Studies on Hydrolysis Mechanism of Anticancer Ruthenium Drug ImHtrans-Ru（Im）2Cl4 via ABEEMσπ Polarizable Force Field Combined with QM and MD-FEP

摘要

We used ABEEMon（atom-bond electronegativity equalization method） polarizable force field（ABEEMσπ PFF） method combined with QM and molecular dynamics-free energy perturbation（MD-FEP） methods to investigatethe function of water molecules in hydrolysis process of ImH[trans-Ru（Im）2Cl4]（ICR）. The activation free energiesobtained via MD-FEP calculation are in fair agreement with the experimental data. In addition, QM/MM（ABEEM）rationally describes the charge distributions and the electrostatic interaction between molecules. ABEEMσπ fluctua-ting charge model has the following good characteristics： （1） not only atomic charge regions but also σ,π bond andlone pair charge regions are explicitly represented for a molecule; （2） the region charges are geometry dependent andcalculated from time to time in the dynamic simulation without any iterative procedure so that its performance istime-saving compared with the Drude model and induced dipole model.