Temperature-Controlled Chain Dynamics in Polyimide Doped with CoCl2 Probed Using Dynamic Mechanical Analysis.

Cobalt(II) chloride (CoCl2) being in the vicinity of polyimide chains entails modifications in terms of the molecular dynamics, which are mainly governed by the possible presence of amic acid residual groups, by the transition-metal-type characteristics of cobalt and by the CoCl2 content. Polyimide was synthesized using poly(amic acid) according to the reaction of 2,2'-bis(3,4-dicarboxylphenyl)hexafluoropropane dianhydride (6FDA) with 3,3'-dimethyl-4,4'-diaminodiphenylmethane (MMDA) in N,N-dimethylacetamide. CoCl2 was added before the thermal imidization of the poly(amic acid). An experimental approach was designed to establish the interaction between the polyimide and CoCl2 and whether the interaction depends on the quantity of the salt. Evidence for the existence of residual amic acid groups was obtained using second derivative Fourier Transform Infrared Spectroscopy (FTIR) and with the help of 2D correlation spectroscopy (2D-COS). Moreover, FTIR, along with X-ray photoelectron spectroscopy (XPS), revealed the interaction between the polymer and CoCl2, primarily in the form of Co(II)-N coordinated bonds. Nevertheless, the coordination of cobalt with suitable atoms from the amic acid groups is not precluded. The results of dynamic mechanical analysis (DMA) featured a specific relaxation assigned to the presence of CoCl2 in the polymeric film and demonstrated that its (non)reinforcing effect depends on its content in the polyimide.

Zein/Polysaccharide Nanoscale Electrostatic Complexes: Preparation, Drug Encapsulation and Antibacterial Properties.

Characterization of zein aqueous solutions, as a function of the ethanol content and pH, was performed, giving information on the zein aggregation state for the construction of complexes. The aggregation state and surface charge of zein was found to depend on the mixed solvent composition and pH. Nonstoichiometric complex nanoparticles (NPECs) were prepared by electrostatically self-assembling zein, as the polycation, and sodium alginate or chondroitin sulfate, as the polyanions, at a pH of 4. A wide range of parameters were investigated: the alcohol-water content in the zein solutions, the charge molar ratios, the solution addition order and the addition rate. The resulting nanoparticles were characterized by dynamic and electrophoretic light scattering, circular dichroism and scanning electron microscopy. The smallest size for the NPECs (100 nm) was obtained when the polysaccharides acted as the titrate with an addition rate of 0.03 mL·min-1. The NPECs with the best characteristics were selected for loading with ciprofloxacin and then deposited on a cellulosic material in order to evaluate their antibacterial activity. Substantial drug encapsulation with desired drug release profiles were found together with notable antibacterial efficiency, showing the tunability of the properties for both the zein and its complexes with polysaccharides, together with their application potential in the biomedical field.

Evidence through Thermal Analysis of Retro Diels-Alder Reaction in Model Networks Based on Anthracene Modified Polyester Resins.

The present work is focused on polyester resins obtained from the diglycidyl ether of bisphenol A and anthracene modified 5-maleimidoisophthalic acid. Because the maleimide-anthracene Diels-Alder (DA) adduct is stable at high temperatures, it is considered a good option for high performance polymers. However, the information related to the retroDA reaction for this type of adduct is sometimes incoherent. A detailed thermal study (conventional TGA, HiRes TGA, MTGA, DSC, MDSC) was performed in order to establish whether the rDA reaction can be revealed for this type of anthracene modified polyester resins. The TGA method confirmed the cleavage of the anthracene-maleimide DA adduct, while the DSC demonstrated the presence of anthracene in the system. At high temperatures, unprotected maleimide homopolymerizes and/or reacts with allyl groups according to the -ene reaction. Therefore, the thermal DA reaction is not displayed anymore upon the subsequent cooling, and the glass transition region is registered at a higher temperature range during the second heating. The use of sample-controlled thermal analysis (HiRes TGA) and MTGA improved the TGA result; however, it was not possible to separate the very complex degradation processes that are interconnected.

