Supramolecular synthetic transporters are crucial to
understand
and activate the passage across lipid membranes of hydrophilic effector
molecules. Herein, we introduce photoswitchable calixarenes for the
light-controlled transport activation of cationic peptide cargos across
model lipid bilayers and inside living cells. Our approach was based
on rationally designedp-sulfonatocalix[4]arene receptors
equipped with a hydrophobic azobenzene arm, which recognize cationic
peptide sequences at the nM range. Activation of membrane peptide
transport is confirmed, in synthetic vesicles and living cells, for
calixarene activators featuring the azobenzene arm in theEconfiguration. Therefore, this method allows the modulation
of the transmembrane transport of peptide cargos uponZ–Ephotoisomerization of functionalized calixarenes
using 500 nm visible light. These results showcase the potential of
photoswitchable counterion activators for the light-triggered delivery
of hydrophilic biomolecules and pave the way for potential applications
in remotely controlled membrane transport and photopharmacology applications
of hydrophilic functional biomolecules.