Applying Computation to Molecular Hinges

With the support of the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Professor Eric Simanek of Texas Christian University aims to gain a better understanding of the structure-function relationships of molecular hinges. Remarkably, in the world of molecular machines and topologies, hinges are largely unexplored. This research will develop computational models to provide insights into an experimental training set wherein conformation and dynamics of molecular hinges are both understood, measurable and tunable. Broader impacts include 1) informing design of new organic materials, and 2) cross-training of undergraduate and graduate students in both experimental synthetic organic chemistry and computation. The project will commence with 24-atom macrocycles for which a rich experimental data set exists. These molecular door hinges present two flat leaves connected with flexible domains that serve as the hinge pin. This model system is compelling based on ease of synthesis, diversity of targets, and predictable behaviors. These efforts will deliver workflows that yield (1) pKa values, (2) chemical shifts, (3) environment-dependent conformational ensemble sampling, (4) equilibrium position analysis, and (5) the thermodynamics of hinge motion. Furthermore, the energetic bases for quantitative cyclization will be probed. Subsequently, this work will be elaborated to additional ring sizes, ranging from 22-28 atoms. 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.