Design of a Zr-based metal–organic framework as an efficient fosfomycin carrier: a combined experimental and DFT study

Abstract

Biomolecule carrier systems based on metal–organic frameworks (MOFs) are highly promising owing to a high degree of structural tunability, high surface area, porosity, and higher chemical/thermal stability. UiO-66, one of the most stable Zr_(IV)-based MOFs, has a pore aperture of 0.6 nm and a theoretical pore volume of 0.77 cm³ g⁻¹, ideal for high storage capacity of biomolecule cargo; however, its potential to be implemented as an efficient carrier for fosfomycin is yet to be investigated. The UiO-66 nanocrystal, synthesized at room temperature, as a fosfomycin carrier was reported. Drug modulated synthesis (in situ encapsulation) and post-synthesis (adsorption/impregnation) were applied to incorporate fosfomycin in and/or on UiO-66 nanocrystals. We determined the effect of room temperature synthesis conditions on the structural properties of the UiO-66 nanocrystals as a functional carrier for fosfomycin. The incorporation of fosfomycin either by encapsulation or adsorption did not change the inherent crystal structure and UiO-66 nanocrystals retained their morphology. The addition of fosfomycin into the reaction medium led to an increase in the particle size from 127 ± 45 nm to 203 ± 52 nm. Our FTIR results indicated the development of a Zr–O–P connection due to the capture of drug molecules by adsorption. Antibacterial activity studies unveiled the drug concentration dependent bactericidal and bacteriostatic activities towards S. aureus and E. coli for fosfomycin loaded UiO-66 nanocrystals. Investigations with the help of density functional theory were performed to reveal the interaction mechanism between fosfomycin and UiO-66. Our theoretical findings indicated that fosfomycin strongly interacts with the metal center in the defected UiO-66 through its oxygen atom in the phosphite group with a Zr–O distance of 2.087 Å. Additionally, the energy of interaction for the adsorption process was found to have a large negative value of −74.3 kcal mol⁻¹, which supports the strong interaction between the two systems.