Linear PAA Research Articles

Synthesis by RAFT polymerization and properties of anionic cylindrical molecular brushes bearing poly(acrylic acid) side chains

RAFT polymerization of acrylic acid (AA) in the presence of low-molecular chain transfer agent (2-(butylthiocarbonothioylthio) propanoic acid and polyacrylate-based backbone bearing multiple butylthiocarbonothioylthio moieties is reported demonstrating successful synthesis of linear pAA with low polydispersity and anionic cylindrical molecular brushes, respectively. Twofold excess of butylthiocarbonothioylthio moieties attached to polyacrylate-based backbone over the initiator was optimal enabling to synthesize graft copolymers with rather low polydispersity (PDI 1.23–1.36) and reasonably high DP of pAA side chains (up to 25). Anionic cylindrical molecular brushes were characterized by SEC with triple detection, DLS, 1H NMR spectroscopy, and potentiometric titration. Thermal transitions and thermal stability of the brush polymers bearing pAA side chains were determined by DSC and TGA.

ELECTRODYNAMICS CALCULATION OF LINEAR PAA WITH MATCHING PERIODICAL STRUCTURE

Matching of PAA with external space is an important problem. There are various methods of improvement of matching by usage of magnito-dielectric inserts and layers, diaphragms [1], inductive irises, impedance flanges [2], etc. In this work use of the matching device in the matching periodical structure (MPS) is considered. The MPS represents a subarray with the same cross sizes as the main antenna array ones, being at a certain distance over the main antennas. Calculation is carried out with integral equation method based on splitting of penetrating area. Numerical research of matching of PAA with external space showed that MPS improve matching at defined sizes and its arrangement. The parameters of MPS providing matching were numerically determined. On average the reflection coefficient when using MPS decreases by 3–4 times in the range of angles of scan from 0° to 60°.

Increased protein sorption in poly(acrylic acid)-containing films through incorporation of comb-like polymers and film adsorption at low pH and high ionic strength.

In principle, incorporation of comb-like block copolymers in multilayer polyelectrolyte films can both increase film thickness relative to coatings containing linear polymers and provide more swollen films for increased sorption of proteins. In the absence of added salt, alternating adsorption of 5 bilayers of protonated poly(allylamine) (PAH) and comb-like poly(2-hydroxyethyl methacrylate)-graft-poly(acrylic acid) (PHEMA-g-PAA) leads to ∼2-fold thicker coatings than adsorption of PAH and linear PAA, and the difference in the thicknesses of the two coatings increases with the number of bilayers. Moreover, the (PAH/PHEMA-g-PAA)n films sorb 2- to 4-fold more protein than corresponding films prepared with linear PAA, and coatings deposited at pH 3.0 sorb more protein than coatings adsorbed at pH 5.0, 7.0, or 9.0. In fact changes in deposition pH and addition of 0.5 M NaCl to polyelectrolyte adsorption solutions alter protein sorption more dramatically than variations in the constituent polymer architecture. When deposited from 0.5 M NaCl at pH 3.0, both (PAH/PHEMA-g-PAA)5 and (PAH/PAA)5 films increase in thickness more than 400% upon adsorption of lysozyme. These films contain a high concentration of free -COOH groups, and subsequent deprotonation of these groups at neutral pH likely contributes to increased protein binding. Lysozyme sorption stabilizes these films, as without lysozyme films deposited at pH 3.0 from 0.5 M NaCl desorb at neutral pH. Films deposited at pH 9.0 from 0.5 M NaCl are more stable and also bind large amounts of lysozyme. The high binding capacities of these films make them attractive for potential applications in protein isolation or immobilization of enzymes.

Bioreducible poly(amido amine)s with different branching degrees as gene delivery vectors

Based on the knowledge that cationic polymers with different topographical structures behave differently in gene transfection process, herein, we synthesized three biodegradable poly(amido amine)s (PAAs) with the same repeating units and molecular weights except for degree of branching: linear PAA (LPAA), low-branched PAA (LBPAA), and high-branched PAA (HBPAA). We found that LBPAA could more effectively compact pDNA into positively charged nanoparticles than both HBPAA and LPAA. LBPAA polyplexes had the highest transfection efficiency among the three PAA polyplexes, and the difference in transfection efficiency is mainly attributed to the endocytosis rate. The cytotoxicity of PAAs was negligible at the transfection doses, probably due to the degradable disulfide bonds. Therefore, we could use branching as a parameter to simply tune a polymer's cellular uptake behavior and transfection efficiency.

