Towards bilirubin imprinted poly(methacrylic acid-co-ethylene glycol dimethylacrylate) for the specific binding of α-bilirubin

With α-bilirubin as a molecular template, polymerization of methacrylic acid (MAA) was carried out with the aid of the initiator 2,2-azobisisobutyronitrile (AIBN) and the cross-linking agent ethylene glycol dimethylacrylate (EGDMA). Bulk polymerization was successfully carried out so that poly(methacrylic acid-co-ethylene glycol dimethylacrylate) (poly(MAA-EGDMA)) imprinted with α-bilirubin was first developed. UV irradiation polymerization and heated polymerization methods were compared. Effect of different ratios of monomer to EGDMA during the polymerization was also discussed. Proper solvent for better desorption of α-bilirubin from the imprinted poly(MAA-EGDMA) was investigated. In addition, SEM photos were provided for observing the differences between the surfaces of the imprinted poly(MAA-EGDMA) before and after extraction. The corresponding binding results of α-bilirubin imprinted poly(MAA-EGDMA) and non-imprinted poly(MAA-EGDMA) both after extraction were compared. How the pH values during extraction stage affected the binding capacities of the imprinted polymer as well as non-imprinted polymer were also discussed. Similar study and comparison were made for different binding pH values. Different compounds of similar molecular weight were used to show the specific binding of the imprinted polymer for bilirubin. The results further confirmed the successful binding as well as specificity of the imprinted poly(MAA-EGDMA) for α-bilirubin.     

Sensitive determination of yohimbine in plasma by micropipette tip-based poly(methacrylic acid-co-ethylene glycol dimethacrylate) monolith SPME coupled with HPLC method

A simple, miniaturized micropipette tip-based poly(MAA-co-EGDMA) monolith was prepared by in situ polymerization for sensitive micro-extraction of yohimbine in aqueous and plasma samples. Several parameters for monolith preparation were systematically optimized to obtain monolith with better permeability and absorption property. Methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) were selected as monomer and crosslinker and the ratio of MAA and EGDMA was 1:6. Methanol containing 30% dimethyl sulfoxide was selected as porogens. The prepared micropipette tip-based poly (MAA-co-EGDMA) monolith could be easily connected with a syringe infusion pump for loading solutions. Several factors such as washing solvents, flow rate of sampling, sample volume, and pH of sample solutions which affect enrichment efficiency of yohimbine were also evaluated in this work. Under optimized conditions, good enrichment capacity and stability of poly(MAA-co-EGDMA) monolith were obtained. Finally, the prepared micropipette tip-based poly(MAA-co-EGDMA) monolith solid phase micro-extraction combined with high-performance liquid chromatography was also used to analyze yohimbine in plasma samples. The developed method exhibited good sensitivity with limit of detection as low as 0.5?ng/mL, and also showed wide linearity in the range of 1.0–2000 ng/mL with R²?≥?0.998, excellent reproducibility with relative standard deviation (RSD) ≤?2.5%, and good recoveries in the range of 97.9–103.8% of yohimbine in human plasma.     

Complexation between poly(methacrylic) and poly(acrylic) acids and star-shaped poly(ethylene glycol) based on pyrogallol

Complex formation between polymethacrylic (PMAA) and polyacrylic acids, and star-shaped poly(ethylene glycol) prepared by ethoxylation of pyrogallol (Pyr–PEG) has been studied viscometrically and by potentiometric titration in water solution. The competitive ability of Pyr–PEG and of the derivatives of the ethoxylation of phenol and hydroquinone in complex formation with PMAA has been compared by UV spectroscopy. Pyr–PEG turns out to be the weakest competitor because of its chemical structure. © 1996 John Wiley & Sons, Inc.     

Influence of stereoregularity on binding of counterions by poly(methacrylic acid)

The activity coefficient γ, of sodium ion, in aqueous solutions of both isotactic and conventional poly(methacrylic acid) (PMA) has been studies throughout the whole range of degree of neutralization α with a Beckman Na electrode and membrane electrodes. The results show that the fraction of sodium ions bound to isotactic PMA is higher than that bound to conventional (or syndiotactic) PMA over the entire range of α. The binding of divalent counterions (Mg⁺², Cu⁺², Co⁺², and Ni⁺²) by the two forms of PMA (at α = 0.95) has been evaluated from the release of Na⁺ ions with the Beckman Na electrode. Turbidimetric determinations of the critical amount of various divalent cation chlorides necessary to bring about precipitation of both isotactic and conventional PMA (at α = 0.95) have also been carried out.     

