Special Issue "Metal–Oxo Complexes"

A special issue of Inorganics (ISSN 2304-6740). This special issue belongs to the section "Bioinorganic Chemistry".

Deadline for manuscript submissions: closed (31 January 2018)

Special Issue Editor

Guest Editor
Prof. Dr. Samuel De Visser

Manchester Institute of Biotechnology and School of Chemical Engineering and Analytical Science, The University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom
Website | E-Mail
Interests: computational chemistry; density functional theory; QM/MM; reaction mechanisms; biomimetic models

Special Issue Information

Dear Colleagues,

Nature utilizes metalloenzymes for important biotransformations, ranging from biosynthesis to biodegradation of compounds. Often, molecular oxygen is used on a catalytic center and converted into a high-valent metal–oxo species. For instance, the active species of typical drug metabolizing enzymes in the human liver, namely the cytochromes P450, is an iron(IV)–oxo heme species called Compound I. However, the ligand system of these metal–oxo species strongly affects the reactivity and chemical properties so that heme and non-heme metal–oxo species have different properties and functionalities. Due to the short lifetime of these metal–oxo complexes, they are difficult to trap and characterize experimentally but in recent year’s advances through the use of biomimetic and synthetic model complexes alongside computational modelling has been made. These combinations of experimental and computational studies on synthetic models and enzymes has given insight into the reactivity patterns of these systems, as well as the properties and structure that determine the reactivity patterns. Thus, metal–oxo species are efficient oxidants that react with substrates through oxygen atom transfer, dehydrogenation, but also may be intermediates in water oxidation processes in general catalysis. Therefore, they are important intermediates in catalysis and biochemistry and understanding their intrinsic chemical features enables future design of novel catalysts.

Prof. Dr. Sam P. de Visser
Guest Editor

Manuscript Submission Information

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Keywords

  • high-valent metal–oxo species
  • transition metal oxo complexes
  • metalloenzymes
  • catalysis
  • biochemistry
  • computational chemistry
  • density functional theory
  • QM/MM
  • reaction mechanisms
  • biomimetic models

Published Papers (1 paper)

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Research

Open AccessArticle Biodegradation of Cosmetics Products: A Computational Study of Cytochrome P450 Metabolism of Phthalates
Inorganics 2017, 5(4), 77; doi:10.3390/inorganics5040077
Received: 10 October 2017 / Revised: 1 November 2017 / Accepted: 7 November 2017 / Published: 12 November 2017
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Abstract
Cytochrome P450s are a broad class of enzymes in the human body with important functions for human health, which include the metabolism and detoxification of compounds in the liver. Thus, in their catalytic cycle, the P450s form a high-valent iron(IV)-oxo heme cation radical
[...] Read more.
Cytochrome P450s are a broad class of enzymes in the human body with important functions for human health, which include the metabolism and detoxification of compounds in the liver. Thus, in their catalytic cycle, the P450s form a high-valent iron(IV)-oxo heme cation radical as the active species (called Compound I) that reacts with substrates through oxygen atom transfer. This work discusses the possible degradation mechanisms of phthalates by cytochrome P450s in the liver, through computational modelling, using 2-ethylhexyl-phthalate as a model substrate. Phthalates are a type of compound commonly found in the environment from cosmetics usage, but their biodegradation in the liver may lead to toxic metabolites. Experimental studies revealed a multitude of products and varying product distributions among P450 isozymes. To understand the regio- and chemoselectivity of phthalate activation by P450 isozymes, we focus here on the mechanisms of phthalate activation by Compound I leading to O-dealkylation, aliphatic hydroxylation and aromatic hydroxylation processes. We set up model complexes of Compound I with the substrate and investigated the reaction mechanisms for products using the density functional theory on models and did a molecular mechanics study on enzymatic structures. The work shows that several reaction barriers in the gas-phase are close in energy, leading to a mixture of products. However, when we tried to dock the substrate into a P450 isozyme, some of the channels were inaccessible due to unfavorable substrate positions. Product distributions are discussed under various reaction conditions and rationalized with valence bond and thermodynamic models. Full article
(This article belongs to the Special Issue Metal–Oxo Complexes)
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