Branched Dextran‐graft‐Polyacrylamide Copolymers as Perspective Materials for Nanotechnology

AbstractBranched dextran‐graft‐polyacrylamide copolymers (D‐g‐PAAn) with different number of PAA‐grafts have been synthesized for further conversion them to polyelectrolytes dextran‐graft‐(polyacrylamide‐co‐polyacrylic acid). It is shown that D‐g‐PAAn internal structure in water solution is more compact in comparison with linear polyacrylamide and depends upon the distance between PAA grafts. The branched polyelectrolytes are obtained by alkaline hydrolysis of synthesized D‐g‐PAAn samples. The conversion of nonionic polymers to partial anionic form depends upon the macromolecular internal structure of D‐g‐PAAn. The degree of transformation of amide groups to carboxylate ones is higher for branched copolymers than for linear PAA at the same condition. The synthesized branched copolymers are shown to be perspective as flocculation agents and the matrices for synthesis of the stable Ag nanosystems.

Effects of branched or linear architecture of bioreducible poly(amido amine)s on their in vitro gene delivery properties

In this study, the gene delivery properties of new hyperbranched poly(amido amine)s (PAAs) with disulfide linkages in the main chain were investigated in comparison with their linear analogs. Eight different bioreducible PAAs were prepared by Michael addition of N,N′-bisacryloylpiperazine (BP) with cystamine (CYST) or N,N′-dimethylcystamine (DMC) and of N,N′-cystaminebisacrylamide (CBA) with N,N′-ethylenediamine (EDA) or N,N′-dimethylethylenediamine (DMEDA). In order to study the effect of terminal groups on the transfection efficiency, each polymer was terminated with 4-aminobutanol (ABOL) or with 2-aminoethanol (ETA). The hyperbranched and the linear PAAs generally formed polyplexes with plasmid DNA with sizes around 200nm and positive zeta potentials ranging from +10 to +22mV at polymer/DNA weight ratios equal or higher than 3/1. Remarkably low or no cytotoxicity was observed for both hyperbranched and linear PAAs. Hyperbranched CBA-containing PAAs showed higher gene expression in DNA transfection tests with COS-7 cells than their linear analogs and up to two times higher than linear PEI that was used as the reference polymer. Transfection efficiencies of the branched PAAs were generally enhanced by the presence of serum, which is a promising property for future in vivo studies with these hyperbranched PAAs.In this study the ease of synthetic modification of both linear and hyperbranched poly(amido amide)s and the versatility of hyperbranched PAAs in regulating DNA transfection and cytotoxicity are demonstrated. The results show the large possibilities for this class of polymers to provide polymeric vectors with controllable properties for gene therapy applications.

Solid-Phase Synthesis of Asymmetrically Branched Sequence-Defined Poly/Oligo(amidoamines)

We present for the first time the synthesis of asymmetrically branched sequence-defined poly/oligo(amidoamines) (PAAs) using solid-phase synthesis with the capability of introducing diversity at the side chains. We introduce two new versatile (diethylenetriamine) building blocks for solid-phase synthesis bearing Fmoc/Boc and Fmoc/Alloc protecting groups expanding recently used Fmoc/Boc protecting group strategy for linear PAAs to an Fmoc/Alloc/Boc strategy. This allows for orthogonal on-resin cleavage of Fmoc and Alloc protecting groups during solid-phase synthesis of PAAs with backbones differing in chain length and sequence. With these structures we then demonstrate the potential for generating asymmetrical branching by automated multiple on-resin cleavage of Alloc protecting groups as well as the introduction of side chains varying in length and number. Such systems have high potential as nonviral vectors for gene delivery and will allow for more detailed studies on the correlation between the degree of branching of PAAs and their resulting biological properties.