New chromatographic insights on drug:cyclodextrin inclusion complexes and their potential use in drug delivery.

OBJECTIVES: Cyclodextrins (CDs) play a pivotal role in the controlled release of drugs; however, their ability to gradually release drugs is here interrogated: can cyclodextrins, even those that form strong inclusion complexes, sustain a prolonged release of drugs? METHODS: An original chromatographic approach was developed and accordingly we classified and determined drugs that form the most stable inclusion complexes with cyclodextrins. ß-CD and hydroxypropyl-ß-CD (HP-ß-CD) were coupled to pullulan (Pul) microspheres and packed into a chromatographic column. Then, different drugs or model compounds were eluted, and values of the retention time (RT) were determined. In vitro release studies were performed for drugs that form the most stable inclusion complexes. RESULTS: The drugs with the longest RT value form the most stable inclusion complexes with Pul/ß-CD and Pul/HP-ß-CD microspheres. Pul/ß-CD microspheres form more stable inclusion complexes than Pul/HP-ß-CD microspheres. However, in spite of their high stability, they were not able to gradually release the included drug (15 min release time). The cross-chromatographic experiments confirmed the hypothesis that in aqueous solution, drug/cyclodextrin complexes are continuously associated and dissociated. CONCLUSIONS: If the dissociation of the guest molecule is very rapid, why is it expected that these complexes gradually release the drug?

Chitosan-Based Therapeutic Systems for Superficial Candidiasis Treatment. Synergetic Activity of Nystatin and Propolis.

The paper deals with new approaches to chitosan (CS)-based antifungal therapeutic formulations designed to fulfill the requirements of specific applications. Gel-like formulations were prepared by mixing CS dissolved in aqueous lactic acid (LA) solution with nystatin (NYS) powder and/or propolis (PRO) aqueous solution dispersed in glycerin, followed by water evaporation to yield flexible mesoporous (pore widths of 2-4 nm) films of high specific surfaces between 1 × 103 and 1.7 × 103 m2/g. Morphological evaluation of the antifungal films showed uniform dispersion and downsizing of NYS crystallites (with initial sizes up to 50 µm). Their mechanical properties were found to be close to those of soft tissues (Young's modulus values between 0.044-0.025 MPa). The films presented hydration capacities in physiological condition depending on their composition, i.e., higher for NYS-charged (628%), as compared with PRO loaded films (118-129%). All NYS charged films presented a quick release for the first 10 min followed by a progressive increase of the release efficiency at 48.6%, for the samples containing NYS alone and decreasing values with increasing amount of PRO to 45.9% and 42.8% after 5 h. By in vitro analysis, the hydrogels with acidic pH values around 3.8 were proven to be active against Candida albicans and Candida glabrata species. The time-killing assay performed during 24 h on Candida albicans in synthetic vagina-simulative medium showed that the hydrogel formulations containing both NYS and PRO presented the faster slowing down of the fungal growth, from colony-forming unit (CFU)/mL of 1.24 × 107 to CFU/mL < 10 (starting from the first 6 h).

Cu(II)/Guanidine Functionalized Disiloxane Complex of Supramolecular Structures for Visible Light-Driven Photocatalysis of Congo Red.

The present study focuses on the synthesis of a new guanidine-functionalized disiloxane used as a ligand to obtain copper(II) complexes linked through hydrogen bonding into supramolecular structures. A two-step procedure was used to prepare the guanidine functionalized disiloxane ligand. Firstly, the hydrosilylation reaction between the siloxane precursor, namely 1,1,3,3-tetramethyldisiloxane (DS), and the allyl glycidyl ether (AGE) was performed in the presence of a platinum catalyst resulting in glycidoxypropyldisiloxane (DS-PMO) intermediary compound. In the second step, DS-PMO derivative was modified with 1,1,3,3-tetramethyl guanidine (TMGu) to obtain the guanidine-functionalized disiloxane ligand (bGu-DS) that was further used for the coordination of copper(II) acetate hydrate. The structures of the ligand and of its Cu(II) complex were confirmed by spectral methods (IR, UV-Vis, NMR, XRF) and correlated with theoretical calculations using semi-empirical PM6 and DFT methods. The copper(II) complex was found to exhibit low optical band gap energy (2.9 eV) and good photocatalytic activity under visible light irradiation in the decomposition of Congo Red (CR). A dye removal efficiency higher than 97% at the catalyst and CR concentrations of 1 and, respectively, 200 mg/L was obtained.

