Synthesis and Characterization of Nitrogen and Sulfur Donor-Acceptor Stenhouse Adducts

Project Summary/Abstract This proposal describes the use of fundamental chemical properties to alter the reactivity of reagents for the synthesis of biomedically important compounds. Specifically, the chemical properties of C–S bonds will be used for the synthesis of novel photoswitches named donor-acceptor Stenhouse adducts, DASAs. Though

Stenhouse adducts were introduced in 2014, they have been explored in drug delivery, dynamic phase transfer, polymers, liquid crystals, selective photoswitching, and chemosensing applications. Despite their promising applications, DASAs are currently limited by their structural diversity. Only amine donors and two acceptors are

generally used in DASA systems today. As a result, the physical properties and applications are limited. The overarching goal is to develop and characterize novel DASA molecules with a narrow HOMO-LUMO gap such that the newly developed molecules may be activated within the biological window of 650–1450 nm

light. Doing so puts photoswitchable molecules into the realm of challenging photopharmacological and specific light-emission applications. Specifically, the unique ability for DASA photoswitches to go from linear, uncharged structures to cyclic, zwitterionic intermediates presents an opportunity to permeate the blood-brain barrier and

to develop interesting thermally activated delayed fluorescence (TADF) species. In order to access new DASA molecules with the desired characteristics, adducts with sulfur, phosphine, oxygen, and additional conjugation will be investigated. 2-Thiophenecarboxaldehyde bears a weaker and longer C–S bond in place of the C–O bond

responsible for the inability to incorporate other donor functionality in DASAs when using furfural as a starting material; thiophene derivatives also carry less electron density on the carbon atoms, making it a perfect substrate for ring opening upon condensing an acceptor molecule. If the C–S bond is not sufficiently weak, the polarizable

sulfur will be activated using thiophilic Lewis acids. Synthesizing novel Stenhouse adducts 1) provides additional DASAs to explore applications listed above, 2) enables further research on the chemical properties of these new photoswitches, and 3) provides an opportunity to develop additional uses like those listed in photopharmacology

and light emission applications.