Metallothioneins (MTs) are associated with diverse biological roles including zinc homeostasis and scavenging of heavier group 12 metal ions acquired from the environment. Despite the taxonomic ubiquity of MTs, there is a surprising dearth of structurally characterized d10 metal clusters with either the [M3S3] or [M4S5] cluster architectures associated with their metal-saturated structures. Since small molecule thiolato-metal clusters tend to form multiple species with various stoichiometries, it is exceptionally difficult to achieve saturation in a single cluster for isolation and characterization by X-ray crystallography. Taking inspiration from the discovery of the aromatic nitrogen-containing amino acid histidine in non-mammalian forms of MT, mixed aromatic amine, monothiolato () ligands have been used to overcome this complication and prepare metallothionein-like group 12 metal ion clusters. The nitrogen and sulfur donors of these multidentate ligands serve as synthetic counterparts of the bridging and non-bridging ligands present in MT clusters, respectively. This approach has provided the first non-proteinaceous [Cd3S3] and [Hg3S3] metallocycles with metals linked only by single thiolate bridges, as well as additional examples of comparable [Zn3S3] clusters. The solid-state structures suggest pi-stacking interactions are key assembly elements. Synthetic complexes share multiple structural features with protein-protected clusters. Characterization of these complexes by variable temperature NMR spectroscopy indicated the likely presence of multiple ligand environments during crystallization from predominantly acetonitrile solutions.

Synthetic approaches to understanding the metal ion miscellany of metallothionein

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