Clickable Photolabile Linkers for Convenient Immobilization and Light-Controlled Release of Substrates from Solid Support

Abstract Photolabile linkers (PLLs) enable spatiotemporal control over substrate release but often suffer from slow photorelease kinetics, low quantum yields, or limited functionalization options. Here, we report a family of heterobifunctional PLLs based on (3-hydroxy-5-alkoxynaphthalen-2-yl)methyl (NQMP) chromophores that combine rapid, high-yielding photochemical cleavage with orthogonal conjugation chemistries for efficient substrate immobilization and light-triggered release. Six heterobifunctional NQMP-based linkers bearing terminal acetylene, cyclooctyne, amine, carboxyl, allyl, and biotin groups were synthesized and employed for the immobilization of fluorescent dyes, acetylsalicylic acid, biotin, avidin, and doxorubicin on silica microspheres and mesoporous silica nanoparticles. Mild UV-A irradiation resulted in efficient release of the attached payloads while preserving the integrity of the solid support. Mesoporous silica nanoparticles provide high loading capacity and are suitable for light-controlled drug delivery. The modular design, excellent photochemical efficiency, orthogonal conjugation chemistries, and compatibility with diverse substrates make NQMP-based PLLs versatile tools for reversible surface functionalization, controlled cargo release, affinity capture, and photoresponsive drug delivery applications.