethyl groups containing polymers with potassium salt of 8‐hydroxy quinoline. The antimicrobial activity of the polymers obtained was examined against gram‐negative bacteria (Escherichia coli) and gram‐positive bacteria (Bacillus subtilus) as well as the fungus Trichophyton rubrum. Generally, all three polymers proved effective against the tested microorganisms, but growth inhibitory effects varied from one another. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 1364–1374, 2001     

Physico-chemical characterization of hybrid polymers obtained by 2-hydroxyethyl(methacrylate) and alkoxides of zirconium

Hybrid monolithic materials were prepared through polymerisation of 2-hydroxyethyl methacrylate (HEMA) mixed with zirconium alkoxides (Zr(OBuⁿ)₄, Zr(OPrⁿ)₄ and Zr(OEt)₄), modified by acetylacetonate groups. The molar ratio HEMA/Zr varied between 1 and 4. Thermo-Gravimetry coupled with Mass Spectroscopy (TG-MS) analyses, ¹³C MAS NMR and Dynamical Mechanical Thermal Analysys (DMTA) indicated the polymeric chains were interconnected by the inorganic component.The presence of zirconium alkoxides modified substantially the poly-HEMA properties. Glass transition temperature of hybrid materials derived from butoxy and propoxy was found in the range 50-80 °C, depending on the composition. The typical swelling of p-HEMA in the water, was suppressed by the presence of zirconium compounds. After immersion in distilled water, hybrid polymers showed an initial slight weight increase, followed by a small mass loss, which increases proportionally to the length of alkoxyl group (ethoxide(propoxide(butoxide) and reaches a constant value after about 40 days. The hybrids remained always rigid and transparent. Flexural modulus and strength of about 400-900 and 4-8 MPa were measured.     

Boric acid binding studies with diol containing polyethylenimines as determined by 11B NMR spectroscopy

Three water‐soluble polymers incorporating increasing levels of 2,3‐dihydroxy propyl attached to polyethylenimine (PEI) backbone were synthesized, characterized by NMR, and investigated for their ability to bind boric acid (BA). ¹¹B NMR spectroscopy showed that BA interacted with the polymeric 2,3‐dihydroxy propyls by forming borate monoester and borate diesters in the boron concentration range of 100–1000 ppm and at 0.0775M polymer. Borate monoester species predominated for low functionalization levels (33% of the PEI amines functionalized), whereas borate diester species dominated for the higher functionalized polymers (66–100% of the PEI amines functionalized). All three polymers showed that 100% of the BA was bound as a mixture of borate mono‐ and diesters at 100‐ppm boron. The overall best performer based on total borate ester formation was the 2/3‐PEI, with a binding K_d of 631 at 200 ppm boron. Borate ion concentration was measured from the ¹¹B NMR chemical shift of the BA/borate peak and it decreased as 1/3‐PEI > 2/3‐PEI > 3/3‐PEI. Variable temperature ¹¹B NMR showed drastic reduction of borate ester species at 65°C. Thus, PEI polymers, as the ones investigated in this work, are reasonable candidates for the selective recovery and recycle of BA. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 4411–4418, 2006     

Effect of the crosslinking agent on porous networks formation of hema-based copolymers

New copolymers of ethylene glycol dimethacrylate/2-hydroxyethyl methacrylate [poly(EGDMA-co-HEMA)],2,2′,2″-nitrilotriethyl triacrylate/2-hydroxyethyl methacrylate [poly(NTETA-co-HEMA)] and pentaerythritol tetraacrylate/2-hydroxyethyl methacrylate [poly(PETA-co-HEMA)] were obtained by suspension polymerization at 70 or 85 °C, using cyclohexane (Cyc) as porogen. In this work, the influence of the crosslinking agent (di, tri, or tetravinyl monomer) on the morphology of the polymeric networks was investigated. Swelling studies, Fourier Transform Infrared (FTIR) and mercury intrusion porosimetry, demonstrated that when both the vinyl groups number and molecular chain length between double bonds of the crosslinking agent decreased, networks with high porosity and crosslinking degree were generated.     

