Mechanism of aquation and nucleobase binding of ruthenium (II) and osmium (II) arene complexes: A systematic comparison DFT study

A systematic mechanistic study is reported for the aquation and nucleobase binding process of a series of Ru II and Os II arene-based anticancer drug complexes using density functional theory and COSMO implicit solvent model. The structures of Ru II and Os II complexes are similar to each other because of lanthanide contraction of osmium. However, the aquation was substantially more facile for Ru II complexes than Os II complexes. As to nucleobase substitution, various possible paths were explored based on considering the initial conformation of ethylenediamine (en) and the orientation of guanine (G) and adenine (A). Both Ru and Os complexes exhibited much lower free energy barrier for G than A. This observed predominance toward G mainly originated from larger stabilization energy for the initially formed complex, compared with A, in combination with favored kinetics and thermodynamics. Moreover, the calculations indicated that pK as of Os-bound water molecules were uniformly much lower than those of Ru-bound water molecules. Analysis of the natural bond orbital (NBO) charge reveals that Os II has a higher net positive charge than Ru II, leading to a stronger electrostatic attractive interaction between Os II and chloride or water, resulted in higher activation barrier for their departure. These differences between Ru II and Os II en complexes discussed in our study may partly explain the inertness of the Os II complexes in biological system. © 2011 Elsevier B.V. All rights reserved