Inclusion of capecitabine into cucurbiturils: DFT study for supramolecular encapsulation of anticancer drug

Electronic structure and stability of the encapsulated complexes of capecitabine (CAP, prodrug of 5-fluorouracil) with cucurbit [ n = 5 ~ 8]urils (CB[ n ]) in water were studied by means of DFT computations with dispersion (D3) and geometrical counterpoise (gCP) corrections. Among CB [ n = 5 ~ 8] with different inner sizes, CB [ n = 6, 7] can form more stable inclusion complexes (CAP@CB[ n ]) with CAP than CB [ n = 5, 8]. DFT computations showed that CAP@CB[7] with the normal CB[7] was the most stable in water, and some inverted CB[7] and CB[6] can also form relatively stable inclusion complexes. Dispersion correction played an important role in calculation of interaction energy between CAP and C [ n ]. Intermolecular non-covalent interaction and natural bond orbital analysis showed that electron transfer from CB[7] to CAP made CAP@CB[7] stable, when two hydrogen bonds (N–H…O and O–H…O) between CAP and CB[7] played positive role. Graphic abstract