Crystal Structure of a Tetrameric Type II ß-Carbonic Anhydrase from the Pathogenic Bacterium Burkholderia pseudomallei.

Carbonic anhydrase (CA) is a zinc enzyme that catalyzes the reversible conversion of carbon dioxide to bicarbonate and proton. Currently, CA inhibitors are widely used as antiglaucoma, anticancer, and anti-obesity drugs and for the treatment of neurological disorders. Recently, the potential use of CA inhibitors to fight infections caused by protozoa, fungi, and bacteria has emerged as a new research line. In this article, the X-ray crystal structure of ß-CA from Burkholderia pseudomallei was reported. The X-ray crystal structure of this new enzyme was solved at 2.7 Å resolution, revealing a tetrameric type II ß-CA with a "closed" active site in which the zinc is tetrahedrally coordinated to Cys46, Asp48, His102, and Cys105. B. pseudomallei is known to encode at least two CAs, a ß-CA, and a γ-CA. These proteins, playing a pivotal role in its life cycle and pathogenicity, offer a novel therapeutic opportunity to obtain antibiotics with a different mechanism of action. Furthermore, the new structure can provide a clear view of the ß-CA mechanism of action and the possibility to find selective inhibitors for this class of CAs.

Sulfonamide Inhibition Studies of an α-Carbonic Anhydrase from Schistosoma mansoni, a Platyhelminth Parasite Responsible for Schistosomiasis.

Schistosomiasis is a debilitating infection provoked by parasitic flatworms called schistosomes. The species Schistosoma mansoni is endemic in Africa, where it causes intestinal schistosomiasis. Recently, an α-carbonic anhydrase (CA, EC 4.2.1.1) was cloned and characterized from this organism and designated as SmCA. The protein is expressed in the tegument (skin) of S. mansoni at the host-parasite interface. Recombinant SmCA possesses high catalytic activity in the CO2 hydration reaction, similar to that of human CA isoform II with a kcat of 1.2 × 106 s-1 and a kcat/KM of 1.3 × 108 M-1·s-1. It has been found that schistosomes whose SmCA gene is suppressed using RNA interference are unable to establish a robust infection in mice, suggesting that the chemicals that inhibit SmCA function should have the same debilitating effect on the parasites. In this study, a collection of aromatic/heterocyclic sulfonamides were investigated as possible SmCA inhibitors. Several sulfonamides inhibited SmCA with medium to weak potency (KI values of 737.2 nM-9.25 µM), whereas some heterocyclic compounds inhibited the enzyme with KI values in the range of 124-325 nM. The α-CA from S. mansoni, SmCA, is proposed as a new anti-schistosomiasis drug target.

Evaluation of Thio- and Seleno-Acetamides Bearing Benzenesulfonamide as Inhibitor of Carbonic Anhydrases from Different Pathogenic Bacteria.

A series of 2-thio- and 2-seleno-acetamides bearing the benzenesulfonamide moiety were evaluated as Carbonic Anhydrase (CA, EC 4.2.1.1) inhibitors against different pathogenic bacteria such as the Vibrio cholerae (VchCA-α and VchCA-ß), Burkholderia pseudomallei (BpsCA-ß and BpsCA-γ), Mycobacterium tuberculosis (Rv3723-ß) and the Salmonella enterica serovar Typhimurium (StCA2-ß). The molecules represent interesting leads worth developing as innovative antibacterial agents since they possess new mechanism of action and isoform selectivity preferentially against the bacterial expressed CAs. The identification of potent and selective inhibitors of bacterial CAs may lead to tools also useful for deciphering the physiological role(s) of such proteins.

Fe(III) doped carbon nanodots with intense green photoluminescence and dispersion medium dependent emission.

