In this International Collaboration in Chemistry (ICC) project supported by the Chemical Structure, Dynamics and Mechanisms Program of the Division of Chemistry, Professor Steve Scheiner and his research group at Utah State University will conduct quantum mechanical calculations to explore the influence of C-H--O hydrogen bonding on the secondary structure of low molecular weight unnatural foldamers. The research group of the collaborating partner, Professor Martin Smith of Oxford University will synthesize the same foldamer species studied theoretically by the Scheiner group, and characterize their structure and conformations using nuclear magnetic resonance spectroscopy (NMR). The United Kingdom funding agency, the Engineering and Physical Sciences Research Council (EPSRC), will support the work of the Professor Smith. The collaborative interactions of the Scheiner and Smith groups will enable an iterative cycle of synthesis and computation, whose goal is the deconvolution of the non-covalent interactions that direct conformational ordering. Initial efforts will focus on amino acids containing alpha-fluoro and aryl triflouromethyl functional groups. The computational component will utilize natural bond orbital (NBO) and atoms in molecules (AIM) treatments.
This project has the potential to make a significant impact across a number of disparate fields in both organic and theoretical chemistry. This collaboration will represent the union of these two fields in the belief that a fundamental understanding of hydrogen-bonding, and the ability to manipulate this phenomenon as a tool is essential in the design of catalysts with enzyme-like reactivity and selectivity. The international collaboration will provide an excellent opportunity for the exchange and transfer of knowledge between synthetic and theoretical groups, providing valuable education and training opportunities for the postdoctoral researchers involved in the project. The computer equipment to be acquired for Utah State will be made available to graduate and undergraduate students enrolled in an introductory computational chemistry course developed by Prof. Scheiner. In addition, teachers from local high schools and faculty and students from Weber State University (a primarily undergraduate institution), will be enlisted to participate in this project during summers, providing both groups some experience with PhD level research.
Hydrogen bonds (HBs) are one of the most important sorts of interactions between molecules. They are responsible for the transmission of genetic information, and for the proper functioning of enzymes and other proteins. It was commonly thought that only certain atoms (O, N, F) could engage in HBs, but it has become increasingly apparent that C may function in this way as well. It was the goal of this project to examine the properties of CH??O HBs, to see how they compare with conventional HBs, and more importantly, how CH??O HBs can influence the structure of proteins. This was to be done by a combination of experimental and computational work. The results have first confirmed the ability of CH??O HBs to alter the geometry of related molecules. Their presence was confirmed in a variety of different settings. Their influence affected the structure adopted by molecules that model proteins, and the interactions between the peptide groups that are characteristic of proteins. They are responsible in some measure for the zipping up of β-sheets, another prominent substructure within proteins. Ionic CH??O HBs were found to be particularly strong, and are important contributors to the binding of certain proteins and the substrates on which they act. In terms of broader impacts, the outcomes had significance for broad swaths of chemistry and biochemistry, experimental and computational. There are impacts on foldamer design and asymmetric catalysis, and there are implications for design and synthesis of new materials with valuable catalytic properties. The work also led to a tigher connection between the computational group at Utah State University, and experimental research groups at Oxford University and the University of Michigan. As such, it provided excellent cross-fertilization for the exchange and transfer of knowledge between synthetic and theoretical groups, providing valuable education and training opportunities for the student researchers involved in the project.
