Oxidation of DNA by high‐valent metal‐oxo porphyrins Mn‐TMPyP and Fe‐TMPyP (768.12)

Abstract

The goal of this project is to regulate the reactivity of high‐valent metal‐oxo porphyrins by the control of the axial ligand trans to the oxo group. This work will allow a better understanding of the mechanism of metalloporphyrins oxidation. The chosen substrate is a DNA model. The oxidation products are analyzed by HPLC and LC/ESI‐MS. Meso‐tetrakis(4‐N‐methylpyridiniumyl)porphyrinatomanganese(III) (Mn‐TMPyP) and its iron analogue (Fe‐TMPyP) mimic the reaction mechanism of natural heme enzymes namely peroxidases and cytochrome P450. Mn‐TMPyP and Fe‐TMPyP become high‐valent metal‐oxo species when activated by dissymmetric peroxide such as KHSO5 and are able to oxidize DNA. Previous work has shown that Mn‐TMPyP/ KHSO5 was sensitive to pH and produced variable oxidation products of the DNA duplex model 5’‐d(CAGCTG) by electron transfer (ET) and oxygen atom transfer (OAT). At pH 8, the main products observed were those of OAT, whereas at pH 6 the dominant products were obtained from ET. Fe‐TMPyP as Mn‐TMPyP is a powerful oxidizing agent; however, its reactivity towards DNA is unknown. What is known is that it exists as a µ‐oxo species in basic and neutral medium. The µ‐oxo characteristic of Fe‐TMPyP should make it insensitive to pH. We showed that its oxidation products did not vary between pH 6 and pH 8. The present work has shown that the oxidation reactivity of manganese and iron porphyrins can be directed based on their proximal axial ligand (L‐ or X‐type). The proximal ligand can be controlled by simple modulation of the pH of the reaction in the case of manganese porphyrin or by the nature of the metal (iron porphyrins form iron µ‐oxo dimers). The control of metalloporphyrins reactivity may also prove useful in fine chemistry where these compounds are used as oxidation catalysts.Grant Funding Source: Supported by NSF‐CHM 1156907