The mechanisms of interaction between morin and the catalytic zinc ion (Zn^2＋) in matrix metalloproteinases (MMPs) are investigated by using PM6 quantum chemistry method and designing ligand-exchange reactions. It is found that the electron transfer from morin molecule to catalytic zinc ion occurs when the groups at the various positions of A, B and C rings of morin molecule coordinate with catalytic zinc ion in MMPs, and the more the electron transfer, the stronger coordinating ability between them. We further find that among the groups at the various positions of morin molecule, the coordinating ability between the oxygen atom of the carbonyl group at the 4-position and catalytic zinc ion is the strongest, which indicates that the inhibition of MMPs activities is produced mainly by the carbonyl group at the 4-position of morin, rather than the hydroxy groups at the other positions. Regression analysis show that there are better linear relationships between the calculated free energy changes (DG₂₉₈) for the 6 ligand-exchange reactions and the Zn—O bond length, total atomic charges in the morin molecule, and the charges of coordinating O atoms in the produced coordinating ions. Our calculated results are in agreement with available experimental and theoretical results. These results of the interaction mechanisms may provide important reference data for the structural modifications of the morin molecule to design the MMPs inhibitors whose biological activities can obviously be improved.

Key words: morin, matrix metalloproteinases (MMPs), mechanism, PM6, free energy