(413g) Synthesis and Solution-Phase Characterization of Hydroxylated Sulfonated Oligothioetheramides

Nature has long demonstrated the importance of chemical sequence to develop structure and tune physical interactions. By balancing electrostatic charge, length, hydrophobicity, and entropy, many naturally advanced structures (e.g. stem loops, alpha helices) create sensitive stimuli-response, allostery, and signaling. Thus, understanding the strength and balance of these physical forces can lead toward the development of structured macromolecules for biological function. We have recently described the rapid and efficient assembly of sequence-defined oligothioetheramides (oligoTEAs), featuring a tunable abiotic thioether backbone and diverse pendant groups. Structural characterization can now facilitate sequence-structure-function relationships by observing the oligomer chain dynamics and conformation.

In this work, we have systematically characterized linear sulfonated oligoTEAs. To characterize structure, we have developed methodology to describe flexible macromolecules with variable temperature diffusion ordered spectroscopy (VT-DOSY) and electron paramagnetic resonance (EPR) to constrain the Stokes-Einstein-Sutherland (SES) equation. With this characterization, we have examined the contributions of synthetic length (2-12mer), permanently positive and negative charged pendant groups, backbone hydroxylation and hydrophobicity, as well as the use of structured monomers on the resulting oligomer structure. We confirm the strength of entropy and hydrophobicity to create polymer “collapse” as a function of synthetic length and composition, described by increased flexibility and decreased aspect ratio (shape). Our results also suggest that hydrophobicity and entropy can overwhelm intramolecular electrostatic repulsion. While low resolution, this solution-phase characterization appears robust in its ability to describe flexible structures that can jeopardize other techniques, especially at this length-scale. As such, we have begun to apply this structural characterization to develop sequence-structure-function relationships with flexible, but biologically functional materials.