Improved Synthetic Access to Longer Wavelength Functional AZO Molecular Photoswitches
Description
Photoswitchable micelles hold significant promise for controlled drug delivery systems, but their reliance on ultraviolet light (365 nm) for photoswitching presents safety concerns for human applications. This research focuses on developing improved synthetic pathways to longer wavelength functional arylazopyrazole (AAP) molecular photoswitches through selective azo-Lewis acid chelation. A key challenge is controlling the chelation pattern to favor the smaller exocyclic chelate for photoswitching ability, rather than the larger endocyclic chelate, which prohibits photoswitching. This work explores a kinetic control approach to manipulate Lewis acid-azo chelation, successfully synthesizing precursor compounds: a hydrazone intermediate (50% yield) and a "power ring" structure through Knorr pyrazole synthesis (80% yield). Both compounds were characterized using UV-Vis, FTIR, and NMR spectroscopy. While some analytical results were inconclusive (FTIR data for both compounds and 13C NMR for the hydrazone), the UV-Vis spectroscopy showed promising evidence of azo bonding with strong signals suggesting photoswitching capability. The research provides foundational steps toward the future development of photoswitchable micelles capable of responding to longer, safer wavelengths of light for biomedical applications, particularly in photopharmacology and optogenetics. Future work will focus on introducing boron trifluoride under kinetic control conditions to achieve the target chelation