Understanding the guest binding in the cucurbit[7]uril inclusion complexes of CDK4/6 inhibitors, palbociclib, and ribociclib from a combined experimental and computational study

We have studied the cucurbit[7]uril inclusion complexes of two anti-cancer drugs, palbociclib and ribociclib, in the solution and solid-state with the help of experimental and computational approaches. The formation of the cucurbit[7]uril inclusion complex, binding stoichiometry, and binding free energies in aqueous solution was determined from 1H-NMR, UV-spectroscopy and ITC studies. The binding of drugs in the ionized and unionized forms with cucurbit[7]uril was studied with the help of QTAIM analysis and free energy computations. We report the development of new co-amorphous solids of the cucurbit[7]uril inclusion complexes of drugs with enhanced thermal stability. We also report three new crystalline salt forms of palbociclib oxalate and a new dimethyl sulfoxide solvate of ribociclib succinate dihydrate in the study. The phase interrelationship between the palbociclib oxalate forms (1a, 1b, and 1c) was established from DSC and PXRD study.