Structure-activity relationships of copper-based metal-organic Frameworks: Investigating antibacterial mechanisms against gram-positive and gram-negative bacteria

Bacterial infection poses a significant concern and represents a global threat. The misuse of antibacterial drugs causes resistance, often multi-resistance, of bacteria to one or more of these antibiotics. New approaches are needed to overcome such limitations of the antibiotic therapy. The copper based metal organic framework (Cu-MOFs) showed an extraordinary antibacterial effectiveness and can be considered as broad-spectrum antibacterial agents. This study focuses on investigating the specific chemical and physical characteristics of Cu-MOFs, investigating their antibacterial capabilities on three representative bacterial strains, and linking their structure to their function. Several techniques for characterization were employed. Analysis through Fourier Transform Infrared Spectroscopy (FTIR) of untreated and Cu-MOF-treated bacterial cells revealed distinct features indicating surface modifications of bacterial cells due to Cu-MOF interaction. The crystalline structure of synthesized Cu-MOFs was validated using X-ray diffraction (XRD) analysis, exhibiting peaks at 14.7° and 24.3°. X-ray photoelectron spectroscopy (XPS) was used for the analysis of the Cu-MOFs showing characteristic peaks confirming their elemental composition (Cu, C, N, O, S). Transmission Electron Microscopy (TEM) analysis verified the significant biocidal activity of Cu-MOFs against both the Gram-negative ( Escherichia coli ) and Gram-positive ( Staphylococcus aureus and Bacillus subtilis ) bacteria, by disrupting their cell membranes and inducing cell death primarily through Cu 2+ ion release. The findings demonstrated the role and mechanisms of synthesized Cu-MOFs as broad-spectrum antibacterial agents. However, their structure is shown to be more potent against the Gram-positive bacteria, which keep their shape, although they accumulate the Cu-MOFs intracellularly. The Cu-MOFs nanoparticles entered the cell of the Gram-negative cells of E. coli and caused a clear change in the form, from rod to swollen-circular. Overall, the study highlights the broad-spectrum potential of Cu-MOFs, making them strong candidates for developing active antimicrobial agents in the future, such as antibiotics. • Cu-MOFs show promise as broad-spectrum antibacterial agents. • Cu-MOFs combat bacteria via Cu 2+ ion release, disrupting cell membranes. • Cu-MOFs' antibacterial activity is linked to their structure. • Cu-MOFs show potent activity against Gram-positive bacteria. • Study explores Cu-MOF mechanisms against Gram-positive/negative bacteria.