Bactericidal Metal-Organic Gallium Frameworks - Synthesis to Application

Gallium, a trace metal not found in its elemental form in nature, has garnered significant interest as a biocide, given its ability to interfere with iron metabolism in bacteria. Consequently, several gallium compounds have been developed and studied for their antimicrobial properties but face challenges of poor solubility and formulation for delivery. Organizing the metal into three-dimensional, hybrid scaffolds, termed metal-organic frameworks (MOFs), is an emerging platform with potential to address many of these limitations. Gallium MOFs show improved solubility and antibacterial potency relative to the free metal due to their ability to coload antibiotics and functional biomolecules. Synthetic strategies are equally versatile, with several rapid, cost-effective, and scalable methods available. In this review, we present the advantages and disadvantages of these various synthetic strategies with respect to their antibacterial efficiency, product purity, and reaction control. The activity of gallium-based MOFs against Gram-positive and Gram-negative pathogens in mono- and combinatorial therapeutic settings is discussed in the context of their mechanisms of action and structure-function-performance relationships collated from recent studies. While gallium MOF development as antibacterials is still in its nascent stages, the examples discussed here highlight their potential as a novel class of therapeutics poised to impact the fight against pan-drug-resistant bacterial pathogens.