Superabsorbent polymeric materials. I. Swelling behaviors of crosslinked poly(sodium acrylate-co-hydroxyethyl methacrylate) in aqueous salt solution

A series of crosslinked poly(sodium acrylate-co-hydroxyethyl methacrylate) based on sodium acrylate (SA), 2-hydroxyethyl methacrylate (HEMA), and N,N′-methylene-bis-acrylamide (NMBA) are prepared by inverse suspension polymerization. The resultant crosslinking polymers are xerogellants. This work investigates not only the absorbency or swelling behavior for these xerogellants composed of different ratios of HEMA/SA in water, but also the effects of various salts and pH values on the swelling properties. Experimental results indicate that the absorbency in deionized water decreases with an increase in the HEMA in copolymeric gel, which is related to the degree of expansion of the network and the strength of the hydrophilic group. The absorbency in the chloride salt solutions decreases with an increase in the salt concentration (swelling is 50 times for the IA group chloride salt solutions, but is less than 5 times for the IIA group salt solution), owing to the osmosis of water and ions between the polymeric gel and the external solution. A decrease in the extent of swelling occurs for divalent and trivalent chloride salt solutions. For the salt solutions of the same ionic strength, the swelling amount has the following tendency: LiCl(aq) = NaCl(aq) = KCl(aq), CaCl₂(aq) < SrCl₂(aq) < BaCl₂(aq), and Fe³⁺ > Ca²⁺ > Zn²⁺ > Cu²⁺. These orders are related to the complexing ability between metallic cations and the carboxylate group in the polymeric chains. Finally, the adsorption of ferric ion by these gels is also investigated. © 1996 John Wiley & Sons, Inc.     

Novel amino acid-based polymers for pharmaceutical applications

Summary Entirely amino acid-based polymers were prepared by side-chain attachment to polysuccinimide derived from the thermal polycondensation of aspartic acid. Following deprotonation of various amino acid ester hydrochlorides by a secondary amine, the restored primary amino groups initiated the ring-opening of succinimide to form amide bonds. ¹H and ¹³C NMR measurements revealed that the mole fraction of the introduced amino acid side chains could be controlled by the reaction time, while no hydrolysis of methyl ester groups was observed. The synthesized polymers contain exclusively amino acids, which makes them promising candidates as base materials of controlled drug delivery systems.     

13C nuclear magnetic resonance spectral confirmation of Δ6-and Δ7-trans-18:1 fatty acid methyl ester positional isomers

Trans octadecenoic acid methyl ester isomers were obtained from a partially hydrognated soybean oil and isolated by silver-ion high-performance liquid chromatography. Recently, the double-bond positions for nine individual trans octadecenoic acid positional isomers (Δ8 through Δ16) were confirmed by gas chromatography-electron ionization mass spectrometry after derivatization to 2-alkenyl-4,4-dimethyloxazoline. In this communication, the presence of two additional trans-18:1 fatty acid methyl ester positional isomers (Δ6 and Δ7) in the same mixture is confirmed by ¹³C nuclear magnetic resonance spectroscopy. The identity of the Δ5-trans-18:1 fatty acid methyl ester positional isomer is inferred. Summer student researcher.     

Free-radical propagation rate coefficients for hydroxyalkyl methacrylates and cyclohexyl methacrylate

Free-radical propagation rate coefficients (k _p ) at 30°C for the homopolymerization of cyclohexyl methacrylate (CHMA), 4-hydroxybutyl methacrylate (HBMA), 2-hydroxypropyl methacrylate (HPMA), and 2-hydroxyethyl methacrylate (HEMA) were determined to be 1070, 917, 640, and 71.9 (L mol⁻¹s⁻¹), using the rotating-sector method. The k _p value increases rapidly, and the value of life time of free radicals (τ_s) increases smoothly with increasing the alkyl chain length in the hydroxyalkyl pendant group of the monomer. Values for the steady-illumination polymerization rate for CHMA, HBMA and HPMA are much larger than that for HEMA. Comparisons of k _p values from different sources were also made.     

The effects of zwitterionic and anionic charge densities in polymer chains on the viscosity behavior of a pH‐responsive hydrophobically modified ionic polymer

Sulfur dioxide, N,N‐diallyl‐N‐carboethoxymethylammonium chloride, and the hydrophobic monomer N,N‐diallyl‐N‐octadecylammonium chloride were cyclocopolymerized in dimethyl sulfoxide using azobisisobutyronitrile (AIBN) as the initiator to afford water‐soluble cationic polyelectrolytes (CPE) having a five‐membered cyclic structure on the polymeric backbone. The CPE on acidic hydrolysis of the pendent ester groups gave the corresponding cationic acid salts (CAS), which, on treatment with sodium hydroxide, were converted to polybetaines (PB) and anionic polyelectrolytes (APE), as well as polymers PB/APE containing various proportions of zwitterionic (PB) and anionic fractions (APE) in the polymer chain. The solution properties of the CPE, APE, and PB/APE systems containing varying amounts of the hydrophobic monomers in the range 0–4 mol % were investigated by viscometric techniques. Treating the pH‐responsive CAS polymers 4 with different equivalents of NaOH varied the zwitterionic and anionic charge densities in the polymer chain. It was found that the PB/APE polymer with a ratio of 33 : 67 for the zwitterionic and anionic fractions in the polymer chain, respectively, gave the highest viscosity value. The polymers showed that concentration (C*_HA) of around 1 g/dL was required for the manifestation of significant hydrophobic associations. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 1404–1411, 2005     

