Tailoring Metal–Organic Frameworks for Antimicrobial Applications: Post-Synthetic Modifications and Mechanisms

Metal-organic frameworks (MOFs) have established themselves as a useful material with a variety of uses, such as drug delivery. However, their intrinsic antimicrobial activity often falls short, necessitating post-synthetic modifications (PSM) to enhance their efficacy. This review delves into diverse PSM strategies, including linker and metal node alterations, guest species adsorption or exchange, and surface modifications, to bolster the antimicrobial capabilities of MOFs. Key findings from recent studies indicate that covalent functionalization with bioactive ligands, metal ion substitution (e.g., Ag, Cu, Zn), and tandem modification approaches are particularly effective, with some PSM-MOFs achieving over 90% inhibition against multidrug-resistant Gram-negative bacteria. Particle size reduction, tailored surface chemistry, and optimized pore structure were found to significantly enhance reactive oxygen species generation, regulation of metal ion liberation, and pathogen membrane destabilization. In addition, advancements in MOF membranes and guest-based modifications are discussed alongside mechanistic insights, including photocatalytic activity, metal ion chelation, and physical cell wall damage. By emphasizing recent breakthroughs and translational potential, this review emphasizes the importance of tailored PSM-MOFs in combating antimicrobial resistance (AMR) and guides future innovation in combating hard-to-treat microbial infections.