Morphology-size map of zeolitic imidazolate frameworks: unveiling the bactericidal effects upon varying their zinc/cobalt ion contents

Abstract

Zeolitic imidazolate frameworks (ZIFs) show promise in fighting bacterial resistance, yet crucial gaps in research hinder their clinical use. For the first time, through meticulous exploration, we unravel the correlation between the size, shape, and zinc/cobalt ion content of 25 ZIF variants and their antibacterial performance in addition to their mechanism pattern, giving special focus to oxidative stress. Notably, a novel morphology-size map of the 25 different ZIFs is established under five main groups namely, small cubes (SC), large cubes (LC), rhombic dodecahedron-large cubes (RD-LC), rhombic dodecahedron (RD), and spherical-rhombic dodecahedron (S-RD) ZIFs. The antibacterial experiments against Staphylococcus aureus showed that ZIFs in the SC group with higher cobalt content had the lowest minimum inhibition concentration (MIC) of 12.5 μg mL⁻¹. Conversely, increased zinc content yielded better antibacterial activity for the other groups. Furthermore, our investigation into the mechanisms revealed cobalt's crucial role in fostering reactive oxygen species (ROS) accumulation, correlating with glutathione (GSH) depletion. Remarkably, the differential responses of ZIF-8 and ZIF-67 to the antioxidant N-acetyl cysteine (NAC) shed light on nuanced pathways governing antibacterial performance. While ZIF-8 demonstrated reduced efficacy, the antibacterial performance of ZIF-67 remained either sustained or modestly improved under antioxidant conditions. Overall, these findings not only enrich our comprehension of ZIFs but also propel their potential for targeted antibacterial interventions, thereby fostering confidence in their clinical translation.