Synthetic approaches to flexible fluorescent conjugated polymers

Conjugated polymers (CPs) are intrinsically fluorescent materials that have been used for various biological applications including imaging, sensing, and delivery of biologically active substances. The synthetic control over flexibility and biodegradability of these materials aids the understanding of the structure-function relationships among the photophysical properties, the self-assembly behaviors of the corresponding conjugated polymer nanoparticles (CPNs), and the cellular behaviors of CPNs, such as toxicity, cellular uptake mechanisms, and sub-cellular localization patterns. ^ Synthetic approaches towards two classes of flexible CPs with well-preserved fluorescent properties are described. The synthesis of flexible poly( p-phenylenebutadiynylene)s (PPBs) uses competing Sonogashira and Glaser coupling reactions and the differences in monomer reactivity to incorporate a small amount (∼10%) of flexible, non-conjugated linkers into the backbone. The reaction conditions provide limited control over the proportion of flexible monomer incorporation. Improved synthetic control was achieved in a series of flexible poly(p-phenyleneethynylene)s (PPEs) using modified Sonogashira conditions. In addition to controlling the degree of flexibility, the linker provides disruption of backbone conjugation that offers control of the length of conjugated segments within the polymer chain. Therefore, such control also results in the modulation of the photophysical properties of the materials. ^ CPNs fabricated from flexible PPBs are non-toxic to cells, and exhibit subcellular localization patterns clearly different from those observed with non-flexible PPE CPNs. The subcellular localization patterns of the flexible PPEs have not yet been determined, due to the toxicity of the materials, most likely related to the side-chain structure used in this series. ^ The study of the effect of CP flexibility on self-assembly reorganization upon polyanion complexation is presented. Owing to its high rigidity and hydrophobicity, the PPB backbone undergoes reorganization more readily than PPE. The effects are enhanced in the presence of the flexible linker, which enables more efficient π-π stacking of the aromatic backbone segments. Flexibility has minimal effects on the self-assembly of PPEs. Understanding the role of flexibility on the biophysical behaviors of CPNs is key to the successful development of novel efficient fluorescent therapeutic delivery vehicles.^

Tortoiseshell or Polymer? Spectroscopic Analysis to Redefine a Purported Tortoiseshell Box with Gold Decorations as a Plastic Box with Brass

The study and preservation of museum collections requires complete knowledge and understanding of constituent materials that can be natural, synthetic, or semi-synthetic polymers. In former times, objects were incorporated in museum collections and classified solely by their appearance. New studies, prompted by severe degradation processes or conservation-restoration actions, help shed light on the materiality of objects that can contradict the original information or assumptions. The selected case study presented here is of a box dating from the beginning of the 20th century that belongs to the Portuguese National Ancient Art Museum. Museum curators classified it as a tortoiseshell box decorated with gold applications solely on the basis of visual inspection and the information provided by the donor. This box has visible signs of degradation with white veils, initially assumed to be the result of biological degradation of a proteinaceous matrix. This paper presents the methodological rationale behind this study and proposes a totally non-invasive methodology for the identification of polymeric materials in museum artifacts. The analysis of surface leachates using 1H and 13C nuclear magnetic resonance (NMR) complemented by in situ attenuated total reflection infrared spectroscopy (ATR FT-IR) allowed for full characterization of the object s substratum. The NMR technique unequivocally identified a great number of additives and ATR FT-IR provided information about the polymer structure and while also confirming the presence of additives. The pressure applied during ATR FT-IR spectroscopy did not cause any physical change in the structure of the material at the level of the surface (e.g., color, texture, brightness, etc.). In this study, variable pressure scanning electron microscopy (VP-SEM-EDS) was also used to obtain the elemental composition of the metallic decorations. Additionally, microbiologic and enzymatic assays were performed in order to identify the possible biofilm composition and understand the role of microorganisms in the biodeterioration process. Using these methodologies, the box was correctly identified as being made of cellulose acetate plastic with brass decorations and the white film was identified as being composed mainly of polymer exudates, namely sulphonamides and triphenyl phosphate.

Chemo-, Regio- And Stereoselective Heck Arylation Of Allylated Malonates: Mechanistic Insights By Esi-ms And Synthetic Application Toward 5-arylmethyl-γ-lactones.

We describe herein a general method for the controlled Heck arylation of allylated malonates. Both electron-rich and electron-poor aryldiazonium salts were readily employed as the aryl-transfer agents in good yields and in high chemo-, regio-, and stereoselectivity without formation of decarboxylated byproducts. Reaction monitoring via ESI-MS was used to support the formation of chelated Pd species through the catalytic cycle. Additionally, some Heck adducts were successfully used in the total synthesis of pharmacologically active γ-lactones.

Antiproliferative Activity Of Synthetic Fatty Acid Amides From Renewable Resources.

