Cyclopentanone-based chalcone derivatives: Synthesis, characterization, DFT, drug-likeness and molecular docking studies

In this study, five novel chalcone derivatives—۲,۵-di((E)-benzylidene)cyclopentan-۱-one (۴a-۱), ۲,۵-bis((E)-۴-methylbenzylidene)cyclopentan-۱-one (۴a-۲), ۲,۵-bis((E)-۴-bromobenzylidene)cyclopentan-۱-one (۴a-۳), ۲,۵-bis((E)-۴-methoxybenzylidene)cyclopentan-۱-one (۴a-۴), and ۲,۵-bis((E)-۴-(dimethylamino)benzylidene)cyclopentan-۱-one (۴a-۵)—were successfully synthesized via a base-catalyzed condensation reaction between cyclopentanone and para-substituted benzaldehyde derivatives. The resulting compounds were isolated, purified, and structurally characterized using Fourier Transform Infrared Spectroscopy (FT-IR) and Nuclear Magnetic Resonance (NMR) spectroscopy (۱H and ۱۳C). To complement experimental findings, Density Functional Theory (DFT) calculations at the B۳LYP/cc-pVDZ level were performed to optimize molecular geometries, predict vibrational spectra, and simulate theoretical ۱H and ۱۳C NMR chemical shifts. The strong agreement between theoretical and experimental data validated the proposed structures. Furthermore, key quantum chemical descriptors—including dipole moment (μ_D), hardness (η), softness (σ), electronegativity (χ), electrophilicity index (ω), nucleophilicity, and chemical potential (μ)—were computed to evaluate the compounds' potential as corrosion inhibitors. Monte Carlo simulations were conducted to investigate the adsorption behavior of the chalcone derivatives (۴a-۱ to ۴a-۵) on Fe(۱۱۰) and Cu(۱۱۱) surfaces under vacuum conditions. All compounds demonstrated spontaneous and energetically favorable adsorption, with ۴a-۵ exhibiting the highest binding affinity, indicating its superior corrosion inhibition efficiency. Additionally, in silico pharmacokinetic and toxicity assessments—including oral toxicity prediction, drug-likeness screening, and BOILED-Egg modeling—were employed to evaluate bioavailability and therapeutic prospects. Molecular docking studies targeting the ۱۱β-HSD۱ enzyme revealed significant binding affinities, particularly for compounds ۴a-۱ and ۴a-۲, suggesting potential pharmacological activity. Collectively, these results underscore the dual functionality of the synthesized chalcone derivatives as both effective corrosion inhibitors and promising pharmacological candidates.

کلیدواژه ها:

Chalcone derivatives ، NMR ، DFT ، Corrosion Inhibition ، pharmacokinetic ، Docking