The Interaction of Glutathione with Platinum, and the Role of pH in Altering Ligand Formation between Platinum and N-Acetylcysteine

Cisplatin is an important anti-cancer drug. Structurally, cisplatin is a coordination complex, which means that it has a central metallic atom: platinum. Side interactions prevent cisplatin from effectively treating cancerous cells by reaction with DNA. Cisplatin has a high rate of forming protein adducts, primarily with sulfur containing amino acids. To better understand how cisplatin interacts with sulfur containing amino acids in the body, a platinum compound with an ethylenediamine ligand attached was reacted with N-acetylcysteine and glutathione. The reactions of cysteine with platinum were performed at three pH values: 7.0, 8.5, and 10. NMR spectroscopy was used to examine these reaction over time. A COSY and HMQC spectrum of glutathione’s reaction with platinum were collected to better identify the reaction products. All 1H NMR spectra were taken on a JOEL Eclipse 500 MHz NMR instrument. The appearance of a free ethylenediamine ligand signal, in many cases, suggests that the amino acids react to form products in which the ethylenediamine ligand is displaced as the amino acids react via both sulfur and nitrogen atoms