Reversibly and Irreversibly Formed Products from the Reactions of Mercaptalbumin (AlbSH) with Et₃PAuCN and of AlbSAuPEt₃ with HCN

The reactions of AlbSAuPEt₃(cysteinyl-34-(triethylphosphine)gold(I) albumin) with HCN and of mercaptalbumin (AlbSH) with Et₃PAuCN were examined by ¹³C and ³¹P NMR spectroscopy, gel exclusion chromatography, and ¹⁴CN^- radiotracer methods. The reaction of HCN with AlbSAuPEt₃ yields irreversibly formed products, Et₃PO, [Au(CN)₂]^-, and a proteingold complex, AlbSAuX, where X ≠ CN^- or PEt₃. During the reaction, a transient, reversibly formed product, Et₃PAuCN, is generated but reacts further to yield the final products. The reaction of independently prepared Et₃PAuCN with AlbSH gives the same set of irreversibly formed products. Here, also, transient, reversibly formed products, AlbSAuPEt₃ and HCN, are observed. Thus, each set of reactants yields the same irreversibly formed products and the other set as transient, equilibrium products. These results are explained by proposing a common three-coordinate transition state, [AlbSAu(PEt₃)CN^-]^‡, for the equilibration of the two sets of reactants/products and the formation of the irreversibly formed products. Et₃P and AlbSAuCN^- are proposed to be intermediates leading from the transition state to the irreversibly formed products. We report the first direct evidence that the oxidation of Et₃P to Et₃PO is accompanied by the reduction of the albumin disulfide bonds (formula omitted) [(Et₃P)₂Au]⁺, which is generated in solutions of Et₃PAuCN via ligand disproportionation, reacts with AlbSH to produce AlbSAuPEt₃ and Et₃PO. The new thiol groups, (HS)₂BSA, generated by the phosphine oxidation, react with the [(Et₃P)₂Au]⁺ to produce (Et₃PAuS)BSA, which is characterized by a ³¹P NMR resonance at 35.8 ppm. The relevance of these biochemical reactions to the gold metabolism of cigarette smoking chrysotherapy patients is discussed.