Efficiency of C = Se as hydrogen bond acceptor in controlling regioselective amination of 5,7-dinitroquinazoline-4-selenone: Quantum mechanical, AIM and docking analysis by density functional method

Abstract

Herein, we explored the theoretical aspect of reaction between 5,7-dinitroquinazoline-4-selenone and methylamine by employing density functional theory (DFT) calculations. The energetic parameters confirmed that the reaction progressed via. concerted mechanism with the single step process instead of two step process via intermediate formation. Further, role of Se = C bond as non-conventional H-bond acceptor is reported in reaction controlling factors that monitors the regioselectivity of the present proposed reaction. Despite of substantial steric hindrance at ortho-position of 5,7-dinitroquinazoline-4-selenones, the regioselective amination resulted into ortho-substituted product (P2) rather than para-substituted product (P1) attributed to non-conventional NH---Se = C intramolecular hydrogen bonding. The topological properties of the electron density distributions have been studied by using quantum theory of atoms in molecules (QTAIM). The presence of non-conventional hydrogen bond acceptor–donor interactions (NH---Se = C) in ortho-positioned amination is achieved by electron density ρ(r) and Laplacian of electron density ∇2ρ(r) in QTAIM analysis and supported the results of DFT studies hybrid with B3LYP/6-31G(d,p) basis set. Due to the lack of intramolecular hydrogen bonding interactions (NH---Se = C), the para-positioned amination on 5,7-dinitroquinazoline-4-selenone is founded to be less feasible. Further, the DFT technique has been used to investigate frontier molecular orbital (FMO) analysis and global reactive parameters using the aforesaid level of theory and basis set. HOMO-LUMO analysis revealed that ortho-substituted product (P2) has a wider energy gap (3.0684 eV) than para-substituted product (P1) (2.6402 eV) suggesting more stability of P2. The presence of hydrogen bonding interactions is further confirmed by the change in electrostatic potential regions in ortho-substituted product (P2) as compared to reactants in molecular electrostatic potential surface (MEPS) studies. Both para-substituted product (P1) and ortho-substituted product (P2) have been docked into the protein 5FCT's active site to predict favored binding location, activity and affinity by using docking studies.