Synthesis and solution isomerization of water-soluble Au9 nanoclusters prepared by nuclearity conversion of [Au11(PPh3)8Cl2]Cl

Abstract

Water-soluble gold nanoclusters (AuNCs) are popular in biomedical applications such as bioimaging, labelling, drug delivery, and biosensing. Despite their widespread applications, the synthesis of water-soluble phosphine-capped AuNCs is not as straightforward as their organic-soluble equivalents. Organic soluble phosphine-passivated [Au₉(L)₈]³⁺ are 6-electron closed-shell AuNCs that are generally prepared via the reduction of a phosphine–Au(I) complex by NaBH₄. A similar approach attempted for the water-soluble ligand triphenylphosphine monosulfonate (TPPMS) using [AuTPPMS]Cl resulted in a mixture of cluster sizes that required gel electrophoresis or fractional precipitation to isolate the Au₉ product. In this work, we report the synthesis of water-soluble [Au₉(L)₈]³⁺ nanoclusters in high yield through the biphasic ligand exchange of [Au₁₁(PPh₃)₈Cl₂]Cl with water-soluble phosphines such as TPPMS and 4-(diphenylphosphino)benzoic acid (DPPBA). The small molecule byproducts can be completely removed by size-based separation methods, like size exclusion chromatography or dialysis, as confirmed by ³¹P and ¹H nuclear magnetic resonance (NMR) as well as diffusion ordered spectroscopy (DOSY). Furthermore, [Au₉(DPPBA)₈]Cl₃ underwent a visible pH- and temperature-induced isomerization in ethanol between the ‘crown’ and ‘butterfly’ isomers of [Au₉(L)₈]³⁺ which has not been previously reported. Cytotoxicity evaluation of these water-soluble nanoclusters gave CC₅₀ values of 36 μg mL⁻¹ and 70 μg mL⁻¹ against A549 human alveolar epithelial cells, and 30 μg mL⁻¹ and 40 μg mL⁻¹ against NIH/3T3 mouse fibroblast cells for [Au₉(TPPMS)₈]Cl₃ and [Au₉(DPPBA)₈]Cl₃, respectively. For comparison, auranofin, an FDA-approved gold drug, is more than an order of magnitude more toxic with a CC₅₀ value of 7.7 μg mL⁻¹ against A549 cells.