Baylis–Hillman Adducts as a Versatile Module for Constructing Fluorogenic Release System

The controlled release of a molecule
of interest (MOI) is useful
in probe design, prodrug construction, and drug delivery. We report
herein a versatile thiol-triggered fluorogenic release system using
the Baylis–Hillman (BH) adducts as a module. Common functional
groups (e.g., amino, hydroxyl, carboxylic, and sulfhydryl groups)
in a MOI are readily integrated into the module. The MOI release is
fast (∼10 min) with a nearly quantitative yield and a >250-fold
fluorescence increment. We further prepared two prodrugs to release
camptothecin and nitric oxide (NO) using the two-photon excitable
template, and the activation of prodrugs was visualized in live cells
and mouse tissues. The therapeutic potential of the NO prodrug was
also validated in a stroke model. This BH adduct-based fluorogenic
release features multiple advantages, such as easy preparation, compatibility
of various functional groups, fast response, high release yield, and
tunable emission spectra, and is expected to have broad applications.