Multicomponent Reactions in Polymer Science

The rapid development of science and technology has brought urgent demand for diversity in polymer structures and functionalities, and the pursuit of new polymerizations and new polymer structures is the constant goal in polymer chemistry. Multicomponent reactions (MCRs)—reactions of three or more starting materials able to generate a single product in a one-pot manner—feature a series of advantages such as simple reactants, easy operation, mild conditions, high efficiency, environmental benefit, and, most importantly, the great diversity of product structures. Since the first report of the Strecker synthesis of amino acids from a three-component reaction of aldehydes, hydrogen cyanide, and amines in 1850,[1] a large number of MCRs have been reported including the Mannich reaction, Passerini reaction, Ugi reaction, Biginelli reaction, Hantzsch reaction, Kabachnik–Fields reaction, Debus–Radziszewski reaction, and many more. MCRs have been gradually developed into powerful tools to efficiently construct libraries of compounds with structural diversity, and have found applications in organic synthesis, combinational chemistry, and the pharmaceutical industry.[2] Attracted by the opportunity what MCRs could bring to polymer science, considerable efforts have been made to utilize MCRs in polymer synthesis, despite of the challenges including preparation of bi-/multi-functional monomers, polymerization specificity, polymer solubility, and control of molecular weight. During the past decade, some pioneering works have been reported and great progress has been made to construct polymers efficiently and economically through multicomponent polymerizations (MCPs) or post-polymerization modification via MCRs. In early contributions, Meier and co-workers reported the synthesis of polyesters with amide moieties in their side chain via a combination of Passerini reaction and olefin metathesis,[3] Li and co-workers utilized the Passerini reaction to prepare sequence-controlled poly(ester-amide) in a one-pot process,[4] Tang and co-workers developed an A3-coupling polymerization of alkynes, aldehydes, and amines,[5] Choi and co-workers developed a Cu(I)-catalyzed MCP of alkynes, sulfonyl azides, and amines,[6] Endo and co-workers prepared poly(thiourethane-phenylenevinylenesulfide)s by the MCP of alkynes, amines, and dithiocarbonates through a combination of chemoselective nucleophilic and radical additions,[7] Theato and co-workers reported the preparation of poly(N-sulfonylamidine) derivatives via post-polymerization modification with MCR of terminal alkynes, sulfonyl azide, and amine,[8] and Du Prez and co-workers reported the one-pot double modification of poly(N-isopropyl acrylamide) through the ring-opening reaction of thiolactone by primary amine and the subsequent Michael addition of the generated thiol groups to an acrylate.[9] Later, a large number of multicomponent polymerizations have been developed, and a series of MCRs have been used in the post-modification of polymers. Compared with classic polymerizations, besides those benefits inherent to the nature of MCRs, MCPs also feature a series of unique advantages, such as great diversity of polymer structure and functionality, facile tuning of the polymer backbone and topological structures, strong designability of polymerization procedures and conditions. There are a few recent reviews summarizing the advances in this field with the emphasis on topics including isocyanide-based MCPs,[10] alkyne-based MCPs,[11] alkyne and sulfonyl azide-based MCPs,[12] the Biginelli reaction,[13] the Hantzsch reaction,[14] and the Debus-Radziszewski reaction applied to polymer synthesis,[15] as well as MCPs for the synthesis of sulfur-containing polymers.[16] With the rapid development of MCPs or MCRs involving polymer synthesis and modification, while it is impossible to include all ongoing progress in this prosperous field, this special issue in Macromolecular Rapid Communications introduces the state-of-art of this area with representative examples, describing new advances and aiming to provide an inspiring source for future work. Thankfully, many polymer synthetic experts have made great effort to complete their work and succeed to contribute to this special issue despite the challenging situation caused by the Covid-19 pandemic. This special issue is composed of eleven research articles and eight overview articles, covering most of the important aspects in the area. The most extensively investigated MCRs in polymer synthesis are the Passerini three-component reaction and the Ugi four-component reaction. Take the Passerini reaction of a carboxylic acid, an isocyanide, and an oxo-component (aldehyde or ketone) for example, it has been exploited for the synthesis of monomers, multifunctional RAFT agents, star-shaped unimolecular micelles, and linear polymers.