Poly(amidoamine) Polymers: Soluble Linear Amphiphilic drug-delivery Systems for genes, Proteins and Oligonucleotides

Polymer-drug and polymer-protein conjugates are emerging as a robust and well-characterized class of therapeutic entity. Although there are no low-molecular-weight soluble polymer conjugates in routine clinical use, there are many examples of routinely used high-molecular-weight drugs conjugated to soluble polymers (e.g., Oncospar). Advances in synthetic polymer chemistry have fostered the development of linear poly(amidoamine)s (PAA)s that impart both biodegradability, 'smart' (pH responsive) biological activity and biocompatibility. In their linear form, such as hyper-branched poly(amidoamine) (PAMAM) dendrimers, linear PAAs can be used to deliver large therapeutic entities such as peptides, proteins and genes to either the cytosol or nucleus. Furthermore, these polymers offer great potential in vivo due to their ability to either target the liver or be directed away from the liver and enter tumor mass via the enhanced permeability and retention (EPR) effect. PAAs also exhibit minimal toxicity (dependent upon backbone chemistry), relative to well-characterized polymers used for gene delivery. The propensity of PAAs to modulate intracellular trafficking resulting in their cytosolic translocation has also recently been quantified in vivo and is the primary focus of this article.

Synthetic poly(ester amine) and poly(amido amine) nanoparticles for efficient DNA and siRNA delivery to human endothelial cells

Biodegradable poly(ester amine) (PEA)-based and poly(amido amine) (PAA)-based nanoparticles were developed for efficient in vitro siRNA delivery to human umbilical vein endothelial cells (HUVECs). They were screened, characterized, and compared with traditionally studied DNA-containing particles. Several of the polymeric nanoparticles tested were found to be effective for delivering functional siRNA to green fluorescent protein (GFP) + HUVECs, achieving 60%–75% GFP knockdown while maintaining high viability. While PEAs have been used previously to form polyplexes or nanoparticles for DNA delivery, highly effective siRNA delivery in hard-to-transfect human cell types has not been previously reported. PEAs and linear nondendrimeric PAAs were also found to be effective for DNA delivery to HUVECs using GFP-encoding plasmid DNA (up to 50%–60% transfection efficiency). PEAs and PAAs can be separated into groups that form polymeric nanoparticles effective for siRNA delivery, for DNA delivery, or for both.

Fluorescence Verses Radioactivity Labeling for Lab-Scale Investigation of the Fate of Water-Soluble Polymers in Wastewater Treatment Plants

Water-soluble synthetic polymers are extensively used in cosmetics, detergents and paints. Many end up in wastewater and, later on, in wastewater-treatment plants. In order to gain an insight into their fate in such plants, fluorescence and radioactivity labelings were compared using a lab-scale reactor designed to mimic industrial conditions. Two fermentation media were considered, namely a mixture of E402 and E204 micro-organisms and an activated sludge collected from a water-treatment plant located in the south of France. A sample of low molar mass commercial poly(acrylic acid) (PAA) was labeled by radioactivity with tritium and by coupling the 6-aminofluorescein fluorescent dye. Labeled PAA-containing sludges were allowed to ferment. To monitor the fate of the polymers, aliquots of the fermented mixtures were withdrawn at selected times and centrifuged. Liquid and solid phases were analyzed by scintigraphy or UV spectrometry, depending of the labeling techniques. Both techniques led to similar distributions, c.a. 75% in the supernatant and 25% in the solid phase. Distributions remained constant during the biological tests. There was no degradation of the commercial PAA after aqueous size exclusion chromatography (SEC), in agreement with literature. These features showed that fluorescence-labeling can be used instead of the complex and expensive radiolabeling. The validated fluorescence-based method was then applied to a linear poly(acrylic acid) synthesized by ATRP and labeled with 6-aminofluorescein. There was no significant difference between the commercial and the linear poly(acrylic acid)s. In contrast, a linear PAA with 5% of tert-butyl ester repeating units was predominantly found in the solid phase although adsorption or absorption by micro-organisms could not be demonstrated. The method based on fluorescence labeling should be applicable to other water soluble polymers provided that the dye remains attached to the polymer as it was the case for the studied poly(acrylic acid)s.

