N-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)Au^IBr, 1) 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)₂Au^I]⁺, 7), which is subsequently oxidized to the dibromidobis[3-ethyl-4-(4-methoxyphenyl)-5-(2-methoxypyridin-5-yl)-1-propylimidazol-2-ylidene]gold(III) ([(NHC)₂Au^IIIBr₂]⁺, 9). 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)Au^IBr)₂ dimer (2) that rearranges to the T-shaped intermediate Br(NHC)₂Au^I–Au^IBr (3). The dissociation of Br^– from 3 and recombination lead to (NHC)₂Au^I–Au^IBr₂ (5) followed by the separation into [(NHC)₂Au^I]⁺ (7) and [Au^IBr₂]⁻ (8). [Au^IBr₂]⁻ is not stable in an aqueous environment and degrades in an internal redox reaction to Au⁰ and Br₂. The latter in turn oxidizes 7 to the gold(III) species 9. The reported ligand rearrangement of the (NHC)Au^IBr 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.

中文翻译：

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N-杂环卡宾金(I)配合物：配体加扰反应的机理及其在水溶液中氧化成金(III)

N-杂环卡宾 (NHC) 金 (I) 配合物在药物化学中作为抗增殖剂、抗癌剂和抗菌剂具有广阔的前景。然而，进一步的开发需要彻底了解它们在水性介质中的反应行为。在此，我们报告了溴代[3-乙基-4-(4-甲氧基苯基)-5-(2-甲氧基吡啶-5-基)-1-丙基咪唑-2-亚基]金(I) ((NHC) Au ^I Br, 1 ) 在乙腈/水混合物中与双[3-乙基-4-(4-甲氧基苯基)-5-(2-甲氧基吡啶-5-基)-1-丙基咪唑-2-亚基]金络合物( I) ([(NHC) ₂ Au ^I ] ⁺ , 7)，随后被氧化成二溴双[3-乙基-4-(4-甲氧基苯基)-5-(2-甲氧基吡啶-5-基)-1-丙基咪唑-2-亚基]金(III)([(NHC ) ₂ Au ^III Br ₂ ] ⁺ , 9 )。通过将 HPLC、NMR 和 (LC-)/HR-MS 的实验数据与 DFT 计算的计算结果相结合，我们概述了详细的配体加扰反应机制。关键步骤是形成堆叠的 ((NHC)Au ^I Br) ₂二聚体 ( 2 )，该二聚体重新排列为 T 形中间体 Br(NHC) ₂ Au ^I –Au ^I Br ( 3 )。Br的离解^——从3和重组导致 (NHC) ₂ Au ^I –Au ^I Br ₂ ( 5 ) 然后分离成 [(NHC) ₂ Au ^I ] ⁺ ( 7 ) 和 [Au ^I Br ₂ ] ^- ( 8 )。[Au ^I Br ₂ ] ^-在水性环境中不稳定并且在内部氧化还原反应中降解为Au ⁰和Br ₂。后者反过来将7氧化为金 (III) 物种9. 报道的 (NHC)Au ^I Br 配合物的配体重排不同于相关银 (I) 类似物的配体重排。详细了解这种加扰机制对于解释它们的生物活性至关重要，并将有助于进一步优化它们以用于生物医学和其他应用。