Computational studies of new homoleptic transition metal(II) complexes containing 1,3-dimesitylpropane-1,3-dione: DFT calculations and biological properties

In this investigation, we present a combined density functional theory and molecular docking study to explore the structural, reactivity, spectroscopic properties, and anticancer activity of new Cu(II) and Zn(II) complexes with 1,3-dimesitylpropane-1,3-dione (L Mes ) in both the gas phase and ethanol solvent. Geometric parameter scanning elucidates the intramolecular interactions, revealing the steric and electronic effects of the metal centers on the molecular geometry. A good correlation is observed between the experimental and calculated geometric parameters, validating the theoretical model. The obtained results indicate that the Cu(II) complex adopts a square–planar geometry, whereas the Zn(II) complex exhibits a tetrahedral geometry. Molecular reactivity descriptors and the molecular electrostatic potential maps were calculated to identify the most reactive sites within the molecular framework. Moreover, a good agreement is found between the experimental and theoretical vibrational frequencies, confirming the reliability of the computational approach. The UV–visible absorption spectra were also analyzed, revealing that the metal center significantly influences the electronic transitions, with a notable shift in λ max to 424.71 nm for the Cu-complex and 320.84 nm for the Zn-complex. Finally, the Cu(II) complex demonstrates superior stability, specificity, and structural reinforcement within the epidermal growth factor receptor active site, supported by stronger hydrogen bonding, π–π interactions, and reduced protein flexibility. In contrast, the Zn(II) complex adopts a more hydrophobic and flexible binding mode, indicating weaker stabilization and lower inhibitory potential. These findings suggest that both complexes possess promising anticancer potential, warranting further experimental validation and pharmacological evaluation to confirm their therapeutic efficacy.