Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency

A tailored series of coumarin-based ferrocenyl 1,3-oxazine hybrid compounds was synthesized and investigated for potential antiparasitic activity, drawing inspiration from the established biological efficacy of the constituent chemical motifs. The structural identity of the synthesized compounds was confirmed by common spectroscopic techniques: NMR, HRMS and IR. Biological evaluation studies reveal that the compounds exhibit higher in vitro antiparasitic potency against the chemosensitive malarial strain (3D7 P. falciparum) over the investigated trypanosomiasis causal agent (T. b. brucei 427) with mostly single digit micromolar IC₅₀ values. When read in tandem with the biological performance of previously reported structurally similar non-coumarin, phenyl derivatives (i.e., ferrocenyl 1,3-benzoxazines and α-aminocresols), structure-activity relationship analyses suggest that the presence of the coumarin nucleus is tolerated for biological activity though this may lead to reduced efficacy. Preliminary mechanistic studies with the most promising compound (11b) support hemozoin inhibition and DNA interaction as likely mechanistic modalities by which this class of compounds may act to produce plasmocidal and antitrypanosomal effects.     

Functionalized bismuth ferrite harmonic nanoparticles for cancer cells labeling and imaging

Journal of Nanoparticle Research - Nanoparticles form the fundamental building blocks for many exciting applications in various scientific disciplines. However, the problem of the large-scale...     

Synthesis,characterization, and rheological properties of hybrid titanium star‐shaped poly(n‐butyl acrylate)

The synthesis of hybrid star‐shaped polymers was carried out by atom transfer radical polymerization of n‐butyl acrylate from a well‐defined multifunctional titanium‐oxo‐cluster initiator. Conditions were identified to prevent possible side reactions among monomer, polymer, and the titanium‐oxo‐cluster ligands. Polymerizations provided linear first‐order kinetics and the evolution of the experimental molecular weight is also linear with the conversion. ¹H DOSY NMR and cleavage of the polymeric branches from the multifunctional initiator by hydrolysis were used to (i) prove the star‐shaped structure of the polymer, and (ii) demonstrate that the shoulder observed on size exclusion chromatograms is not due to a noncontrolled polymerization but to ungrafting of polymeric branches during analysis. Rheological properties of the hybrid star‐shaped poly(n‐butyl acrylate) were studied in the linear regime and show that the Ti‐oxo‐cluster not only increases significantly the viscosity of the polymer relative to its ungrafted arm but has a rheological signature which is qualitatively different from that of stars with organic cores suggesting that the Ti cluster reduces significantly the molecular mobility of the star. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Optical order of the polymer phase within polymer/fullerene blend films

This study reports on how the degree of polymer order within a polymer/fullerene blend can be investigated by spectroscopic methods. Non‐annealed blend compositions with 0–80 wt % fullerene content were analyzed using temperature dependent photoluminescence (PL) and room temperature spectroscopic ellipsometry (SE) measurements. To evaluate the SE data with respect to the optical order, an optical model was developed, including a lower and higher ordered polymer phase within a fullerene matrix. This was done using an effective medium approach describing the polymer by combining lower and higher ordered polymer properties (polymer‐EMA). The polymer/fullerene blend was then evaluated using another EMA consisting of the polymer‐EMA and the dielectric function of the disordered fullerene. The degree of optical order obtained by SE, was confirmed using another independent measurement, photoluminescence spectroscopy, according to the method of Francis C. Spano (2005). The volume fraction of the ordered polymer within the polymer‐EMA was found to be between 70 and 60 vol % for fullerene contents lower than 20 wt % in the polymer/fullerene blend. Above 20 wt % fullerene, the optical order of the polymer strongly decreases all the way down to 0 vol %. In contrast to the complementary performed X‐ray diffraction measurements, which address only the long‐range structural order of the blends, we give quantitative information on the optical order, including information on the composition, that is, volume fractions of the higher and lower ordered polymer. The gained information on the tilt of the polymer molecules with respect to the substrate is discussed comparing XRD results from the literature with those obtained by our SE model. Finally, the developed model is used to describe the influence of the P3HT molecular weight on the optical order. Results obtained with our model were compared to the structural data and mobility data in the literature. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012     

Mediating Gel Formation from Structurally Controlled Poly(Electrolytes) Through Multiple “Head‐to‐Body” Electrostatic Interactions

Tuning the chain‐end functionality of a short‐chain cationic homopolymer, owing to the nature of the initiator used in the atom transfer radical polymerization (ATRP) polymerization step, can be used to mediate the formation of a gel of this poly(electrolyte) in water. While a neutral end group gives a solution of low viscosity, a highly homogeneous gel is obtained with a phosphonate anionic moiety, as characterized by rheometry and diffusion nuclear magnetic resonance (NMR). This novel type of supramolecular control over poly(electrolytic) gel formation could find potential use in a variety of applications in the field of electro‐active materials.

     

A Synthesis of 9-Methoxy-1-Methyl-1H,6H-Pyrazolo[4,3-c]Carbazole

The synthesis of 9-Methoxy-1-methyl-1H,6H-pyrazolo[4,3-c]carbazole is reported in four steps from 6-nitroindazole. Palladium acetate mediated cyclization gave only the “bent” tetracyclic derivative.     

Multicomponent Alginate-Derived Hydrogel Microspheres Presenting Hybrid Ionic-Covalent Network and Drug Eluting Properties

The development of multifunctional encapsulation biomaterials could help the translation of cell-based therapies into standard medical care. One of the major hurdles in the field of encapsulated cell transplantation is the current lack of materials presenting optimal properties, including long term stability, mechanical durability and non-immunogenic character. Modification of sodium alginate (Na-alg) with polyethylene glycol (PEG) derivatives, without restricting its gelling abilities, appeared as an efficient strategy to produce dual ionic-covalent spherical hydrogels with enhanced mechanical performance as well as drug-eluting microspheres (MS) for the mitigation of inflammatory response after transplantation. In this study, the combination of PEGylated alginates equipped with cross-reactive functionalities and the anti-inflammatory drug ketoprofen (KET) resulted in the assembly of multifunctional (MF) hybrid MS, merging the advantages of ionic-covalent hydrogels with the ability for controlled drug delivery. Physical characterization confirmed their improved mechanical resistance, their higher shape recovery performance and increased stability toward non-gelling ions, as compared to pure Ca-alg hydrogels. In vitro release kinetics revealed the controlled and sustained delivery of KET for over two weeks.