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.
