-Heterocyclic Carbene Gold(I) Complexes: Mechanism of the Ligand Scrambling Reaction and Their Oxidation to Gold(III) in Aqueous Solutions.

-Heterocyclic carbene (NHC) gold(I) complexes offer great prospects in medicinal chemistry as antiproliferative, anticancer, and antibacterial agents. However, further development requires a thorough understanding of their reaction behavior in aqueous media. Herein, we report the conversion of the bromido[3-ethyl-4-(4-methoxyphenyl)-5-(2-methoxypyridin-5-yl)-1-propylimidazol-2-ylidene]gold(I) ((NHC)AuBr, ) complex in acetonitrile/water mixtures to the bis[3-ethyl-4-(4-methoxyphenyl)-5-(2-methoxypyridin-5-yl)-1-propylimidazol-2-ylidene]gold(I) ([(NHC)Au], ), which is subsequently oxidized to the dibromidobis[3-ethyl-4-(4-methoxyphenyl)-5-(2-methoxypyridin-5-yl)-1-propylimidazol-2-ylidene]gold(III) ([(NHC)AuBr], ). By combining experimental data from HPLC, NMR, and (LC-)/HR-MS with computational results from DFT calculations, we outline a detailed ligand scrambling reaction mechanism. The key step is the formation of the stacked ((NHC)AuBr) dimer () that rearranges to the T-shaped intermediate Br(NHC)Au-AuBr (). The dissociation of Br from and recombination lead to (NHC)Au-AuBr () followed by the separation into [(NHC)Au] () and [AuBr] (). [AuBr] is not stable in an aqueous environment and degrades in an internal redox reaction to Au and Br. The latter in turn oxidizes to the gold(III) species . The reported ligand rearrangement of the (NHC)AuBr complex differs from that found for related silver(I) analogous. A detailed understanding of this scrambling mechanism is of utmost importance for the interpretation of their biological activity and will help to further optimize them for biomedical and other applications.