Engineering Photolabile Cyclopentane-Fused Coumarins: From One-Pot Synthesis to Mechanistic Study for Visible Light-Triggered Photolysis.

A series of cyclopentane-fused coumarins were synthesized via a one-pot Heck-Aldol annulation cascade from diethylaminocoumarin derivative and evaluated as visible light-responsive photocages. Compared to conventional coumarin photocages, these fused systems exhibited substantially different photolysis behavior. UV-vis spectroscopic analysis showed distinctive evolution of absorption profiles during photolysis, with pronounced bathochromic shifts and emergence of new bands at 405-415 nm, contrasting sharply with the minimal spectral changes seen in conventional photocages. Kinetic studies revealed that the cyclopentane-fused derivatives underwent significantly slower photorelease (k = 0.2106 h) and lower photolytic quantum yields (Φ = 1.0 × 10) than nonfused analogs, with pronounced solvent dependence not observed in traditional photocages. The spectral transformations, together with HPLC and LC-MS data, suggested a photo-elimination pathway involving heterolytic C─O bond cleavage followed by β-proton elimination rather than the conventional photo-S1 mechanism, with the photoproduct identified as a cyclopentene-fused structure (m/z 314.1). Fluorescence spectroscopy demonstrated a direct correlation between emission intensity decrease and uncaging progress, providing a convenient real time monitoring method. The contrasting kinetic profiles and spectroscopic signatures between rapid-release conventional photocages and sustained-release fused systems offer complementary tools for applications requiring different payload delivery rate, expanding the photochemical toolbox for controlled release applications.