Visible-Light-Promoted Fe(III)-Catalyzed N-H Alkylation of Amides and N-Heterocycles.

The combination of the radical chemistry of ligand-to-metal charge transfer with metal catalysis by a single iron salt helps to realize the visible-light-promoted N-H alkylation of amides and N-heterocycles. A wide variety of amides and nitrogen-containing heterocycles were tolerated in our protocol to give N-alkylated products. The applicability of this protocol was further demonstrated by late-stage alkylation of N-H-containing pharmaceuticals. Moreover, N-H-alkylated α-amino tetrahydrofurans could be transformed into versatile ring-opened amino alcohols under reducing conditions. A mechanistic study revealed that hydrogen atom transfer by a tert-butoxyl radical and a chlorine radical was responsible for the activation of C(sp3)-H precursors.

"One body and two wings" novel nanozyme combined with photothermal therapy for Combat Drug-Resistant Bacteria.

Bacterial resistance caused by antibiotic therapy is a serious problem. Therefore, there is an urgent need to find alternative methods to overcome bacterial resistance. Herein, we synthesized a new type of iridium oxide (IrOx) as an alternative to antibiotics. Iridium oxide not only has good catalytic properties, but also has photothermal properties, and then realizes the "one body and two wings" strategy to enhance the antibacterial effect. Research results show that near-infrared light can enhance the peroxidase catalytic activity of IrOx and generate highly toxic hydroxyl radicals (·OH) by catalyzing hydrogen peroxide (H2O2). Hydroxyl radicals have a high redox potential, which can overcome the drug resistance of gram-positive and negative bacteria. Importantly, IrOx has no obvious cellular and in vivo toxicity. Accordingly, the novel photothermal nanozyme is expected to be applied to bacterial infectious diseases, such as wound healing, sepsis, and implant-related infections.

Preparation of lapatinib ditosylate solid dispersions using solvent rotary evaporation and hot melt extrusion for solubility and dissolution enhancement.

The objective of this study was to enhance solubility and dissolution of lapatinib (LB) ditosylate (DT) using solid dispersions (SD) prepared by solvent rotary evaporation (SRE) and hot melt extrusion (HME). A series of models based on solubility parameter, the solid-liquid equilibrium equation, and the Flory-Huggins equation were employed to provide insight to data and evaluate drug/polymer interactions. Experimentally, nine SD formulas were prepared and characterized by various analytical techniques including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscope (SEM), solubility, and dissolution. It was found that both material attributes (e.g., drug loading and solid state) and process parameters (e.g., extrusion temperature) significantly affected manufacturability and solubility/dissolution behaviors. Among the formulas investigated, Formula #9 containing LB-DT, Soluplus®, and poloxamer 188 at a weight ratio of 1:3:1 was screened as the first ranked one. While comparing production routes, the SDs prepared by SRE showed more amorphicity as well as higher solubility/dissolution. This study provided the insight of introducing theoretical models to guide SD formulation/process development and illustrating the potential of bioavailability enhancement for LB-DT.