Structural, Mechanistic, and Ultradilute Catalysis Portrayal of Substrate Inhibition in the TAML-Hydrogen Peroxide Catalytic Oxidation of the Persistent Drug and Micropollutant, Propranolol.

TAML activators enable unprecedented, rapid, ultradilute oxidation catalysis where substrate inhibitions might seem improbable. Nevertheless, while TAML/H2O2 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 kI for H2O2 oxidation of the resting FeIII-TAML (RC) to the activated catalyst (AC), while the second-order rate constant kII 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, 1H NMR, and IC examination and DFT calculations. Propranolol binds to FeIII-TAMLs via combinations of noncovalent hydrophobic, coordinative, hydrogen bonding, and Coulombic interactions. Across four studied TAMLs under like conditions, propranolol reduced kI 4-32-fold (pH 7, 25 °C) indicating that substrate inhibition is controllable by TAML design. However, based on the measured kI and calculated equilibrium constant K for propranolol-TAML binding, it is possible to project the impact on kI 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/H2O2 destruction of propranolol in London wastewater while giving a substrate inhibition assessment tool for use in the new field of ultradilute oxidation catalysis.

Homogeneous Catalysis Under Ultradilute Conditions: TAML/NaClO Oxidation of Persistent Metaldehyde.

TAML activators enable homogeneous oxidation catalysis where the catalyst and substrate (S) are ultradilute (pM-low µM) and the oxidant is very dilute (high nM-low mM). Water contamination by exceptionally persistent micropollutants (MPs), including metaldehyde (Met), provides an ideal space for determining the characteristics and utilitarian limits of this ultradilute catalysis. The low MP concentrations decrease throughout catalysis with S oxidation (kII) and catalyst inactivation (ki) competing for the active catalyst. The percentage of substrate converted (%Cvn) can be increased by discovering methods to increase kII/ki. Here we show that NaClO extends catalyst lifetime to increase the Met turnover number (TON) 3-fold compared with H2O2, highlighting the importance of oxidant choice as a design tool in TAML systems. Met oxidation studies (pH 7, D2O, 0.01 M phosphate, 25 °C) monitored by 1H NMR spectroscopy show benign acetic acid as the only significant product. Analysis of TAML/NaClO treated Met solutions employing successive identical catalyst doses revealed that the processes can be modeled by the recently published relationship between the initial and final [S] (S0 and S∞, respectively), the initial [catalyst] (FeTot) and kII/ki. Consequently, this study establishes that ΔS is proportional to S0 and that the %Cvn is conserved across all catalyst doses in multicatalyst-dose processes because the rate of the kII process depends on [S] while that of the ki process does not. A general tool for determining the FeTot required to effect a desired %Cvn is presented. Examination of the dependence of TON on kII/ki and FeTot at a fixed S0 indicates that for any TAML process employing FeTot < 1 × 10-6 M, small catalyst doses are not more efficient than one large dose.

TAML/H2O2 Oxidative Degradation of Metaldehyde: Pursuing Better Water Treatment for the Most Persistent Pollutants.

The extremely persistent molluscicide, metaldehyde, widely used on farms and gardens, is often detected in drinking water sources of various countries at concentrations of regulatory concern. Metaldehyde contamination restricts treatment options. Conventional technologies for remediating dilute organics in drinking water, activated carbon, and ozone, are insufficiently effective against metaldehyde. Some treatment plants have resorted to effective, but more costly UV/H2O2. Here we have examined if TAML/H2O2 can decompose metaldehyde under laboratory conditions to guide development of a better real world option. TAML/H2O2 slowly degrades metaldehyde to acetaldehyde and acetic acid. Nuclear magnetic resonance spectroscopy ((1)H NMR) was used to monitor the degradation-the technique requires a high metaldehyde concentration (60 ppm). Within the pH range of 6.5-9, the reaction rate is greatest at pH 7. Under optimum conditions, one aliquot of TAML 1a (400 nM) catalyzed 5% degradation over 10 h with a turnover number of 40. Five sequential TAML aliquots (2 µM overall) effected a 31% removal over 60 h. TAML/H2O2 degraded metaldehyde steadily over many hours, highlighting an important long-service property. The observation of metaldehyde decomposition under mild conditions provides a further indication that TAML catalysis holds promise for advancing water treatment. These results have turned our attention to more aggressive TAML activators in development, which we expect will advance the observed technical performance.

Activation of Dioxygen by a TAML Activator in Reverse Micelles: Characterization of an Fe(III)Fe(IV) Dimer and Associated Catalytic Chemistry.

Iron TAML activators of peroxides are functional catalase-peroxidase mimics. Switching from hydrogen peroxide (H2O2) to dioxygen (O2) as the primary oxidant was achieved by using a system of reverse micelles of Aerosol OT (AOT) in n-octane. Hydrophilic TAML activators are localized in the aqueous microreactors of reverse micelles where water is present in much lower abundance than in bulk water. n-Octane serves as a proximate reservoir supplying O2 to result in partial oxidation of Fe(III) to Fe(IV)-containing species, mostly the Fe(III)Fe(IV) (major) and Fe(IV)Fe(IV) (minor) dimers which coexist with the Fe(III) TAML monomeric species. The speciation depends on the pH and the degree of hydration w0, viz., the amount of water in the reverse micelles. The previously unknown Fe(III)Fe(IV) dimer has been characterized by UV-vis, EPR, and Mössbauer spectroscopies. Reactive electron donors such as NADH, pinacyanol chloride, and hydroquinone undergo the TAML-catalyzed oxidation by O2. The oxidation of NADH, studied in most detail, is much faster at the lowest degree of hydration w0 (in "drier micelles") and is accelerated by light through NADH photochemistry. Dyes that are more resistant to oxidation than pinacyanol chloride (Orange II, Safranine O) are not oxidized in the reverse micellar media. Despite the limitation of low reactivity, the new systems highlight an encouraging step in replacing TAML peroxidase-like chemistry with more attractive dioxygen-activation chemistry.