[10] Based on this and other classic MCRs, progresses have been made to synthesize functional polymers. For example, Meier, Alexander, and co-workers further exploited the versatility of the Passerini reaction for the synthesis of amphiphilic diblock copolymers, which could be self-assembled into polymersomes to serve as versatile drug carriers and encapsulate both hydrophobic molecules within the bilayer and hydrophilic molecules in the aqueous core (2000321). Koyama and co-workers utilized the Ugi four-center three-component reaction of aldehydes/ketones, alkyl ammonium salt, and an ambident molecule comprising isocyanide and potassium carboxylate to synthesize highly viscoelastic polypeptides with elastin-mimetic amino acid sequence (2000480), and these alternating peptides exhibited excellent adhesive properties, including high adhesive strength, unique re-adhesion capacity, and shear-induced adhesion. In Tao and co-workers’ review (2000515), they summarized the recent progress on the application of amino acid-based Ugi reaction for the preparation of polypeptoids and sequence-defined polypeptoids. In Tao and co-worker's review (2000459), four strategies of applying Hantzsch reaction in polymer synthesis, including a monomer-to-polymer strategy, polycondensation, polymer post-modification, and a one-pot strategy, for protein conjugation, formaldehyde detection, drug carrier, and anti-bacterial adhesion are summarized. Sui and co-workers also utilized the Hantzsch reaction for the fabrication of fluorescent cellulosic materials through the surface acetoacetylation of cotton fabrics, followed by the Hantzsch reaction of the obtained acetoacetyl-bearing fabrics with formaldehyde and ammonium acetate in water under ambient temperature (2000496). Polymer chemists have also made great effort to introduce new MCRs for polymer synthesis, with the emphasis on the design of new monomers, new reactions, new catalysts, new product structures and functionalities. Of all the potential monomers, alkynes possess rich chemistry and with their various MCRs, the alkyne-based MCPs have been developed into powerful tools for the construction of a great diversity of polymer structures that cannot be accessed from other synthetic methods. For example, in Han, Lam, Tang, and co-worker's review (2000386), alkyne-based MCPs for the construction of heterochain polymers including trivalent Group 15 elements-containing polymers, chalcogen-containing polymers, polymers containing both Group 15 and 16 elements, and halogen-containing polymers are summarized. Most of the alkyne-based MCPs are currently conducted with transition-metal catalysts, and a recent trend is to develop metal-free polymerization conditions by structural and reaction design of activated alkyne monomers. For example, Hu, Tang, and co-workers have designed carboxylic acid group-activated alkyne monomers and developed a catalyst-free four-component polymerization of propiolic acids, benzylamines, organoboronic acids, and formaldehyde under mild condition, affording poly(propargylamine)s with high yields and high molecular weights, good solubility and processibility, high thermal stability and light refractivity, and unique photophysical properties (2000633). Through the ester group-activated alkyne monomers, a catalyst-free multicomponent cyclopolymerization of activated alkynes, diisocyanides, and 1,4-dibromo-2,3-butanedione is also described by Shi, Dong, and co-workers (2000463), to prepare iminofuran-containing polymers with high molecular weights, high yields, good solubility and thermal stability. Natural reagents such as O2, H2O, CO2, and S8 can also serve as abundant, nontoxic, economic, environmentally friendly, and sustainable monomers in MCPs and be incorporated as building blocks of the polymer products. Qin, Tang, and co-worker's review (2000547) summarizes the recent development of MCPs using O2, H2O, or CO2 as one of the monomers. The catalytic systems, polymerization conditions, as well as chemical and topological structural engineering of polymer products are also discussed. Yan and co-workers utilized a three-component reaction of triarylborane, triarylphosphine, and CO2 to develop a double-cross-linked polymer gel based on frustrated Lewis pair network, which is composed of permanent chemical crosslinks and dynamic CO2 gas-bridged connections, and possesses CO2-dependent mechanical reinforcement and self-healing ability (2000699). In Mutlu, Theato, and co-worker's research article, elemental sulfur, as a waste product from modern oil and gas refineries, is adopted as the monomer of a sulfur-based polycondensation with diketone molecules in the presence of aniline and a strong Brønsted acid to produce polythiophenes (2000695). Other compounds with high reactivity and rich chemical property are also developed as monomers of MCPs. For example, Meldrum's acid with a six-membered heterocycle, two symmetric ester groups, and highly active methylene group is susceptible to electrophilic attack and nucleophilic attack. Zhang, You, Hong, and co-workers have hence developed a three-component polymerization of Meldrum's acid, dialdehyde, and diindole using proline as a catalyst, affording polymers with complex and well-defined structures. This reaction is also proved to be a powerful tool for post-polymerization modification to efficiently introduce two different functional groups by one-step modification (2000610). The unique advantages of MCPs enable the construction of new polymer structures in terms of elemental composition, backbone conjugation, and topological structures. In Tuten and Barner-Kowollik's review (2000495), the recent progress of MCPs with Group 13-16 elements involved in both monomer and polymer product structures are summarized. By the incorporation of the less traditional main group elements such as boron, phosphorous, sulfur, or selenium into polymer structures, unique properties that are not readily achieved with only C, N, and/or O elements can be obtained. The product of MCPs has also recently extended from non-conjugated structures to