PhD Scientific Days 2026

Poster Session 3.H - Pharmaceutical Sciences and Health Technologies

Kinetic Study of Metalloporphyrin-based Biomimetic Oxidation Using One-Shot and Continuous Oxidizing Agent Addition Modes

Name of the presenter

Csillag, Balázs

Institute/workplace of the presenter

Semmelweis University

Authors

Balázs Csillag¹, Ferenc Ernák Várda², Anna Kiss², Zsombor Hámor², Zsombor Márton Mohácsi¹, Anna Vincze¹, András Márton², Balázs Decsi², Arash Mirzahosseini¹, Diána Balogh-Weiser², Balázs Volk³, György Tibor Balogh^1,2
1: Semmelweis University
2: Budapest University of Technology and Economics
3: EGIS Pharmaceuticals PLC

Text of the abstract

Introduction
Biomimetic oxidation systems based on metalloporphyrins are widely used to model cytochrome P450-mediated drug metabolism. However, the kinetic behavior of these systems, especially the effect of the mode of oxidant addition, remains insufficiently understood.

Aims
This study aims to investigate the kinetics of metalloporphyrin-catalyzed biomimetic oxidation and to compare one-shot and continuous oxidant addition. A further goal was to develop a kinetic model and evaluate its relevance to physiological drug metabolism.

Methods
Oxidation reactions were performed using an FeTPPS-based magnetically separable catalyst under controlled conditions with tert-butyl hydroperoxide as oxidant. Experiments were conducted with both one-shot and continuous oxidant addition across multiple substrates and pH values. Reaction progress was monitored by LC-MS. A kinetic model was fitted to the experimental data using nonlinear regression.

Results
Continuous oxidant addition enabled gradual reaction progress and reliable kinetic analysis, whereas one-shot addition led to rapid, poorly resolved reactions. The developed kinetic model, incorporating catalyst activation, substrate oxidation, and catalyst deactivation, showed excellent agreement with experimental data. In specific cases, inclusion of a non-catalytic oxidation pathway improved model accuracy. The derived substrate-specific rate constants correlated well with literature intrinsic clearance values, supporting the physiological relevance of the system. pH-dependent differences in kinetics were observed, reflecting changes in catalyst behavior and oxidizing species.

Conclusion
Continuous oxidant addition provides superior conditions for kinetic studies of biomimetic oxidation. The combined experimental and modeling approach offers a robust framework for interpreting reaction mechanisms and establishes a connection between biomimetic oxidation and enzymatic drug metabolism.

Funding
This study was funded by the grant of the Higher Education Institutional Excellence Programme within the Framework of the Molecular Biology Thematic Programme of Semmelweis University (TKP2021-EGA-24)