Electronic structures and SARs of the isomeric complexes α-, β-, γ-[Ru(mazpy)2Cl2] with different antitumor activities

Three recently found isomeric complexes alpha-, beta-, gamma-[Ru(mazpy)(2)Cl-2] 1-3 (mazpy=4-methyl-2-phenylazopyridine) with different antitumor activities have been computed using the DFT-B3LYP method. The electronic and geometric structures as well as the structure-activity relationships (SARs) of such a type of isomers were investigated. The results show that the differences of isomeric structures of these Ru(II) complexes have very important effects on their electronic structures and related properties. Some interesting electronic and geometric structural characteristics of these complexes have been revealed. First, the main-body (azopyridine) planes of two conjugative ligands (mazpy) in gamma-[Ru(mazpy)(2)Cl-2] 3 are almost located on the same plane, but those in alpha- or beta-[Ru(mazpy)(2)Cl-2] (1 or 2) are almost intervertical. Second, the energy order of the lowest unoccupied molecular orbitals (LUMOs) of the isomers is epsilon(L)(2) > epsilon(L)(1) > epsilon(L)(3), and the HOMOLUMO gap is Delta epsilon(L-H)(3) < Delta epsilon(L-H)(1) < Delta epsilon(L-H)(2). Third, the total dipole moments (mu) of the isomers are in the sequence of mu(2) > mu(1) > mu(3), while the order of the positive charges (Q(L)) in the ligand mazpy is Q(L)(3) > Q(L)(1) > Q(L)(2). These electronic and geometric structural characteristics can be used to reasonably explain the trend in the anticancer-activities (A) of these isomers, i.e. A(2) < A(1) < A(3). (c) 2005 Elsevier B.V. All rights reserved.