聚(甲基丙烯酸-乙二醇二甲基丙烯酸酯)搅拌棒吸附萃取与液相色谱-质谱联用检测牛奶中的磺胺类药物

将聚(甲基丙烯酸-乙二醇二甲基丙烯酸酯) (poly(MAA-co-EDMA))聚合物原位聚合于玻璃内插管外表面上,得到一种多孔聚合物涂层;将其作为搅拌棒吸附萃取的萃取介质,考察了其对磺胺类药物的萃取性能;最后将其与高效液相色谱-电喷雾质谱(HPLC-ESI-MS)联用,建立了一种牛奶中4种磺胺类药物的检测方法。在最佳条件下,牛奶中4种磺胺类药物的检出限(S/N=3)和定量限(S/N=10)分别为0.11～0.52 μg/L和0.35～1.72 μg/L。在1～500 μg/L的范围内峰面积与质量浓度具有良好的线性关系,日内、日间测定的相对标准偏差不高于11.3%。结果表明,该方法简便、灵敏度高且成本低,适合于牛奶中磺胺类药物的检测。     

Thermoresponsive copolymers of methacrylic acid and poly(ethylene glycol) methyl ether methacrylate

Copolymers of methacrylic acid (MAA) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) were prepared and their cloud points in aqueous solution were studied as a function of comonomer ratio, solution pH, and presence of hydrophobic comonomers. Under acidic conditions, the cloud point falls below 0 °C for copolymers with between 25% to 60% ether content, because of the formation of hydrophobic H‐bonded ether–acid complexes. The cloud point also decreases with solution pH. For equivalent ether to acid ratios, the cloud point decreases with decreasing PEG chain length, because of the presence of a larger number of hydrophobic methyl and methacrylate groups. Similarly, the cloud point decreases upon incorporation of hydrophobic comonomers such as butyl, lauryl, or glycidyl methacrylates. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 6095–6104, 2005     

Molecular structure and dynamics of poly(methacrylic acid) and poly(acrylic acid) complexes with dodecyl-substituted poly(ethylene glycol)

The molecular dynamics and the structure of molecular complexes formed by micelles of dodecyl-substituted poly(ethylene glycol) with poly(methacrylic acid) and poly(acrylic acid) in aqueous solutions were studied by viscosimetry, pH measurement, and electron spin resonance spin-probe techniques. At low surfactant concentrations, the conformation of the complex is a compact globule. The local mobility of surfactant molecules in such a complex is much slower than that in the free micelle. At high surfactant concentration, the nonionic micelles and polyacids form hydrophilic associates. The associates have the conformation of extended coils. In an associate, a major part of the micellar poly(ethylene glycol) groups is free. The local mobility of the micellar phase depends on the number of micelles involved in an associate. The mobility of surfactant molecules is slower in the complexes of poly(methacrylic acid) than in the complexes of poly(acrylic acid).     

Isosorbide dinitrate template-based molecularly imprinted poly(methacrylic acid) nanoparticles: effect of initiator concentration on morphology and physicochemical properties

In this work, poly(methacrylic acid) (PMAA)-based molecularly imprinted polymer nanoparticles (MIP NPs) using isosorbide dinitrate (ISDN) as a template were prepared via a precipitation polymerization. The morphology and performance of the samples were investigated by varying different concentrations of azobisisobutyronitrile (AIBN) as an initiator. The MIP NP sample characterization as a function of the initiator concentration was evaluated utilizing Fourier transform infrared (FTIR) spectroscopy and field emission-scanning electron microscopy (FE-SEM) analyses. Regarding the washed MIP NP samples, the FTIR spectra results showed two main characteristic peaks located at 3339 and 1734 cm^?1 wavenumbers corresponding to hydroxyl (–OH) and carbonyl (–C=O) groups, respectively. The intensity of these main peaks for the washed MIP NPs was higher than that of those for unwashed MIP NPs in which the active sites were appropriately formed between the polymer and template. These observations were occurred at the maximum amount of AIBN concentration (3 mmol). Moreover, the FE-SEM micrograph images exhibited an average diameter of approximately 40 nm for the MIP NP sample prepared with a low concentration of the initiator (0.5% of polymerizable double bonds). Furthermore, another two key factors for the MIP NPs such as binding capacity, and surface area using Barrett–Joyner–Halenda (BJH) method were studied to apply them for drug delivery systems potentially. On the other hand, the release of ISDN from MIP NP was considered through phosphate buffer saline (PBS, pH 7.4) at 37 °C for 5 days. The results showed higher ability of the sample compared with the non-imprinted polymer (NIP) ones to control the drug release, and kinetic trend of the drug absorption within the MIP NPs followed the pseudo-first model. Finally, the obtained outcomes showed that the low amounts of the initiator concentration have an indispensable role on the physicochemical properties of the synthesized MIP NPs.     

