Long, multifunctional sequence-defined oligomers were obtained on solid support from a protecting-group-free two-step iterative protocol, based on the inherent reactivity of a readily available molecule containing an isocyanate and a thiolactone. Aminolysis of the latter entity with an amino alcohol liberates a thiol that reacts with an acrylate or acrylamide, present in the same medium. Subsequently, a new thiolactone can be reinstated by means of an α-isocyanato-γ-thiolactone. Different acrylic compounds were used to incorporate diverse functionalities in the oligomers, which were built up to the level of decamers. The reaction conditions were closely monitored in order to fine-tune the applied strategy as well as facilitate the translation to an automated protocol.

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.

During the previous decade, many popular chemical reactions used in the area of "click" chemistry and similarly efficient "click-inspired" reactions have been applied for the design of sequence-defined and, more generally, sequence-controlled structures. This combination of topics has already made quite a significant impact on scientific research to date and has enabled the synthesis of highly functionalized and complex oligomeric and polymeric structures, which offer the prospect of many exciting further developments and applications in the near future. This minireview highlights the fruitful combination of these two topics for the preparation of sequence-controlled oligomeric and macromolecular structures and showcases the vast number of publications in this field within a relatively short span of time. It is divided into three sections according to the click-(inspired) reaction that has been applied: copper-catalyzed azide-alkyne cycloaddition, thiol-X, and related thiolactone-based reactions, and finally Diels-Alder-chemistry-based routes are outlined, respectively.

A thiolactone derivative of 10-undecenoic acid was used as a renewable AB′ monomer for the one-pot synthesis of diversely substituted polyamide structures, containing amide moieties both in the polymer backbones and in their side chains. Nucleophilic aminolysis of the thiolactone entity liberates a thiol, which further reacts in a stepwise thiol–ene photopolymerization reaction. Using different primary amines, several structurally diverse polyamides, with physical properties dependent on the length and chemical identity of the side chain, were obtained. Postpolymerization oxidation of the sulfide linkages in the polymer backbone to their corresponding sulfoxides and sulfones altered the material, with the degree of oxidation having an impact on the final mechanical properties. Furthermore, this mild and straightforward polymerization procedure was applied for the synthesis of functional polymer networks.

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.

Comprehensive two-dimensional liquid chromatography (LC × LC) allows for substantial gains in theoretical peak capacity in the field of liquid chromatography. However, in practice, theoretical performance is rarely achieved due to a combination of undersampling, orthogonality, and refocusing issues prevalent in many LC × LC applications. This is intricately linked to the column dimensions, flow rates, and mobile-phase compositions used, where, in many cases, incompatible or strong solvents are introduced in the second-dimension (D) column, leading to peak broadening and the need for more complex interfacing approaches. In this contribution, the combination of temperature-responsive (TR) and reversed-phase (RP) LC is demonstrated, which, due to the purely aqueous mobile phase used in TRLC, allows for complete and more generic refocusing of organic solutes prior to the second-dimension RP separation using a conventional 10-port valve interface. Thus far, this was only possible when combining other purely aqueous modes such as ion exchange or gel filtration chromatography with RPLC, techniques which are limited to the analysis of charged or high MW solutes, respectively. This novel TRLC × RPLC combination relaxes undersampling constraints and complete refocusing and therefore offers novel possibilities in the field of LC × LC including temperature modulation. The concept is illustrated through the TRLC × RPLC analysis of mixtures of neutral organic solutes.

A straightforward synthetic procedure for the double modification and polymer-polymer conjugation of telechelic polymers is performed through amine-thiol-ene conjugation. Thiolactone end-functionalized polymers are prepared via two different methods, through controlled radical polymerization of a thiolactone-containing initiator, or by modification of available end-functionalized polymers. Next, these different linear polymers are treated with a variety of amine/acrylate-combinations in a one-pot procedure, creating a library of tailored end-functionalized polymers. End group conversions are monitored via SEC, NMR, and MALDI-TOF analysis, confirming the quantitative modification after each step. Finally, this strategy is applied for the synthesis of block copolymers via polymer-polymer conjugation and the successful outcome is analyzed via LCxSEC measurements.

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 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.