Engineering of Artificial Antioxidase Enables Boosted Catalytic Activity in Inflammatory Bowel Disease Alleviation

Abstract

ABSTRACT Developing artificial antioxidases represents a promising strategy for treatment of oxidative‐stress‐related disorders; however, their practical application is often hindered by insufficient catalytic activity. Here, we report a dual‐cobalt coordinated phthalocyanine carboxylate derivative (biCoPc) as an efficient artificial antioxidase with markedly enhanced reactive oxygen species scavenging capability for the alleviation of inflammatory bowel disease (IBD). Experimental studies combined with theoretical calculations reveal that the extended π‐conjugation and π‐electron delocalization within the dimeric phthalocyanine framework, together with the protonation‐deprotonation dynamics of peripheral carboxyl groups, synergistically promote a potential proton‐coupled electron transfer process at the dual‐cobalt active sites. This architecture accelerates electron transfer kinetics and creates a favorable catalytic microenvironment. Consequently, biCoPc exhibits high catalytic superoxide dismutase‐like and glutathione peroxidase‐like activities, along with robust stability under harsh conditions. Notably, biCoPc demonstrates pronounced anti‐inflammatory efficacy, efficiently alleviating IBD symptoms at both the cellular level and animal models. This work provides mechanistic insights into the rational design of high‐performance artificial enzymes and broadens their potential for biomedical applications.