Competitive complex forming reactions between monosubstituted and nonsubstituted poly(ethylene glycol)s with poly(methacrylic) acid

A competitive complex forming reaction between a number of monosubstituted poly(ethylene glycol)s (PEG*) containing a hydrophobic group of differing chemical nature and nonsubstituted PEG of various molecular weights with poly(methacrylic acid) (PMAA) was studied. A UV spectroscopy method was used. During the transfer of the hydrophobic chromophoric group from the aqueous medium into the hydrophobic domains of the polycomplex (PMAA.PEG*), a bathochromic effect was observed. The introduction of a hydrophobic group into the PEG chain leads to stabilization of the polycomplex (PMAA.PEG) that is formally the same as growing the chain length of PEG. The polymerization degree of PEG having the same competitive power as PEG* can be used as the peculiar scale of the complex forming ability of PEG* in the complexation with PMAA. © 1996 John Wiley & Sons, Inc.     

Stereoregular poly(methacrylic acids)

A convenient method is described for the preparation of isotactic and syndiotactic poly(trimethylsilyl methacrylates) by using the monomer trimethyl silyl methacrylate and butyllithium initiation in toluene and tetrahydrofuran, respectively. The structure of these polymers enables complete hydrolysis to the corresponding poly(methacrylic acids), which were characterized with respect to tacticity and molecular weight. The asymmetric induction in toluene produced 89% isotactic polymer, while that in tetrahydrofuran gave polymer <90% syndiotactic and heterotactic in terms of triads. A method of fractionation of the polyelectrolytes by gel-permeation chromatography on a preparative scale was shown to be applicable.     

Binding of Cu(II) to poly(methacrylic acid)

The binding of Cu(II) ions to partly neutralized poly(methacrylic acid) (PMA) has been investigated by potentiometric titration and dialysis to determine the stoichiometry the Cu–PMA complexes formed. Partly ionized PMA was titrated with solutions of the metal ion to enable a large range of metal ion/polymer ratios to be studied. Combination of the results from these two techniques at ionic strength 0.1 indicates that at very low Cu(II)/polymer ratios, a 4:1 complex exists, but at higher ratios the complex breaks down to give a mainly 2:1 coordination with some 1:1 binding. Conductance titrations support these results. Viscometric titrations show strong interactions between the metal and polymer, preventing the full extension of the polyion at high degrees of ionization, and spectrophotometric titrations support the existence of at least two types of complexes in the solution.     

Synthesis of double hydrophilic graft copolymer containing poly(ethylene glycol) and poly(methacrylic acid) side chains via successive ATRP

A well‐defined double hydrophilic graft copolymer, with polyacrylate as backbone, hydrophilic poly(ethylene glycol) and poly(methacrylic acid) as side chains, was synthesized via successive atom transfer radical polymerization followed by the selective hydrolysis of poly(methoxymethyl methacrylate) side chains. The grafting‐through strategy was first used to prepare poly[poly(ethylene glycol) methyl ether acrylate] comb copolymer. The obtained comb copolymer was transformed into macroinitiator by reacting with lithium diisopropylamine and 2‐bromopropionyl chloride. Afterwards, grafting‐from route was employed for the synthesis of poly[poly(ethylene glycol) methyl ether acrylate]‐g‐poly(methoxymethyl methacrylate) amphiphilic graft copolymer. The molecular weight distribution of this amphiphilic graft copolymer was narrow. Poly(methoxymethyl methacrylate) side chains were connected to polyacrylate backbone through stable C? C bonds instead of ester connections. The final product, poly[poly(ethylene glycol) methyl ether acrylate]‐g‐poly(methacrylate acid), was obtained by selective hydrolysis of poly(methoxymethyl methacrylate) side chains under mild conditions without affecting the polyacrylate backbone. This double hydrophilic graft copolymer was found be stimuli‐responsive to pH and ionic strength. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4056–4069, 2008     

Binding of a surfactant counterion to low-charge-density poly(acrylic acid) and poly(methacrylic acid)

