Western Kentucky University
The Unorthodox Reaction Rates of Anti-cancer Familial Platinum Compounds with Methionine and Guanosine Monophosphate
Institution
Western Kentucky University
Faculty Advisor/ Mentor
Kevin Williams
Abstract
Nuclear magnetic resonance spectroscopy has been used to determine the effects of various Nheterocyclic ligands on the reaction rate of platinum compounds with both DNA and protein. Common anti-cancer drugs such as cisplatin and oxaliplatin are known to react faster with methioinine residues when compared to guanosine monophosphate (5’ GMP). This leads to cytotoxic side effects. The study synthesized multiple platinum analogs, differing only in the attached N-heterocyclic ligands. Comparisons on the reaction rates of these compounds with GMP and methionine were made and differing reaction speeds were observed. The addition of the heterocyclic ligand adds steric hindrance cis to the leaving ligand, and thus larger ligands will greatly diminish the rate of substitution. This steric hindrance retarded the methionine reactions to a degree that very much exceeded the adverse effects on the 5’ GMP reaction. Also, it was found that once 5’ GMP had reacted, methionine was unable to displace it but the reverse did not hold true as 5’ GMP displaced a complete methionine reaction. It also appeared that regardless of the ratio of the reagents present in the various reactions, the products distribution remained constant. These findings could lead to an eventual reduction of cytotoxicity caused by platinum based anti-cancer drugs.
The Unorthodox Reaction Rates of Anti-cancer Familial Platinum Compounds with Methionine and Guanosine Monophosphate
Nuclear magnetic resonance spectroscopy has been used to determine the effects of various Nheterocyclic ligands on the reaction rate of platinum compounds with both DNA and protein. Common anti-cancer drugs such as cisplatin and oxaliplatin are known to react faster with methioinine residues when compared to guanosine monophosphate (5’ GMP). This leads to cytotoxic side effects. The study synthesized multiple platinum analogs, differing only in the attached N-heterocyclic ligands. Comparisons on the reaction rates of these compounds with GMP and methionine were made and differing reaction speeds were observed. The addition of the heterocyclic ligand adds steric hindrance cis to the leaving ligand, and thus larger ligands will greatly diminish the rate of substitution. This steric hindrance retarded the methionine reactions to a degree that very much exceeded the adverse effects on the 5’ GMP reaction. Also, it was found that once 5’ GMP had reacted, methionine was unable to displace it but the reverse did not hold true as 5’ GMP displaced a complete methionine reaction. It also appeared that regardless of the ratio of the reagents present in the various reactions, the products distribution remained constant. These findings could lead to an eventual reduction of cytotoxicity caused by platinum based anti-cancer drugs.