Crystal structure reveals the binding mode and selectivity of a photoswitchable ligand for the adenosine A2A receptor.

Rational synthetic expansion of photoresponsive ligands is important for photopharmacological studies. Adenosine A2A receptor (A2AR) is stimulated by adenosine and related in Parkinson's disease and other diseases. Here, we report the crystal structure of the A2AR in complex with the novel photoresponsive ligand photoNECA (blue) at 3.34 Å resolution. PhotoNECA (blue) was designed for this structural study and the cell-based assay showed a photoresponsive and receptor selective characteristics of photoNECA (blue) for A2AR. The crystal structure explains the binding mode, photoresponsive mechanism and receptor selectivity of photoNECA (blue). Our study would promote not only the rational design of photoresponsive ligands but also dynamic structural studies of A2AR.

Co-Catalyzed atom transfer radical addition of bromodifluoroacetamides, expanding the scope of radical difluoroalkylation.

The atom transfer radical addition (ATRA) of bromodifluoroacetamides to arylalkynes and terminal alkenes was conducted using von Wangelin's Co catalyst system (CoBr2/1,2-bis(diphenylphosphino)benzene/Zn) in acetone/H2O at 30 °C to afford the corresponding functionalized difluoroacetamides in 33-89% yields. Moreover, the Co catalyst was successfully applied to the tandem addition/cyclization of 1,6-diene and -enyne substrates and intramolecular ATRA of N-allyl and N-propargyl bromodifluoroacetamides, significantly expanding the scope of radical difluoroalkylation.