Open Access Thesis
Master of Science (MS)
Dr. Timothy Brewer
Dr. Larry Kolopajlo
Dr. Jose Vites
Cancer is one of the major causes of death in the world. Discovery of platinum metal-based drugs like cisplatin and carboplatin have proved to be successful in cancer treatment. Due to subsequent development of resistance, side effects, and fewer toxic effects of these drugs, the usage of these drugs has been limited. Novel drugs were being synthesized utilizing the transition metals like ruthenium, osmium, and copper.
In this research, ruthenium metal complexes of the formula HL[RuCl4L2] (where L= ligand) were synthesized. These ruthenium-based drugs exist in prodrug forms which are activated into antitumor drugs by means of hydrolysis, redox reactions, or reactions with biological nucleophiles. In these reactions, ruthenium is reduced to the active Ru(II) form from its inactive Ru(III) state. In this research work, three ruthenium complexes with different ligands of varying basicity are synthesized, and their hydrolysis reactions are studied under different pH values using UV-Visible spectrophotometry at room temperature. The ligands utilized in this project are imidazole, thiazole, and 1H-1,2,4-triazole. Among these, ruthenium imidazole has passed the Phase I clinical trials. For the ruthenium-imidazole (RIM) complex and the ruthenium-thiazole (RTZ) complex, rates of the hydrolysis reaction are determined by fitting the experimental data to proposed kinetic models for these complexes. The kinetic models proposed did not help in the determination of the rate of hydrolysis of the ruthenium-triazole (RTrz) complex as the absorbance trend of the RTrz complex in acidic pH values was opposite to the trend displayed by the RIM and RTZ complexes indicating a different hydrolysis mechanism for the RTrz complex.
The comparative data will aid in better drug design and evaluation of pharmacokinetic parameters. Future studies on hydrolysis of these complexes at different pH values using HPLC and NMR spectroscopy might reveal the exact mechanism and may lead to characterizing the products formed in the hydrolysis process.
Koneru, Sudheer, "Analysis of the effect of various ligands on the hydrolysis of ruthenium (III) complexes and interpretation of kinetics of hydrolysis profiles by UV-visible spectrophotometry" (2010). Master's Theses and Doctoral Dissertations. 304.