Applications of Discrete Synthetic Macromolecules in Life and Materials Science: Recent and Future Trends

Abstract

In the last decade, the field of sequence-defined polymers and related ultraprecise, monodisperse synthetic macromolecules has grown exponentially. In the early stage, mainly articles or reviews dedicated to the development of synthetic routes toward their preparation have been published. Nowadays, those synthetic methodologies, combined with the elucidation of the structure-property relationships, allow envisioning many promising applications. Consequently, in the past 3 years, application-oriented papers based on discrete synthetic macromolecules emerged. Hence, material science applications such as macromolecular data storage and encryption, self-assembly of discrete structures and foldamers have been the object of many fascinating studies. Moreover, in the area of life sciences, such structures have also been the focus of numerous research studies. Here, it is aimed to highlight these recent applications and to give the reader a critical overview of the future trends in this area of research.

Keywords: data storage; discrete macromolecules; sequence defined polymers; structure–property relationships.

Figure 1

A schematic representation of the applications discussed within this review.

Figure 2

Encoding the information of a QR code into a set of 71 different uniform macromolecules by using an automated amine‐thiolactone‐ene protocol. Adapted under the terms of the CC BY 4.0 license^{.[ 58 ]} Copyright 2018, The Authors, published by Springer Nature.

Figure 3

Sequencing of sequence‐defined oligourethanes (3) through a self‐immolative process (depicted with green arrows) combined with LC–MS traces at given intervals. Adapted with permission.^{[ 73 ]} Copyright 2020, American Chemical Society.

Figure 4

Discrete ABA‐type block copolymer with ethylene glycol and (l)‐lactic acid blocks studied by Meijer and co‐workers formed a transparent gel in water. Introduction of chain length variation (Đ = 1.2) in the (l)‐lactic acid block inhibited the self‐assembly and led to solubility under the same conditions. Adapted with permission.^{[ 9 ]} Copyright 2018, American Chemical Society.

Figure 5

Duplex assembly process between two hetero‐oligomers bearing a complementary sequence of interacting groups. Adapted with permission.^{[ 129 ]} Copyright 2017, American Chemical Society.

Figure 6

a) Structure of m‐terphenyl–diacetylene oligomers bearing amidine (A) and carboxylic acids (C) moieties that form saltbridges. Adapted with permission.^{[ 130 ]} Copyright 2008, American Chemical Society. b) Structure of duplex‐forming phenylacetylene oligomers with phenol as hydrogen bond donor and phosphine oxide as hydrogen bond acceptor. Adapted with permission.^{[ 131 ]} Copyright 2018, American Chemical Society.

Figure 7

a) Backbone structure of duplex‐forming tetramers containing hydrogen bond donors (D) and acceptors (A). b) Different acceptor and donor pairs with the association constant for the tetrameric duplexes. Adapted with permission.^{[ 132} , ^{134 ]} Copyright 2016, The Royal Society of Chemistry.

Figure 8

a) Structure of a hydrogen bonded duplex formed with two sequence‐complementary oligomers in an antiparallel orientation. b) Calculated populations of the duplexes formed in toluene when all oligomers are mixed in equimolar ratios. Adapted with permission.^{[ 138 ]} Copyright 2017, The American Chemical Society.

Figure 9

a) Structure of amine‐ and aldehyde‐bearing homo‐oligomers and scheme of the duplex formation. Reproduced with permission.^{[ 140 ]} Copyright 2015, The American Chemical Society. b) (Top) Sequence‐selective duplex formation of several pairs of complementary oligomers using the dissociation/extraction/annealing process. (Bottom) matrix assisted laser desorption ionization ‐ time of flight (MALDI) mass spectra of individual encoded molecular ladders assembled via the dissociation/extraction/annealing process, including 10 101 × 0 1010 (bottom, black), 00 111 × 11 000 (second from bottom, red), 11 111 × 00 000 (middle, blue), and a single‐pot solution of all six oligomers to yield three in‐registry molecular ladders (second from top, green). A single‐pot solution of the six oligomers after the single‐step, deprotection and direct assembly process (top, black) is shown for comparison. Reproduced with permission.^{[ 142 ]} Copyright 2020, Springer Nature.

Figure 10

An overview of different architectural motives that are often observed for foldamers; a single helix (left), double helix (middle), and β‐sheets (right).

Figure 11

a) Catalysis of a crossed‐aldol reaction involving two aldehydes by two pyrrolidine moieties cooperatively working together. The catalytic groups are positioned together in space through the folding of β‐ or α/β‐peptides. Adapted with permission.^{[ 202 ]} Copyright 2020, The American Chemical Society. b) The catalyzed cross‐aldol reaction of a bisaldehyde moiety results in the formation of a macrocycle due to the decreased entropic cost. Reproduced with permission.^{[ 205 ]} Copyright 2019, AAAS.

Figure 12

A representative glycomacromolecule. Adapted with permission.^{[ 231 ]} Copyright 2020, Wiley‐VCH. Typically, examples in the literature employ various chain lengths, different number of carbohydrates or topologies. Additional control can be obtained with different carbohydrate units (green circle), different spacers between binding units (blue box), or different functional blocks tolerating a range of chemistries for carbohydrate conjugation to the backbone, etc. (gray box).

Figure 13

Synthesis of oligoTEA's using allyl acrylamide building blocks and different dithiols. Adapted with permission.^{[ 260 ]} Copyright 2017, The American Chemical Society.

Figure 14

Example of an oligo(thiophene)s structure with primary amine moieties A) and inert B) spacer unit, studied by Palermo and co‐workers.^{[ 267 ]}