CHEMISTRY

Reduction of ruthenium(III) complexes to promote reaction with proteins.

STEPHEN C. GIBSON*, and KEVIN M. WILLIAMS, Department of Chemistry, Western Kentucky University, Bowling Green, KY 42101-1079.

Selected ruthenium complexes have been shown to have anticancer activity, most likely due to interaction with DNA. Ruthenium complexes also are known to interact with proteins and react specifically with histidine residues. Such specificity is potentially useful since certain metal ion complexes catalyze amide bond hydrolysis in proteins and thus certain ruthenium complexes could show a selective cleavage at histidine residues. Because ruthenium(III) complexes are generally inert to substitution and ruthenium(II) complexes are generally not air-stable, previous studies involving reaction with proteins have utilized a zinc-amalgam reduction step and a strict argon atmosphere. We are developing methods to reduce ruthenium without using mercury or requiring a glove box. Previous studies have indicated that glutathione can reduce ruthenium(III) to ruthenium(II) under argon, promoting reaction with DNA [Frasca, D.R.; Clarke, M.J. J. Am. Chem. Soc., 1999, 121, 8523-8532]. We are investigating the use of glutathione (under argon), ascorbic acid (with or without argon), and electrochemical reduction of ruthenium to promote similar reactivity with proteins. We have used a combination of UV-Vis and NMR spectroscopy to monitor the reactions. Our preliminary results suggest that histidine or histidine-containing proteins can react with [Ru(NH₃)₅Cl]Cl₂ or [Ru(NH₃)₆]Cl₃ in the presence of glutathione or ascorbic acid, suggesting that histidine can displace a chloride or an ammine group.