Designing Temperature-Responsive Biocompatible Copolymers and Hydrogels Based on 2-Hydroxyethyl(meth)acrylates

Free-radical copolymerization of 2-hydroxyethyl methacrylate with 2-hydroxyethyl acrylate can be successively utilized for the synthesis of water-soluble polymers and hydrogels with excellent physicochemical properties, thus showing promise for pharmaceutical and biomedical applications. In the work presented it has been demonstrated that water-soluble copolymers based on 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate exhibit lower critical solution temperature in aqueous solutions, whereas the corresponding high molecular weight homopolymers do not have this unique property. The temperature-induced transitions observed upon heating the aqueous solutions of these copolymers proceed via liquid−liquid phase separation. The hydrogels were also synthesized by copolymerizing 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate in the absence of a bifunctional cross-linker. The cross-linking of these copolymers during copolymerization is believed to be due to the presence of bifunctional admixtures or transesterification reactions. Transparency, swelling behavior, mechanical properties, and porosity of the hydrogels are dependent upon the monomer ratio in the copolymers. Hydrogel samples containing more 2-hydroxyethyl methacrylate are less transparent, have lower swelling capacity, higher elastic moduli, and pores of smaller size. The assessment of the biocompatibility of the copolymers using the slug mucosal irritation test revealed that they are also less irritant than poly(acrylic acid).

Synthesis of beaded poly(vinyl ether) solid supports with unique solvent compatibility

Poly(vinyl ether) gels SLURPS (Superior Liquid Uptake Resin for Polymer-supported synthesis) with low cross-linking levels have been synthesized for the first time in beaded form using a non-aqueous inverse suspension polymerisation approach. The synthetic protocol was optimized with regards to several parameters including reactions conditions, type and concentration of suspension stabilizer and controlled low temperature addition of co-initiator. Particle size measurements confirm the production of beads with average diameters of 700e950 mm. Optimization of the monomer composition of the poly (vinyl ether) gels resulted in a novel beaded polymer support with considerably improved as well as unique swelling characteristics in solvents ranging from hexane to water. The synthetic utility of the new gel was confirmed by carrying out a set of transformations with complete conversion leading to a useful amino and hydroxy terminated solid-phase precursor resin. Reaction progress could be monitored easily by 1H and 13C gel-phase NMR.

Multivalency in healable supramolecular polymers: the effect of supramolecular cross-link density on the mechanical properties and healing of noncovalent polymer networks

Polymers with the ability to heal themselves could provide access to materials with extended lifetimes in a wide range of applications such as surface coatings, automotive components and aerospace composites. Here we describe the synthesis and characterisation of two novel, stimuli-responsive, supramolecular polymer blends based on π-electron-rich pyrenyl residues and π-electron-deficient, chain-folding aromatic diimides that interact through complementary π–π stacking interactions. Different degrees of supramolecular “cross-linking” were achieved by use of divalent or trivalent poly(ethylene glycol)-based polymers featuring pyrenyl end-groups, blended with a known diimide–ether copolymer. The mechanical properties of the resulting polymer blends revealed that higher degrees of supramolecular “cross-link density” yield materials with enhanced mechanical properties, such as increased tensile modulus, modulus of toughness, elasticity and yield point. After a number of break/heal cycles, these materials were found to retain the characteristics of the pristine polymer blend, and this new approach thus offers a simple route to mechanically robust yet healable materials.

Stabilization of the i-motif structure by the intra-strand cross-link formation

The i-motif structures are formed by oligonucleotides containing cytosine tracts under acidic conditions. The folding of the i-motif under physiological conditions is of great interest because of its biological role. In this study, we investigated the effect of the intra-strand cross-link on the stability of the i-motif structure. The 4-vinyl-substituted analog of thymidine (T-vinyl) was incorporated into the 5′-end of the human telomere complementary strand, which formed the intra-strand cross-link with the internal adenine. The intra-strand cross-linked i-motif displayed CD spectra similar to that of the natural i-motif at acidic pH, which was transformed into a random coil with the increasing pH. The pH midpoint for the transition from the i-motif to random coil increased from pH 6.1 for the natural one to pH 6.8 for the cross-linked one. The thermodynamic parameters were obtained by measuring the thermal melting behaviors by CD and UV, and it was determined that the intra-strand cross-linked i-motif is stabilized due to a favorable entropy effect. Thus, this study has clearly indicated the validity of the intra-strand cross-linking for stabilization of the i-motif structure.

