Revealing the effect of stereocontrol on intermolecular interactions between abiotic, sequence-defined polyurethanes and a ligand

The development of precision polymer synthesis has facilitated access to a diverse library of abiotic structures, wherein chiral monomers are positioned at specific locations within macromolecule chains. These structures are anticipated to exhibit folding characteristics similar to biotic macromolecules and possess comparable functionalities. However, the extensive sequence space and numerous variables make selecting a sequence with the desired function challenging. Therefore, revealing sequence-function dependencies and developing practical tools are necessary to analyze their conformation and molecular interactions. In this study, we investigate the effect of stereochemistry, which dictates the spatial location of backbone and pendant groups, on the interaction between sequence-defined oligourethanes and bisphenol A ligands. Various methods are explored to analyze the receptor-like properties of model oligomers and the ligand. The accuracy of molecular dynamics simulations and experimental techniques is assessed to uncover the impact of discrete changes in stereochemical arrangements on the structure of the resulting complexes and their binding strength. Detailed computational investigations providing atomistic details show that the formed complexes demonstrate significant structural diversity depending on the sequence of stereocenters, thus affecting the oligomer-ligand binding strength. Among the tested techniques, the fluorescence spectroscopy data, fitted to the Stern-Volmer equation, are consistently aligned with the calculations, thus validating the developed simulation methodology. The developed methodology opens a way to engineer the structure of sequence-defined oligomers with receptor-like functionality to explore their practical applications, e.g., as sensory materials.