Traditional polymers are usually consist of one repeating unit or several repeating units, arranged in random sequences. Sequence-controlled polymers are composed of different repeating units, which are arranged in an ordered manner. In order to control the sequence, various kinds of synthetic methodologies are developed.
Sequence-controlled biological polymerization DNA, RNA and proteins are most common sequence-controlled polymers in living creatures. Inspired by them, polymerization methods, utilizing DNA or RNA as templates to control sequences of polymer, are developed. At first, taking DNA or RNA as templates, scientists developed a series of
peptide nucleic acid (PNA)-based polymers, without using DNA
polymerases. But this method is limited to polymerization scale and yield. By employing enzymes, the yields and scales are greatly increased, but the specificity of
enzymes towards natural peptides limits this technique to a certain degree. Nowadays, more attention is paid to utilization of ribosomes to directly mimic the transcription and translation process. This technology called
protein engineering is considered as the most promising biological polymerization method for synthesis of sequence-controlled polymers.
Sequence-controlled chemical polymerizations Other than biological polymerization methods, scientists have also developed numerous chemical synthetic methods for sequence-controlled polymers. Compared with biological polymerization, chemical polymerization can provide better diversity but most of the chemical methods cannot offer the efficiency and specificity of biological methods. which can be removed under base and acid environment respectively to participate into next-round chain elongation.
Sequence-controlled radical polymerization Radical polymerization is one of the most commonly used polymerization methods. About 50% of commercially available polymers are synthesized via radical polymerization. However, the disadvantages of this method are apparent that sequences and polymeric features cannot be well modulated. To overcome these constraints, scientists optimized the employed protocols. The first reported example was the time-controlled sequential addition of highly-reactive N-substituted
maleimides in the
atom transfer radical polymerization of
styrene, which led to programmed sequences of functional monomers. The development of single-molecule addition into
atom-transfer radical polymerization (ATRP), which enhances the sequence control of radical polymerization was also reported. Other solutions include the use of intermediate purification steps to isolate the desired oligomer sequence in between subsequent
reversible addition−fragmentation chain-transfer polymerization (RAFT-polymerizations). Both flash column chromatography and recycling size exclusion chromatography have been proven successful in this regard. RAFT single unit monomer insertion (SUMI) is recently developed as an emerging technology for precise control of monomer sequence.
Sequence controlled non-radical polymerization For the intrinsic shortages of radical polymerization for sequence-controlled polymers, other non-radical polymerizations are also developed. Within those non-radical methods, azide-alkyne cycloaddition (also known as click reaction),
olefin metathesis among others are utilized to construct sequence-controlled polymers. Depending on these specific chemical reactions, monomers are accurately added to the polymer chain and a well-ordered chain is accomplished stepwise. Meanwhile, by applying multiple chemical reactions, chemists have also developed multi-component reactions to accelerate the construction of polymer skeletons and also enhance variety. Beyond the aforementioned, there was a research group developing a molecule machine, which successfully achieve a sequence-controlled polymerization of
oligopeptides. == Methodology towards improving sequence control ==