Theoretical Study on Adduct Formations of PD(II) and NI(II) Complexes With an Engineered Oligonucleotide

Metal-based anticancer drugs containing Pt (II) (e.g., cisplatin) are among the most effective drugs used in chemotherapy. These agents interfere with DNA’s functions and inhibit its ability to divide, thus destroying cancer cells. However, studies have shown that these types of drugs show limitations because of their lack of specificity in destroying cells. Thus, it is of interest to investigate other candidates as possible anticancer drugs. In this investigation, the binding effects of metal complexes (analogue to cisplatin) with an engineered oligonucleotide were analyzed using theoretical approaches. The metal complexes considered contained the transition metals Pd(II) and Ni(II), with different halide ligands, as well as the NH3 and NH2 substituents. The selected oligonucleotide was a DNA octamer duplex, engineered in 1995, with its structure determined by high-resolution NMR. The theoretical approach consisted of the hybrid computational procedure called ONIOM. Within the ONIOM partition scheme, the “active” parts of the systems (where chemical bonds break and form) were treated at the quantum mechanical level using hybrid density exchange functionals. The “real” system was treated using molecular mechanics with universal force field parameters. No atoms were included as “link atoms” between the two layers. The heat of reactions for the binding processes of these adduct formations was calculated.