Copper and Zinc Metal-Organic Frameworks with Bipyrazole Linkers Display Strong Antibacterial Activity against Both Gram+ and Gram- Bacterial Strains

Sonila Xhafa; Laura Olivieri; Corrado Di Nicola; Riccardo Pettinari; Claudio Pettinari; Alessia Tombesi; Fabio Marchetti

doi:10.3390/molecules28166160

Copper and Zinc Metal-Organic Frameworks with Bipyrazole Linkers Display Strong Antibacterial Activity against Both Gram+ and Gram- Bacterial Strains

Molecules. 2023 Aug 21;28(16):6160. doi: 10.3390/molecules28166160.

Authors

Sonila Xhafa¹, Laura Olivieri¹, Corrado Di Nicola¹, Riccardo Pettinari², Claudio Pettinari², Alessia Tombesi², Fabio Marchetti¹

Affiliations

¹ ChIP Research Center, School of Science and Technology, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, MC, Italy.
² ChIP Research Center, School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, MC, Italy.

Abstract

Here, we report a new synthetic protocol based on microwave-assisted synthesis (MAS) for the preparation of higher yields of zinc and copper in MOFs based on different bis(pyrazolyl)-tagged ligands ([M(BPZ)]_n where M = Zn(II), Cu(II), H₂BPZ = 4,4'-bipyrazole, [M(BPZ-NH₂)]_n where M = Zn(II), Cu(II); H₂BPZ-NH₂ = 3-amino-4,4'-bipyrazole, and [M_x(Me₄BPZPh)] where M = Zn(II), x = 1; Cu(II), x = 2; H₂Me₄BPZPh = bis-4'-(3',5'-dimethyl)-pyrazolylbenzene) and, for the first time, a detailed study of their antibacterial activity, tested against Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria, as representative agents of infections. The results show that all MOFs exert a broad-spectrum activity and strong efficiency in bacterial growth inhibition, with a mechanism of action based on the surface contact of MOF particles with bacterial cells through the so-called "chelation effect" and reactive oxygen species (ROS) generation, without a significant release of Zn(II) and Cu(II) ions. In addition, morphological changes were elucidated by using a scanning electron microscope (SEM) and bacterial cell damage was further confirmed by a confocal laser scanning microscopy (CLSM) test.

Keywords: Cu(II) and Zn(II) MOFs; ROS generation; antibacterial activity; bis(pyrazolate) ligands; chelation theory.

MeSH terms

Anti-Bacterial Agents / pharmacology
Bacteria
Copper* / pharmacology
Escherichia coli
Metal-Organic Frameworks*
Staphylococcus aureus
Zinc / pharmacology

Substances

Copper
Metal-Organic Frameworks
Zinc
Anti-Bacterial Agents

Grants and funding

This research was supported by the project Nano4-Fresh—Nanomaterials for an environmentally friendly and sustainable handling of perishable products (PRIMA19_00246), which is part of the Partnership on Research and Innovation in the Mediterranean Area (PRIMA) Programme supported by the European Union and funded by the national funding bodies of Participating States, in our case financed by Italian Ministry of University and Research (MUR).