The mechanochemical release of Naphthalimide fluorophores from β-carbonate and β-carbamate disulfide-centered polymers

The covalent attachment of cargo molecules (e.g., drugs and fluorophores) in β-position to a disulfide moiety through carbamate and carbonate bonds finds many applications in responsive release systems. Recently, we showed that the combination of this release process with polymer mechanochemistry-induced disulfide scission enabled the remote-controlled release of small molecule drugs and fluorophores from their inactive parent macromolecules using ultrasound. The nature of the linker bond largely governed the subsequent release kinetics, an aspect that has not been investigated so far. To compare the differences, we here employ disulfide-centered polymers releasing either hydroxyl- or amino-naphthalimides from their respective β-carbonate or -carbamate linkers by force-induced intramolecular 5-exo-trig cyclization. We present the synthesis, characterization, and cell imaging evaluation of three naphthalimides featuring colorimetric and green fluorescence turn-on upon release, allowing monitoring of the release process. We believe that the insights gained from these experiments would advance the tailoring of release rates for force-induced pharmacotherapy.