Comparative study of the SOD-like activity of porphyrinic metal-organic framework nanozymes

Superoxide dismutase (SOD) is a pivotal metalloenzyme for mitigating oxidative stress, yet its practical use is constrained by extraction, purification, and scale-up challenges. Porphyrinic MOF nanozymes offer cost-effective, stable, and tunable SOD mimetics, but the roles of mixed metalloporphyrins and framework architecture remain underexplored. Here, we synthesized two porphyrinic MOF series derived from PCN-223, featuring elliptic distortions along either the major or minor axis, by co-assembling TCPP–Mn and TCPP–Cu at defined ratios. Both frameworks share TCPP and Zr 6 O 4 (OH) 4 nodes but differ in topology. Materials were characterized by SEM, PXRD, UV–vis, and zeta potential; SOD-like activity was quantified using a WST-8 superoxide assay, and intracellular ROS scavenging was assessed in RAW 264.7 cells. The SOD-like activity is governed primarily by the fraction of catalytically active metal centers—Mn–porphyrin sites outperform Cu analogues—and secondarily by framework morphology, with negligible dependence on particle size. In both series, activity increases monotonically with TCPP–Mn content; at Mn/Cu = 0.8/0.2, mixed-ligand MOFs approach or exceed their single-ligand Mn counterparts. Morphology modulates performance: the minor axis PCN-223 derivatives exhibit lower activity than the major axis PCN-223 analogues. In cells, the minor axis PCN-223–Mn 0.8 Cu 0.2 shows stronger ROS scavenging than the major axis PCN-223–Mn 0.8 Cu 0.2 , likely due to smaller particle size enhancing uptake, but with higher cytotoxicity at elevated doses. These results identify metal-center speciation and morphology as the principal design levers for SOD-mimetic porphyrinic MOFs and provide a basis for engineering efficient, application-tailored antioxidative nanozymes.