Iterative exponential growth of stereo- and sequence-controlled polymers

Abstract

Chemists have long sought sequence-controlled synthetic polymers that mimic nature's biopolymers, but a practical synthetic route that enables absolute control over polymer sequence and structure remains a key challenge. Here, we report an iterative exponential growth plus side-chain functionalization (IEG+) strategy that begins with enantiopure epoxides and facilitates the efficient synthesis of a family of uniform >3 kDa macromolecules of varying sequence and stereoconfiguration that are coupled to produce unimolecular polymers (>6 kDa) with sequences and structures that cannot be obtained using traditional polymerization techniques. Selective side-chain deprotection of three hexadecamers is also demonstrated, which imbues each compound with the ability to dissolve in water. We anticipate that these new macromolecules and the general IEG+ strategy will find broad application as a versatile platform for the scalable synthesis of sequence-controlled polymers.

Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation

“…Further, bulk reactions have been conducted in flow systems based on iterative synthesis33. In addition, iterative exponential growth can lead to sequence-defined macromolecules343536. In parallel, strategies involving the consecutive insertion of single monomer units (vinyl or acrylate) based on radical processes started to emerge for the synthesis of sequence-defined polymers3738.…”

Biosynthetic Polymers as Functional Materials

“…In a recent example by the Johnson group, an iterative exponential growth (IEG)-inspired approach was demonstrated for the economically scalable synthesis of sequence- and stereocontrolled unimolecular polymers. 88 In this IEG plus side chain functionality strategy, 1 R and 1 S epoxy alkynes were either subjected to azide substitution followed by functionalization or to deprotection in order to afford species that were coupled efficiently by CuAAC “click” chemistry, generating four different epoxy–alkyne diastereomers (Figure 3). These “dimers” were then matched appropriately to synthesize macromolecules with the desired tacticity through multiple cycles of azide-instructed epoxide opening, alkyne deprotection, and subsequent CuAAC click conjugation.…”

“…(a) Example of a 32-mer prepared by (b) orthogonal azidification, functionalization and silyl deprotection of two chiral monomers (1 S , 1 R ) followed by CuAAC “click” of key stereoisomeric intermediates to generate polymers with precise sequences and stereochemistry. Adapted with permission from ref (88). …”

The plastics revolution: how chemists are pushing polymers to new limits

“…Last year, a team led by Jeremiah Johnson, a chemist at the Massachusetts Institute of Technology in Cambridge, showed 11 that they could achieve that kind of control through iterative exponential growth -first uniting two different monomers to make a dimer, then connecting two dimers to make a tetramer, and so on. Modifying each monomer's chemical side-chains between cycles adds complexity, and a semi-automated system can make the process less laborious 12 .…”