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Hemoprotein-Mediated Activation of Nitroalkanes

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2009, Doctor of Philosophy in Clinical-Bioanalytical Chemistry, Cleveland State University, College of Science.
Chemicals and drugs are known to be metabolized mostly by Cytochrome P450 xenobiotic metabolizing enzymes. However, the detailed mechanism of nitro-compounds metabolism is still unclear. The activation of nitro-xenobiotics by heme-P450 enzymes is a potential explanation for the origin of nitro-compound carcinogenesis. Investigating the interaction of simple nitro-compounds with redox activity of heme enzymes is therefore critical to explore the mechanism and products of activation.In this study, multiple analytical methods and instrumentations are employed and graphic and simulation software such as Origin® and Digisim® are utilized to quantitatively derive parameters from experimental raw data. This study shows that myoglobin, iron-protoporphyrin-IX (hemin), and the oxygenase domain of inducible nitric oxide synthase (iNOSoxy) act as efficient electrocatalysts for nitroalkane reductions in the surfactant films on pyrolytic graphite electrodes. In the study using myoglobin as a model electrocatalyst for the electroreduction of nitromethane, the catalytic activity is evaluated using Michaelis-Menten kinetics. The apparent Km and the turnover number kcat are derived from non-linear regression of Michaelis-Menten plot using Origin software. The reductive products of catalytic electroreduction of nitromethane are identified by a mass spectrometric method. We also identified a ferrous heme-nitrosomethane as the intermediate in the catalytic process using UV-Vis spectroscopy and electrochemical techniques. We show the electrochemical signature of a nitrosoalkane-heme complex that is possibly involved in the mechanism of activation of aliphatic nitro-compounds xenobiotics. A possible heme-mediated electroreductive pathway is proposed. In this work, we also explored the comparative study of the electroreduction of nitromethane using myoglobin, hemin, and iNOSoxy as the electrocatalysts. We discussed the role of the protein shell in the activation process. We also studied four different aliphatic nitroalkanes as substrates to study their electro activation using hemin and iNOSoxy as electrocatalysts, and used a mass spectrometric method to identify the reduction products. By comparing the catalysis of each nitroalkane substrate and by varying experimental conditions such as scan rate of cyclic voltametry, substrate concentration, and pH, we discussed the effects caused by the physical and chemical properties of the substrates on their electrocatalytic reductions.
Mekki Bayachou, PhD (Committee Chair)
Alan Riga, PhD (Committee Member)
Robert Wei, PhD (Committee Member)
Stan Duraj, PhD (Committee Member)
Tobili Sam-Yellowe, PhD (Committee Member)
157 p.

Recommended Citations

Citations

  • Li, L. (2009). Hemoprotein-Mediated Activation of Nitroalkanes [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1268069794

    APA Style (7th edition)

  • Li, Ling. Hemoprotein-Mediated Activation of Nitroalkanes. 2009. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1268069794.

    MLA Style (8th edition)

  • Li, Ling. "Hemoprotein-Mediated Activation of Nitroalkanes." Doctoral dissertation, Cleveland State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=csu1268069794

    Chicago Manual of Style (17th edition)