IRES: Development of Enantioselective Catalysts

University Of Notre Dame, Notre Dame IN

Investigators

Abstract

This NSF International Research Experiences for Students program will provide support for a total of 12 Ph.D. students pursuing dissertation research in several subdisciplines of chemistry at the University of Notre Dame to do research in any of three closely aligned laboratories in Sweden. Four students will be selected each year during this three-year program to spend four summer months pursuing research on a unified theme of development of new enantioselective catalysts. Initial emphasis will be placed on catalysts for the synthesis of chiral amines, which represent a broad class of compounds of importance as pharmaceutical products, agricultural compounds, and small molecule probes in molecular biology and biochemistry. The mentors, who have collaborations amongst themselves and with Notre Dame faculty members, are Professor Per-Ola Norrby at Gothenburg University, Professor Pher Andersson at Stockholm University, and Professor Jan-Erling Bäckvall at Stockholm University. They are world leaders in the development of computational methods for prediction of enantioselectivities of chiral transition metal catalysts, the development and characterization of new metal catalysts, the evaluation of catalyst performance, and the use of molecular biology methods to develop new peptide-based catalysts. They will direct IRES student projects in these areas of specialization, blending computational studies with experimental chemistry and the tools of molecular biology to develop new transition metal- and peptide-based enantioselective catalysts. Quantum mechanics calculations will be used to define structures of transition states for selected reactions employing chiral metal catalysts. The calculated transition states will be used to generate force fields that will be applied to the in silico screening of chiral catalyst libraries to predict enantioselectivity of new or previously known catalysts in advance of their preparation and experimental validation. Molecular biology in the form of directed evolution will be employed for developing complementary peptide-based catalysts. The combination of these capabilities in the three program laboratories is unique and brings powerful new tools to bear on catalyst development. The specific IRES student projects interface well with research programs at Notre Dame and will be of interest to Ph.D. students having dissertation projects in synthetic organic chemistry, inorganic chemistry, organometallic chemistry, analytical chemistry, materials science, biochemistry, and molecular biology. The participating students will gain experience with advanced computational and experimental methods for small-molecule and polypeptide-based catalyst development. The students will present their research in an international setting, and write reports and manuscripts for publication in scientific journals. Upon returning to the Notre Dame, the participating students will be encouraged to apply their newly gained knowledge towards their dissertation research projects and, with their dissertation directors, to maintain collaborations with their Swedish mentors to pursue further aspects of their IRES projects. The collective IRES experience will prepare the participants for careers in an increasingly competitive technological world in which scientists are expected to have multiple skills and to succeed in an international setting. Moreover, students will be personally enriched from immersion in a different scientific and societal culture. In the national interest, the research outcomes of this IRES project, namely development of new enantioselective catalysts, can be translated into improved production of pharmaceuticals, agricultural agents, and chemical tools for use in biochemistry and molecular biology. These areas are long-standing strengths of the U.S., applicable to large-scale manufacturing of products for both domestic use and export. Retention of these strengths requires training of students who can contribute their expertise in an increasingly competitive, technologically based, global economy.