Bioinspired, Multidisciplinary, Iterative Catalyst Design Creates the Highest Performance Peroxidase Mimics and the Field of Sustainable Ultradilute Oxidation Catalysis (SUDOC)

Abstract

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.

Predicting Properties of Iron(III) TAML Activators of Peroxides from Their III/IV and IV/V Reduction Potentials or a Lost Battle to Peroxidase

“…All knowni ron(III) TAML activators are five-coordinate square pyramidal species in the solid phase. [6,8,17] Despite the nature of an axial ligand,w hich is usually water,t hey transform into diaqua six-or monoaqua five-coordinate complexes (cases A and B, respectively,inScheme 1). [17][18][19] In turn, both Aand Bundergo deprotonation in the pH range 8-11.5.…”

Zero‐Order Catalysis in TAML‐Catalyzed Oxidation of Imidacloprid, a Neonicotinoid Pesticide

“…Buffer solutions were prepared using KH 2 PO 4 (Acros);t he pH was adjusted with concentrated solutions of KOH or H 3 PO 4 .H ydrogen peroxide (30 %) was purchased from Fischer.I midacloprid was purchased as as olid from Sigma-Aldrich. Stock solutions of imidacloprid were prepared by dissolving appropriate amount of imidacloprid solid in buffer.T AMLs 1, [9] 2, [6] and 3 [44] were prepared as described elsewhere. Stock solutions of 1 and 2 were prepared in HPLC grade water.C atalase from bovine liver (lyophilized powder, 2000-5000 units mg À1 of protein) was purchased from Sigma-Aldrich.…”

“…This result is trulys ignificant because 1 used to be considered the best TAML catalyst in terms of catalytic activity and operational stability. [9] We have previouslys hown that 2 is seven times more reactive than 1 toward propranolol, [6] but the reactivity gap increases furthera st he target imidacloprid becomes more resistant to oxidation than propranolol. H 2 O 2 does not degrade imidacloprid in the absence of 2 ( Figure S1, see the Supporting Information).…”

“…[2] The genesiso fT AML activators aimed at increasing their catalytic activity at neutral pH [3] madei tp ossible to degrade resistant-to-oxidation targets such as Safranin O [4] andm etaldehyde. [5] The most recentT AML specimens 2,c ontainingt wo sulfonamide units instead of two amide residues in the 'tail' part of the molecule [6] (see Figure 1), appeared to be exceptionally active under neutral reactionc onditions;t his openeda gate to detoxificationo fs uper resistant-to-oxidation targets such as imidacloprid (Figure 1), whichb elongs to the neonicotinoids-a new class of highly active, systemic insecticides. [7] Neonicotinoidsa re ar elatively new class of pesticides that have dominated the globalm arket since their development in the 1990s due to their broad activity in insects andl ow toxicity in humans.…”

“…In this study we have therefore explored the options for the TAML-catalyzed degradation of imidacloprid by H 2 O 2 and found that only the recently introduced bis-sulfonamide TAML activator 2 [6] is catalytically active;t he tetraamide catalyst 1, previously rated as superior, [9] is drastically less active than 2 ( Figure 1). We have also found that although imidacloprid could not be destroyed without 2 under the catalytic conditions, the rate of disappearance of imidacloprid depends insignificantlyo nt he concentration of 2 when [2] > [imidacloprid].…”