Sequence- and stereo-defined macromolecules: Properties and emerging functionalities

Natural macromolecules, such as proteins and nucleic acids, display various complex functionalities in biological systems. These functionalities depend on the macromolecular structure, which is determined by the sequence of monomers as well as stereochemical factors. Over the past decade, synthetic methods have evolved to enable complete control over sequential monomer assembly. The precise control over the primary structure of abiotic macromolecules holds the promise to realize complex functionality, similar to natural biopolymers. One of the key features in biological processes involves chirality. Therefore, stereochemical considerations are a prerequisite for mimicking biological systems using synthetic polymers. Here, the progress made in the field of stereo-controlled, sequence-defined polymers is summarised. The impact of monomer sequence and stereocontrol on the physicochemical properties of polymers and their emerging functions is discussed, which underlines the importance of controlling macromolecular structure with high precision. In addition to describing synthetic methods leading to stereocontrolled and sequence-defined macromolecules, limitations and problems in their fabrication are highlighted. The review also includes examples showing how sequence and stereocontrol affect the thermal properties and degradation of polymers, which are critical in the engineering and application of polymer materials. The secondary and tertiary structures are responsible for the functions of natural polymers; therefore, the ability of abiotic macromolecules to fold and self-assemble is discussed in detail, with an emphasis on systems beyond polyamides related to protein skeletons. Furthermore, examples of functions that have been displayed by abiotic macromolecules of defined sequence and chirality are presented. The review article focuses on discrete macromolecules built based on abiotic backbones, including oligomers. In the concluding section, the collected examples are used to elucidate how monomer arrangement and stereocontrol can bring abiotic polymers to a high level of functionality, as manifested by natural macromolecules.