Author: Paul C. Tarves
Publisher:
ISBN:
Category :
Languages : en
Pages : 468
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Book Description
Abstract: Mononuclear non-heme iron oxygenase (MNO) enzymes utilize ferrous iron and dioxygen to perform a variety of thermodynamically challenging reactions at standard temperatures and pressures. The potent oxidizing power of these enzymatic systems has led to increased interest from the bioinorganic and synthetic organic communities. Presented herein is the preparation and characterization of an a-keto acid dependent synthetic system that closely models the active site electronic and dioxygen reactivity properties of the Fe II/a-ketoglutarate dependent class of MNH iron oxygenase enzymes. The ferrous complex utilized possesses a facially coordinating N,N,O- donor ligand reminiscent of a common active site motif observed for MNO iron enzymes. The labile coordination sites opposite the ligand framework allow for the ligation of exogenous a-keto acid cofactor as well as the binding and activation of dioxygen. The coordination of exogenous a-keto acid cofactor has been shown to greatly enhance the rate of dioxygen reactivity of the ferrous complex and lead to the catalytic decarboxylation of the cofactor. The enhancement in rate is attributed to the coupling of the dioxygen reduction step to the oxidative decarboxylation of the bound cofactor, which is a thermodynamically favorable process. The oxidative decarboxylation pathway suggests the formation of a high valent iron-oxo intermediate, which has been further supported by the concentration dependence of solvent oxidation during catalysis. The mechanism of dioxygen reactivity was further probed by Hammett analysis using substituted aromatic a-keto acid cofactors. The data presented suggest that the model system prepared proceeds via a biomimetic mechanism capable of catalytic dioxygen activation and substrate oxidation under ambient conditions. Investigation of differential carboxylate and phenolate ligation as it pertains to MNO iron enzymes is also reported. The synthesis and characterization of both ferrous and ferric compounds containing ligands with similar ethylene diamine backbones and either one or two phenolate moities: 2-(((2-(dimethylamino)ethyl)(methyl)amino)-methyl)phenol (N2O1-Ph) and 2,2'-((ethane-1,2-diylbis(methylazanediyl))bis-(methylene))diphenol (N2O2-Ph). The replacement of carboxylate moiety with a phenolate led to a significant decrease in reduction potential and subsequent enhancement in dioxygen sensitivity. This observation may provide insight into the reactivity of other iron containing enzymes with coordinated tyrosine residues, such as intradiol catechol dioxygenases.
Author: Sam P. De Visser
Publisher: Royal Society of Chemistry
ISBN: 1849731810
Category : Science
Languages : en
Pages : 463
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Book Description
Mononuclear iron containing enzymes are important intermediates in bioprocesses and have potential in the industrial biosynthesis of specific products. This book features topical review chapters by leaders in this field and its various sub-disciplines.
Author:
Publisher: Academic Press
ISBN: 9780443313042
Category : Science
Languages : en
Pages : 0
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Book Description
Mononuclear Non-heme Iron Dependent Enzymes, Volume 703 focuses on methods for studying, characterizing, and leveraging the chemistry of mononuclear non-heme iron dependent enzymes. Chapters in this new release include Photoreduction for Rieske oxygenase chemistry, Insights into the Mechanisms of Rieske Oxygenases from Studying the Unproductive Activation of Dioxygen, Non-heme iron and 2-oxoglutarate enzymes catalyze cyclopropane and azacyclopropane formations, Obtaining precise metrics of substrate positioning in Fe(II)/2OG dependent enzymes using Hyperfine Sublevel Correlation Spectroscopy, Xe-pressurization studies for revealing substrate-entrance tunnels, and much more. Additional chapters cover A tale of two dehydrogenases involved in NADH recycling, Rieske oxygenases and/or their partner reductase proteins, Expression, assay and inhibition of 9-cis-epoxycarotenoid dioxygenase (NCED) from Solanum lycopersicum and Zea mays, Biocatalysis and non-heme iron enzymes, In vitro analysis of the three-component Rieske oxygenase cumene dioxygenase from Pseudomonas fluorescens IP01, Structure and function of carbazole 1,9a-dioxygenase, Characterization of a Mononuclear Nonheme Iron-dependent Mono-oxygenase OzmD in Oxazinomycin Biosynthesis, and much more.
