Abstract: The electronic and geometric structures of a series of isomeric complexes α-, β-, γ-, δ-, ε-[Ru(azpy)2Cl2](azpy = 2-phenylazopyridine) (1~5) have been systemically studied, using the density functional theory(DFT) method at the B3LYP/LanL2DZ level. In particular, the structure-activity relationship(SAR) of 1~3 reported recently to be well-known antitumors, 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, it must be advantageous to the conjugative ligand intercalating between DNA-base-pairs, whereas those in α- and β-[Ru(azpy)2Cl2](1 and 2) are almost intervertical and thus it must be unadvantageous to their DNA-binding affinities due to their greater steric hindrance. (ii) The energies (εL) of the lowest unoccupied molecular orbitals(LUMO) playing a main role in the electrophilic reaction, are in sequence of εL(2) >εL(1) >εL(3); The energy differences (ΔεL-H) between LUMOs and HOMOs, being closely relative to the reaction activity, are in sequence of ? ΔεL-H(3)<ΔεL-H(1)<ΔεL-H(2). (iii) The total dipole moments (µ) of the isomer, being closely relative to the hydrophobic parameter of the molecule, are in sequence of µ(2) >µ(1) >µ(3). (iv) The positive charges (QL) in the ligand azpy, being also 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-, ε-[Ru(azpy)2Cl2](4 and 5) have been predicted.

Key words: Ru(II) isomeric complex, Anticancer activity, Phenylazopyridine, Density functional theory, Structure-activity relationship