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

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 C2-symmetric metal–organic cage Pd6L2412+ and an expanded version of the Fujita cage Pd6L1412+, 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. Pd6L1412+ binds hydrophobic bile acids and other steroids by forming a 1:1 complex. In contrast, the expanded Pd6L2412+ cage exhibits an affinity for amphiphilic bile acids and selective steroids to encapsulate them as dimers, promoted by cooperative interguest hydrogen bonding. Pd6L2412+ has a 5 times stronger solubility enhancement ability for cholic acid compared to Pd6L1412+. Further, the expanded Pd6L2412+ cage can selectively sense bile acids in nanomolar detection limits through indicator displacement assay by employing sulforhodamine 101 (SR101).