The preparation and investigation of Fe(III) doped carbon nanodots (CNDs) with intense green photoluminescence and emission dependence on the dispersion medium are reported. Their unusual photoluminescence is especially highlighted in water where the initial blue emission is gradually shifted to intense deep green, while in other common solvents (chloroform, acetone etc.) this behavior has not been observed. Through embedding in a polymer matrix (e.g., PVA) the color transition becomes reversible and dependent on water content, ranging from a full blue emission, when completely dried, to an intense green emission, when wetted. The preparation path of the Fe(III) doped CNDs undergoes two main stages involving the initial obtaining of Fe(III)-N-Hydroxyphthalimide complex and then a thermal processing through controlled pyrolysis. Morphostructural investigations of the prepared Fe(III) doped CNDs were performed through TG, FT-IR, XPS, DLS, TEM and AFM techniques whereas absolute PLQY, steady state and lifetime fluorescence were used to highlight their luminescence properties. The results issued from structural and fluorescence investigations bring new insights on the particular mechanisms involved in CNDs photoluminescence, a topic still open to debate.

Entrapment of N-Hydroxyphthalimide Carbon Dots in Different Topical Gel Formulations: New Composites with Anticancer Activity.

In the present study, the antitumoral potential of three gel formulations loaded with carbon dots prepared from N-hydroxyphthalimide (CD-NHF) was examined and the influence of the gels on two types of skin melanoma cell lines and two types of breast cancer cell lines in 2D (cultured cells in normal plastic plates) and 3D (Matrigel) models was investigated. Antitumoral gels based on sodium alginate (AS), carboxymethyl cellulose (CMC), and the carbomer Ultrez 10 (CARB) loaded with CD-NHF were developed according to an adapted method reported by Hellerbach. Viscoelastic properties of CD-NHF-loaded gels were analyzed by rheological analysis. Also, for both CD-NHF and CD-NHF-loaded gels, the fluorescence properties were analyzed. Cell proliferation, apoptosis, and mitochondrial activity were analyzed according to basic methods used to evaluate modulatory activities of putative anticancer agents, which include reference cancer cell line culture assays in both classic 2D and 3D cultures. Using the rheological measurements, the mechanical properties of gel formulations were analyzed; all samples presented gel-like rheological characteristics. The presence of CD-NHF within the gels induces a slight decrease of the dynamic moduli, indicating a flexible gel structure. The fluorescence investigations showed that for the gel-loaded CD-NHF, the most intense emission peak was located at 370 nm (upon excitation at 330 nm). 3D cell cultures displayed visibly larger structure of tumor cells with less active phenotype appearance. The in vitro results for tested CD-NHF-loaded gel formulations revealed that the new composites are able to affect the number, size, and cellular organization of spheroids and impact individual tumor cell ability to proliferate and aggregate in spheroids.

The first activation study of the ß-carbonic anhydrases from the pathogenic bacteria Brucella suis and Francisella tularensis with amines and amino acids.

The activation of the ß-class carbonic anhydrases (CAs, EC 4.2.1.1) from the bacteria Brucella suis and Francisella tularensis with amine and amino acids was investigated. BsuCA 1 was sensitive to activation with amino acids and amines, whereas FtuCA was not. The most effective BsuCA 1 activators were L-adrenaline and D-Tyr (KAs of 0.70-0.95 µM). L-His, L-/D-Phe, L-/D-DOPA, L-Trp, L-Tyr, 4-amino-L-Phe, dopamine, 2-pyridyl-methylamine, D-Glu and L-Gln showed activation constants in the range of 0.70-3.21 µM. FtuCA was sensitive to activation with L-Glu (KA of 9.13 µM). Most of the investigated compounds showed a weak activating effect against FtuCA (KAs of 30.5-78.3 µM). Many of the investigated amino acid and amines are present in high concentrations in many tissues in vertebrates, and their role in the pathogenicity of the two bacteria is poorly understood. Our study may bring insights in processes connected with invasion and pathogenic effects of intracellular bacteria.

Structural and sorption properties of bio-nanocomposite films based on κ-carrageenan and cellulose nanocrystals.

