Jovica D. Badjić

We describe the preparation, dynamic, assembly characteristics of vase‐shaped basket 1 3− along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1 H Nuclear Magnetic Resonance (NMR), 1 H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [ 1 2 ] 6− , to be in equilibrium with monomers 1 ( R ) 3− (relaxed) and 1 ( S ) 3− (squeezed). Through simultaneous line‐shape analysis of 1 H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1 ( R ) 3− includes anticancer drug mitoxantrone ( MTO 2+ ) in its pocket to give stable binary complex [ MTO ⊂ 1 ] − ( K d =2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well‐characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep‐cavity baskets.