The Chemical Synthesis Program of the Chemistry Division supports the project by Professor W. Dean Harman. Professor Harman is a faculty member and current chair in the Department of Chemistry at the University of Virginia. He is developing new methods for the preparation of novel chemical compounds that have the potential to serve as lead compounds for pharmaceutical development. His unique approach exploits the unusual chemical properties that arise when an aromatic ring is complexed to a metal. These unusual chemical properties lead to new chemical reactions that convert the originally flat aromatic ring into a significantly more complex molecule. The presence of the metal allows for introduction of the complexity in a controlled fashion. The invention of the new methods allows for completely new approaches to the synthesis of a variety of interesting and potentially useful molecules. While not part of this proposal. The project lies at the interface of organic, inorganic, and medicinal chemistry. Students work in a fully interdisciplinary research environment on a wide range of problems and become integrated into the scientific community through attendance and presentations at professional meetings, participation in writing peer-reviewed manuscripts, participating in the proposal-writing process, and meeting other scientists. Thus, it is well suited for the education of scientists at all levels. Professor Harman's group is also well positioned to provide the highest level of education and training for students underrepresented in science. Outreach activities involving K-12 students will also be part of the funded project. Finally, collaborations with professors from undergraduate institutions allow these professors greater exposure to current research methods, and expose their students to major research programs.
The goal of this work is the development of new methods for the syntheses of novel molecular substances from aromatic molecules. This is being accomplished by leveraging the unique chemical properties of an aromatic molecule that result from its dihapto-coordination to a transition metal. Such action modifies the chemical reactivity of the aromatic substrate, allowing its elaboration into novel organic compounds. Significantly, these dearomatization reactions are leading to new molecules with considerable stereochemical complexity that are well suited for biological evaluation. Previously, heavy metal dearomatization agents derived from osmium, rhenium, and tungsten have been investigated, exploiting their powerful pi-donating abilities. In this work, the PI is exploring the feasibility and practicality of a dihapto-coordinate dearomatization methodology based on a second-row metal. Fundamental chemical features of molybdenum-based aromatic complexes are being investigated and compared to the analogous heavy metal systems. Differences in bond energies, oxidation state stabilities, pi-interactions, tolerance of chemical reagents, cost, and recyclability are ultimately leading to new synthetic opportunities that complement those provided by the heavy metal based systems. The molecular frameworks that are formed through these studies are providing novel architectures that ultimately will be valuable in the development of new biologically active materials. In many cases there are simply no other means for easily obtaining these compounds. Other broader impacts of this work are related to the professional training of graduate and undergraduate students in the areas of Organic, Inorganic, and Organometallic Chemistry. In addition, graduate students develop their mentoring skills by training and collaborating with undergraduate students.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
