Immunogenic cell death (ICD) offers a method of stimulating the immune system to attack and remove cancer cells. We report a copper(II) complex containing a Schiff base ligand and a polypyridyl ligand, 4, capable of inducing ICD in breast cancer stem cells (CSCs). Complex 4 kills both bulk breast cancer cells and breast CSCs at sub‐micromolar concentrations. Notably, 4 exhibits greater potency (one order of magnitude) towards breast CSCs than salinomycin (an established breast CSC‐potent agent) and cisplatin (a clinically approved anticancer drug). Epithelial spheroid studies show that 4 is able to selectively inhibit breast CSC‐enriched HMLER‐shEcad spheroid formation and viability over non‐tumorigenic breast MCF10 A spheroids. Mechanistic studies show that 4 operates as a Type II ICD inducer. Specifically, 4 readily enters the endoplasmic reticulum (ER) of breast CSCs, elevates intracellular reactive oxygen species (ROS) levels, induces ER stress, evokes damage‐associated molecular patterns (DAMPs), and promotes breast CSC phagocytosis by macrophages. As far as we are aware, 4 is the first metal complex to induce ICD in breast CSCs and promote their engulfment by immune cells.

A simple, efficient and sustainable method for the general synthesis of NHC gold(I) complexes is described. The reaction of imidazolium salts, of different electronic and steric requirements, with [AuX(tht)] (tht = tetrahydrothiophene) derivatives, in the presence of NBu₄(acac), in air and at room temperature leads to the NHC gold species in good yields and with very short reaction times.

The synthesis of tetranuclear gold complexes, a structurally unprecedented octanuclear complex with a planar [Au^I₈] core, and pentanuclear [Au^I₄M^I] (M=Cu, Ag) complexes is presented. The linear [Au^I₄] complex undergoes C−H functionalization of carbonyl compounds under mild reaction conditions. In addition, [Au^I₄Ag^I] catalyzes the carbonylation of primary amines to form ureas under homogeneous conditions with efficiencies higher than those achieved by gold nanoparticles.

We have developed a new family of ortho-oligophenylene ethynylene (o-OPE) metallofoldamers. The folding of these helicates is induced by nucleating carbon–metal interactions between Ag(I) cations and the alkynes of the inner core of the o-OPEs. These o-OPEs form metal–organic assemblies where at least three alkyne moieties are held in close proximity to form novel Ag(I)-complexes with the metal ion lodged into the helical cavity. NMR titration experiments and photokinetic studies have provided quantitative data about the thermodynamic and kinetic features of such binding/folding phenomena. X-ray diffraction and DFT studies have been performed to extract structural information on how the Ag(I) cation is accommodated into the cavity. The great simplicity and versatility of these new metallofoldamers open up the possibility to develop novel structures with applications in material science and/or in asymmetric catalysis.

The anti-breast cancer stem cell (CSC) properties of a series of gold(I) complexes comprising of various non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine 1-8 are reported. The most effective gold(I)-NSAID complex 1, containing indomethacin, exhibits greater potency for breast CSCs than bulk breast cancer cells (up to 80-fold). Furthermore, 1 reduces mammosphere viability to a better extent than a panel of clinically used breast cancer drugs and salinomycin, an established anti-breast CSC agent. Mechanistic studies suggest 1-induced breast CSC death results from breast CSC entry, cytoplasm localisation, an increase in intracellular reactive oxygen species levels, cyclooxygenase-2 downregulation and inhibition, and apoptosis. Remarkably, 1 also significantly inhibits tumour growth in a murine metastatic triple-negative breast cancer model. To the best of our knowledge, 1 is the first gold complex of any geometry or oxidation state to demonstrate anti-breast CSC properties.