Development of films based on blends of gelatin and poly(vinyl alcohol) cross linked with glutaraldehyde

Both gelatin and poly(vinyl alcohol) (PVA) can be cross linked with glutaraldehyde (GLU). In the case of gelatin, the GLU reacts with each e-NH2 functional group of adjacent lysine residues, while for PVA, the GLU reacts with two adjacent hydroxyl groups, forming acetal bridges. Thus it can be considered possible to cross link adjacent macromolecules of gelatin and PVA using GLU. In this context, the aims of this work were the development of biodegradable films based on blends of gelatin and poly(vinyl alcohol) cross linked with GLU, and the characterization of some of their main physical and functional properties. All the films were produced from film-forming solutions (FFS) containing 2 g macromolecules (PVA + gelatin)/100 g FFS, 25 g glycerol/100 g macromolecules, and 4 g GLU (25% solution)/100 g FFS. The FFS were prepared with two concentrations of PVA (20 or 50 g PVA/100 g macromolecules) and two reaction temperatures: 90 or 55 degrees C, applied for 30 min. The films were obtained after drying (30 degrees C/24 h) and conditioning at 25 degrees C and 58% of relative humidity for 7 days, and were then characterized. The results for the color parameters, mechanical properties, phase transitions and infrared spectra showed that some chemical modifications occurred, principally for the gelatin. However, in general, all the characteristics of the films were either typical of films based on blends of these macromolecules without cross linking, or slightly higher. A greater improvement in the properties of this material was probably not observed due to the crystallinity of the PVA, which has a melting point above 90 degrees C. The presence of microcrystals in the polymer chain probably reduced macromolecular mobility, hindering the reaction. Thus more research is necessary to produce biodegradable films with improved properties. (C) 2011 Elsevier Ltd. All rights reserved.

Recoverable rhodium nanoparticles: Synthesis, characterization and catalytic performance in hydrogenation reactions

We here report the first magnetically recoverable Rh(0) nanoparticle-supported catalyst with extraordinary recovery and recycling properties. Magnetic separation has been suggested as a very promising technique to improve recovery of metal-based catalysts in liquid-phase batch reactions. The separation method is significantly simple, as it does not require filtration, decantation, centrifugation, or any other separation technique thereby, overcoming traditional time- and solvent-consuming procedures. Our new magnetically separable catalytic system, comprised of Rh nanoparticles immobilized on silica-coated magnetite nanoparticles, is highly active and could be reused for up to 20 times for hydrogenation of cyclohexene (180,000 mol/mol(Rh)) and benzene (11,550 mol/mol(Rh) under mild conditions. (c) 2007 Elsevier B. V. All fights reserved.

Preparation of recoverable Ru catalysts for liquid-phase oxidation and hydrogenation reactions

We here report the synthesis, characterization and catalytic performance of new supported Ru(III) and Ru(0) catalysts. In contrast to most supported catalysts, these new developed catalysts for oxidation and hydrogenation reactions were prepared using nearly the same synthetic strategy, and are easily recovered by magnetic separation from liquid phase reactions. The catalysts were found to be active in both forms, Ru(III) and Ru(0), for selective oxidation of alcohols and hydrogenation of olefins, respectively. The catalysts operate under mild conditions to activate molecular oxygen or molecular hydrogen to perform clean conversion of selected substrates. Aryl and alkyl alcohols were converted to aldehydes under mild conditions, with negligible metal leaching. If the metal is properly reduced, Ru(0) nanoparticles immobilized on the magnetic support surface are obtained, and the catalyst becomes active for hydrogenation reactions. (c) 2009 Elsevier B.V. All rights reserved.

