Oxidation catalysts called NewTAMLs, macrocyclic complexes with TAML carbonamido-N donors replaced by more nucleophile-resistant binders, sulfonamido-N, for example, [Fe{4-NO 2 C 6 H 3 -1,2-(NCOCMe 2 NSO 2 ) 2 CHMe}] − (5d), deliver record-setting technical performance parameters (TPPs) for functional peroxidase mimicry. NewTAMLs were designed to test the previously discounted hypothesis that nucleophilic decay of carbonamido-N iron chelators is TAML catalyst lifetime-limiting and, for precautionary reasons, to escape fluorine in the best-performing TAML (1c) for catalyzing ultradilute water purification by H 2 O 2 . Replacing two of four TAML carbonamides with less σ-donating sulfonamides in 5 was found to more than compensate for eliminating 1c's F-substituents to increase substrate oxidation rates and, following the discovery and parametrization of an additional decomposition mechanism, to alter catalyst degradation rates protectively. At pH 7 in less than 5 min, the best-performing NewTAML 5d activates H 2 O 2 to eliminate the β-blocker drug and sentinel micropollutant (MP) propranolol to the limit of UPLC detection under very dilute starting conditions that pass through the ultradilute regime (≤2 ppb): [5d] = 100 nM (∼60 ppb), [propranolol] = 53 nM (15.6 ppb), [H 2 O 2 ] = 330 μM (11.2 ppm). This is ca. 10 times faster than 1c/H 2 O 2 under comparable conditions giving an important advance in the real-world potential for time-, concentration-, and cost-sensitive MP water treatments. The separate decomposition mechanism involves carbon acids bridging the two sulfonamides, a discovery that expands design control over operating NewTAML lifetimesthese features we have named "kill switches" are analyzed for impacts on catalytic function, process control, and sustainable design. Mouse uterotrophic assays show no low-dose adverse effects (lodafs) for the prototype NewTAML (5a) or for the process solution from the 5a/H 2 O 2 destruction of the contraceptive pill estrogen, ethinyl estradiol (EE2), a potent MP. The multidisciplinary catalyst design protocol that led to NewTAMLs is presented graphically to highlight how five key sustainability performancestechnical, cost, health, environmental, fairnessare being optimized together for sustainable oxidation catalysis and water treatment. The results validate the "bioinspired" descriptor and the name sustainable ultradilute oxidation catalysis (SUDOC) for this emerging field while highlighting to chemists that dealing with the lodafs and locafs (low-concentration adverse effects) of everyday−everywhere chemicals is essential for sustainability.

TAML activators enable unprecedented, rapid, ultradilute oxidation catalysis where substrate inhibitions might seem improbable. Nevertheless, while TAML/HO rapidly degrades the drug propranolol, a micropollutant (MP) of broad concern, propranolol is shown to inhibit its own destruction under concentration conditions amenable to kinetics studies ([propranolol] = 50 μM). Substrate inhibition manifests as a decrease in the second-order rate constant k for HO oxidation of the resting Fe-TAML (RC) to the activated catalyst (AC), while the second-order rate constant k for attack of AC on propranolol is unaffected. This kinetics signature has been utilized to develop a general approach for quantifying substrate inhibitions. Fragile adducts [propranolol, TAML] have been isolated and subjected to ESI-MS, florescence, UV-vis, FTIR, H NMR, and IC examination and DFT calculations. Propranolol binds to Fe-TAMLs via combinations of noncovalent hydrophobic, coordinative, hydrogen bonding, and Coulombic interactions. Across four studied TAMLs under like conditions, propranolol reduced k 4-32-fold (pH 7, 25 °C) indicating that substrate inhibition is controllable by TAML design. However, based on the measured k and calculated equilibrium constant K for propranolol-TAML binding, it is possible to project the impact on k of reducing [propranolol] from 50 μM to the ultradilute regime typical of MP contaminated waters (≤2 ppb, ≤7 nM for propranolol) where inhibition nearly vanishes. Projecting from 50 μM to higher concentrations, propranolol completely inhibits its own oxidation before reaching mM concentrations. This study is consistent with prior experimental findings that substrate inhibition does not impede TAML/HO destruction of propranolol in London wastewater while giving a substrate inhibition assessment tool for use in the new field of ultradilute oxidation catalysis.

