One-Step Formation Method of Plasmid DNA-Loaded, Extracellular Vesicles-Mimicking Lipid Nanoparticles Based on Nucleic Acids Dilution-Induced Assembly.

We propose a nucleic acids dilution-induced assembly (NADIA) method for the preparation of lipid nanoparticles. In the conventional method, water-soluble polymers such as nucleic acids and proteins are mixed in the aqueous phase. In contrast, the NADIA method, in which self-assembly is triggered upon dilution, requires dispersion in an alcohol phase without precipitation. We then investigated several alcohols and discovered that propylene glycol combined with sodium chloride enabled the dispersion of plasmid DNA and protamine sulfate in the alcohol phase. The streamlined characteristics of the NADIA method enable the preparation of extracellular vesicles-mimicking lipid nanoparticles (ELNPs). Among the mixing methods using a micropipette, a syringe pump, and a microfluidic device, the lattermost was the best for decreasing batch-to-batch differences in size, polydispersity index, and transfection efficiency in HepG2 cells. Although ELNPs possessed negative ζ-potentials and did not have surface antigens, their transfection efficiency was comparable to that of cationic lipoplexes. We observed that lipid raft-mediated endocytosis and macropinocytosis contributed to the transfection of ELNPs. Our strategy may overcome the hurdles linked to supply and quality owing to the low abundance and heterogeneity in cell-based extracellular vesicles production, making it a reliable and scalable method for the pharmaceutical manufacture of such complex formulations.

CO Gas-free Intramolecular Cyclocarbonylation Reactions of Haloarenes Having a C-Nucleophile through CO-Relay between Rhodium and Palladium.

We describe transfer carbonylation reactions of 2-bromoarenes that contain a carbon-nucleophile using aldehydes as a substitute for CO, leading to the formation of indanone derivatives. The transformation proceeds efficiently under RhI /Pd0 -hybrid catalytic conditions consisting of two discrete transition metals, rhodium and palladium, which catalyze the decarbonylation of aldehydes and the subsequent carbonylation of bromoarenes using the resulting carbonyl moiety, respectively. The majority of the abstracted CO is transferred directly to the product via a CO-relay process from rhodium to palladium.

Mechanistic Study on Allylic Arylation in Water with Linear Polystyrene-Stabilized Pd and PdO Nanoparticles.

The catalytic cycle of allylic arylation in water catalyzed by linear polystyrene-stabilized Pd or PdO nanoparticles (PS-PdNPs or PS-PdONPs) was investigated. Stoichiometric stepwise reactions indicated that the reaction did not proceed stepwise on the surface of the catalyst. In the case of the reaction with PS-PdNPs, the leached Pd species is the catalytically active species and the reaction takes place through a similar reaction pathway accepted in the case of a complex catalyst. In contrast, allylic arylation using PS-PdONPs as a catalyst occurs via a Pd(II) catalytic cycle.

Synthesis of alpha,omega-diarylbutadienes and -hexatrienes via decarboxylative coupling of cinnamic acids with vinyl bromides under palladium catalysis.

Readily available cinnamic acid derivatives such as ferulic acid couple with beta-bromostyrenes and 1-bromo-4-phenylbutadiene under palladium catalysis accompanied by decarboxylation to produce the corresponding alpha,omega-diarylbutadienes and -hexatrienes, respectively. Some of the products exhibit solid-state fluorescence.

Fused ring construction around pyrrole, indole, and related compounds via palladium-catalyzed oxidative coupling with alkynes.

The selective synthesis of 1,2,3,4-tetrasubstituted carbazoles can be performed effectively through the palladium-catalyzed oxidative coupling reactions of N-substituted indoles or their carboxylic acid derivatives with alkynes. Unsymmetrically octasubstituted carbazoles can also be obtained by the stepwise couplings of 1-methylpyrrole-2-carboxylic acid with two different alkynes. In addition, the present coupling procedure is applicable to the synthesis of other various heteroarenes possessing di-, tri-, and tetracyclic cores. Some of the products exhibit intense fluorescence in the solid state.

Synthesis of condensed heteroaromatic compounds by palladium-catalyzed oxidative coupling of heteroarene carboxylic acids with alkynes.

The palladium-catalyzed oxidative coupling of indole-3-carboxylic acids with alkynes effectively proceeds in a 1:2 manner accompanied by decarboxylation to produce the corresponding 1,2,3,4-tetrasubstituted carbazoles, some of which exhibit solid-state fluorescence. Pyrrole-, benzofuran-, and furancarboxylic acids also undergo the decarboxylative coupling to afford highly substituted indole, dibenzofuran, and benzofuran derivatives, respectively.