Don L. Warner
University of Utah, Salt Lake City, UT Chemistry B.S. 1995
University of Wisconsin, Madison, WI Chemistry M.S. 1998
University of Michigan, Ann Arbor, MI Chemistry Ph.D. 2002
My teaching interests and experience are primarily focused on teaching all aspects of organic chemistry to students through classes, research, and personal interaction. My understanding in organic chemistry has been solidified through exposure to a number of accomplished professors—I have been fortunate to experience the teaching of organic chemistry at four universities, each using a different approach. While an undergraduate student at the University of Utah, an effective introductory organic chemistry professor demonstrated the value of a well-organized lecture that was delivered in a clear and concise manner. As a teaching assistant at the University of Wisconsin, a professor illustrated that seemingly small things make a tremendous difference. In a class of over 100 students, she learned every person’s name. At the University of Michigan, group projects and presentations, both traditional and internet-based, were an integral part of organic chemistry courses. The overall effect of the various strategies is to make a traditionally overwhelming class seem manageable to students. Now, at Boise State University, I attempt to incorporate all of these ideas in order to make the class more invigorating while maintaining a high level of rigor, which in turn helps students master the subject.
I. Ariziridinomitosene Synthesis and DNA Binding Properties.
An aziridinomitosene, a compound related to the clinically used anticancer agent mitomycin C, has recently been shown to form DNA interstrand cross-links under non-reductive conditions. The occurrence of the cross-link is significant for two reasons. First, mitomycin C prohibits cell proliferation via the formation of rare interstrand DNA cross-links. Second, aziridinomitosenes were previously thought to be responsible solely for formation of less toxic DNA monoadducts. Several factors may facilitate this previously unobserved cytotoxic event, including the presence of additional electrophilic sites on the quinone ring at C-6 and C-7. Evidence suggests that the C-1 and C-10 electrophilic sites are key to cross-link formation, as is the case with mitomycin C, but the molecular structure of the cross-link is not known. The mechanism of DNA cross-linking by the synthetic aziridinomitosene is hypothesized to involve monoalkylation of DNA at C-1 followed by nucleophilic attack at C-6 or C-7 of the quinone ring, which in turn activates C-10 for a second alkylation of DNA. Our current research efforts aim to identify the molecular structure of the DNA-aziridinomitosene interstrand cross-link, determine the role of the four electrophilic sites, and investigate the physical properties required to induce cross-link formation. Specifically, we are currently preparing relevant mitosene analogs, characterizing mitosenes with respect to physical properties, and are conducting in vitro assessments of DNA alkylation by mitosene derivatives.
II. Synthetic and Computational Investigations of Electrocyclization and Cycloaddition Reactions of Azomethine Ylides.
Electrocyclization and cycloaddition of azomethine ylides and azaallyl anions offer potential for regio- and stereocontrolled formation of azacycles. Thus, these reactive intermediates have been investigated computationally. Specifically, we have studied the properties of conjugated azomethine ylide and azaallyl anion systems that are theoretically capable of undergoing disrotatory electrocyclization due to their six pi electrons. As ring closure is dependent on the geometry of the intermediates, a computational study of conformer energies and interconversion energy barriers has been conducted. Initial studies suggest that intermediates substituted at the four position favor the U-geometry required for electrocyclization. Further calculations indicate that added steric hindrance at this position gives increased bias toward the U conformer while simultaneously lowering the activation energy required for electrocyclization. Related studies have examined the structural properties that facilitate spontaneous ring opening of 4-oxazolines to produce stabilized azomethine ylides.