| 1. |
- Johansson, Adam Johannes, 1976-
(författare)
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Biomimetic Transition Metal Catalysts : Insights from Theoretical Modeling
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The scientific interest in the chemistry of synthetic transition metal complexes is motivated by at least two arguments:1.These can be regarded as models of biological transition metal complexes, e.g. metalloenzymes, whose functions can be difficult to reveal in detail due to their complexity.2.Transition metal complexes are used for catalytic purposes in the industrial synthesis of chemicals. There is a large potential for further development of this technology, which can be motivated both by economic and environmental arguments.In the present thesis, density functional theory (a quantum mechanical method) has been applied to model reactions involving synthetic iron and copper complexes in solution. The complexity of the solvent environment is a challenging problem for theoretical investigations and a significant part of the theses has been to investigate the mechanistic effects of metal-coordinating solvent molecules, Lewis bases and counter ions. For example, it is explained why the cleavage of the O-O bond in heme-diiron-peroxides is faster in the presence of a coordinating Lewis base. Furthermore, the experimentally observed structure-activity relationship between the Fe(III)(µ-O)2Fe(IV) and (H2O)Fe(III)(µ-O)Fe(IV)O motifs is given an explanation. In addition, the present thesis presents a systematic investigation of how the self-interaction error in density functional theory (DFT) affects the modeling of transition metal catalysis.
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| 2. |
- Noack, Holger, 1976-
(författare)
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Biomimetic Iron Complexes involved in Oxygenation and Chlorination : A Theoretical Study
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biomimetic chemistry is directed towards the simulation of enzymatic reactivity with synthetic analogues. In this thesis a quantum chemical method has been employed to study the mechanism of highly reactive iron-oxo complexes involved in oxygenation and chlorination of organic substrates. The aim of this research is to gain greater understanding for the reactivity paradigm of the iron-oxo group. One reaction deals with the conversion of cyclohexane into adipic acid, a key chemical in industrial chemistry, catalyzed by an iron(II)-porphyrin complex in the presence of dioxygen. This process constitutes a ’green’ alternative to conventional adipic acid production, and is thus of great interest to synthetic chemistry. Another reaction investigated herein regards the selective chlorination observed for a new group of non-heme iron enzymes. With help of theoretical modeling it was possible to propose a mechanism that explains the observed selectivity. It is furthermore demonstrated how a biomimetic iron complex simulates the enzymatic reactivity by a different mechanism. Other topics covered in this thesis regard the structure-reactivity relationship of a binuclear iron complex and the intradiol C-C bond cleavage of catechol catalyzed by an iron(III) complex.
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| 3. |
- Roos, Katarina, 1982-
(författare)
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Manganese and Iron Heterodimers and Homodimers in Enzymes : Insights from Density Functional Theory
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The enzyme ribonucleotide reductase (RNR) catalyzes the reduction of ribonucleotides to deoxyribonucleotides, the building blocks of DNA, and is essential for all organisms. Canonical class I RNR R2 proteins use a diiron cofactor to generate a tyrosyl radical, which is required for catalysis. Recent discoveries have established that the different subgroups of class I RNR employ different metal cofactors. Class Ib R2 (R2F) utilizes a dimanganese cofactor and a flavoprotein to generate the tyrosyl radical. Class Ic R2 (R2c) lacks the radical-bearing tyrosine, and instead has an oxidized heterodinuclear manganese-iron center, the first known redox active MnFe cofactor. A second group of MnFe proteins with different functions, denoted R2-like ligand binding oxidases (R2lox), was later identified. R2lox proteins are capable of performing two-electron oxidations and are believed to be hydrocarbon oxidases. In the present thesis density functional theory, a quantum mechanical method, is employed to study the manganese and iron heterodimers and homodimers in the R2 and R2lox proteins, with the aim to shed light on the mechanistic details and stress the main features of the alternative metal centers. Some of the questions addressed are the radical generation with the homodimers and heterodimer in R2, the radical transfer between R2 and the RNR catalytic subunit, and the function of R2lox. A Mn(IV)Fe(III) state is shown to be an equally strong oxidant as a tyrosyl radical, giving a rationalization for the presence of the heterodimer in R2c. A reaction mechanism for the formation of an unprecedented tyrosine-valine crosslink catalyzed by the heterodimer in R2lox is modeled, and the potential of the protein to perform hydroxylations of hydrocarbons based on calculated barriers for methane hydroxylation is discussed. An energetically possible reaction mechanism is suggested for activation of dimanganese R2F by hydrogen peroxide, and a hypothetical role of the flavoprotein in radical generation is proposed.
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| 4. |
- Rudbeck, Maria, 1979-
(författare)
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The Beauty of the Bitter Devils : A Theoretical Study on Phosphate Molecules
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Phosphate transfer reactions are catalyzed by a large number of enzymes comprising kinases, mutases and phosphatases. These enzymes play a fundamental role in controlling numerous life processes and it is therefore important to understand the origin of their potent catalytic power. An example is the Ca2+-ATPase. In the E2P-state, this enzyme hydrolyses the phosphorylated amino acid, Asp351, 106 to 107 fold faster than when the model compound, acetyl phosphate, is hydrolyzed in in water.This thesis explores the catalytic power of Ca2+-ATPase using theoretical method based on quantum mechanics. The studies of this protein were made by performing quantum chemical calculations on models of phosphoric monoesters as well as on the explicit reaction pathway of the hydrolysis. The studies show the importance of electrostatic interactions as well as the role of the specific active site residue Glu183, a residue that acts as a base in the catalytic pathway. Furthermore, based on the calculations, the interpretation of the experimental infrared spectrum of the E2P-state of Ca2+-ATPase, could be further elucidated as well as modified.The experimental infrared spectrum of phosphoenol pyruvate in water has also been elucidated through calculations. This molecule is converted into pyruvate in the last step of the glycolytic pathway, a reaction that is catalyzed by pyruvate kinase (PK). These results further enabled the interpretation of the experimental spectrum of the PK's catalytic reaction.These two processes, the transport of Ca2+ into the sarcoplasmatic reticulum against a concentration gradient and the glycolysis, are two important actions of a muscle cell.
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| 5. |
- Hopmann, Kathrin H.
(författare)
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Quantum chemical studies of epoxide-transforming enzymes
- 2007
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Density functional theory is employed to study the reaction mechanisms of different epoxide-transforming enzymes. Calculations are based on quantum chemical active site models, which are build from X-ray crystal structures. The models are used to study conversion of various epoxides into their corresponding diols or substituted alcohols. Epoxide-transforming enzymes from three different families are studied. The human soluble epoxide hydrolase (sEH) belongs to the α/β-hydrolase fold family. sEH employs a covalent mechanism to hydrolyze various epoxides into vicinal diols. The Rhodococcus erythrobacter limonene epoxide hydrolase (LEH) constitutes a novel epoxide hydrolase, which is considered the founding member of a new family of enzymes. LEH mediates transformation of limone-1,2-epoxide into the corresponding vicinal diol by employing a general acid/general base-mediated mechanism. The Agrobacterium radiobacter AD1 haloalcohol dehalogenase HheC is related to the short-chain dehydrogenase/reductases. HheC is able to convert epoxides using various nucleophiles such as azide, cyanide, and nitrite. Reaction mechanisms of these three enzymes are analyzed in depth and the role of different active site residues is studied through in silico mutations. Steric and electronic factors influencing the regioselectivity of epoxide opening are identified. The computed energetics help to explain preferred reaction pathways and experimentally observed regioselectivities. Our results confirm the usefulness of the employed computational methodology for investigating enzymatic reactions.
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