Diving into Unknown Waters: Water-Soluble Clickable Au₁₃ Nanoclusters Protected with N-Heterocyclic Carbenes for Bio-Medical Applications

The use of gold nanoclusters in biomedical applications has been steadily increasing in recent years. However, water solubility is a key factor for these applications, and water-soluble gold nanoclusters are often difficult to isolate and susceptible to exchange or oxidation in vivo. Herein, we report the isolation of N-heterocyclic carbene (NHC)-protected atomically precise gold nanoclusters functionalized with triethylene glycol monomethyl ether groups. These clusters are highly luminescent and water soluble and are shown to be stable in biological media. Importantly, the core structure, stability, and high quantum yield of the nanoclusters were conserved after backbone modification. Depending on the nature of the halide group, clusters have high stability in simulated biofluids and resist attack by glutathione. In vivo studies show that no abnormal cellular morphology is introduced in the kidney, liver, or spleen of mice treated with [Au₁₃(NHC)₅Br₂]Br₃ nanoclusters protected by 1,8-dimethylnaphthyl-linked NHCs. This cluster has a blood elimination half-life of 0.68 h. Functionalization of the wingtip groups of the cluster with azide groups is demonstrated, and complete reaction of all 10 azide groups with strained alkynes is shown, highlighting the potential of these clusters in biological settings.