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

Cyclopentane fusion in coumarin photocages transforms their behavior from rapid S_N1-mediated release (minutes) to a slower elimination pathway (hours), accompanied by dramatic spectral changes upon photolysis, providing complementary tools for controlled-release applications requiring different payload delivery rates.

Abstract

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⁻¹) and lower photolytic quantum yields (Φ _u = 1.0 × 10⁻³) 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-S_N1 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.

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