There is an increased interest on changing the synthetic based materials to biodegradable ones, especially with natural polymers, polysaccharides or proteins. In this research we prepared bio-nanocomposite formulations with different component concentrations and investigated their structural features, with focus on the interactions, sorption properties, and how the combination between them influences these properties. By infrared spectroscopy, principal component analysis (PCA) and two-dimensional correlation spectroscopy (2DCOS) was identified that in the blending process are involved the -SO4 and C(4)-O-S groups of ß-d-galactose, CO groups, (O=S=O) of carrageenan and -OH and CO groups from CNCs. The water uptake and water sorption properties decrease with increasing the CNCs content in the formulations from about 15% for κ to 10% for κC15 and from about 128% for κ to 115% for κC15, respectively. The increase of the CNCs content induced an increase of the water contact angle from 47° for κ to 90° for κC15, indicating once again the involvement of the free hydroxyl groups in the hydrogen bonded interactions.

Inhibition of bacterial α-, ß- and γ-class carbonic anhydrases with selenazoles incorporating benzenesulfonamide moieties.

A series of benzenesulfonamides incorporating selenazoles with diverse substitution patterns were investigated as inhibitors of six bacterial carbonic anhydrases (CAs, EC 4.2.1.1) from bacterial pathogens, such as Helicobacter pylori (hpCAα was the investigated enzyme), Vibrio cholerae (all the three CAs from this pathogen were considered, VchCAα, VchCAß and VchCAγ) and Burkholderia pseudomallei (with its two CAs, BpsCAß and BpsCAγ). All these sulfonamides were effective CA inhibitors, with potencies in the low micromolar or submicromolar range, making them attractive as lead compounds for designing antibacterials with a novel mechanism of action, which could counteract the extensive resistance problem observed with many clinically used antibiotics.

Inhibition of α-, ß-, γ-, δ-, ζ- and η-class carbonic anhydrases from bacteria, fungi, algae, diatoms and protozoans with famotidine.

Famotidine, an antiulcer drug belonging to the H2 antagonists class of pharmacological agents, was recently shown to potently inhibit human (h) and bacterial carbonic anhydrases (CAs, EC 4.2.1.1). We investigated the inhibitory effects of famotidine against all classes of CAs from the pathogenic bacteria Vibrio cholerae, Burkholderia pseudomallei and Mycobacterium tuberculosis Rv3273 ß-CA, as well as the CAs from the nonpathogenic bacteria/cyanobacteria Sulfurihydrogenibium yellowstonensis, S. azorense, Pseudoalteromonas haloplanktis, Colwellia psychrerythraea and Nostoc commune. The δ- and ζ-CAs from the diatom Thalassiosira weissflogii, the fungal enzymes from Cryptococcus neoformans, Candida glabrata and Malassezia globosa, as well as the protozoan enzymes from Trypanosoma cruzi and Plasmodium falciparum, were also investigated. Anopheles gambiae ß-CA was also investigated. All these enzymes were effectively inhibited by famotidine, with affinities between the low nanomolar to the micromolar range. The best inhibition was observed against C. glabrata ß-CA and TweCAζ, with KIs ranging between 13.6 and 22.1 nM.

Erosion as a possible mechanism for the decrease of size of plastic pieces floating in oceans.

A sea water wave tank fitted in an artificial UV light weathering chamber was built to study the behaviour of polypropylene (PP) injected pieces in close ocean-like conditions. In air, the same pieces sees a degradation in the bulk with a decrease of mechanical properties, a little change of crystal properties and nearly no change of surface chemistry. Weathering in the sea water wave tank shows only a surface changes, with no effect on crystals or mechanical properties with loss of small pieces of matter in the sub-micron range and a change of surface chemistry. This suggests an erosion dispersion mechanism. Such mechanism could explain why no particle smaller than about one millimeter is found when collecting plastic debris at sea: there are much smaller, eroded from plastic surfaces by a mechano-chemical process similar to the erosion mechanism found in the dispersion of agglomerate under flow.