Author: Samuel P de Visser
Publisher: Royal Society of Chemistry
ISBN: 1849732981
Category : Science
Languages : en
Pages : 463
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Book Description
There are many mononuclear iron containing enzymes in nature that utilize molecular oxygen and transfer one or both oxygen atoms of O2 to substrates. These enzymes catalyze many processes including the biosynthesis of hormones, the metabolism of drugs, DNA and RNA base repair and, the biosynthesis of antibiotics. Therefore, mononuclear iron containing enzymes are important intermediates in bioprocesses and have great potential in the commercial biosynthesis of specific products since they often catalyze reactions regioselectively or stereospecifically. Understanding their mechanism and function is important and will assist in searches for commercial exploitation. In recent years, advances in experimental as well as theoretical methodologies have made it possible to study the mechanism and function of these enzymes and much information on their properties has been gained. This book highlighting recent developments in the field is, therefore, a timely addition to the literature and will interest a broad readership in the fields of biochemistry, inorganic chemistry and computational chemistry. The Editors, leaders in the field of nonheme and heme iron containing monoxygenases, have filled the book with topical review chapters by leaders in the various sub-disciplines.
Author: Christopher J Schofield
Publisher: Royal Society of Chemistry
ISBN: 1849739501
Category : Science
Languages : en
Pages : 508
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Book Description
Since the discovery of the first examples of 2-oxoglutarate-dependent oxygenase-catalysed reactions in the 1960s, a remarkably broad diversity of alternate reactions and substrates has been revealed, and extensive advances have been achieved in our understanding of the structures and catalytic mechanisms. These enzymes are important agrochemical targets and are being pursued as therapeutic targets for a wide range of diseases including cancer and anemia. This book provides a central source of information that summarizes the key features of the essential group of 2-oxoglutarate-dependent dioxygenases and related enzymes. Given the numerous recent advances and biomedical interest in the field, this book aims to unite the latest research for those already working in the field as well as to provide an introduction for those newly approaching the topic, and for those interested in translating the basic science into medicinal and agricultural benefits. The book begins with four broad chapters that highlight critical aspects, including an overview of possible catalytic reactions, structures and mechanisms. The following seventeen chapters focus on carefully selected topics, each written by leading experts in the area. Readers will find explanations of rapidly evolving research, from the chemistry of isopenicillin N synthase to the oxidation mechanism of 5-methylcytosine in DNA by ten-eleven-translocase oxygenases.
Author:
Publisher: Academic Press
ISBN: 9780443346477
Category : Science
Languages : en
Pages : 0
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Book Description
Mononuclear Non-heme Iron Dependent Enzymes, Volume 703 PART B focuses on methods for studying, characterizing, and leveraging the chemistry of mononuclear non-heme iron dependent enzymes. Chapters in this new release include Photoreduction for Rieske oxygenase chemistry, Insights into the Mechanisms of Rieske Oxygenases from Studying the Unproductive Activation of Dioxygen, Non-heme iron and 2-oxoglutarate enzymes catalyze cyclopropane and azacyclopropane formations, Obtaining precise metrics of substrate positioning in Fe(II)/2OG dependent enzymes using Hyperfine Sublevel Correlation Spectroscopy, Xe-pressurization studies for revealing substrate-entrance tunnels, and much more. Additional chapters cover A tale of two dehydrogenases involved in NADH recycling, Rieske oxygenases and/or their partner reductase proteins, Expression, assay and inhibition of 9-cis-epoxycarotenoid dioxygenase (NCED) from Solanum lycopersicum and Zea mays, Biocatalysis and non-heme iron enzymes, In vitro analysis of the three-component Rieske oxygenase cumene dioxygenase from Pseudomonas fluorescens IP01, Structure and function of carbazole 1,9a-dioxygenase, Characterization of a Mononuclear Nonheme Iron-dependent Mono-oxygenase OzmD in Oxazinomycin Biosynthesis, and much more.