In the work, the in vitro antiproliferative activity of a series of synthetic fatty acid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fatty acid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line-the most aggressive CNS cancer.

Molecularly Imprinted Solid Phase Extraction Of Fluconazole From Pharmaceutical Formulations.

This work encompasses a direct and coherent strategy to synthesise a molecularly imprinted polymer (MIP) capable of extracting fluconazole from its sample. The MIP was successfully prepared from methacrylic acid (functional monomer), ethyleneglycoldimethacrylate (crosslinker) and acetonitrile (porogenic solvent) in the presence of fluconazole as the template molecule through a non-covalent approach. The non-imprinted polymer (NIP) was prepared following the same synthetic scheme, but in the absence of the template. The data obtained from scanning electronic microscopy, infrared spectroscopy, thermogravimetric and nitrogen Brunauer-Emmett-Teller plot helped to elucidate the structural as well as the morphological characteristics of the MIP and NIP. The application of MIP as a sorbent was demonstrated by packing it in solid phase extraction cartridges to extract fluconazole from commercial capsule samples through an offline analytical procedure. The quantification of fluconazole was accomplished through UPLC-MS, which resulted in LOD≤1.63×10(-10) mM. Furthermore, a high percentage recovery of 91±10% (n=9) was obtained. The ability of the MIP for selective recognition of fluconazole was evaluated by comparison with the structural analogues, miconazole, tioconazole and secnidazole, resulting in percentage recoveries of 51, 35 and 32%, respectively.

Antimycobacterial and cytotoxicity activity of synthetic and natural compounds

Antimycobacterial and cytotoxicity activity of synthetic and natural compounds. Secondary metabolites from Curvularia eragrostidis and Drechslera dematioidea, Clusia sp. floral resin, alkaloids from Pilocarpus alatus, salicylideneanilines, piperidine amides, the amine 1-cinnamylpiperazine and chiral pyridinium salts were assayed on Mycobacterium tuberculosis H37Rv. N-(salicylidene)-2-hydroxyaniline was the most effective compound with a minimal inhibitory concentration (MIC) of 8 µmol/L. Dihydrocurvularin was moderately effective with a MIC of 40 µmol/L. Clusia sp. floral resin and a gallocatechin-epigallocatechin mixture showed MIC of 0.02 g/L and 38 µmol/L, respectively. The cytotoxicity was evaluated for N-(salicylidene)-2-hydroxyaniline, curvularin, dihydrocurvularin and Clusia sp. floral resin, and the selectivity indexes were > 125, 0.47, 0.75 and 5, respectively.

Impact and fracture resistance of an experimental acrylic polymer with elastomer in different proportions

The purpose of this study was to evaluate the impact and fracture resistance of acrylic resins: a heat-polymerized resin, a high-impact resin and an experimental polymethyl methacrylate with elastomer in different proportions (10, 20, 40 and 60%). 120 specimens were fabricated and submitted to conventional heat-polymerization. For impact test, a Charpy-type impact tester was used. Fracture resistance was assessed with a 3-point bending test by using a mechanical testing machine. Ten specimens were used for each test. Fracture (MPa) and impact resistance values (J.m-1) were submitted to ANOVA - Bonferroni's test - 5% significance level. Materials with higher amount of elastomer had statistically significant differences regarding to impact resistance (p < 0.05). Fracture resistance was superior (p < 0.01) for high-resistance acrylic resin. The increase in elastomer concentration added to polymethyl methacrylate raised the impact resistance and decreased the fracture resistance. Processing the material by injection decreased its resistance to impact and fracture.

Evaluation of capillaries with different inner coatings for DNA analysis using dilute polymer solutions by capillary electrophoresis

In this work three capillary columns, one with uncoated inner wall and two with covalently-bound internal coatings - poly(vinyl alcohol) (PVA) and poly(dimethylacrylamide) (PDMA) - both covalently covered - were used to separate DNA fragments and compared to DNA separation using replaceable polymer solutions. The separations were performed using hydroxyethylcellulose (HEC) (90-105 kDa) in concentrations ranging from 0.00 to 2.00% m/v. The results indicated that the separation efficiency was higher in the PVA capillary than in the PDMA in all evaluated concentrations of HEC. In addition, higher resolution was also observed in PVA-coated capillary since in PDMA the shape of the peaks was not reproducible when subsequent runs were performed. Contrary to what has previously been reported in the literature, no reasonable separation was possible in bare fused silica.

Conducting polymer- hydrogel blends for electrochemically controlled drug release devices

Blends formed by electrochemical polymerization of polypyrrole (PPy) into polyacrylamide (PAAm) hydrogels were used as devices for controlled drug release. The influence of several parameters in the synthesis, such as type of hydrogel matrix and polymerization conditions was studied by using a fractional factorial design. The final goal was to obtain an adequate device for use in controlled release tests, based on electrochemical potential control. For controlled release tests, Safranin was used as model drug and release curves (amount of drug vs. time) have shown that these blends are promising materials for this use. The optimized blends obtained were characterized by cyclic voltammetry and Raman spectroscopy.

