There are currently fewer than 10 antifungal drugs in clinical development, but new fungal strains that are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents. In this work, we report the evaluation of 1039 metal-containing compounds that were screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD). We show that 20.9% of all metal compounds tested have antimicrobial activity against two representative Candida and Cryptococcus strains compared with only 1.1% of the >300,000 purely organic molecules tested through CO-ADD. We identified 90 metal compounds (8.7%) that show antifungal activity while not displaying any cytotoxicity against mammalian cell lines or hemolytic properties at similar concentrations. The structures of 21 metal complexes that display high antifungal activity (MIC ≤1.25 μM) are discussed and evaluated further against a broad panel of yeasts. Most of these have not been previously tested for antifungal activity. Eleven of these metal complexes were tested for toxicity in the Galleria mellonella moth larva model, revealing that only one compound showed signs of toxicity at the highest injected concentration. Lastly, we demonstrated that the organo-Pt(II) cyclooctadiene complex Pt1 significantly reduces fungal load in an in vivo G. mellonella infection model. These findings showcase that the structural and chemical diversity of metal-based compounds can be an invaluable tool in the development of new drugs against infectious diseases.

The structure of a novel metallamacrocyclic phosphine gold(I) thiolate cluster, [Au₉(μ-dppm)₄(μ-p-tc)₆](PF₆)₃, where dppm = bis(diphenylphosphine)methane and p-tc = p-thiocresolate, is reported and shows Au⋯Au attractions of ∼3.0 Å and gold(I) atoms linked to thiolate and phosphine ligands in distorted trigonal and nearly linear geometries.

Catalysis under harsh environmental conditions requires robust nanoparticles that can resist leaching of the organic shell and possess significant resistance to aggregation. Robust gold core-carbon shell gold–aryl nanoparticles (AuNPs–COOH) were fabricated by mild reduction of the water-soluble aryldiazonium salt [HOOC-4–C₆H₄NN]AuCl₄, and were fully characterized in solution and solid state. The nanoparticles showed high stability in the presence of 0.01–1.00 M NaCl salt, acidic and basic pH values (1–13) and moderate temperatures (20–90 °C). DFT calculations of the optimized model system Au₃₈–C₆H₄–COOH show an Au–C (aryl) distance of 2.04 Å, which is related to a binding energy of −59.2 kcal mol⁻¹. The 4-nitrophenol (4-NPh) reduction model was used to study the viability of AuNPs–COOH as a catalyst. Nitrophenols are among the most common organic pollutants in industrial and agricultural wastewaters due to their toxicity, anthropogenic and inhibitory nature. The AuNPs–COOH show high catalytic activity, where the reduction of 80 μM 4-NPh was complete in less than five minutes with a high k_app (2.26 × 10⁻² s⁻¹) and a relatively low E_a (25 kJ mol⁻¹) compared to literature values. Catalytic activity decreases with subsequent cycles of the reaction, along with a decrease in intensity and red shift in the LSPR band, and an increase in aggregation of nanoparticles in the TEM following each reaction cycle.

Modified colloids and flat surfaces occupy an important place in materials science research due to their widespread applications. Interest in the development of modifiers that adhere strongly to surfaces relates to the need for stability under ambient conditions in many applications. Diazonium salts have evolved as the primary choice for the modification of surfaces. The term “diazonics” has been introduced in the literature to describe “the science and technology of aryldiazonium salt-derived materials”. The facile reduction of diazonium salts via chemical or electrochemical processes, irradiation stimuli, or spontaneously results in the efficient modification of gold surfaces. Robust gold–aryl nanoparticles, where gold is connected to the aryl ring through bonding to carbon and films modified by using diazonium salts, are critical in electronics, sensors, medical implants, and materials for power sources. Experimental and theoretical studies suggest that gold–carbon interactions constructed via chemical reactions with diazonium salts are stronger than nondiazonium surface modifiers. This invited feature article summarizes the conceptual development of recent studies of diazonium salts in our laboratories and others with a focus on the surface modification of gold nanostructures, flat surfaces and gratings, and their applications in nanomedicine engineering, sensors, energy, forensic science, and catalysis.