Peptide catalyzed asymmetric conjugate addition reactions of aldehydes to nitroethylene--a convenient entry into gamma2-amino acids

The peptide H-D-Pro-Pro-Glu-NH2 is a highly effective catalyst for conjugate addition reactions between aldehydes and nitroethylene. Only 1 mol % of H-d-Pro-Pro-Glu-NH2 and a 1.5-fold excess of aldehyde with respect to nitroethylene suffice to obtain gamma-nitroaldehydes and, after reduction, monosubstituted gamma-nitroalcohols in excellent yields and optical purities. The products can be readily converted into gamma2-amino acids, thereby opening an effective direct entry into this important class of compounds.     

Global Wave-Front Properties for Fourier Integral Operators and Hyperbolic Problems

We illustrate the composition properties for an extended family of \({\text {SG}}\) Fourier integral operators. We prove continuity results on modulation spaces, and study mapping properties of global wave-front sets for such operators. These extend classical results to more general situations. For example, there are no requirements on homogeneity for the phase functions. Finally, we apply our results to the study of the propagation of singularities, in the context of modulation spaces, for the solutions to the Cauchy problems for the corresponding linear hyperbolic operators.     

Discovery of Novel Cyclic Ethers with Synergistic Antiplasmodial Activity in Combination with Valinomycin

With drug resistance threatening our first line antimalarial treatments, novel chemotherapeutics need to be developed. Ionophores have garnered interest as novel antimalarials due to their theorized ability to target unique systems found in the Plasmodium-infected erythrocyte. In this study, during the bioassay-guided fractionation of the crude extract of Streptomyces strain PR3, a group of cyclodepsipeptides, including valinomycin, and a novel class of cyclic ethers were identified and elucidated. Further study revealed that the ethers were cyclic polypropylene glycol (cPPG) oligomers that had leached into the bacterial culture from an extraction resin. Molecular dynamics analysis suggests that these ethers are able to bind cations such as K⁺, NH₄⁺ and Na⁺. Combination studies using the fixed ratio isobologram method revealed that the cPPGs synergistically improved the antiplasmodial activity of valinomycin and reduced its cytotoxicity in vitro. The IC₅₀ of valinomycin against P. falciparum NF54 improved by 4–5-fold when valinomycin was combined with the cPPGs. Precisely, it was improved from 3.75 ± 0.77 ng/mL to 0.90 ± 0.2 ng/mL and 0.75 ± 0.08 ng/mL when dosed in the fixed ratios of 3:2 and 2:3 of valinomycin to cPPGs, respectively. Each fixed ratio combination displayed cytotoxicity (IC₅₀) against the Chinese Hamster Ovary cell line of 57–65 µg/mL, which was lower than that of valinomycin (12.4 µg/mL). These results indicate that combinations with these novel ethers may be useful in repurposing valinomycin into a suitable and effective antimalarial.     

Fluorescent core-shell silica nanoparticles: towards "Lab on a Particle" architectures for nanobiotechnology

Novel nanoscale fluorescent materials are integral to the progress of emergent fields such as nanobiotechnology and facilitate new research in a variety of contexts. Sol-gel derived silica is an excellent host material for creating fluorescent nanoparticles by the inclusion of covalently-bound organic dyes. Significant enhancements in the brightness and stability of organic dye emission can be achieved for silica-based core-shell nanoparticle architectures at length scales down to tens of nanometers with narrow size distributions. This tutorial review will highlight these findings and describe the evolution of the fluorescent core-shell silica nanoparticle concept towards integration of multiple functionalities including mesoporosity, metal nanoshells and quantitative chemical sensing. These developments point towards the development of "lab on a particle" architectures with promising prospects for nanobiotechnology, drug development and beyond.     

Block Copolymer Directed Nanoporous Metal Thin Films

Porous metal thin films have high potential for use in applications such as catalysis, electrical contacts, plasmonics, as well as energy storage and conversion. Structuring metal thin films on the nanoscale to generate high surface areas poses an interesting challenge as metals have high surface energy. In this communication, we demonstrate direct access to nanostructured metal nanoparticle hybrid thin films with high nanoparticle loadings through spin coating of a mixture of block copolymer and ligand stabilized platinum and palladium nanoparticles. Plasma cleaning to remove the organics results in a conductive metal thin film. We expect that the methods described here can be generalized to other metals, mixtures of metal nanoparticles, and intermetallics.