Summary Oxidative water purification of micropollutants (MPs) can proceed via toxic intermediates calling for procedures for connecting degrading chemical mixtures to evolving toxicity. Herein, we introduce a method for projecting evolving toxicity onto composite changing pollutant and intermediate concentrations illustrated through the TAML/H 2 O 2 mineralization of the common drug and MP, propranolol. The approach consists of identifying the key intermediates along the decomposition pathway (UPLC/GCMS/NMR/UV-Vis), determining for each by simulation and experiment the rate constants for both catalytic and noncatalytic oxidations and converting the resulting predicted concentration versus time profiles to evolving composite toxicity exemplified using zebrafish lethality data. For propranolol, toxicity grows substantially from the outset, even after propranolol is undetectable, echoing that intermediate chemical and toxicity behaviors are key elements of the environmental safety of MP degradation processes. As TAML/H 2 O 2 mimics mechanistically the main steps of peroxidase catalytic cycles, the findings may be relevant to propranolol degradation in environmental waters.

We describe the use of TAML/peroxide to reduce micropollutants (MPs) in Tucson, AZ, secondary municipal wastewater. The laboratory studies establish simple-to-apply MP abatements rivaling ozone in technical performance. The approach rests on the latest-generation TAML catalyst, 2, currently the highest-technical performance H 2 O 2 activator across both chemistry and biology. Thirty-eight MPs were examined with five 2/H 2 O 2 treatments (50 nM 2 with 22.4 ppm H 2 O 2 , 100 nM 2 with 11.2 ppm H 2 O 2 , 100 nM 2 with 22.4 ppm H 2 O 2 , 200 nM 2 with 11.2 ppm H 2 O 2 , and 200 nM 2 with 22.4 ppm H 2 O 2 ) and four ozone treatments (2, 4, 6, and 8 ppm). Satisfactory analytical data were returned for 25 MPs that were monitored kinetically (LC-MS/MS) from 6 min to 6 h. For all 2/H 2 O 2 conditions, decreases in MP concentration had either ceased at 30 min or showed marginal improvements at 1 h remaining constant to 6 h. The highestperformance 2/H 2 O 2 system (200 nM 2 with 22.4 ppm H 2 O 2 ) outperformed 2 ppm ozone virtually across the board, delivering micropollutant percent reductions (MPPRs) of 26−98% corresponding to performance advantage ratios over 2 ppm ozone of ∼0.9− 8. These data indicate that 2 (1 kg at 70 nM) and H 2 O 2 (53.55 kg at 11.2 ppm) would treat the daily wastewater output of 150,000 Europeans [150 L day −1 (population equivalent) −1 , 22,500 tons total] in a manner comparable to that of a common ozone administration of 3 ppm, establishing a new approach worthy of further optimization for municipal wastewater MP treatment.

Studies of the oxidative degradation of picric acid (2,4,6trinitrophenol) by H 2 O 2 catalyzed by a fluorine-tailed tetraamido macrocyclic ligand (TAML) activator of peroxides [Fe III {4,5-Cl 2 C 6 H 2 -1,2-(NCOCMe 2 NCO) 2 CF 2 }(OH 2 )] − (2) in neutral and mildly basic solutions revealed that oxidative degradation of this explosive demands components of phosphate or carbonate buffers and is not oxidized in their absence. The TAML-and buffer-catalyzed oxidation is subject to severe substrate inhibition, which results in at least 1000-fold retardation of the interaction between the iron(III) resting state of 2 and H 2 O 2 . The inhibition accounts for a unique pH profile for the TAML catalysis with the highest activity at pH 7. Less aggressive TAMLs such as [Fe III {C 6 H 4 -1,2-(NCOCMe 2 NCO) 2 CMe 2 }(OH 2 )] − are catalytically inactive. The roles of buffer components in modulating catalysis have been clarified through detailed kinetic investigations of the degradation process, which is first order in the concentration of 2 and shows ascending hyperbolic dependencies in the concentrations of all three participants, i.e., H 2 O 2 , picrate, and phosphate/carbonate. The reactivity trends are consistent with a mechanism involving the formation of double ([LFe III −Q] 2− ) and triple ([LFe III −{Q−H 2 PO 4 }] 3− ) associates, which are unreactive and reactive toward H 2 O 2 , respectively. The binding of phosphate converts [LFe III −Q] 2− to the reactive triple associate. Density functional theory suggests that the stability of the double associate is achieved via both Fe−O phenol binding and π−π stacking. The triple associate is an outer-sphere complex where phosphate binding occurs noncovalently through hydrogen bonds. A linear free energy relationship analysis of the reactivity of the mono-, di-, and trinitro phenols suggests that the rate-limiting step involves an electron transfer from phenolate to an oxidized ironoxo intermediate, giving phenoxy radicals that undergo further rapid oxidation that lead to eventual mineralization.