Metal–Organic Cage Receptors for Encapsulation and Sensing of Bile Acids

Abstract

Developing synthetic supramolecular receptors to solubilize, scavenge, recognize, encapsulate, and sense steroids is challenging. Despite a limited number of receptors having affinity with steroids, none exists to bind steroidal bile acids selectively. Herein, we report a C 2 -symmetric metal–organic cage [Pd 6 L2 4 ] 12+ and an expanded version of the Fujita cage [Pd 6 L1 4 ] 12+, built with a conformationally flexible ligand L2, accessed through coordination-driven self-assembly. We examined both cages for steroid recognition in water: both have certain shared characteristics and distinctive features. [Pd 6 L1 4 ] 12+ binds hydrophobic bile acids and other steroids by forming a 1:1 complex. In contrast, the expanded [Pd 6 L2 4 ] 12+ cage exhibits an affinity for amphiphilic bile acids and selective steroids to encapsulate them as dimers, promoted by cooperative interguest hydrogen bonding. [Pd 6 L2 4 ] 12+ has a 5 times stronger solubility enhancement ability for cholic acid compared to [Pd 6 L1 4 ] 12+ . Further, the expanded [Pd 6 L2 4 ] 12+ cage can selectively sense bile acids in nanomolar detection limits through indicator displacement assay by employing sulforhodamine 101 (SR101).