Targeted delivery of potent cytotoxic drugs to cancer cells minimizes systemic toxicity and several side effects. NHC*−Au−Cl has already been proven to be a potent anticancer agent. In this study, we explore a strategy based on chemoselective cysteine conjugation of NHC*−Au−Cl to albumin and trastuzumab (Thiomab LC‐V205C) to potentiate drug‐ligand ratio, pharmacokinetics, as well as drug efficacy and safety. This strategy is a step forward towards the use of gold‐based anticancer agents as targeted therapies.

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The synthesis of six novel N-heterocyclic carbene silver(I) acetate complexes, three symmetrical and three non-symmetrical, were achieved using 4,5-diphenylimidazole to produce intermediate imidazolium salts and then obtain the corresponding silver(I) complexes through complexation with silver acetate via the Youngs' method. In vitro biological testing, using the Kirby-Bauer disk diffusion method, was conducted against Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli, with a NHC-silver(I) acetate compound, SBC3, and Tetracycline as standards. Silver(I) acetate complex 7 resulted in a 4 mm clearance against MRSA, showing the highest antibiotic activity of the novel derivatives. Crystallographic data revealed similar bond lengths and angles to previously reported NHC-silver(I) acetate complexes, with complex 8 showing interesting g 2-coordination between the silver atom and acetate oxygens. 109 Ag NMR studies were conducted, highlighting the effects of the substituents of the imidazole ring on the silver atom shown by the corresponding shifts in the 109 Ag NMR spectra. The incorporation of isopropyl groups to several of the novel complexes resulted in larger upfield 109 Ag NMR shift values compared to all other substituents.