Alkaline hydrolysis of homopolymers and copolymers of 2-hydroxypropyl methacrylate

Homopolymers of 2-hydroxypropyl methacrylate (HPMA) and copolymers with acrylic acid (AA) were prepared in 1,4-dioxane. The reactivity ratios were determined to be r_AA = 0.27 ± 0.04 and r_HPMA = 2.2 ± 0.2. The alkaline hydrolysis by sodium hydroxide of the HPMA monomer and polymers showed that while the HPMA monomer hydrolyzed readily as expected for a low-molecular-weight carboxylic ester the HPMA homopolymer and water-soluble sodium acrylate (NaA) copolymers were extremely resistant to alkaline hydrolysis. The saponification reaction followed a second-order rate equation, being first order with respect to both HPMA and hydroxide ion concentration. The Arrhenius parameters, activation energy E and frequency factor A, for the alkaline hydrolysis of HPMA monomer in water were found to be E = 10.3 Kcal/mol and A = 1.5 × 10⁸ L/mol min, and those for the NaA–HPMA copolymers in water were found to be E = 24 kcal/mol and A = 4 × 10¹² L/mol min. The NaA–HPMA copolymers had a limiting extent of hydrolysis, ranging from 9–90% ester conversion. A sharp rate decrease at low conversion was noted during the HPMA homopolymer hydrolysis in 58/42 dimethyl sulfoxide/water, allowing the calculation of two distinct reaction rates. © 1992 John Wiley & Sons, Inc.     

Thiophene‐ and silarylene‐containing polyesters. Resonance effect on conductivity after polarization in an external electric field

Polyesters were synthesized by direct polycondensation of thiophene‐2,5‐dicarboxylic acid and five different silarylene‐containing diphenols using a tosyl chloride/pyridine/N,N‐dimethylformamide system as a condensing agent. Polymers were obtained in good yields and were characterized using Fourier transform infrared and NMR (¹H, ¹³C, 135‐DEPT and ²⁹Si) spectroscopy and elemental analysis. All polymers were completely soluble in aprotic organic polar solvents such as dimethylformamide, dimethylsulfoxide and N‐methyl‐2‐pyrrolidone. The range of effective mass of the polymers (m/z) was 1 × 10⁵–2 × 10⁵, determined using electrospray ionization mass spectrometry. Asymmetry and steric hindrance prevented dense packing of the polymeric chains, showing glass transition temperatures between ? 78 and ? 51 °C and loss of thermal stability at 177–199 °C (10% weight loss). Additionally, the melting points of the polyesters were found to be in the range 62–67 °C. Because of this, the samples were semi‐solid at room temperature. The optical band gaps of the polymers were observed between 4.54 and 4.48 eV, corresponding in all cases to insulator behavior. The molecular structure of the samples was studied using X‐ray diffraction, showing a degree of order that was associated with two monoclinic lattices. Additionally, the conductivity was studied using a two‐point method with contacts on top of polymer films. Prior to the electrical measurement, the samples were polarized in an external electric field of 0.8 to 6.4 V cm^?1, and the alignment of the dipoles increased the electrical conductivity. Copyright © 2012 Society of Chemical Industry     

Photo-induced crosslinking of water-soluble polymers with a new photobase generator

A strong bicyclic guanidine base, 1,5,7-triaza-bicyclo[4.4.0]dec-5-ene (TBD), is photo-generated from its tetraphenylborate salt (TBD·HBPh₄) and can effectively catalyze the transesterification reaction between the ester and hydroxy groups in polymers. Accordingly, with TBD·HBPh₄ as a photobase generator, a water-soluble polymer blend, namely poly(1-vinylpyrrolidone-co-2-dimethylaminoethyl methacrylate) and 2-hydroxyethyl cellulose, has been developed as a potential eco-friendly photoresist. This photoresist system uses only water as a solvent and as a developer, rather than organic solvents and aqueous alkaline developers. The effects of the amount of photobase generator, polymer composition and photolithographic conditions on the photo-induced crosslinking and patterning of water-soluble polymers were studied.     

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