Author:
Publisher: Academic Press
ISBN: 0128187743
Category : Science
Languages : en
Pages : 134
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Book Description
Nonheme Iron Enzymes: Structures and Mechanisms, Volume 117, highlights new advances in the field, with this new volume presenting new and interesting chapters on the topics. Each chapter is written by an international board of authors. Targeted to a very wide audience of specialists, researchers and students Contains timely chapters written by well-renowned authorities in their field Includes a number of high quality illustrations, figures and tables
Author:
Publisher: Elsevier
ISBN: 0443313059
Category : Science
Languages : en
Pages : 348
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Book Description
Mononuclear Non-heme Iron Dependent Enzymes, Volume 703 focuses on methods for studying, characterizing, and leveraging the chemistry of mononuclear non-heme iron dependent enzymes. Chapters in this new release include Photoreduction for Rieske oxygenase chemistry, Insights into the Mechanisms of Rieske Oxygenases from Studying the Unproductive Activation of Dioxygen, Non-heme iron and 2-oxoglutarate enzymes catalyze cyclopropane and azacyclopropane formations, Obtaining precise metrics of substrate positioning in Fe(II)/2OG dependent enzymes using Hyperfine Sublevel Correlation Spectroscopy, Xe-pressurization studies for revealing substrate-entrance tunnels, and much more. Additional chapters cover A tale of two dehydrogenases involved in NADH recycling, Rieske oxygenases and/or their partner reductase proteins, Expression, assay and inhibition of 9-cis-epoxycarotenoid dioxygenase (NCED) from Solanum lycopersicum and Zea mays, Biocatalysis and non-heme iron enzymes, In vitro analysis of the three-component Rieske oxygenase cumene dioxygenase from Pseudomonas fluorescens IP01, Structure and function of carbazole 1,9a-dioxygenase, Characterization of a Mononuclear Nonheme Iron-dependent Mono-oxygenase OzmD in Oxazinomycin Biosynthesis, and much more. Provides detailed articles regarding how to study the structures and mechanisms of mononuclear non-heme iron dependent enzymes Guides readers on how to use partner proteins in non-heme iron enzyme catalysis Includes strategies to employ mononuclear non-heme iron enzymes in biocatalytic applications
Author: Lei Liu
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Mononuclear non-heme iron enzymes catalyze wide varieties of important biological reactions with industrial, medical, and environmental applications. These enzymes can be classified into two classes, O2 activating FeII enzymes and substrate activating FeIII enzymes. This thesis focuses on understanding the geometric and electronic structures of the peroxo level intermediates and their reactivities in two O2 activating FeII enzymes, bleomycin and Rieske dioxygenases related model complexes, by using a combination of spectroscopic and computational methods. Bleomycin is a glycopeptide anticancer drug capable of effecting single- and double-strand DNA cleavage. The last detectable intermediate prior to DNA cleavage is a low spin S = 1/2 FeIII--OOH species, termed activated bleomycin (ABLM). The DNA strand scission is initiated through the abstraction of the C-4' hydrogen atom of the deoxyribose sugar unit. Nuclear resonance vibrational spectroscopy (NRVS) aided by extended X-ray absorption fine structure (EXAFS) spectroscopy and density functional theory (DFT) calculations are applied to define the natures of FeIIIBLM and ABLM as (BLM)FeIII--OH and (BLM)FeIII([eta]1--OOH) species, respectively. The NRVS spectra of FeIIIBLM and ABLM are strikingly different because in ABLM the Fe--O--O bending mode mixes with, and energetically splits, the doubly degenerate, intense O--Fe--Nax trans-axial bends. DFT calculations of the reaction of ABLM with DNA, based on the species defined by the NRVS data, show that the direct H-atom abstraction by ABLM is thermodynamically favored over other proposed reaction pathways. Previously, the rate of ABLM decay had been found, based on indirect methods, to be independent of the presence of DNA. In this thesis, we use a circular dichroism (CD) feature unique to ABLM to directly monitor the kinetics of ABLM reaction with a DNA oligonucleotide. Our results show that the ABLM + DNA reaction is appreciably faster, has a different kinetic isotope effect, and has a lower Arrhenius activation energy than does ABLM decay. In the ABLM reaction with DNA, the small normal kH/kD ratio is attributed to a secondary solvent effect through DFT vibrational analysis of reactant and transition state (TS) frequencies, and the lower Ea is attributed to the weaker bond involved in the abstraction reaction (C--H for DNA and N--H for the decay in the absence of DNA). The DNA dependence of the ABLM reaction indicates that DNA is involved in the TS for ABLM decay and thus reacts directly with (BLM)FeIII([eta]1--OOH) instead of its decay product. Oxygen-containing mononuclear iron species, FeIII--peroxo, FeIII--hydroperoxo and FeIV--oxo, are key intermediates in the catalytic activation of dioxygen by iron-containing metalloenzymes. It has been difficult to generate synthetic analogues of these three active iron--oxygen species in identical host complexes, which is necessary to elucidate changes to the structure of the iron center during catalysis and the factors that control their chemical reactivities with substrates. Here we report the high-resolution crystal structure of a mononuclear non-haem side-on FeIII--peroxo complex, [Fe(III)(TMC)(OO)]+. We also report a series of chemical reactions in