Relative Reaction Rates of the Amino Acids Cysteine, Methionine, and Histidine with Analogs of the Anti-Cancer Drug Cisplatin

We are studying the reaction of analogs of the anticancer drug cisplatin with amino acids that differ in size and shape. The reaction of cisplatin with proteins likely precedes reaction with DNA in the body, forming a variety of products that may be toxic to the human body. The size and shape of the platinum(II) complexes often affects the rate of reaction with proteins, more so than with DNA. In this study, triamine cisplatin analogs are reacted with the amino acids cysteine, methionine, and histidine simultaneously. These reactions are monitored by NMR spectroscopy. The effect of the bulk of the ligand and the pH under which the reaction occurs was explored. It is seen that the bulkier [Pt(Me5dien)(NO3)]+ complex prefers to coordinate with N-Acetylcysteine than L-methionine or L-histidine. When the pH was raised from 4 to 7, the coordination to the platinum complex and N-AcCys occurred at a much faster rate