Supramolecular Chiral Assemblies from Benzoselenadiazole-Alanine-Acylhydrazone Conjugates Enable Cardioprotection

Integrating structural order, permanent porosity, aqueous stability, and biological activity within a single supramolecular platform remains a central challenge in biomaterials science. Herein, we report a C₃-symmetric conjugate (TASe) that unites benzoselenadiazole, alanine, and acylhydrazone motifs, each serving dual roles as both supramolecular interaction sites and bioactive pharmacophores. This multifunctional design enables synergistic noncovalent assembly through cooperative chalcogen and hydrogen bonds, which direct the formation of a porous crystalline framework. In aqueous media, the same molecular modules drive self-assembly into uniform chiral nanospheres. The resulting assemblies efficiently protect cardiomyocytes from doxorubicin-induced injury by scavenging reactive oxygen species, reducing oxidative DNA damage, and attenuating ERK activation, without compromising anticancer efficacy. By embedding both assembly-directing and therapeutic functions within a single molecular scaffold, this work provides a generalizable strategy for constructing biologically active supramolecular materials with coordinated structural order and function.