Efficient Synthesis of Poly(acrylic acid) in Aqueous Solution via a RAFT Process

The direct polymerization of acrylic acid (AA) in aqueous solution for high molecular weight by means of living radical polymerization is still difficult. Here, AA was polymerized homogeneously in water by a reversible addition-fragmentation transfer polymerization (RAFT) in the presence of a water-soluble trithiocarbonate as a RAFT agent. Various ratios [AA]:[RAFT agent] were investigated to aim at different molecular weights. The polymerization exhibited living free-radical polymerization characteristics at different ratios [AA]: [RAFT agent]: controlled molecular weight, low polydispersity and well-suited linear growth of the number-average molecular weight, M n with conversion. The chain transfer to solvent or polymer was suppressed during the polymerization process, thus high linear PAA with high molecular weight and low PDI can be obtained. Moreover, using the generated PAA as a macro RAFT agent, the chain extension polymerization of PAA with fresh AA displayed controlled behavior, demonstrated the ability of PAA to reinitiate sequential polymerization.

Dendrimer porphyrin-terminated polyelectrolyte multilayer micropatterns for a protein microarray with enhanced sensitivity

Through a combination of layer-by-layer (LbL) self-assembly (SA) and lift-off methods, a dendrimer-coated polyelectrolyte multilayer micropattern was prepared for protein microarrays. A silicon substrate was patterned with a photoresist thin film using conventional photolithography, and then poly(ethyleneimine) (PEI) and poly(sodium 4-styrenesulfonate) (PSS) were alternatively deposited onto the substrate surface using spin-assisted self-assembly. A well-defined multilayer microarray was produced by subsequent removal of the photoresist template by a lift-off process. Dendrimer porphyrin (DP) was successively immobilized onto the PEI-terminated micropatterns via electrostatic interactions between the negatively-charged DPs and positively-charged PEI segments. Because of strong fluorescence from focal porphyrins, the homogeneous covering of DPs onto the multilayer micropatterns was easily confirmed using fluorescence microscopy. Atomic force microscopy (AFM) also showed morphological change of micropatterned surfaces by DP immobilization. Based on these results, IgG was immobilized on the DP-coated protein microarrays, and immunoassays were performed to demonstrate that the DP-coated microarrays yielded a higher fluorescence signal and were more sensitive than the control microarrays that were coated with linear PAA polymer instead of DP due to the multiple functional groups present on the DP-coated arrays and their increased surface area relative to control microarrays.

Poly(amidoamine) Conjugates with Disulfide-Linked Cholesterol Pendants Self-Assembling into Redox-Sensitive Nanoparticles

Poly(amidoamine) (PAA) networks that are obtained by the use of cystamine as a cross-linking agent in the reaction with 2,2'-dithiodipyridine turn into linear PAAs with dithiopyridyl side groups that easily undergo an exchange reaction with thiocholesterol. The resultant products represent the first examples of amphiphilic PAA-cholesterol conjugates in which lipophilic cholesterol moieties are linked to the hydrophilic PAA chain by S-S bonds that are stable in blood but cleavable inside cells. In aqueous media, these conjugates self-assemble into nanoaggregates whose inner cores consist of lipophilic cholesterol domains. A series of PAA-cholesterol conjugates that are derived from two different bis-acrylamides, namely 2,2-bis(acrylamido)acetic acid and 1,4-bis(acryloyl)piperazine, and that have different cholesterol contents were obtained. All products were characterized by (1)H and (13)C NMR spectroscopy, and the average molecular weights of the soluble polymers were determined by size exclusion chromatography. In all instances, the segregation of cholesterol residues from the aqueous medium was revealed by the comparison of their NMR spectra in CDCl3 and D2O, respectively. The TEM analysis of the PAA-cholesterol aggregates in aqueous buffers revealed homogeneous round nanospheres whose dimensions and dimension distributions were determined by DLS. Preliminary cytocompatibility tests demonstrated that all prepared PAA-cholesterol samples are cytocompatible and thus show potential for biotechnological applications.