The binding of a cationic surfactant, dodecylpyridinium (C12Py) chloride, with a low-charge-density poly (methacrylic acid) (PMA) was investigated in buffer solutions under the condition of constant pH. The binding isotherms with PMA consisted of two and three steps at a pH lower and higher than 3.2, respectively. Bindings in the first step were independent of pH and this step was considered to correspond to the solubilization of the hydrocarbon chains of C12Py into the nonpolar region of the compact form of PMA. This is the indication of the compact form from the binding isotherm. At pH higher than 3.2, the second step was discriminated and it depended on the pH. In the third step, a sharp rise in the degree of binding (β) was observed accompanying the solubilization of the precipitates of the PMA–C12Py complex. The binding with poly(acrylic acid) (PAA) and PMA in conventional unbuffered NaCl solutions was also examined and the pH profile of the solution during the binding process was determined. In the case of unbuffered NaCl solutions, the binding with PAA took place cooperatively at the critical association concentration (cac). The binding isotherm consisted of two steps and the pH decreased with the increase in β. The binding isotherm of PMA, on the other hand, consisted of three steps: the pH decreased slightly in the first step and considerably in the second step with the increase in β but it increased with β in the third step, exhibiting a pH minimum around 3.2. The binding in the first step coincided with that obtained in the buffered solutions. Linear relationships between β and the pH were found for both polymers. In the case of PMA, no cac was observed in both buffered and unbuffered NaCl solutions. Received: 24 January 2001 Accepted: 23 May 2001     

Effect of urea on poly(methacrylic acid) and poly(acrylic acid) aqueous solutions

The effects of urea on aqueous solutions of both poly(methacrylic acid (PMA) and poly(acrylic acid) (PAA) have been investigated by using potentiometry, viscometry and study of the fluorescence of Auramine O, a cationic dye. The viscosity behaviour of unionized PMA obtained from direct dissolution of solid powder shows that the unneutralized macromolecules can be associated in water. The stability of such “aggregates” seems weak as indicated by their disappearance as soon as the charge density is very low. For PMA salt solution percolated through a cation (H⁺) exchange resin column, no association is observed. The pH-dependent conformational behaviour of PMA which, contrary to PAA, presents compact conformations in water at low charge density is discussed in terms of solvophobic/solvophilic interactions. It is shown that, even for urea concentration up to 8 M, the compact conformations of PMA are not completely destroyed. The formation of H⁺/urea complex is taken into account.     

The effect of pH on charge, swelling and desorption of the dispersant poly(methacrylic acid) from poly(methyl methacrylate) microcapsules

Poly(methyl methacrylate) microcapsules have been prepared using the solvent evaporation technique with poly(methacrylic acid) (PMAA) as dispersant. The charge, swelling and desorption of PMAA from the microcapsules after treating the suspension with base have been followed using microelectrophoresis, X-ray photoelectron spectroscopy and quartz crystal microbalance with dissipation monitoring on model PMMA surfaces. Basic treatment of the microcapsule suspension leads to temporary colloidal stability through the introduction of charges on the PMAA chain. However, the increase in charge causes a continuous desorption of PMAA from the microcapsule surface, eventually leading to aggregation. If instead poly(diallyldimethylammonium chloride) is added to the base treated microcapsule suspension, good colloidal stability is obtained.     

Terpolymerization of methyl methacrylate, poly(ethylene glycol) methyl ether methacrylate or poly(ethylene glycol) ethyl ether methacrylate with methacrylic acid and sodium styrene sulfonate: determination of the reactivity ratios

Materials bearing ionic monomers were obtained through free radical terpolymerization of methyl methacrylate (MMA), poly(ethylene glycol) methyl ether methacrylate (PMEM) or poly(ethylene glycol) ethyl ether methacrylate (PEEM) with methacrylic acid (MA) and sodium styrene sulfonate (NaSS). The reactions were carried out in dimethyl sulfoxide using azobis(isobutyronitrile) as initiator. The reactivity ratios of the different couple of monomers were calculated according to the general copolymerization equation using the Finnemann-Ross, Kelen-Tüdos and Tidwell-Mortimer methods. The values of the reactivity ratios indicate that the different monomer units can be considered as randomly distributed along the chains for terpolymerizations of MMA, PMEM or PEEM with MA and NaSS. The average composition of the comonomers in the different terpolymers were calculated, showing a good agreement between the experimental and theoretical compositions. The instantaneous compositions are constant until about 70% of conversion. For higher conversions, the insertion of ionic monomers increases or decreases according to the system studied.