Investigation of the catalytic cycle of the molybdoenzyme sulfite oxidase: Synthesis and spectroscopic study of model systems.

Persistent Link:
http://hdl.handle.net/10150/186051
Title:
Investigation of the catalytic cycle of the molybdoenzyme sulfite oxidase: Synthesis and spectroscopic study of model systems.
Author:
LaBarre, Michael James.
Issue Date:
1992
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
This research has been directed at the study of the catalytic cycle of the molybdoenzyme, sulfite oxidase, through the use of both functional and structural model chemistry. A biologically relevant synthetic model for the first two steps of the proposed catalytic cycle of sulfite oxidase has been developed. A rapid oxygen atom transfer reaction from a dioxo-molybdenum(VI) center to triphenylphosphine is followed by an intermolecular electron/halogen exchange reaction between tetratolylporphinatoiron(III)-chloride and the now reduced oxo-molybdenum(IV) center. The kinetic and thermo-dynamic parameters of these reactions in dimethylformamide and toluene have been investigated and a self consistent mechanism has been proposed. Structural models for intramolecular electron transfer between the oxo-molybdenum center of the cofactor and the iron heme of sulfite oxidase have been prepared. Modified tetratolylporphyrins have been designed in order to contain a chelating catecholate functionality at discreet distances from the central cavity of the porphyrin ring. An oxo-molybdenum(V) group (which is stabilized by the facially coordinating, hydrotris(3,5-dimethyl-1-pyrazolyl)borate ligand) has been attached to the porphyrin through this catecholate functionality and the resulting bimetallic compounds have been investigated by NMR, EPR, UV/Vis, and electrochemical methods. The use of ³¹P-NMR spectroscopy as a probe of molybdenum-phosphate interactions in sulfite oxidase has been investigated through the synthesis and spectroscopic investigation of a series of six mononuclear oxo-molybdenum(V) and dioxo-molybdenum(VI) compounds which contain pendant phosphate esters. The ³¹P-NMR spectra of the Mo(V) compounds exhibit line broadening due to the absolute distance to the paramagnetic d¹ Mo(V) center. The relaxation times (T₁ and T₂) of the ³¹P center have been determined and are sensitive to the overall structure of the model compounds. The Mo-P distances have been calculated using the relaxation data and the Solomon equation and yield distances which are in reasonable agreement with the structures as determined by computer molecular modeling.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Dissertations, Academic.; Biochemistry.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Chemistry; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Enemark, John H.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleInvestigation of the catalytic cycle of the molybdoenzyme sulfite oxidase: Synthesis and spectroscopic study of model systems.en_US
dc.creatorLaBarre, Michael James.en_US
dc.contributor.authorLaBarre, Michael James.en_US
dc.date.issued1992en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThis research has been directed at the study of the catalytic cycle of the molybdoenzyme, sulfite oxidase, through the use of both functional and structural model chemistry. A biologically relevant synthetic model for the first two steps of the proposed catalytic cycle of sulfite oxidase has been developed. A rapid oxygen atom transfer reaction from a dioxo-molybdenum(VI) center to triphenylphosphine is followed by an intermolecular electron/halogen exchange reaction between tetratolylporphinatoiron(III)-chloride and the now reduced oxo-molybdenum(IV) center. The kinetic and thermo-dynamic parameters of these reactions in dimethylformamide and toluene have been investigated and a self consistent mechanism has been proposed. Structural models for intramolecular electron transfer between the oxo-molybdenum center of the cofactor and the iron heme of sulfite oxidase have been prepared. Modified tetratolylporphyrins have been designed in order to contain a chelating catecholate functionality at discreet distances from the central cavity of the porphyrin ring. An oxo-molybdenum(V) group (which is stabilized by the facially coordinating, hydrotris(3,5-dimethyl-1-pyrazolyl)borate ligand) has been attached to the porphyrin through this catecholate functionality and the resulting bimetallic compounds have been investigated by NMR, EPR, UV/Vis, and electrochemical methods. The use of ³¹P-NMR spectroscopy as a probe of molybdenum-phosphate interactions in sulfite oxidase has been investigated through the synthesis and spectroscopic investigation of a series of six mononuclear oxo-molybdenum(V) and dioxo-molybdenum(VI) compounds which contain pendant phosphate esters. The ³¹P-NMR spectra of the Mo(V) compounds exhibit line broadening due to the absolute distance to the paramagnetic d¹ Mo(V) center. The relaxation times (T₁ and T₂) of the ³¹P center have been determined and are sensitive to the overall structure of the model compounds. The Mo-P distances have been calculated using the relaxation data and the Solomon equation and yield distances which are in reasonable agreement with the structures as determined by computer molecular modeling.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectDissertations, Academic.en_US
dc.subjectBiochemistry.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairEnemark, John H.en_US
dc.contributor.committeememberBates, Robert B.-
dc.contributor.committeememberLichtenberger, Dennis L.-
dc.contributor.committeememberWigley, David E.-
dc.contributor.committeememberBarfield, Michael-
dc.identifier.proquest9309013en_US
dc.identifier.oclc714143370en_US
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