Hydrophobic domain modulation of chemical responsiveness in a bolaamphiphile-based supramolecular monomer.

Abstract

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.