Subject Listing - Biology
Advisor: Dr. Beatriz H. Cardelino
Friday, Poster Session 3, Presentation Kiosk 36 B, Health & Fitness Center
THERMODYNAMIC STUDIES OF ADDUCTS BETWEEN TRANSITION METAL COMPLEXES AND AN OLIGONUCLEOTIDE
The primary goal of this investigation is to study the effect of adduct formation between transition metal complexes and nucleotides. The metal complexes examined were those similar to existing anticancer drugs. Presently, platinum-based anti-tumor drugs, such as Cisplatin, are the most effective and commonly used anticancer drugs. However, the mechanisms of action of the metal complexes on the nucleotides are still unknown, which motivated this study. The adducts investigated contained palladium, a Group VIII transition metal, with two halides and two other ligands attached as leaving groups, such as ammonia ligands. After the leaving group ligands detached, the complexes formed adducts with the nucleotide. The nucleotide examined was the double-stranded DNA dodecamer engineered by Gelasco and Lippard (Biochemistry 37, pp. 9230-9, 1998). Quantum and molecular mechanic calculations were performed on these systems, using the ONIOM approach. The ONIOM approach consists of a hybrid program that allows for treatment of different sections of the systems at different levels of approximation. Thus, the metal complexes were modeled using density functional theory and the adducts between the metal complexes and the nucleotide were modeled using molecular mechanics. The calculations provided energetic information, as well as information relative to the structural changes resulting from the adduct formation. Statistical thermodynamic calculations were used to determine the thermodynamic properties for the adduct formation.
Advisor: Dr. Beatriz H. Cardelino, Professor, Chemistry, Spelman College, Atlanta, Ga