A systematic kinetic study of metalloporphyrin-catalyzed biomimetic oxidation was performed to elucidate the relationships between reaction conditions, catalyst behavior, and oxidation rates of substrates. Using FeTPPS as a model metalloporphyrin catalyst, a preliminary screening established the optimal amount of oxidizing agent and mode of addition. Continuous administration of 10 equiv of oxidant produced gradual, measurable reaction progress suitable for quantitative kinetic modeling. A mechanistic kinetic model was developed based on a system of ordinary differential equations describing catalyst activation, substrate oxidation, and catalyst deactivation, and it was successfully fitted to experimental data obtained under both one-shot and continuous oxidant addition. The approach was extended to multiple substrates and pH conditions. In specific cases, inclusion of a noncatalytic oxidation term improved the fit of the model, indicating a minor parallel oxidation pathway. The substrate-specific rate constants derived from the model showed good proportionality with literature intrinsic clearance values determined from liver microsomal assays, which represent the gold standard for intrinsic clearance estimation, thereby supporting the physiological relevance of the biomimetic system. Overall, the combined experimental and computational framework provides a quantitative basis for interpreting biomimetic oxidation kinetics and establishes a mechanistic bridge between enzymatic catalysis and pharmacokinetic clearance processes.
Csillag et al. (Tue,) studied this question.