which this iron(III)--peroxo complex is cleanly converted to the FeIII--hydroperoxo complex, [Fe(III)(TMC)(OOH)]2+, via a short-lived intermediate on protonation. This iron(III)--hydroperoxo complex then cleanly converts to the ferryl complex, [Fe(IV)(TMC)(O)]2+, via homolytic O--O bond cleavage of the iron(III)--hydroperoxo species. All three of these iron species--the three most biologically relevant iron--oxygen intermediates--have been spectroscopically characterized; we note that they have been obtained using a simple macrocyclic ligand. We have performed relative reactivity studies on these three iron species which reveal that the iron(III)--hydroperoxo complex is the most reactive of the three in the deformylation of aldehydes and that it has a similar reactivity to the iron(IV)--oxo complex in C--H bond activation of alkylaromatics. These reactivity results demonstrate that iron(III)--hydroperoxo species are viable oxidants in both nucleophilic and electrophilic reactions by iron-containing enzymes. The geometric and electronic structure and reactivity of an S = 5/2 (HS) mononuclear non-heme (TMC)FeIII-OOH complex was studied by spectroscopy, calculations, and kinetics for comparison to our past study of an S = 1/2 (LS) FeIII-OOH complex to understand their mechanisms of O-O bond homolysis and electrophilic H-atom abstraction. The homolysis reaction of the HS [(TMC)FeIII-OOH]2+ complex is found to involve axial ligand coordination and a crossing to the LS surface for O-O bond homolysis. Both HS and LS FeIII-OOH complexes are found to perform direct H-atom abstraction reactions but with very different reaction coordinates. For the LS FeIII-OOH, the transition state is late in O-O and early in C-H coordinates. However, for the HS FeIII-OOH, the transition state is early in O-O and further along in the C-H coordinate. In addition, there is a significant amount of electron transfer from substrate to HS FeIII-OOH at transition state, but does not occur in the LS transition state. Thus in contrast to the behavior of LS FeIII-OOH, the H-atom abstraction reactivity of HS FeIII-OOH is found to be highly dependent on both the ionization potential and C-H bond strength of substrate. LS FeIII-OOH is found to be more effective in H-atom abstraction for strong C-H bonds, while the higher reduction potential of HS FeIII-OOH allows it be active in electrophilic reactions without the requirement of O-O cleavage. This is relevant to the Rieske dioxygenases, which are proposed to use a HS FeIII-OOH to catalyze cis-dihydroxylation of a wide range of aromatic compounds. S K-edge XAS is a direct experimental probe of metal ion electronic structure as the pre-edge energy reflects its oxidation state, and the energy splitting pattern of the pre-edge transitions reflects its spin state. The combination of sulfur K-edge XAS and DFT calculations indicates that the electronic structures of {FeNO}7 (S = 3/2) (SMe2N4(tren)Fe(NO), complex I) and {FeNO}7 (S = 1/2) ((bme-daco)Fe(NO), complex II) are FeIII(S=5/2)--NO-- (S = 1) and FeIII(S=3/2)--NO-- (S = 1), respectively. When an axial ligand is computationally added to complex II, the electronic structure becomes FeII(S = 0)--NO[*] (S = 1/2). These studies demonstrate how the ligand field of the Fe center defines its spin state and thus changes the electron exchange, an important factor in determining the electron distribution over {FeNO}7 and {FeO2}8 sites.
Author: Armando J. L. Pombeiro
Publisher: John Wiley & Sons
ISBN: 111937880X
Category : Science
Languages : en
Pages : 680
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Book Description
Presents state-of-the-art information concerning the syntheses of valuable functionalized organic compounds from alkanes, with a focus on simple, mild, and green catalytic processes Alkane Functionalization offers a comprehensive review of the state-of-the-art of catalytic functionalization of alkanes under mild and green conditions. Written by a team of leading experts on the topic, the book examines the latest research developments in the synthesis of valuable functionalized organic compounds from alkanes. The authors describe the various modes of interaction of alkanes with metal centres and examine theoxidative alkane functionalization upon C-O bond formation. They address the many types of mechanisms, discuss typical catalytic systems and highlight the strategies inspired by biological catalytic systems. The book also describes alkane functionalization upon C-heteroatom bond formation as well as oxidative and non-oxidative approaches. In addition, the book explores non-transition metal catalysts and metal-free catalytic systems and presents selected types of functionalization of sp3 C-H bonds pertaining to substrates other than alkanes. This important resource: Presents a guide to the most recent advances concerning the syntheses of valuable functionalized organic compounds from alkanes Contains information from leading experts on the topic Offers information on the catalytic functionalization of alkanes that allows for improved simplicity and sustainability compared to current multi-stage industrial processes Explores the challenges inherent with the application of alkanes as starting materials for syntheses of added value functionalized organic compounds Written for academic researchers and industrial scientists working in the fields of coordination chemistry, organometallic chemistry, catalysis, organic synthesis and green chemistry, Alkane Functionalization is an important resource for accessing the most up-to-date information available in the field of catalytic functionalization of alkanes.
