Metal‐Free Ligand‐Centered Radical Scavenging in Pyridine‐Modified Tetraaza Macrocycles

Pyridine‐modified tetraaza macrocycles are widely studied as ligand platforms for metal coordination, yet their intrinsic redox and radical reactivity in the absence of metals remains unclear. Here, we report the unexpected finding that pyridinophane Py ₂ N ₂ and PyN ₃ macrocycles act as efficient metal‐free radical scavengers toward the stable free radical 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH•). Systematic evaluation of substituent effects reveals distinct structure–reactivity relationships. PyN ₃ derivatives exhibit a linear dependence on electronic parameters, consistent with a donor‐controlled regime, whereas Py ₂ N ₂ macrocycles show a pronounced parabolic dependence on resonance and inductive effects, indicative of cooperative stabilization. ¹ H NMR spectroscopy supports the formation of a transient ligand–DPPH• encounter complex, followed by a rapid hydrogen‐atom transfer (HAT). Density functional theory identifies the β‐C–H position on the macrocyclic backbone as the thermodynamically preferred hydrogen‐donor site. The resulting ligand‐centered radical is formed with the Py ₂ N ₂ and stabilized through delocalization across the macrocyclic framework, enabling a captodative‐like electronic environment that is inaccessible to the PyN ₃ scaffold. Together, these findings establish a ligand‐centered HAT mechanism governed by macrocyclic topology rather than metal coordination and highlight a previously unrecognized design principle for electronically tunable, metal‐free macrocyclic radical scavengers.