Subject Listing - Chemistry
Advisor: Dr. Beatriz H. Cardelino
Thursday, Oral Session 2, Presentation 5, Karpen Hall 038
THEORETICAL STUDIES ON ADDUCT FORMATIONS OF PD(II) AND PD(IV) 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 engineered oligonucleotide were analyzed using theoretical approaches. The metal complexes considered contained the transition metals Pd(II) and Pd (IV), with different halide ligands, as well as CO, CN, and OH substituents. The selected oligonucleotide was a DNA octamer duplex, created by D. Yang et al. in 1995 (Biochemistry, pp. 12912-12920), 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" part of the systems (where chemical bonds break and form) were treated at the quantum mechanical level using hybrid density exchange functionals (B3LYP and PW91). The "real" system was treated using molecular mechanics with the UFF and AMBER force fields. Entropy, enthalpy and free energy for the binding process of these adduct formations were calculated using statistical thermodynamics.
Advisor: Dr. Beatriz H. Cardelino, Professor, Chemistry, Spelman College, Atlanta, GA