Single-crystal X-ray structure, theoretical (Hirshfeld, electronic properties, NBO, NLO, RDG), and molecular docking studies of three phthalimidoethanesulfonamide derivatives

The three N-substituted-2-phtalimidoethanesulfonamide derivatives, 2-(1,3-dioxoisoindolin-2- yl)-N-(2-iso- propylphenyl)ethane-1-sulfonamide (I), N-(2,6-dimethylphenyl)-2-(1,3-dioxoiso indolin-2-yl)ethane-1sulfonamide (II) and 2-(2-(morpholinosulfonyl)ethyl) isoindoline-1,3-dione (III), were analyzed using a combined approach including single-crystal X-ray diffraction (SC-XRD), theoretical calculations with Density Functional Theory (DFT), and molecular docking studies. Phthalimide and sulfonamide compounds have recently attracted attention for their inhibitory properties against AChE and BChE enzymes. In this study, molecular and crystal structures of compounds have been confirmed by the SC-XRD technique. Optimized molecular geometries and vibrational modes have been examined and compared to experimental results. Frontier molecular orbital (HOMO-LUMO) energies, molecular electrostatic potential (MEP), natural bond orbital (NBO) analysis, and nonlinear optical (NLO) properties have been investigated by DFT/B3LYP/6-311G++(d,p) method. The reduced density gradient (RDG) analysis has been performed to analyze the non-covalent interactions. The Hirshfeld surfaces and 2D fingerprint analyses have been used to determine the intermolecular interactions of compounds. Moreover, in silico docking studies are performed to investigate the interactions between N-substituted-2- phtalimidoethane sulfonamide derivatives and AChE and BChE enzymes.