Vittala Sandeepa K, Liu Tingxian, van Zwol Suzanne, Fehér Bence, Voets Ilja K, Kieltyka Roxanne E
Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, Leiden, 2300 RA, The Netherlands.
HUN-REN-SU Nanobiophysics Research Group, HUN-REN-SU Biophysical Virology Research Group, Institute of Biophysics and Radiation Biology, Semmelweis University, Budapest, 1094, Hungary.
Chembiochem. 2025 Feb 3;26(5):e202400348. doi: 10.1002/cbic.202400348. Epub 2024 Nov 4.
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 chemical stimuli 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. 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 chemically responsive filamentous supramolecular polymers based on bolaamphiphiles that can be irreversibly degraded in aqueous solutions for their eventual application as biomedical materials.
对外部刺激以不可逆方式做出响应的自牺牲化学，对于永久性降解丝状超分子生物材料极具吸引力。在单体内部，需要在其超分子聚合能力与以适合特定应用的适当速率降解的能力之间取得平衡。在此，我们揭示了一系列基于方酰胺的双性离子两亲分子的结构-性质-功能关系，这些分子带有基于二硫键的中心自牺牲间隔基，以构建对水溶液中的化学刺激有响应的超分子聚合物。我们研究了改变烷基域长度（2至12个亚甲基单元）对超分子细丝形成及其响应生物抗氧化剂谷胱甘肽的降解速率的影响。至少需要一个辛基间隔基才能稳健地形成超分子聚合物，该聚合物可通过硫醇-二硫键交换引发的自牺牲间隔基的环化消除反应而不可逆地降解。进一步将外围烷基链长度增加到癸基间隔基会增加两亲分子的有序堆积，从而阻碍它们的化学降解。这项研究提供了一个框架，用于设计基于双性离子两亲分子的化学响应性丝状超分子聚合物，这些聚合物在水溶液中可不可逆地降解，最终用作生物医学材料。
