Sequence-defined Macromolecules Research Articles

Monodisperse, sequence-defined macromolecules as a tool to evaluate the limits of ring-closing metathesis

Sequence-defined macromolecules of uniform size unlock the door to many new applications in polymer chemistry, such as structure/property or structure/activity relationship investigations, which cannot be conducted accurately, if the investigated macromolecules exhibit dispersity.

Direct comparison of solution and solid phase synthesis of sequence-defined macromolecules

Sequence-defined macromolecules of high molecular weight are synthesised by the combination of click chemistry with multicomponent reactions. The synthesis is performed on solid phase as well as in solution to directly compare the two approaches.

Multifunctional sequence-defined macromolecules for chemical data storage

Sequence-defined macromolecules consist of a defined chain length (single mass), end-groups, composition and topology and prove promising in application fields such as anti-counterfeiting, biological mimicking and data storage. Here we show the potential use of multifunctional sequence-defined macromolecules as a storage medium. As a proof-of-principle, we describe how short text fragments (human-readable data) and QR codes (machine-readable data) are encoded as a collection of oligomers and how the original data can be reconstructed. The amide-urethane containing oligomers are generated using an automated protecting-group free, two-step iterative protocol based on thiolactone chemistry. Tandem mass spectrometry techniques have been explored to provide detailed analysis of the oligomer sequences. We have developed the generic software tools Chemcoder for encoding/decoding binary data as a collection of multifunctional macromolecules and Chemreader for reconstructing oligomer sequences from mass spectra to automate the process of chemical writing and reading.

Recent Developments in Solid-Phase Strategies towards Synthetic, Sequence-Defined Macromolecules.

Sequence-control in synthetic polymers is an important contemporary research area because it provides the opportunity to create completely novel materials for structure-function studies. This is especially relevant for biomimetic polymers, bioactive and information security materials. The level of control is strongly dependent and inherent upon the polymerization technique utilized. Today, the most established method yielding monodispersity and monomer sequence-definition is solid-phase synthesis. This Focus Review highlights recent advances in solid-phase strategies to access synthetic, sequence-defined macromolecules. Alternatives strategies towards sequence-defined macromolecules are also briefly summarized.

Data storage in sequence-defined macromolecules via multicomponent reactions

Sequence-defined and information coding macromolecules suitable for data storage materials were synthesized via a combination of two multicomponent reactions. Thus, a well-established protocol based on the Passerini reaction was combined for the first time with the Biginelli reaction for monomer synthesis to explore new sequence-defined materials by exploiting the high structural variety of two multicomponent reactions. The information was encoded via the variation of six different components per repeating unit choosing from a list of more than 100 components that can potentially be applied. The structural variety of the oligomers that can achieved using this approach offers an information density of up to 24 bits per repeat unit. The information was read out via tandem mass spectrometry, wherein the predominant fragmentation processes were identified and subsequently applied for reading out the information contained within several macromolecules, i.e. by sequencing and re-establishing the structure of these macromolecules.

Dual Sequence Control of Uniform Macromolecules through Consecutive Single Addition by Selective Passerini Reaction.

The selective Passerini reactions of 4-formylbenzoic acid and 4-isocyanobenzoic acid with aliphatic isocyanides and aldehydes were utilized to synthesize sequence-defined uniform macromolecules. Our strategy does not involve any protecting groups or reactive group transformation steps and allows direct and consecutive propagation of sequence in each step. Introduction of diverse side groups by using different aliphatic components provided a range of sequence-defined uniform macromolecules in high yield and gram scale. The strategy also allows further Passerini self-coupling or cross-coupling of the formed sequences with other small molecules, affording polymers with up to 5098.3 Da and 20 side groups. Thus, this strategy will show promise for more efficient synthesis of new sequence-defined macromolecules.

Combining Two Methods of Sequence Definition in a Convergent Approach: Scalable Synthesis of Highly Defined and Multifunctionalized Macromolecules.

The straightforward convergent synthesis of sequence-defined and multifunctionalized macromolecules is described herein. The first combination of two efficient approaches for the synthesis of sequence-defined macromolecules is reported: thiolactone chemistry and the Passerini three-component reaction (P-3CR). The thiolactone moiety was used as protecting group for the thiol, allowing the synthesis of a library of sequence-defined α,ω-functionalized building blocks. These building blocks were subsequently efficiently coupled to oligomers with carboxylic acid functionalities in a P-3CR. Thus, larger oligomers with molecular weights of up to 4629.73 g mol-1 were obtained in gram quantities in a convergent approach along with the introduction of independently selectable side chains (up to 15), thus clearly demonstrating the high versatility and the efficiency of the reported approach.

Recent Progress in the Design of Monodisperse, Sequence-Defined Macromolecules.

This review describes different synthetic strategies towards sequence-defined, monodisperse macromolecules, which are built up by iterative approaches and lead to linear non-natural polymer structures. The review is divided in three parts: solution phase-, solid phase-, and fluorous- and polymer-tethered approaches. Moreover, synthesis procedures leading to conjugated and non-conjugated macromolecules are considered and discussed in the respective sections. A major focus in the evaluation is the applicability of the different approaches in polymer chemistry. In this context, simple procedures for monomer and oligomer synthesis, overall yields, scalability, purity of the oligomers, and the achievable level of control (side-chains, backbone, stereochemistry) are important benchmarks.

Sequence Control in Polymer Chemistry through the Passerini Three‐Component Reaction

A new strategy to achieve sequence control in polymer chemistry based on the iterative application of the versatile Passerini three-component reaction (P-3CR) in combination with efficient thiol-ene addition reactions is introduced. First, stearic acid was used as a starting substrate to build up a sequence-defined tetramer with a molecular weight of 1.6 kDa. Using an acid-functionalized PEG allowed for an easier isolation of the sequence-defined macromolecules by simple precipitation and led to a sequence-defined pentamer in a block-copolymer architecture. Importantly, this new strategy completely avoids protecting group chemistry. By following this strategy, a different side chain can be introduced to the polymer/oligomer backbone in a simple way and at a defined position within the macromolecule.