Comparative Antifungal Activity of Metal–Organic Frameworks (MOFs) with Different Metal Centers and Structural Dimensionalities against Candida albicans

Abstract Fungal infections, such as those caused byCandida albicans (C. albicans), represent a growing global health threat due to rising antifungal resistance and limited antifungal therapy options. Porous materials, including metal–organic frameworks (MOFs), have shown promise as antifungal agents, but the reported studies are difficult to compare due to the different metrics used to evaluate antifungal activity. Herein, we present a comparative study of a series of 1,3,5-triformylphloroglucinol (Tp)-based MOFs containing Cu, Mn, Fe, and Ni nodes, aiming to elucidate how metal-dependent characteristics, together with inherent framework features, influence their physicochemical properties and antifungal activity. While all four materials show better antifungal activity than the corresponding metal salts, MnTp and FeTp were the most effective at inhibiting planktonicC. albicanscells with >50% decrease in viability over 24 h, likely due to their rich intracellular redox activity.C. albicans biofilm formation was most effectively inhibited by NiTp with >60% biofilm inhibition over the same time period, an observation that we attribute to the highest ζ-potential of NiTp in the MOF series, to the nonendogenous nature of Ni2+ linked to the extracellular matrix trapping of Ni2+ ions, and to a small proportion of Ni2+ release. Ultimately, this study calls for further systematic investigation of MOFs as potential materials for the treatment of fungal infections and for more consistent reporting of antifungal activity in the literature.