Changes in Apoptotic Gene Expression Induced by DNA Cross-Linkers

The Millard Research Laboratory is interested in the cytotoxic mechanisms of the bifunctional alkylators diepoxybutane (DEB), epichlorohydrin (ECH), and (1-chloroethenyl) oxirane (COX). Studies performed in the laboratory examine the dual nature of these DNA cross-linking compounds that can act as carcinogens or anti-cancer agents. The mechanisms through which these compounds induce cell death are explored in this study. Cells either undergo cell death due to necrosis or apoptosis. HL-60 cells were treated with varying concentrations of DEB, ECH, or COX. A caspase 3/7 assay was used to test for induction of apoptosis in the treated cells at varying incubation times. It was concluded that DEB induces apoptosis in HL-60 cells treated with 100 μM for 24 hours. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was then used to explore the changes in gene expression of various genes involved in apoptosis signaling. The results were inconclusive as to specific genes involved in DEB induced apoptosis, but the data does suggest that apoptosis is induced by a mitochondrial-mediated apoptosis signaling pathway.

Preparation and characterization of free films of high amylose/pectin mixtures cross-linked with sodium trimetaphosphate

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influence of phosphated cross-linked high amylose on in vitro release of different drugs

The influence of structural characteristics of high amylose cross-linked at different degrees on the release of drugs with important molecular differences, namely sodium diclophenac (SD) and nicotinamide (NI), was assessed in vitro from non-compacted systems. The release profiles were related with classical kinetic mathematical models for better understanding of the release mechanism. An increase in polymer cross-linking degree resulted in longer release time for both drugs, although SD generally was released slower than NI. SD release from samples cross-linked at 2% of basis was driven mainly by Fickian diffusion, while from samples cross-linked at 4% of basis follows anomalous mechanism. Inversely, anomalous mechanism was responsible for NI release from 2% samples and Fickian diffusion from 4% samples. Results suggest that the performance of cross-linked high amylose as excipient for controlled drug release not only depends on cross-linking degree but also is highly influenced by structural characteristics of the drug. (C) 2009 Elsevier Ltd. All rights reserved.

Modeling a system of phosphated cross-linked high amylose for controlled drug release. Part 1: Synthesis and polymer characterization

High amylose was cross-linked with sodium trimetaphosphate (STMP) using 2% and 4% solutions of NaOH at room temperature with reaction contact times of 0.5, 1, 2 and 4 h. The different polymers obtained were analyzed by FT IR, C-13 and P-31 solid state NMR, SEM and C, H and P elemental analysis. The results were used to propose a two-stage mechanism for phosphate incorporation, the first being kinetically controlled. (C) 2008 Elsevier Ltd. All rights reserved.

Physical properties of pectin-high amylose starch mixtures cross-linked with sodium trimetaphosphate

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Dielectric and viscoelastic properties of cross-linked polyethylene aged under multi stressing conditions

Different measurements were performed in cross-linked polyethylene (XLPE) employed as insulating material in coaxial cables that were field-aged and laboratory-aged under multi-stressing conditions at room temperature. Samples were peeled from the XLPE cable insulation in three different positions: just below the external semiconductor layer (outer layer), in the middle (middle layer) and just above the internal semiconductor layer of the cable (inner layer). The imaginary part of the electric susceptibility showed three peaks that obey the Dissado-Hill model. For laboratory-aged XLPE samples peeled from the inner and from the middle positions the peak at very low frequency region increased while in samples from the outer position a quasi-DC conduction process was observed. In medium frequency range a broadening of the peak was observed for all samples. Viscoelastic properties determined through dynamic mechanical analysis suggested that the aging generates processes that promoted changes of the crystallinity and the cross-linking degrees of the polymer. Fourier transform infrared spectroscopy (FTIR) measurements revealed an increase of oxidation products (esters), evidence of polar residues of the bow-tie tree and the presence of cross-linking by-products (acetophenone). Optical and scanning electronic microscope (SEM) measurements in aged samples revealed the existence of voids and bow-tie trees that were formed during aging in the middle region of the cable.

Tuning the activity of alternative Ru-based initiators for ring-opening metathesis polymerization of norbornene and norbornadiene by the substituent in 4-CH2R-piperidine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Synthesis and characterization of cross-linked molecularly imprinted polyacrylamide for the extraction/preconcentration of glyphosate and aminomethylphosphonic acid from water samples

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)