Antileishmanial Activity of the Hydroalcoholic Extract of Miconia langsdorffii, Isolated Compounds, and Semi-Synthetic Derivatives

The in vitro activity of the crude hydroalcoholic extract of the aerial parts of Miconia langsdorffii Cogn. was evaluated against the promastigote forms of L. amazonensis, the causative agent of cutaneous leishmaniasis in humans. The bioassay-guided fractionation of this extract led to identification of the triterpenes ursolic acid and oleanolic acid as the major compounds in the fraction that displayed the highest activity. Several ursolic acid semi-synthetic derivatives were prepared, to find out whether more active compounds could be obtained. Among these ursolic acid-derived substances, the C-28 methyl ester derivative exhibited the best antileishmanial activity.

Anti-Plasmodium Activity of Angiotensin II and Related Synthetic Peptides

Plasmodium species are the causative agents of malaria, the most devastating insect-borne parasite of human populations. Finding and developing new drugs for malaria treatment and prevention is the goal of much research. Angiotensins I and II (ang I and ang II) and six synthetic related peptides designated Vaniceres 1-6 (VC1-VC6) were assayed in vivo and in vitro for their effects on the development of the avian parasite, Plasmodium gallinaceum. Ang II and VC5 injected into the thoraces of the insects reduced mean intensities of infection in the mosquito salivary glands by 88% and 76%, respectively. Although the mechanism(s) of action is not completely understood, we have demonstrated that these peptides disrupt selectively the P. gallinaceum cell membrane. Additionally, incubation in vitro of sporozoites with VC5 reduced the infectivity of the parasites to their vertebrate host. VC5 has no observable agonist effects on vertebrates, and this makes it a promising drug for malaria prevention and chemotherapy.

Structure of disordered gold-polymer thin films using small angle x-ray scattering

We have investigated the structure of disordered gold-polymer thin films using small angle x-ray scattering and compared the results with the predictions of a theoretical model based on two approaches-a structure form factor approach and the generalized Porod law. The films are formed of polymer-embedded gold nanoclusters and were fabricated by very low energy gold ion implantation into polymethylmethacrylate (PMMA). The composite films span (with dose variation) the transition from electrically insulating to electrically conducting regimes, a range of interest fundamentally and technologically. We find excellent agreement with theory and show that the PMMA-Au films have monodispersive or polydispersive characteristics depending on the implanted ion dose. (C) 2010 American Institute of Physics. [doi:10.1063/1.3493241]

Surface plasmon resonance of gold nanoparticles formed by cathodic arc plasma ion implantation into polymer

Shallow subsurface layers of gold nanoclusters were formed in polymethylmethacrylate (PMMA) polymer by very low energy (49 eV) gold ion implantation. The ion implantation process was modeled by computer simulation and accurately predicted the layer depth and width. Transmission electron microscopy (TEM) was used to image the buried layer and individual nanoclusters; the layer width was similar to 6-8 nm and the cluster diameter was similar to 5-6 nm. Surface plasmon resonance (SPR) absorption effects were observed by UV-visible spectroscopy. The TEM and SPR results were related to prior measurements of electrical conductivity of Au-doped PMMA, and excellent consistency was found with a model of electrical conductivity in which either at low implantation dose the individual nanoclusters are separated and do not physically touch each other, or at higher implantation dose the nanoclusters touch each other to form a random resistor network (percolation model). (C) 2009 American Vacuum Society. [DOI: 10.1116/1.3231449]

Structural properties of buried conducting layers formed by very low energy ion implantation of gold into polymer

We have investigated the fundamental structural properties of conducting thin films formed by implanting gold ions into polymethylmethacrylate (PMMA) polymer at 49 eV using a repetitively pulsed cathodic arc plasma gun. Transmission electron microscopy images of these composites show that the implanted ions form gold clusters of diameter similar to 2-12 nm distributed throughout a shallow, buried layer of average thickness 7 nm, and small angle x-ray scattering (SAXS) reveals the structural properties of the PMMA-gold buried layer. The SAXS data have been interpreted using a theoretical model that accounts for peculiarities of disordered systems.

Conducting polymer formed by low energy gold ion implantation

A buried conducting layer of metal/polymer nanocomposite was formed by very low energy gold ion implantation into polymethylmethacrylate. The conducting layer is similar to 3 nm deep and of width similar to 1 nm. In situ resistivity measurements were performed as the implantation proceeded, and the conductivity thus obtained as a function of buried gold concentration. The measured conductivity obeys the behavior well established for composites in the percolation regime. The critical concentration, below which the polymer remains an insulator, is attained at a dose similar to 1.0 x 10(16) atoms/cm(2) of implanted gold ions. (C) 2008 American Institute of Physics.