Table of Contents
Metal-Based Drugs
Volume 1 (1994), Issue 5-6, Pages 351-362

Redox Chemistry and [Au(CN)2-] in the Formation of Gold Metabolites

1Medizinisches Institut für Umwelthygiene, Department of Immunobiology, Postfach 10 37 51, Düsseldorf D-40225, Germany
2The Department of Chemistry, The University of Wisconsin-Milwaukee, PO. Box 413, Milwaukee WI53201-0413, USA

Copyright © 1994 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The role of hypochlorite ion, which can be generated by the enzyme myleoperoxidase, in the biochemistry of gold(I) anti-arthritic drugs was investigated. Sodium hypochlorite (OCl) directly and rapidly oxidizes AuSTm, Au(CN)2-, AuSTg (gold thioglucose) and auranofin (Et3PAuSATg). The resulting gold(III) species were detected by an Ion Chromotography Ion-Pairing technique that was developed to distinguish gold(I) and gold(III). Formation of Au(III) was also demonstrated spectrophotometrically after the conversion to AuCl4. The reactions of AuSTm, AuSTg, and auranofin are complex and gold(III) appears only after the initial oxidation of the thiolate (and phosphine) ligands.

The enzymatic reaction, using MPO with H2O2 and Cl as substrates, leads to slow oxidation of Au(CN)2-, AuSTm or AuSTg. The extent and rate of reaction depend on the concentrations of MPO, H2O2, and Au(I). The continued presence of Au(I) during the initial stages of reaction (oxidation of the thiolates in AuSTm and AuSTg) and the conversion to Au(III) in the latter stages of the reaction were demonstrated.

Au(CN)2-, a gold metabolite, binds tightly to serum albumin. Unlike other gold(I) complexes, aurocyanide reacts almost negligibly at Cys-34 via ligand exchange. Instead, there is a strong association (K1 = 5.5 × 104 and K2 = 7.0 × 103; n1 = 0.8 and n2 = 3) of intact Au(CN)2-. The full extent of binding is revealed only by equilibrium methods such as NMR or ultrafiltration; the bound gold dissociates extensively on conventional gel-exclusion columns and partially on Penefesky spun columns.

The immunological and pharmacological significance of these results are discussed.