Dynamic control and self-assembly of ortho-phenylene foldamers

Miami University, Oxford OH

Investigators

Abstract

With this award, the Macromolecular, Supramolecular, and Nanochemistry Program in the Division of Chemistry is funding Dr. C. Scott Hartley from Miami University to develop molecules that replicate and ultimately complement the remarkable capabilities of naturally occurring macromolecules. For a very long time, synthetic chemists have struggled to prepare molecules of comparable size and complexity to proteins and nucleic acids. It takes the human body anywhere between 20 seconds to a couple of minutes to make a protein. In contrast, preparing and assembling hundreds of amino acids into a long chain of the same protein would take a chemist days to months, if it is even possible at all. Further, designing new structurally-complex systems based on biochemical building blocks is extremely challenging. This project avoids tedious synthetic paths by taking advantage of the assembly of smaller and more-easily prepared molecules. The results from this award are expected to provide fundamental answers about the nature, dynamics and interactions between structurally complex molecules, which are of relevance to developing artificial systems with similar capabilities to large biological molecules. While the target compounds are not necessarily chemically equivalent to biomacromolecules, their behavior in relevant processes such as folding and recognition is similar. The broader impacts of this work include the development of laboratory modules for introductory organic chemistry courses, undergraduate involvement in research, and participation in a consortium of Ohio universities aimed at supporting underrepresented minority students in the STEM fields. This work is focused on the investigation of the dynamic control and self-assembly of ortho-phenylene foldamers. In developing these foldamers, the capabilities of biomacromolecules, such as molecular recognition, catalysis, and responsive behavior (molecular "machinery"), can potentially be replicated, providing access to complex processes through simple and non-tedious molecular design. Several studies are carried out in order to achieve this goal, involving the development of fluorinated o-phenylenes, controlling dynamic systems with switchable twist and long-range conformational communication, and structure-property effects for the assembly of twisted macrocycles. The use of fluorine nuclear magnetic resonance spectroscopy is particularly interesting because this technique is simple and yet offers an impactful method for elucidating the folding behavior of these ortho-phenylene systems. Conceptually, this work is expected to provide fundamental answers in the context of the foldamer field, conformational dynamics, and the synthesis of complex structures. 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.