A DFT study of inclusion complexes of substituted calix[n]arenes with dasatinib and lapatinib

Herein, we have presented the results of Density Functional Theory (DFT) based calculations of inclusion complexes of lapatinib and dasatinib with calix[n]arene macrocycles. A total of 48 calix [n]arene complexes were modeled via considering varied ring sizes (n = 4,5,6,8) and upper-rim functionalization viz. SO₃H, tert-Butyl, iso-Propyl, COOH, C₂H₅OH, and C₂H₅NH₂. From the results of multilevel molecular docking, DFT energetics, and reactivity descriptors; it has been demonstrated that dasatinib form optimal complexes with calix 4f, 3f (-35 to -40 kcal/mol). Moreover, for lapatinib, hosts 3f, 4a, 1f, 3d have the capability to generate promising complexes (>35 kcal/mol). Based on counterpoise corrected binding energies (E_bind) and global reactivity descriptors, we anticipate that the proposed complexes can vitally be used as analogous to carrier-mediated-drug-delivery.