Solvent effect on cycloaddition of C20 nanofullerene with indoline‐2‐one, at density functional theory

Abstract

AbstractThe biologically active (E)‐3‐(furan‐2‐yl)methylene‐indoline‐2‐one (I) is studied, in the gas phase, C6H6, C2H4Cl2, EtOH, MeNO2, DMSO, and H2O using the self‐consistent reaction field (SCRF)—density functional theory (DFT). This species has been used in tumor growth, metastasis, and angiogenesis. A mainly interesting issue is the solvent effect on the stability, geometry, and energy of intermolecular hetero‐Diels–Alder cycloaddition of I with C20 to yield drug delivery (Ia). By optimization of adduct (Ia) from gas phase to nonpolar and then polar solvent, the following results is obtained: (1) The trend of thermodynamic and kinetic stability and also polarity seem proportional to the dielectric constant of the used solvent and formation of the hydrogen bonding. (2) In contrast to general belief that the endo isomer appears more stable than exo isomer, here, the exo isomer appears more stable than endo isomer. (3) The exo cycloaddition can be carried out thermally at room temperature and currently hold responsible for regioselectivity. (4) The possibility of endo cycloaddition is favorable by the lowest energy barrier of 4.2 kcal/mol probed in benzene, while the highest energy barrier of 7.3 kcal/mol is estimated in water. (5) Nonbonding electrostatic interaction between the sulfur heteroatom and nanocage, as well as the π–π aromatic stacking, appears to have significant destabilizing effect on the endo isomer. (6) In going from exo transition state (TS) and endo TS to and Ia cycloadduct, the molecular electrostatic potential is changed as a function of shape, size, symmetry, and regioselectivity.