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.

The main features of iron-tetra-amido macrocyclic ligand complex (a sub-branch of TAML) catalysis of peroxide oxidations are rationalized by a two-step mechanism: Fe(III) + H2O2 → Active catalyst (Ac) (kI), and Ac + Substrate (S) → Fe(III) + Product (kII). TAML activators also undergo inactivation under catalytic conditions: Ac → Inactive catalyst (ki). The recently developed relationship, ln(S0/S∞) = (kII/ki)[Fe(III)]tot, where S0 and S∞ are [S] at time t = 0 and ∞, respectively, gives access to ki under any conditions. Analysis of the rate constants kI, kII, and ki at the environmentally significant pH of 7 for a broad series of TAML activators has revealed a 6 orders of magnitude reactivity differential in both kII and ki and 3 orders differential in kI. Linear free energy relationships linking kII with ki and kI reveal that the reactivity toward substrates is related to the instability of the active TAML intermediates and suggest that the reactivity in all three processes derives from a common electronic origin. The reactivities of TAML activators and the horseradish peroxidase enzyme are critically compared.

The results of low-temperature investigations of the oxidations of 9,10-dihydroanthracene, cumene, ethylbenzene, [D10]ethylbenzene, cyclooctane, and cyclohexane by an iron(V)-oxo TAML complex (2; see Figure 1) are presented, including product identification and determination of the second-order rate constants k2 in the range 233-243 K and the activation parameters (ΔH(≠) and ΔS(≠)). Statistically normalized k2 values (log k2') correlate linearly with the C-H bond dissociation energies DC-H, but ΔH(≠) does not. The point for 9,10-dihydroanthracene for the ΔH(≠) vs. DC-H correlation lies markedly off a common straight line of best fit for all other hydrocarbons, suggesting it proceeds via an alternate mechanism than the rate-limiting C-H bond homolysis promoted by 2. Contribution from an electron-transfer pathway may be substantial for 9,10-dihydroanthracene. Low-temperature kinetic measurements with ethylbenzene and [D10]ethylbenzene reveal a kinetic isotope effect of 26, indicating tunneling. The tunnel effect is drastically reduced at 0 °C and above, although it is an important feature of the reactivity of TAML activators at lower temperatures. The diiron(IV) μ-oxo dimer that is often a common component of the reaction medium involving 2 also oxidizes 9,10-dihydroanthracene, although its reactivity is three orders of magnitude lower than that of 2.

17α-ethinylestradiol (EE2), a synthetic oestrogen in oral contraceptives, is one of many pharmaceuticals found in inland waterways worldwide as a result of human consumption and excretion into wastewater treatment systems. At low parts per trillion (ppt), EE2 induces feminisation of male fish, diminishing reproductive success and causing fish population collapse. Intended water quality standards for EE2 set a much needed global precedent. Ozone and activated carbon provide effective wastewater treatments, but their energy intensities and capital/operating costs are formidable barriers to adoption. Here we describe the technical and environmental performance of a fast- developing contender for mitigation of EE2 contamination of wastewater based upon small- molecule, full-functional peroxidase enzyme replicas called “TAML activators”. From neutral to basic pH, TAML activators with H2O2 efficiently degrade EE2 in pure lab water, municipal effluents and EE2-spiked synthetic urine. TAML/H2O2 treatment curtails estrogenicity in vitro and substantially diminishes fish feminization in vivo. Our results provide a starting point for a future process in which tens of thousands of tonnes of wastewater could be treated per kilogram of catalyst. We suggest TAML/H2O2 is a worthy candidate for exploration as an environmentally compatible, versatile, method for removing EE2 and other pharmaceuticals from municipal wastewaters.

The unique properties of entirely aliphatic TAML activator [FeIII{(Me2CNCOCMe2NCO)2CMe2}-OH2]− (3), namely the increased steric bulk of the ligand and the unmatched resistance to the acid-induced demetalation, enables the generation of high-valent iron derivatives in pure water at any pH. An iron(V)oxo species is readily produced with NaClO at pH values from 2 to 10.6 without any observable intermediate. This is the first reported example of iron(V)oxo formed in pure water. At pH 13, iron(V)oxo is not formed and NaClO oxidizes 3 to an iron(IV)oxo derivative.