Self‐immolative chemistries that respond in an irreversible manner to external stimuli
are highly attractive to permanently degrade filamentous supramolecular biomaterials.
Within the monomer, a balance needs to be struck between its capacity to be supramolecularly
polymerized and degraded at an appropriate rate for a given application. Herein, we
unravel the structure‐property‐function relationships of a library of squaramide‐based
bolaamphiphiles bearing a central disulfide‐based self‐immolative spacer to construct
supramolecular polymers responsive to a chemical stimulus in aqueous solutions. We
examine the impact of changing the alkyl domain length (2 to 12 methylene units) on
the formation of supramolecular filaments and their rate of degradation in response
to a biological antioxidant, glutathione. A minimum of an octyl spacer is required
to robustly form supramolecular polymers that can be irreversibly degraded through
a cyclization‐elimination reaction of the self‐immolative spacer triggered by thiol‐disulfide
exchange within several hours. Further increasing the peripheral alkyl chain length
to a decyl spacer increases the ordered packing of the amphiphiles, hindering their
chemical degradation. This study provides a framework to design small molecule chemically
responsive filamentous supramolecular polymers based on bolaamphiphilic monomers that
can be irreversibly degraded in aqueous solutions for their eventual application as
biomedical materials.
