Precision Polymers by Click Chemistries

Regulating the sequence of building blocks in polymers has been the subject of many recent studies. The ability of controlling the composition of polymer chains in an exact manner has been a challenge for polymer chemists aiming to reach the precision exhibited by Nature in natural macromolecules such as DNA, proteins, peptides etc. Various sophisticated strategies have been established for creating synthetic precision polymers. Recent studies have taken advantage of click chemistry techniques to achieve this goal.

CuAAC Click for Sequence-Controlled Polymers

Researchers at Massachusetts Institute of Technology have reported an iterative exponential growth strategy for sequence-controlled polymers using flow synthesis technique. In the process, a functional monomer was utilized to perform further functionalization and deprotection steps generating suitable functional sites to carry out the copper-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction. Repeating these functionalization, deprotection and finally CuAAC click processes resulted in the exponential growth of polymers reaching molecular weights up to 6000 g mol-1 comprised of 32 monomer units within four cycles. The authors were able to introduce new functionalities in each cycle enabling them to further establish control over the stereochemistry of the polymers. As a result, uniform macromolecules with controlled monomer sequence and stereochemical properties were produced.

Exponential iterative growth
Iterative exponential growth for precision polymers. Nature Publishing Groups.

Read more on this work:

Iterative exponential growth of stereo- and sequence-controlled polymersNature Chemistry2015, 7, 810–815

And also,

Scalable synthesis of sequence-defined, unimolecular macromolecules by Flow-IEGProc. Natl. Acad. Sci. U.S.A., 2015, 112, 10617-10622

 

Thiol Click for Sequence-Controlled Polymers

In a conceptually distinct approach, a group of researchers based at the University of Colorado, Boulder, has introduced a new strategy for sequence-control in polymers utilizing thiol-click reactions, namely thiol-ene and thiol-Michael addition reactions. In their recent work published in the journal Angewandte Chemie, Bowman and co-workers polymerized a series of nucleobase functional monomers using thiol click reactions to form polymers in a sequence-specific manner. The monomers used were structurally analogous to oligonucleotides in DNA and comprised of a thiol and an allyalmine (for thiol-ene click) or a thiol and an acrylamide (for thiol-Michael) functional group. Thiol-ene photopolymerization was used to form nucleobase-containing sequence-controlled homo polymers as well as diblock copolymers. A combination of thiol-ene and thiol-Michael approaches led to more specific and robust strategies in synthesizing DNA-like macromolecules such as organogels with reversible crosslinks and also incorporating a wide range of functional groups in a sequence-controlled manner. 

Sequence control- thiol click
Sequence controlled polymers by thiol click reactions- Image credit: Angewandte Chemie Internationa Edition

Read more on this work:

Clickable Nucleic Acids: Sequence-Controlled Periodic Copolymer/Oligomer Synthesis by Orthogonal Thiol-X ReactionsAngew. Chem. Int. Ed., 2015, 54, 14462-14467