Binding of citromycetin with bivalent metals in solvents: DFT, reactivity analysis, solvent effects, docking and md investigations

Citromycetin (DOCA), a structurally well-characterized frequentic acid derivative, can act as a bidentate ligand in coordination with metal ions. In this work, the complexation behavior of DOCA with Cd, Cu, Mg, Ni, Pb, and Zn was systematically investigated using density functional theory (DFT), molecular docking, and molecular dynamics (MD) simulations. The calculated binding energies and thermochemical parameters indicate the formation of stable DOCA–metal complexes and reveal differences in metal binding affinity. The results show that the interaction patterns of DOCA with Cd, Cu, Mg, and Zn are relatively similar, whereas Ni and Pb exhibit distinct coordination behavior. Non-covalent interaction (NCI) analysis further confirms the presence of strong attractive interactions within the complexes. The influence of solvent environments (water, DMSO, and ethanol) on the stability and solvation behavior of DOCA and its metal complexes was also investigated through solvation free energy calculations, revealing more favorable stabilization in water and ethanol than in DMSO. In addition, docking and MD simulations were performed to examine the interaction of the most favorable complexes with the target protein and to evaluate their structural stability during binding. This study provides new insights into the stability, electronic properties, and interaction characteristics of DOCA–metal complexes, contributing to a better understanding of their coordination behavior and potential biological interactions. KEY WORDS: DFT, Frequentic acid, Metal binding, Solvation energies, MD simulations Bull. Chem. Soc. Ethiop. 2027, 41(1), 55-68. DOI: https://dx.doi.org/10.4314/bcse.v41i1.5