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Abstract
The photo-cleavage reaction of o-naphthoquinone methide pre-caged substrates (o-NQMP) is an efficient and controllable way to release small molecules under specific light irradiation. NQMP related chemistry has been applied in organic synthesis, biochemistry systems, and material science. We first studied the kinetic of thiol-NQMP Michael addition using laser flash photolysis, we observed the pH-related rate constant change of the reaction and measured the lifetime of o-NQMP intermediate and different reaction constants with varies of thiolates existence. We then applied thiol-NQMP Michael addition on cysteine protein, we synthesized fluorescent NQMP derivative and successfully introduced it to the BSA and ferritin. Then we used PEG-NQMP which has moderate water solubility and successfully achieves the photo-induced inhibitor for papain enzyme. By combining our compound with azide-alkyne click chemistry, we designed a series of NQMP based linker for photo-cleavable polymer, we modified NQMP with propargyl and Aza-dibenzocyclooctyne (ADIBO) which react with azide under different reaction condition, we linked of two different monomers through click chemistry and break the conjugation by light irradiation. Then we designed and synthesized o-NQMP derivatives for the silica nanoparticle project, the NQMP-caged Aspirin with triethoxysilane function group can be easily applied on the surface and in mesopores of Mesoporous Silica Nanoparticles (MSNs), then successfully released Aspirin molecules from MSNs under 300 or 350 nm light irradiation in aqueous solution. This strategy has moderate drug release ability (12 mg Aspirin per gram of particles) and low cytotoxicity without side reaction. In the last project, we took advantage of Avidin-Biotin Complex to design an MSNs based photo-triggered drug release strategy using the NQMP-Biotin compound.