Metalated porphyrinic covalent organic frameworks provide a structurally invariant platform for resolving how local M-N4 electronics govern oxygen activation inside π-conjugated pores. Here, an isoreticular TpTAPP β-ketoenamine series comprising H2Por-COF and partially metalated Fe-, Co-, Cu-, and Zn-Por-COFs was constructed to decouple metal-center effects from framework topology in visible-light pramipexole (PRX) detoxification. PXRD, FTIR, XPS, ICP-OES, electron microscopy, XANES/EXAFS, and sorption analyses verify retention of the crystalline layered COF, homogeneous metal distribution, 34–41% metalation, and isolated porphyrinic M-N4 coordination without detectable metallic/oxide domains. Although H2Por-COF exhibits the largest BET surface area, O₂ uptake, charge extraction, ROS output, and PRX oxidation follow Fe > Co > Cu > Zn > H₂Por-COF, with Fe-Por-COF achieving 99% PRX removal, k_app = 0.1023 min⁻¹ , 64% TOC removal, and the highest AQY response while retaining 93% removal after 10 cycles. Atmosphere control, scavengers, calibrated NBT kinetics, probe assays, and DMPO-EPR identify hole-assisted O ₂ activation followed by superoxide-dominated oxidation, with ¹O ₂ and • OH as secondary channels. Spin-polarized, solvent-corrected DFT assigns this hierarchy to open-shell metal-oxygen orbital communication: Fe-N4 and Co-N4 most efficiently bind O ₂ , populate O ₂ π* states, elongate O-O, and stabilize superoxide-like intermediates, whereas Cu is intermediate and closed-shell Zn is mainly electrostatic. PRX adsorption is exergonic across the series, but detoxification requires coupling substrate polarization to M-N4-mediated O ₂ activation. LC-HRMS/MS and ecotoxicity assays confirm oxidative fragmentation and biological detoxification.
