A Novel Class of Sequence-Defined Polymers: Design, Synthesis and Applications

Sequence control is a crucial parameter for tuning the structure, property, and function of synthetic macromolecules. However, achieving precise control of monomer sequence with fast reaction kinetics has been the key hurdle. Herein, I will demonstrate an effort to circumvent this difficulty via a de novo approach for the synthesis of a novel class of sequence-defined polymers, named as oligothioetheramides (oligoTEAs). The oligoTEAs look like the biopolymers in our body, but are instead created with synthetic molecules designed in the lab. This unique approach is based on the strategic design of ‘allyl acrylamide monomer’ with orthogonal reactive sites and a liquid-phase fluorous support. Key strengths of our approach include fast solution kinetics, step-wise characterization via common spectroscopic techniques, and a large structural diversity due to the ease of monomer synthesis.

By creating these synthetic polymers from the bottom up in an iterative and controlled manner, we can precisely tune their size, composition and properties. We further advanced our synthetic strategy by designing monomers that can afford oligoTEA macrocycles via a one-pot acid catalyzed cascade reaction. With an eye towards biological applications, various bioactive side chains were introduced into the primary sequence. The effects of these side chain and backbone groups on the chemical properties and biological function will be discussed.