Thiophenoporphyrins as biomimetic models of Cytochrome P450: catalysis of hydrocarbons and triazine herbicides

Abstract

The Metalloporphyrins are heme enzymes of cytochrome P450 (P450), responsible for oxidative catalysis of exogenous compounds, such as drugs and pesticides. The prospect of reproducing the highly specific and selective reactions promoted by P450 enzymes has led to the development of synthetic metalloporphyrins (MePs). Currently one of the bigger challenges of modern chemistry today is the design of new porphyrin systems capable of reproducing the catalytic activity of P450 enzymes, for example, in the study of the metabolism of xenobiotics (eg natural products, pharmaceuticals, pesticides). In this sense, this project search to synthesize and explore the catalytic properties of meso-tetraenyl porphyrins (H2TThP), replaced with nitro (-NO2) groups, as biomimetic catalysts of P450 enzymes. Mononitrate catalysts (MnTTh (NO2) P) and tetranitrates (MnTTh (NO2) 4P) will be synthesized in order to compare the catalytic efficiency under the electron density withdrawing action from the nitro groups. The reactivity, stability, and selectivity of these new catalysts will be evaluated in oxidation studies of cyclohexane hydrocarbon. Posteriorly, the catalysts will be applied to the metabolism of xenobiotics, with featured on triazine herbicides (terbuthylazine, atrazine, and simazine), widely used in the control of weeds in agricultural crops, such as sugarcane, coffee, bananas, and corn, which present high leaching potential, which can contaminate soil, groundwater, and streams. Exposure to these herbicides can cause neurological and reproductive problems in humans; therefore, it is necessary to identify the metabolites produced during the biotransformation reactions of these herbicides in the human body. In this way, studies within Vitro biomimetic systems based on P450 enzymes may contribute to the identification of these metabolites and possible intermediates.