Temperature‐ and pH‐Sensitive Nanocomposite Gels with Semi‐Interpenetrating Organic/Inorganic Networks

AbstractAn intelligent nanocomposite hydrogel with a semi‐interpenetrating organic/inorganic network was synthesized through in situ free‐radical polymerization of NIPA in the presence of an inorganic clay and linear PAA. The resulting semi‐interpenetrating nanocomposite gels (sI‐NC gels) showed mechanical and swelling/deswelling properties greatly superior to those of other PNIPA/PAA hydrogels. The sI‐NC gels repeatedly changed their swelling behavior in response to both temperature and pH while retaining their remarkable mechanical properties. The structure and homogeneity of these networks were studied and related to the properties of sI‐NC gels and the hydrogen bonding interactions among the constituents.magnified image

Structural Changes of Polyacids Initiated by Their Neutralization with Various Alkali Metal Hydroxides. Diffusion Studies in Poly(acrylic acid)s

The changes in the three-dimensional structure of the poly(acrylic acid), PAA, induced by incorporation of various alkali-metal counterions have been evaluated by studying diffusion of an uncharged probe (1,1'-ferrocenedimethanol) in the polymeric media. The studies are supported by the measurements of conductivity and viscosity of the polymeric media. Solutions of linear PAA of four different sizes (molecular weights: 450,000, 750,000, 1,250,000, 4,000,000) were neutralized with hydroxides of alkali metals of group 1 of the periodic table (Li, Na, K, Rb, Cs) to the desired neutralization degree. The transport properties of the obtained polyacrylates were monitored by measuring the changes in the probe diffusion coefficient during the titration of the polyacids. The probe diffusivity was determined from the steady-state current of the probe voltammetric oxidation at disk microelectrodes. Diffusivity of the probe increases with the increase in the degree of neutralization and with the increase in viscosity. It reaches the maximum value at about 60-80% of the polyacid neutralization. The way the probe diffusion coefficients change is similar in all polyacid solutions and gels. The increase in the size of a metal cation causes, in general, an enhancement in the transport of probe molecules. The biggest differences in the probe diffusivities are between lithium and cesium polyacrylates. The differences between the results obtained for cesium and rubidium are not statistically significant due to lack of good precision of the voltammetric measurements. The measurements of the electric conductivity of polyacrylates and the theoretical predictions supplemented the picture of electrostatic interactions between the polyanionic chains and the metal cations of increasing size. In all instances of the PAAs, the viscosity of the solutions rapidly increases in the 0-60% range of neutralization and then becomes constant in the 60-100% region. With the exception of the shortest chain polyacid, the formation of a rigid medium (gel) has been observed in the experiments with all cations. After the end point of the titration was passed, a sudden drop in the viscosity and the disappearance of the gelatinous structure were seen. The largest value of viscosity has been recorded for the longest chain polyacid. The change in the cation of the strong base used did not affect the viscosity of the polymeric system.

Novel Hybrid Polymer Brushes with Alternating Dendritic Wedges and Linear Side Chains

AbstractSummary: Novel hybrid polymer brushes with alternating dendritic wedge and linear chain as side chains were reported in this paper. Firstly, dendronized polymer initiators of generation one to three, GnMIBr (n = 1, 2, 3), were synthesized through the alternating copolymerization of styryl dendrons and maleimide derivative initiated by AIBN. The linear side chains were then generated through grafting‐from approach using ATRP of tBA initiated with the above‐mentioned macroinitiators. By combining such macromonomers and grafting‐from approach, a new kind of polymer brushes with alternating dendron and linear chain as side chains, GnMI‐g‐PtBA, were thus synthesized and characterized with 1H NMR, SEC, AFM, etc. Morphology studies made by AFM indicate the polymer brushes display a uniform worm‐like structure with a very long contour length. After the hydrolysis of PtBA branches under acidic conditions, amphiphilic dendronized polymer brushes with hydrophilic linear PAA side chains and hydrophobic dendritic side chains of three generations have been prepared.Schematic structure and AFM image of G1MI‐g‐PtBA‐2 dendronized polymer brushes.magnified imageSchematic structure and AFM image of G1MI‐g‐PtBA‐2 dendronized polymer brushes.