conjugated structures. In Dong and co-worker's feature article (2000646), MCPs that provide efficient syntheses of structurally complex π-conjugated polymers are summarized and classified into three categories: linear or branched module approaches, where all monomers are incorporated into π-conjugated backbones in a linear or branched fashion, respectively, and a transformative module approach that non-aromatic units in multiple monomers can be converted into aromatic moieties in the polymer backbones. Moreover, the variation of topological structures of polymer products from different monomer combinations is another unique advantage of MCPs. For example, Meier and co-workers reported the efficient synthesis of monodisperse star-shaped block co-macromolecules through an iterative synthesis cycle of a Passerini three-component reaction and reductive hydrogenolysis, followed by post-modification with monodisperse octaethylene glycol monomethyl ether, and subsequent coupling to a core scaffold (2000467). Calvo, Wagener, Sumerlin, and co-workers have prepared hyperbranched aminobisphosphonic acid polymers via reversible addition-fragmentation chain transfer self-condensing vinyl polymerization of an acrylamide-functional chain transfer monomer, followed by the introduction of the aminobisphosphonate functional group through a three-component Kabachnick-Fields reaction (2000578). The functionalities and applications of products from MCPs are also actively explored. For instance, Song and co-workers developed a catalyst-free MCP of dithiol, formaldehyde, and secondary diamine to prepare water-soluble polycations with tertiary amines as cationic segments to bind DNA, thioether to scavenge reactive oxygen species and reduce the toxicity, as well as hydroxyl group to shield the positive charges, improve the efficiency, and reduce the toxicity, in order to serve as promising nonviral gene delivery vectors with excellent gene transfection efficiency and relatively low cytotoxicity (2000464). In Han, Tang, and co-worker's feature article (2000471), the utilization of one-step MCPs for the construction of polymers with aggregation-induced emission (AIE) feature by adopting AIEgen-containing monomers or in situ generation of AIEgen from the MCP are summarized, and the applications of these AIE-active polymer products, such as stimuli-responsive materials, fluorescent chemosensors, and bioapplications, are introduced. Liu, Zhang, Wei, and co-worker's review introduced the latest advances about using MCRs, such as the Kabachnik-Fields reaction, Biginelli reaction, MALI reaction, Debus-Radziszewski reaction, and Mannich reaction to prepare multifunctional fluorescent polymers for biomedical applications or adsorptive polymeric composites for environmental applications (2000563). Multicomponent polymerizations and multicomponent reaction involving polymer synthesis have been demonstrated to be a very powerful tool for the construction of functional polymers with diversified structures and advanced functionalities, which have become a prosperous branch of polymer chemistry. It is anticipated that this special issue could inspire polymer chemists and material scientists for their future work and accelerate the development of polymer synthetic methodology as well as functional polymer materials. Michael A. R. Meier (Mike) studied chemistry in Regensburg (Germany) and received his Ph.D. degree from the Eindhoven University of Technology (The Netherlands) in 2006. After further stays in Emden and Potsdam, he was appointed as full professor at the Karlsruhe institute of Technology (KIT) in 2010. He received several awards and is associate editor of ACS Sustainable Chemistry & Engineering. His research interests include the sustainable use and derivatization of renewable resources for polymer chemistry as well as the design of novel highly defined macromolecular architectures, often achieved by the development of novel multicomponent reaction approaches for polymer chemistry. Rongrong Hu received her B.S. degree from Peking University in 2007 and Ph.D. degree from the Hong Kong University of Science and Technology (HKUST) in 2011. She conducted her research associate study at HKUST during 2012–2014. She joined the Stake Key Laboratory of Luminescent Materials and Devices in South China University of Technology in 2014 and was promoted to professor in 2016. She is associate editor of Polymer Chemistry. Her current research interests are focused on the development of multicomponent polymerizations and sulfur-containing functional polymers. Ben Zhong Tang received his Ph.D. degree from Kyoto University in 1988, and then conducted his postdoctoral work at University of Toronto during 1989–1994. He joined the Department of Chemistry of The Hong Kong University of Science and Technology (HKUST) in 1994 and was promoted to chair professor in 2008. He is currently the Stephen K. C. Cheong Professor of Science, Chair Professor of Chemistry, Chair Professor of Chemical and Biological Engineering at HKUST. He was elected to Chinese Academy of Sciences (CAS), Royal Society of Chemistry (RSC), Asia Pacific Academy of Materials (APAM), The World Academy of Sciences for the Advancement of Science in Developing Countries (TWAS), and International Union of Societies for Biomaterials Science and Engineering (IUSBSE). He is now serving as Editor-in-Chief of Aggregate. His research interests include materials science, macromolecular chemistry, and biomedical theranostics.