Environmental\nStability Determines the Cytotoxicity\nof Metal–Organic Frameworks to a Nitrogen-Fixing Bacterium Azotobacter vinelandii

During\nwidespread applications of metal–organic frameworks\n(MOFs), the environmental hazards and risks of MOFs have aroused great\nconcerns. In this study, we aimed to reveal the importance of the\nenvironmental stability of MOFs on their toxicity. Two Zn-MOFs, namely,\nZIF-8 with high aqueous stability and Zn-BDC with low aqueous stability,\nwere compared directly in the toxicological evaluations of a nitrogen-fixing\nbacterium Azotobacter vinelandii. Zn-BDC\nshowed strong cytotoxicity at 100 mg/L and higher, inducing growth\ninhibition, cell apoptosis, structural changes, oxidative damage,\nand, consequently, loss of nitrogen fixation ability. In contrast,\nZIF-8 was nearly nontoxic to A. vinelandii. The transcriptome analysis showed that Zn-BDC directly disturbed\nthe ribosome pathway and lowered the expression level of nitrogen-fixing <i>nif</i> cluster genes. On the other hand, ZIF-8 stress could\nregulate the flagellar assembly, siderophore group nonribosomal peptide\nbiosynthesis, bacterial chemotaxis, and amino sugar and nucleotide\nsugar metabolism pathways to promote the cell growth of A. vinelandii. Beyond that, the toxicity of Zn-MOFs\nto A. vinelandii was associated with\nthe release of Zn<sup>2+</sup>, but Zn-MOFs were less toxic than the\nmixtures of their starting materials. Overall, our results suggested\nthat the environmental stability of Zn-MOFs determined their environmental\ntoxicity through different molecular pathways. Designing stable MOFs\nis preferred due to environment-friendly considerations.