Synthesis, experimental and theoretical spectroscopic electronic elucidation along with biological assessment and molecular docking studies on 2-(3-(1,4-diazepan-1-yl)propyl)isoindoline-1,3-dione − Antidepressant drug

Abstract

The title compound, 2-[3-(1,4-diazepan-1-yl)propyl]-1H-isoindole-1,3(2H)-dione (2DPID), was synthesized from Boc-protected 2-[3-(1,4-diazepan-1-yl)propyl]-1H-isoindole-1,3(2H)-dione by treating it with trifluoroacetic acid in dichloromethane. This reaction involves the hydrolysis of the tert-butyloxycarbonyl (Boc) group under acidic conditions. The crude product was then purified by column chromatography. The purity and identity of 2DPID were confirmed through spectroscopic techniques, including 1H NMR, 13C NMR, and FT-IR. Additionally, the compound was theoretically investigated using density functional theory (DFT) to complement the experimental findings. This comprehensive approach ensured the accuracy and reliability of the synthesized compound’s characterization and confirmed its structure and purity. The research includes estimating the compound’s optimal structure and molecular geometry in both the gas and solvent phases (water, CCl4, and chloroform). Topological analysis utilizing Multiwfn 3.8 analyzer involved to elucidate the electron localization function (ELF), localized orbital locator (LOL), & Reduced density gradient (RDG) studies to locate important bonding sites and weak interactions inside the molecule. The IEFPCM framework was utilized to analyze the consequences of solvation on distinct solvents. Investigations into the effects of solvation on the electrical characteristics (Frontier molecular orbital (FMO) & UV–visible), Molecular electrostatic potential (MEP), and nonlinear optics (NLO) attributes revealed differences in the compound’s action among the gas & liquid phases. The significant presence of the solvent has a major impact on the compound’s reactivity, as the FMO’s study demonstrates by showing a higher electrophilicity index m4-descriptive value. Natural bond orbital (NBO) simulations were implemented to evaluate inter and intramolecular charge transferand stabilization. According to the MEP study, the electronegative atoms act as electrophiles, whereas the hydrogen & carbon atoms are nucleophilic. Investigations utilizing thermodynamics confirmed that significant molecular characteristics improved with temperature. Drug-likeness evaluations were used to describe the chemical’s drug attributes. Lastly, targeted protein stability was ensured by molecular docking towards antidepressant protein receptors, which was demonstrated by Ramachandran graphs. The chemical interacted with four desired protein targets (3MDM, 4HRG, 5KZN, and 7LWD) according to the molecular docking data; 4HRG had the best binding energy, at −7.63 kcal/mol.