Theoretical studies on the electronic and geometric structures, the trend in DNA-binding affinities as well as the the structure-activity relationship (SAR) of a series of water-soluble Ru(II) methylimidazole complexes, i.e. [Ru(MeIm)4iip]2+ (1) (MeIm=1-methylimidazole, iip=2-(1H-imidazo-4-group)-1H-imidazo[4,5-f][1,10]phenanthroline), [Ru(MeIm)4tip]2+ (2) (tip=2-(thiophene-2-group)-1H-imidazo[4,5-f][1,10]phenanthroline), and [Ru(MeIm)42ntz]2+ (3) (2ntz=2-(2-nitro-1,3-thiazole-5-group)-1H-imidazo[4,5-f][1,10]phenanthroline), were car-ried out using the density functional theory (DFT). The electronic structures of these Ru(II) complexes were analyzed on the basis of their geometric structures optimized in aqueous solution, and the trend in the DNA-binding constants (Kb) was reasonably explained. The results show that the replacement of imidazole ligand by thiophene ligand can effectively improve the DNA-binding affinity of the complex. Meanwhile, it was found that introduc-ing the stronger electronegative N atom and NO2 group on terminal loop of intercalative ligand can obviously reduce the complex's LUMO and HOMO-LUMO gap energies. Based on these findings, the designed complex [Ru(MeIm)42ntz]2+ (3) can be expected to have the greatest Kb value in complexes 1-3. In addition, the structure-activity relationships and antitumor mechanism were also carefully discussed, and the antimetastatic activity of the designed complex 3 was predicted. Finally, the electronic absorption spectra of this series of complexes in aqueous solution were calculated, simulated and assigned using DFT/TDDFT methods as well as conductor-like polarizable continuum model (CPCM), and were in good agreement with the experimental results.