A combined molecular dynamics simulation and quantum mechanics study on mercaptopurine interaction with the cucurbit [6,7] urils: Analysis of electronic structure.

In the current study, the probability of complex formation between mercaptopurine drug with cucurbit[6]urils and cucurbit[7]urils has been investigated. The calculations for geometry optimization of complexes have been carried out by means of DFT (B3LYP), DFT-D (B3LYP-D) and M06-2X methods. The Atoms In Molecules (AIM), Natural Bond Orbital (NBO), NMR, the density of states (DOSs) and frontier molecular orbital (MO) analyses have been done on the inclusion complexes. In addition, the UV-Vis spectra of the first eight states have been obtained by CAM-B3LYP/TD-DFT calculation. The obtained results of the complexation process reveal that CB[7]-DRG complexes are more favorable than that of CB[6]-DRG interactions. Furthermore, our theoretical results show that configurations III and I are the most stable configurations related to the CB[6]/DRG and CB[7]/DRG interactions, respectively. The positive ∇(r) and HC values at the bond critical points indicate that exist the weak H-bonds between CB[6] and CB[7] with H atoms of the drug molecule. The obtained negative binding energy values of CB[7]-DRG interaction in solution phase show the stability of these complexes in the aqueous medium. Also, all of the observed parameters of molecular dynamics simulation such as the number of contacts, hydrogen bonding, center-of-mass distance and van der Waals energy values confirm the encapsulation of mercaptopurine molecule inside the cucurbit[7]urils cavity at about 3.2ns.