Development of Multi-Functional Molecular Systems for Applications on Nanomaterial Surfaces

The glutathione-mediated, retro Michael-type addition reaction is demonstrated to take place at the interface of water-soluble, maleimide-functionalized gold nanoparticles (Maleimide-AuNP). The retro Michael-type addition can be blocked by hydrolyzing the Michael addition thioether adduct at the nanoparticle’s interface. This procedure “locks” the molecule of interest onto the Maleimide-AuNP template, ensuring no loss of the molecular cargo from the nanocarrier. On the other hand, the glutathione-mediated retro Michael-type addition reaction can be exploited for delivering a molecular payload. The Michael donor, 4-mercaptophenylacetic acid was modified with a terminal azide, allowing for addition of cargo through strain-promoted alkyne azide cycloadditions with various functional alkynes. The resulting AuNPs are versatile platforms for the integration of multiple functionalities within a single construct, enabling their use in complex biotic environments. As a proof of concept, a fluorogenic molecular cargo was incorporated onto a Maleimide-AuNP and delivered via the glutathione-mediated, retro Michael-type addition reaction