Structures and Anticancer Activities of a Series of Isomeric Complexes Ru(azpy)2Cl2

The electronic and geometric structures of a series of isomeric complexes α-, β-, γ-, δ-, ɛ-[Ru(azpy)2Cl2](azpy= 2-phenylazopyridine) (1-5) have been systemically studied by using the density functional theory (DFT) method at the B3LYP/ LanL2DZ level. In particular, the structure-activity relationship (SAR) of 1-3, which were reported recently to have good antitumor activities, was emphatically investigated. The computed results show that: (i) The main-body (azopyridine) planes of two conjugative ligands (azpy) in γ-[Ru(azpy)2Cl2] (3) are almost located on the same plane; therefore it must be advantageous for the conjugative ligand to intercalate between DNA-base-pairs, whereas those in α- and β-[Ru(azpy)2Cl2] (1 and 2) are almost inter-vertical; thus it must be disadvantageous to their DNA-binding affinities due to their greater steric hindrance. (ii) The energies (ɛL) of the lowest unoccupied molecular orbitals (LUMO) playing a main role in the electrophilic reaction, are in sequence of ɛL(2)> ɛL(1)>ɛL(3). The energy differences (ΔɛL-H) between LUMOs and HOMOs, being closely relative to the reaction activity, are in sequence of ΔɛL-H(3)< ΔɛL-H1)<ΔɛL-H(2). (iii) The total dipole moments (μ) of the isomers, being closely relative to the hydrophobic parameters of the molecules, are in sequence of μ(2)>μ(1)>μ(3). (iv) The positive charges (QL) in the ligand azpy, also being relative to the ability to accept the electron from DNA, are in sequence of QL(3)>QL(1)>QL(2). In addition, based on the above theoretical analytic method, the heretofore unreported antimetastatic activities of the other two isomeric complexes δ-, ɛ-[Ru(azpy)2Cl2] (4 and 5) have been predicted.