Synthesis and characterization of pH-sensitivity semi-IPN hydrogel based on hydrogen bond between poly( N-vinylpyrrolidone) and poly(acrylic acid)

A novel spherically shaped semi-interpenetrating network (semi-IPN) hydrogel, which is based on hydrogen bond between chemical crosslinked poly( N-vinylpyrrolidone) (PVP) and linear poly(acrylic acid) (PAA), was prepared. The semi-IPN hydrogel was synthesized by three steps: (1) linear PAA with different molecular weights were obtained by a reaction of free radical polymerization used 2,2′-azo-bis-iso-butyronitrile (AIBN) as an initiator; (2) crosslinked PVP bead was obtained by a reaction of N-vinylpyrrolidone with AIBN used as an initiator and N, N′-methylene-bis-acrylamide (NNMBA) used as a crosslinker by the way of suspension polymerization; (3) complexation occurred between suitable amount of aqueous solution of PAA and the porous PVP bead and was stabilized by multiple frost–defrost, from this step the semi-IPN hydrogel was obtained. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) proved the presence of the hydrogen bond in the hydrogel. The swelling behaviour of the hydrogel was studied in buffer solution with different pH and NaCl aqueous solution. The results showed that the semi-IPN hydrogel had excellent pH-sensitivity in the range of pH from 2.25 to 4.00 and the small molecule salt had little influence on the swelling behaviour of the semi-IPN hydrogel over the range of concentration of NaCl aqueous solution investigated. The results were confirmed further by scanning electron microscope (SEM). The mechanism of swelling and deswelling was discussed.

Synthesis of cationic water‐soluble copolymers and hydrogels based on [2‐(methacryloyloxy)ethyl]trimethylammonium chloride and 2‐hydroxyethylacrylate and their complex formation with poly(acrylic acid)

AbstractWater‐soluble cationic copolymers and hydrogels were synthesized by radical copolymerization of [2‐(methacryloyloxy)ethyl]trimethylammonium chloride (MADQUAT) and 2‐hydroxyethylacrylate (HEA). The kinetics of copolymerization has been studied and the reactivity ratios were determined. It was found that MADQUAT exhibits higher reactivity in copolymerization. The complexation between linear MADQUAT‐HEA and linear poly(acrylic acid) (PAA) has been studied in aqueous solutions at different pH. It results in the formation of insoluble polyelectrolyte complexes, whose composition and stability to aggregate depends on MADQUAT content in copolymers and pH. The hydrogels were synthesized by three‐dimensional radical copolymerization of MADQUAT and HEA in the presence of a crosslinker. The effects of the feed mixture composition on yield and swelling properties of the hydrogels were studied. The interactions of these hydrogels with linear PAA result in formation of gel–polyelectrolyte complexes and contraction of the samples. It was found that the contraction depends on copolymer composition, PAA molecular weight, and solution pH. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44:845–853, 2006

Characterization of anion diffusion in polymer hydrogels used for wastewater remediation

Ion exchange systems for the removal of nutrient pollutants, even at extremely low concentrations, from wastewater effluents are a major environmental need. This work reports on the features of batch sorption processes for the ultimate removal and recovery of reactive phosphorus, nitrogen, and sulfur anions from aquaculture production wastewater effluents. The sorbent used was a crosslinked polyamine (PAA·HCl) polymeric hydrogel. The PAA·HCl hydrogels were prepared by chemically crosslinking aqueous solutions of linear PAA·HCl chains with epichlorohydrin (EPI). The nutrient anion binding capacity of the gels was studied as a function of various processing parameters. Lab scale batch and experiments showed maximum anion removal, from aquaculture wastewater, with regard to PO 4 3 − by 99%, NO 3 − by 70%, and SO 4 2 − by 95%. PO 4 3 − diffusivities of 16, 10, and 8×10 −6 cm 2/s were measured at pH levels of 5.5, 7.0, and 8.5.

Interpolymer complexes of poly(acrylic acid) nanogels with some non-ionic polymers in aqueous solutions

Formation of interpolymer complexes (IPC) between the nanogels of poly(acrylic acid) (PAA) and linear polyvinylpyrrolidone (PVP), poly(vinyl methyl ether) (PVME) and poly(vinyl ether of ethyleneglycol) (PVEEG) in aqueous solutions has been studied by viscometric, turbidimetric and FTIR spectroscopic methods. It was found that in the course of complex formation the nanogels are characterised by lower amplitude of conformation changes in comparison with linear PAA. The critical pH values of complexation were determined. It was shown that the nanogels have lower complexation ability than linear PAA with respect to non-ionic polymers because of steric reasons caused by intramolecular cross-linked structure.