Spin-State-Selective Secondary-Sphere Control in Hemicryptophane Cages Enables Tunable Reactivity of Iron-Oxo Centers

High-valent iron-oxo species are key intermediates in oxidation catalysis, yet modulating their electronic structures via the secondary coordination sphere remains challenging. Here, we designed a hemicryptophane-encapsulated iron-oxo complex (FeO-TPA@Hm2) and elucidate how the cage modulates methane C–H activation. Our calculations indicate that the Hm2 framework stabilizes the quintet state as the global minimum, potentially increasing the accessibility of the low-barrier quintet pathway. Crucially, we further uncover a spin-gated regulatory mechanism: on the triplet manifold, the cage exhibits pronounced redox noninnocence, acting as a tunable electron reservoir where remote substituents ″switch″ the electronic topology among Fe(III)–O2–, Fe(III)–O–•, Fe(IV)═O, and Fe(II)–O•• regimes. In contrast, the quintet state displays remarkable electronic rigidity due to exchange stabilization, rendering the cage effectively redox-innocent. Consequently, although the triplet surface is highly sensitive to substituent-induced polarization, the quintet pathway remains robust and dominant. This work establishes a synergy between spin-selective reactivity and spin-differentiated substituent sensitivity, providing a programmable strategy for orchestrating electron-transfer pathways in supramolecular catalysis.