The (4-carboxymethoxy) dinitroindolinyl (CDNI) system is used to cage biologically important agonists, especially neurotransmitters like glutamate (Glu). We have improved the synthesis of CDNI, introduced new versions of caged glutamate, studied their photochemical properties, and employed such systems in biological experiments. Our method reduced the total synthesis time of CDNI-Glu from 200 h to 40 h and doubled previously reported overall yields of ca. 10%. We also successfully protected the other available functional groups in Glu: the α carboxylic acid group and the amine, forming unreported α-CDNI-Glu and N-CDNI-Glu, respectively. These new molecules have the potential to minimize off target GABA inhibition. The photochemical properties of each caged form of Glu were also studied and their rates of photolysis were compared. CDNI-Glu was also uncaged, using two-photon microscopy, in an acute hippocampus brain slice. We also explored broader applications of the CDNI system in photo-initiated catalysis with biological applications beyond neuroscience.

Improved synthesis of the dinitroindolinyl cage (CDNI) and its application in neuroscience and beyond

2019 Spring National Meeting

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