D. Mendeleev University of Chemical Technology of Russia

A novel synthetic route to spirocyclic isoxazolines based on a redox-neutral dearomative cyclization of 3-benzyl-substituted isoxazoline N-oxides has been developed. The reaction likely proceeds through isoxazoline ring opening with generation of an unstable N-oxoiminium cation. The latter acts as an O-electrophile in the cyclization involving the ipso-position of the aryl ring. The reaction exhibits a broad substrate scope and affords spirocyclic isoxazolines featuring novel substitution patterns compared with those accessible by synthetic methods or found in natural sources.

To develop polyelectrolyte multilayer capsules (PMC) loaded with doxorubicin (DOX) and modified with the DR5-B protein to overcome drug resistance in MCF-7 breast cancer cells.

The capsules were prepared by layer-by-layer (LbL) assembly followed by thermal shrinking, DOX encapsulation and DR5-B surface modification. The capsules were characterised using scanning electron microscopy (SEM), dynamic light scattering (DLS), and UV-Vis spectrophotometry. Cellular uptake was assessed by confocal microscopy, flow cytometry, and fluorimetry. Cytotoxicity was evaluated by MTT-test in 2D and 3D in vitro models.

Mean capsule size was 320 ± 90 nm (PDI 0.39), mean ζ-potential was +29 ± 5 mV. The encapsulation efficiencies (ЕЕ) of DOX and DR5-B were 85 ± 7% and 80 ± 4%, with loading capacities (LC) of 9 ± 2 w/w% and 145 ± 40 w/w%, respectively. Shrunken capsules exhibited 3.5-fold higher internalisation than non-shrunken ones. DR5-B increased capsule accumulation by 1.8-fold. The capsules showed synergistic cytotoxicity in DR5-B-resistant MCF-7 spheroids (IC50 227 ± 13 ng/mL), being non-toxic to fibroblasts.

A method for the hydrofluoroalkylation of alkenes with the benzoic ester of 3,3,3-trifluorolactate and bis(trifluoromethyl)-substituted alcohols is described. The reaction is performed with N-phenylphenothiazine photocatalyst and has high tolerance toward functional groups. A key feature of the method is the use of tin(II) chloride/toluenesulfonic acid as a stoichiometric reducing agent.