A Programmable KillSwitch in NewTAML Catalysts Decouples Oxidative Reactivity from Catalyst Lifetime

Abstract Bis-amido-bis-sulfonamido, [Fe{4-NO2C6H3-1,2-(NCOCMe2NSO2)2CR1R2}(OH2)]− [2; R1/R2 = H/H (2a), H/CH3 (2b), CH3/CH3 (2c)], are NewTAML (NT) iron(III) oxidation catalysts. Herein we identify and mechanistically characterize a ligand-centered, catalyst-lifetime-controlling site (CR1R2), termed a KillSwitch (KS), that enables balancing technical performance with potential safety constraints in NT/Oxidant process design. Under catalytic conditions, CR1R2 sites containing two or one hydrogen(s), (2a, 2b, respectively), undergo deprotonation to form electron-rich ylides that accelerate NT oxidative degradation. The 2a–c series defines a KS susceptibility gradient arising from differential C–H bond acidities controlling the ylide-forming deprotonation─2a, 2b, and 2c represent high-susceptibility-, intermediate-susceptibility-, and null-susceptibility KS states, respectively, thereby providing substantial catalyst functional lifetime control with 2a < 2b ≪ 2c. Kinetic analysis gives similar 2a–c rate constants for H2O2 activation (kI) and substrate oxidation (kII), while catalyst inactivation rate constants (ki) increase markedly and differentially with increasing pH for 2a and 2b, but remain pH-independent for 2c, which degrades more slowly through a separate pathway. Access to null-KS 2c─essential for testing the KS hypothesis─required a decade-long synthetic effort culminating in the quantitative methylation of deprotonated 2b. The KS is expected to be transferable to other NTs with oxidative reactivities distinct from 2a–c, enabling a new dimension in catalyst design that broadly decouples catalytic oxidative aggression from catalyst lifetime. The KS thus provides a practical, safe, and sustainable by design strategy for balancing technical performances against catalyst lifetimes, should shorter-lived NTs become desirable in response to discoveries of postrelease NT adverse environmental effects.