Graduation Year

2017

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Chemistry

Major Professor

Li-June Ming, Ph.D.

Committee Member

Jiangeng Cai, Ph.D.

Committee Member

Wayne Guida, Ph.D.

Committee Member

Shengqian Ma, Ph.D.

Committee Member

Prahathees Eswara, Ph.D.

Keywords

copper, dioxygenase, beta-amyloid, metallopeptide, bacitracin

Abstract

Metal ions are ubiquitously found in all living systems and play vital roles in supporting life forms by performing an array of biological activities. Such biological activities include binding and transforming organic molecules, and also acting as active centers and cofactors for catalysis of various acid-base and redox reactions in biological system. The main focus in bioinorganic chemistry is to elucidate the structural and functional roles of metals in biological systems. Among all transition metal ions, Cu2+ and Fe3+ are especially versatile and important due to their abilities to go through redox efficiently.

This dissertation can be divided into four main chapters. The bioinorganic chemistry of Cu- and Fe-containing proteins were briefly discussed in Chapter one. The next chapter focuses on bacitracin, a cyclic peptide-based antibiotic produced by soil bacteria Bacillus subtilis. Bacitracin is a metalloantibiotics that can coordinate with many transition metal ions and exhibit different biological activities. In the first part of Chapter two, the aim is to explore the chemicals interactions in soil micro-ecology by investigating the interactions of different flavonoids and Cu(II)-bacitracin complex. The second part of chapter two demonstrated the binding and oxidation activity of iron(III)-bacitracin. Metal-mediated oxidative stress plays a crucial role in the development of different neurodegenerative diseases. In chapter 3, various synthetic and natural compounds were used to inhibit the oxidation chemistry mediated by Cu(II)-beta-amyloid complex associated with Alzheimer’s disease. Many proteins incorporate copper ions at their active sites for different functions, and among all of the chemistry copper-containing-proteins can perform, one of the most interesting aspect is the ability to bind and activate O2. Therefore, the biomimetic of two different Cu(II) complexes were investigated. In all studies, a combination of kinetic and different spectroscopic methods (UV-vis, NMR and resonance Raman spectroscopy) were used to study their metal binding and activity.

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