Synthesis, crystal structure, and electrochemical properties of 5-benzoyl-6-phenyl-pyrimidin-4-one-2-thione compound; voltammetric, spectrophotometric, and molecular docking studies of its interaction with DNA

Abstract

A novel heterocyclic compound, 5-benzoyl-6-phenyl-pyrimidin-4-one-2-thione (PT), was synthesized for the first time via the cyclocondensation reaction of dibenzoyl acetic acid-N-carboxymethylamide with thiourea. The structure of the compound was characterized using elemental analysis, FT-IR, NMR, X-ray crystallography, and API-ES mass spectrometry. Electrochemical behavior of PT was investigated by cyclic voltammetry on a glassy carbon electrode in an anhydrous medium (0.1 M TBAP), revealing an irreversible cathodic peak at −0.83 V, indicative of irreversible redox behavior and surface interaction. The interaction between PT and DNA was explored using voltammetric, spectrophotometric, and molecular docking techniques. Differential pulse voltammetry demonstrated a concentrationdependent decrease in the guanine oxidation signal, with a calculated binding free energy of −6.5 kcal/mol. Spectrophotometric studies further supported the occurrence of a stable PT–DNA complex. Molecular docking revealed a strong binding affinity (−8.12 kcal/mol), suggesting minor groove and electrostatic interaction modes. The consistency among electrochemical, spectroscopic, and computational findings indicates that PT forms a thermodynamically favorable and specific interaction with DNA. These results provide a foundation for future research on the therapeutic potential of PT and related pyrimidine thione derivatives.