Biopolymers/poly(ε-caprolactone)/polyethylenimine functionalized nano-hydroxyapatite hybrid cryogel: Synthesis, characterization and application in gene delivery.

Nano-hydroxyapatite (nHAp), surface functionalized with linear polyethylenimine (LPEI), was used for the preparation of biocomposites in combination with biopolymers and poly(ε-caprolactone) (PCL), by cryogelation technique, to yield biomimetic scaffolds with controlled interconnected macroporosity, mechanical stability, and predictable degradation behavior. The structural characteristics, swelling and degradation behavior of hydroxyapatite and hydroxyapatite/ß-tricalcium phosphate (ß-TCP) filled matrices were investigated as compared to the corresponding naked polymer 3D system. It was found that the homogeneity and cohesivity of the composite are significantly dependent on the size and amount of the included inorganic particles, which are thus determining the structural parameters. Surface modification with LPEI and nanodimensions favored the nHAp integration in the organic matrix, with preferential location along protein fibers, while ß-TCP microparticles induced an increased disorder in the hybrid system. The biocomposite including nHAp only was further investigated targeting biomedical uses, and proved to be non-cytotoxic and capable of acting as gene-activated matrix (GAM). It allowed sustained delivery over time (until 22days) of embedded PEI25-pDNA polyplexes at high levels of transgene expression, while insuring a decrease in cytotoxicity as compared to polyplexes alone. Experimental data recommend such biocomposite as an attractive material for regenerative medicine.

Superparamagnetic Composites Based on Ionic Resin Beads/CaCO3 /Magnetite.

The preparation of superparamagnetic composites obtained by CaCO3 mineralization from supersaturate aqueous solutions is presented. The preparation was conducted in the presence of oleic acid stabilized magnetite nanoparticles as a water-based magnetic fluid and insoluble templates as gel-like cross-linked polymeric beads. The presence of the magnetic particles in the composites provides a facile way for external manipulation using a permanent magnet, thus allowing the separation and extraction of magnetically modified materials. Two ion exchangers based on divinylbenzene/ethyl acrylate/acrylonitrile cross-linked copolymer-a cation ion exchanger (CIE) and an amphoteric ion exchanger (AIE)-were used, as well as different addition orders of magnetite and CaCO3 crystals growth precursors. The morphology of the composites was investigated by SEM, the polymorphs content by X-ray diffraction, and the thermal stability by thermogravimetric analysis. Polymer, CaCO3 , and magnetite in the composite particles were shown to be present by energy dispersive X-ray (EDX), XPS, and TEM. The sorption capacity for CuII ions was tested, as compared to samples prepared without magnetite.

Dual crosslinked iminoboronate-chitosan hydrogels with strong antifungal activity against Candida planktonic yeasts and biofilms.

Chitosan based hydrogels are a class of cross-linked materials intensely studied for their biomedical, industrial and environmental application, but their biomedical use is limited because of the toxicity of different organic crosslinkers. To overcome this disadvantage, a new strategy to produce supramolecular chitosan hydrogels using low molecular weight compounds able to form covalent linkages and H-bonds to give a dual crosslinking is proposed. For this purpose we used 2-formylphenylboronic acid, which brings the advantage of imine stabilization via iminoboronate formation and potential antifungal activity due to the presence of boric acid residue. FTIR and NMR spectroscopy indicated that the gelling process took place by chemo-physical crosslinking forming a dual iminoboronate-chitosan network. Further, X-ray diffraction demonstrated a three-dimensional nanostructuring of the iminoboronate network with consequences on the micrometer-scale morphology and on the improvement of mechanical properties, as demonstrated by SEM and rheological investigation. The hydrogels proved strong antifungal activity against Candida planktonic yeasts and biofilms, promising to be a friendly treatment of the recurrent vulvovaginitis infections.

ROMP Synthesis of Iron-Containing Organometallic Polymers.

The paper overviews iron-containing polymers prepared by controlled "living" ring-opening metathesis polymerization (ROMP). Developments in the design and synthesis of this class of organometallic polymers are highlighted, pinpointing methodologies and newest trends in advanced applications of hybrid materials based on polymers functionalized with iron motifs.