Guanine quadruplex DNA (G-quadruplex DNA) is a kind of secondary structure of DNA that formed at the bottom of chromosome (telomere). owadays, the different G-quadruplex DNAs are used as novel targets for the design and development of anticancer drugs (organic and inorganic compounds). Meloxicam, as a nonsteroidal anti-inflammatory drug (NSAID), has anticancer activity and recently has been used as a ligand in metal complexes. It has been shown that the functionality and the interaction of meloxicam with targets improve when it is used as a ligand in the structure of metal complexes. The main aim of this thesis is to investigate the effect of central metal (the kind of atom and its oxidation number) on the interaction of the metal complexes, containing meloxicam as a ligand, with the G-quadruplex DNA. For this purpose, the octahedral complexes trans -[M(Hmel) 2 (EtOH) 2 ] (M= Cr 2+ , Cr 3+ , Mn 2+ , Mn 3+ , Fe 2+ , Fe 3+ , Co 2+ , Co 3+ , Ni 2+ , Ni 4+ , Cu 2+ , Cu 4+ , Zn 2+ , Mo 4+ , Ru 2+ , Ru 3+ , Rh 2+ , Rh 3+ , Pd 4+ , Os 2+ , Os 3+ , Ir 2+ , Ir 3+ , Pt 4+ ), which have two mono-anionic meloxicam molecule in their equatorial positions were selected. Two different computational techniques including molecular docking and ONIOM were used for calculating the interaction of complexes with G-quadruplex. The docking calculations were performed on ten complexes containing metal atoms with +2 and +3 oxidation numbers It is observed that the calculated free binding energies of the complexes with the different metal atoms and the same oxidation number are nearly equal to each other. Also, the docking calculations show that the oxidation number of central atom has significant effect on the increase of the interaction energy. For more accurate investigation, the calculations were performed in the ONIOM scheme in two different ways: (a) The complex and DNA were considered in the high and low layers, respectively and the interaction energy between complex and DNA was calculated using molecular mechanics (b) the complex and a part of DNA, which has the dominant interaction with the complex, were considered in the high layer and the rest of DNA was i in low layer, respectively. In this case, the interaction of the complex and DNA was calculated using quantum mechanics. In both ways, the structure of complex was flexible while, the structure of DNA was rigid. The calculated interaction energies show the same result similar to the docking calculations.
