The aim of this research is the investigation of the difference between the interaction of two enantiomers of Ni(II), ?-[Ni(phen)2(dppz)]+2 and ?-[Ni(phen)2(dppz)]+2, with DNA using the theoretical methods. Also, the effect of this interaction energy difference on the absorption and circular dichroism (CD) spectra of the enantiomers was investigated. The reason for performing this research is (a) this is the first theoretical study on the interaction of the enantiomers of an inorganic complex with DNA (b) experimental spectral and kinetic information about the conversion of mentioned enantiomers interacting with DNA are available in the literature. In the first part of the study, a detailed molecular docking study was performed for each enantiomer separately, to find the best interaction site of the DNA for the enantiomers. The docking of one and two enantiomers to the DNA was performed separately, and the structure of complexes including ?-DNA, ?-DNA, ?-?-DNA, ?-?-DNA, ?-?-DNA, and ?-?-DNA were determined. Two different interaction modes were explored for each enantiomer, so that the ?-enantiomer tends to locate its dppz and one phen ligands in the groove of DNA, while the ?-enantiomer tends to locate its dppz ligand in the groove of DNA. In the docking of the second enantiomer to ?-DNA and ?-DNA complexes, it was observed that the second enantiomer tends to locate near the first enantiomer, and the probability of locating two enantiomers far away from each other interacting with DNA is low. To obtain more reasonable values for the interaction energies of enantiomers and examine the tendency of enantiomers for the intercalation interaction, the semiempirical quantum study employing PM6 method and quantum calculation in the ONIOM scheme was performed in the gas phase and water, separately. In the ONIOM method, the enantiomers were considered in the high layer employing M06-2X functional. It was observed that the interaction of the ? enantiomer with DNA is stronger than that of ? enantiomer. The optimized structures of complexes obtained from the quantum calculations were compared to the corresponding structures obtained from the docking study to investigate the effect of the interaction on the position of the DNA base pairs in the direct interaction with enantiomers. The absorption and CD spectra of isolated enantiomers and enantiomers interacting with DNA were calculated and compared with each other. The calculations showed that the interaction with DNA decreased the optical rotatory strength of the enantiomers compared to that of isolated enantiomers, which this
