RESUMEN
We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 13- 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 Hâ 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 [12 ]6- , to be in equilibrium with monomers 1(R) 3- (relaxed) and 1(S) 3- (squeezed). Through simultaneous line-shape analysis of 1 Hâ NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R) 3- includes anticancer drug mitoxantrone (MTO2+ ) in its pocket to give stable binary complex [MTOâ1]- (Kd =2.1â µM) that can be precipitated inâ vitro with UV light or pH as stimuli. Both inâ vitro and inâ vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity inâ 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.