Quantifying evolving toxicity in the TAML/peroxide mineralization of propranolol.

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/H2O2 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/H2O2 mimics mechanistically the main steps of peroxidase catalytic cycles, the findings may be relevant to propranolol degradation in environmental waters.

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.