Tailoring the Electrocatalytic Properties of Porphyrin Covalent Organic Frameworks for Highly Selective Oxygen Sensing <i>In Vivo</i>

<i>In vivo</i> selective sensing of oxygen (O₂) dynamics in the central nervous system could provide insights into energy metabolism and neural activities. Although the electrocatalytic four-electron oxygen reduction reaction (ORR) paves an effective way to the electrochemical sensing of O₂ <i>in vivo</i>, the concurrent hydrogen peroxide reduction reaction (HPRR) within the potential windows for four-electron ORR unfortunately poses a great challenge to the conventional mechanism employed for selective electrochemical O₂ sensing. In this work, we find that regulation of the linkers within the skeleton of porphyrin-based covalent organic frameworks (COFs) could improve the selectivity of the O₂ sensor against hydrogen peroxide (H₂O₂). The electrochemical results reveal that the Co porphyrin active sites facilitate the direct four-electron pathway for ORR and that the Co porphyrin-based COF, enriched with pyrene units, shows enhanced four-electron ORR kinetics and better tolerance to HPRR. The theoretical calculation suggests that introducing pyrene units essentially weakens the adsorption of H₂O₂, leading to suppression of the HPRR. The microsensor fabricated with the Co porphyrin-based COF as the electrocatalyst features a high selectivity for real-time monitoring of O₂ in a living rat brain.