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Fungal diseases affect millions of humans annually, yet fungal pathogens remain understudied. The mold Aspergillus flavus is a causative agent of both aspergillosis and fungal keratitis infections, but species closely related to A. flavus are not considered clinically relevant. To study the evolution of A. flavus pathogenicity, we examined genomic and phenotypic traits of two strains of A. flavus and three closely related non- pathogenic species: Aspergillus arachidicola (two strains), Aspergillus parasiticus (two strains), and Aspergillus nomiae (one strain). We identified over 3,000 orthologous proteins unique to A. flavus, including seven biosynthetic gene clusters present in A. flavus strains and absent in the three non-pathogenic species. We chose to characterize secondary metabolite production for all seven strains under two clinically relevant conditions, temperature and salt concentration. Temperature impacted metabolite production in all species. Conversely, we found a lack of impact of salinity on secondary metabolite production. Strains of the same species produced different metabolites. Growth under stress conditions revealed additional heterogeneity within species. Using the invertebrate model of fungal disease Galleria mellonella, we found virulence of strains of the same species varied widely, and A. flavus strains were not more virulent than strains of the non-pathogenic species. In a murine model of fungal keratitis, we observed significantly lower disease severity and corneal thickness for A. arachidicola compared to other species at 48 hrs, but not at 72 hrs. Our work identifies key phenotypic, chemical, and genomic similarities and differences between the opportunistic human pathogen A. flavus and its non-pathogenic relatives.

A facile and effective strategy for the preparation of a series of ferricenium complexes bearing either electron-donating or electron-withdrawing substituents with weakly coordinating anions such as [B(C6F5)4]− or SbF6− is reported. These systems were thoroughly investigated for their ground state electronic structures in both solution and solid states using infrared (IR) and nuclear magnetic resonance (NMR) spectroscopies as well as single crystal X-ray crystallography and electrochemical measurements. The X-ray structures of the six electron-deficient ferricenium derivatives are of particular interest as only a handful (∼5) of such derivatives have been structurally characterized to date. Comparison of the structural data for both neutral and oxidized derivatives reveals that the nature of the substituents on the cyclopentadienyl (Cp) ligands displays a more significant impact on the metal–ligand separations (Fe⋯Ct) in the oxidized species than in their neutral analogs. Our 1H-NMR measurements corroborate that in the neutral ferrocene derivatives, electron-donating ring substitutions lead to a greater shielding of the ring protons while electron-withdrawing groups via induction deshield the nearby ring protons. However, the data for the paramagnetic ferricenium derivatives reveals that this substitutional behavior is more complex and fundamentally reversed, which is further supported by our structural studies. We ascribe this reversal of behavior in the ferricenium derivatives to the δ back-donation from the iron atom into the Cp rings which can lead to the overall shielding of the ring protons. Interestingly, our NMR results for the electron-deficient ferricenium derivatives in solution also indicate a direct correlation between the solvent dielectric constant and the energy barrier for rotation around the metal–ligand bond in these systems, whereas such a correlation is absent or not significant in the case of the electron-rich ferricenium species or the corresponding neutral ferrocene analogs. In this work, we also present the electrochemical behavior of the corresponding ferricenium/ferrocene redox couples including potential values (E1/2), peak-to-peak separation (ΔE1/2), and diffusion coefficients (D) of the redox active species in order to provide a concise outline of these data in one place. Our electrochemical studies involved three different solvents and two supporting electrolytes. Notably, our findings point to the significant effect of ion-pairing in lowering the energy necessary for reduction of the ferricenium ion and E1/2 in lower-polarity media. This has significant implications in applications of the ferrocene or ferricenium derivatives as redox agents in low-polarity solvents where an accurate determination of redox potential is critical.