Supramolecular host-guest interactions of TRYVIO and VAFSEO with a benzotriazole nanocapsule: A density functional theory study.

The potential of a benzotriazole-based supramolecular nanocapsule (Cap-GB) as a drug delivery carrier for chronic kidney disease (CKD) therapeutics was investigated using density functional theory (DFT). The geometry optimization and interaction energies were performed at ꞷB97XD/6-31G (d, p) to determine the stability and binding capabilities of the ACT-132577@Cap-GB and AKB-6548@Cap-GB host-guest complexes. The computed interaction energies for both the complexes indicated that the TRYVIO exhibits a stronger binding (-43.20 kcal/mol) compared to the VAFSEO (-35.15 kcal/mol). NCI analysis showed that hydrogen bonding and van der Waals interactions predominantly played a pivotal role in the stability of the complexes. The non-covalent nature of these interactions was also confirmed by the QTAIM analysis, which identifies bond critical points with positive Laplacian values, which rectify the NCI analysis. Frontier molecular orbital analysis showed that the HOMO-LUMO energy gap decreased slightly with drug encapsulation, particularly in the case of AKB-6548@Cap-GB (8.12 eV), which indicates the improved conductivity of the nanocapsule. Charge transfer analyses showed the redistribution of charges between the drugs and the surface of the capsule. The higher value of dipole moments of the complexes indicated their high polarity and improved solubility in the polar solvents. Overall, the findings establish the benzotriazole supramolecular nanocapsule as an effective therapeutic carrier of CKD therapeutics.