Protein metalation by two structurally related gold(I) carbene complexes: An ESI MS study

Abstract

The reactions with a few model proteins of two structurally related gold carbene compounds, namely the gold(I) monocarbene complex Au(NHC)Cl and the corresponding bis-carbene complex [Au(NHC)2]PF6 (where NHC is an N-heterocyclic carbene ligand), were comparatively studied by ESI MS measurements. The investigated proteins were: human serum albumin, human carbonic anhydrase and bovine superoxide dismutase; in addition, the reactions of the two gold carbenes with the C-terminal synthetic dodecapeptide of thioredoxin reductase were analyzed. Formation of metallodrug-protein adducts was observed in all cases made exception for the reactions of [Au(NHC)2]PF6 with carbonic anhydrase and superoxide dismutase. Notably, in line with expectations, the monocarbene gold complex turned out to be more effective than its dicarbene counterpart in forming protein adducts. The reactivity of these gold carbene complexes with model proteins is compared to that of a few other gold(III) and gold(I) complexes whose reactions with model proteins had been previously investigated with the same methodology; it emerges that the two gold carbenes react more selectively with proteins at well-defined anchoring sites. The implications of these results are discussed in the light of the current knowledge on medicinal gold compounds.