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 lifetimesthese 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 performancestechnical, cost, health, environmental, fairnessare 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.
The oxidation of TAML complex(1) by various oxidants is explored in MeCN with 0.2% water at -40 °C where the iron(V)oxo complex is stable enough for reliable spectral identification. The iron(V)oxo state is achieved by using NaClO even faster than in the case of previously explored m-chloroperoxybenzoic acid. In contrast, H 2 O 2 and organic peroxides (benzoyl peroxide, tert-butylperoxide and tert-butylhydroperoxide)all convert 1 into the corresponding diiron(IV)-μ-oxo dimer (2) under the same conditions. The latter does not form when (NH 4 ) 2 [Ce(NO 3 ) 6 ] is employed and the Fe IV product obtained does not seem to contain an oxo moiety. In contrast to all other oxidants, the conversion of 1 by t BuOOH into 2 is characterized by non-conventional kinetics and therefore this reaction was explored in some detail. The evidence is presented that this light-, O 2 -, and TEMPO-and base-dependent reaction is a free-radical process under the conditions used.
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.
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