Haibo Wu

Multicomponent Combinatorial Polymerization via the Biginelli Reaction

A multicomponent combinatorial polymerization method has been exploited as a new intersection between combinatorial chemistry, polymer chemistry, and organic chemistry. The tricomponent Biginelli reaction has been employed as a model multicomponent reaction (MCR) to efficiently prepare a library of polycondensates with continuously changed chain structure but different physical properties. The naturally increased reaction modules (monomers) directly doubled the number of polymers in the library, effectively improving the efficiency of polymer preparation. The glass transition temperatures (Tg) of those homologous polymers have been mapped for the first time to predict the Tg values of absent polymer homologues with good to excellent accuracy. Meanwhile, the Tg maps have also been used to reveal the regular change in Tg according to the polymer structure (linking group, monomer chain length, etc.), initially suggesting the academic significance of the multicomponent combinatorial polymerization system. We believe that the current research paves a straightforward way to synthesize new libraries of polymers via MCRs and might prompt the broader study of MCRs in interdisciplinary fields.

Polymer synthesis by mimicking nature's strategy: the combination of ultra-fast RAFT and the Biginelli reaction

Inspired by natures two-stage strategy to efficiently synthesize numerous proteins using limited amino acids, a two-stage polymer preparation method has been successfully developed via the combination of ultra-fast RAFT polymerization (stage 1) and post polymerization modification (PPM) through the tricomponent Biginelli reaction (stage 2). Only using 3 monomers, 6 polymer precursors with different main-chain sequences have been quickly prepared in stage 1. In stage 2, by combinatorial synthesis, these 6 polymer precursors underwent the Biginelli reaction in a high-throughput (HTP) manner to rapidly generate 60 derivatives with precisely-controlled structures and various molecular diversities, suggesting the straightforward promotion of polymer synthesis efficiency by learning natures strategy. Furthermore, HTP-analyses have been attempted to quickly screen some distinctively functional polymers, such as the possible polymeric radical scavengers, metal chelating agents, CT imaging agents, etc., realizing the benefit of HTP in polymer chemistry to efficiently synthesize and analyze a large number of samples. We believe that current research opens a new way to effectively prepare and characterize new libraries of polymers with abundant diversity and functions, and might promote a broader study of multicomponent reactions, combinatorial synthesis and HTP technologies in polymer science.

Fluorescent protein-reactive polymers via one-pot combination of the Ugi reaction and RAFT polymerization

By the one-pot combination of the four-component Ugi reaction and RAFT polymerization, multifunctional chain transfer agents (CTAs) containing both protein-reactive groups and trithiolcarbonate could be generated in situ while taking part in the RAFT process. As a result, well-defined polymers containing both fluorescent and protein reactive groups at the chain end were facilely synthesized. Those polymers were successfully used in protein conjugation to create multifunctional protein conjugates by introducing both a synthetic polymer and fluorescent group on the protein surface. Biotin can also be directly used in this system to get a fluorescent biotin polymer for conjugation with avidin, suggesting that this one-pot system may become a general way to prepare different multifunctional polymers for protein modification.

Training the old dog new tricks: the applications of the Biginelli reaction in polymer chemistry

Recently, the Biginelli reaction, one of the most famous multicomponent reactions, has been introduced into the polymer chemistry to highly efficiently synthesize some interesting functional polymers. In this mini-review, several applications of the Biginelli reaction in polymer chemistry have been summarized, including polycondensation, post-polymerization modification, one-pot synthesis of well-defined polymer, etc. Meanwhile, the utilization of the Biginelli reaction in material science and chemical biology, and the future development of the Biginelli reaction in polymer chemistry have also been discussed.

Facile synthesis of a multifunctional copolymer via a concurrent RAFT-enzymatic system for theranostic applications

Facile preparation of well-defined and multifunctional polymers is of great importance for the development of polymer-based drug carriers. By performing enzymatic transacylation during RAFT polymerization, diverse monomers with different functions were generated in situ and simultaneously copolymerized via the RAFT process to form a well-defined multifunctional copolymer precursor which contains fluorine, polyethylene glycol (PEG), benzaldehyde and azido groups. The glucose moiety (which represents a possible targeting group for tumor treatment) was conjugated to this precursor via a copper-catalyzed azide alkyne cycloaddition (CuAAc) reaction to generate the polymer drug carrier. A 19F MRI phantom was performed for the polymer drug carrier, indicating its potential as a possible 19F MRI tracer. The polymer drug carrier has been shown to specifically bind to lectin due to the contained glucose moiety, demonstrating its potential targeting effect. Then, doxorubicin (dox, an anticancer drug) was conjugated with the polymer drug carrier through imine chemistry to generate a target polymer–dox complex. This polymer–dox complex possesses amphiphilic character and self-assembles in aqueous solution into spherical micelles with a size of ∼30 nm, which exhibit much faster release of dox at pH 5.5 than at pH 7.4. Subsequent cell experiments showed that the polymer–dox complex is less toxic than native dox to normal cells while retaining similar cytotoxicity against cancer cells, suggesting that the polymer drug carrier is potentially a safe and effective drug delivery system. We believe that as several reactive moieties can be implanted into the polymer structure in a one-pot manner to achieve a multifunctional polymer precursor for efficient post-modification, this concurrent tandem polymerization (CTP) system might be useful for the development of novel anticancer theranostic nanomedicines.

The Hantzsch reaction in polymer chemistry: synthesis and tentative application

The Hantzsch reaction, one of the oldest and most famous multicomponent reactions (MCRs), has been introduced into polymer chemistry recently as an efficient coupling tool to prepare multifunctional polymers. In this mini-review, we summarized recent results of polymer preparation through the Hantzsch reaction, including polycondensation, post-polymerization modification (PPM), one-pot strategy, etc. Since the Hantzsch products provide unique fluorescence properties to thereof obtained polymers, the primary applications of these multifunctional polymers in bio-related fields have also been discussed.

Multicomponent Reactions for Surface Modification

Modification of material surfaces with polymers is an effective method to develop applicable polymer-material composites. Recently, multicomponent reactions (MCRs) have found their roles in advanced polymer chemistry and applied in surface modification. In this mini review, recent results of MCRs for surface modification are summarized, including the utilization of MCRs as coupling tools to link polymers on material surfaces, and polymers containing multicomponent structures for surface modification. The unique properties of these polymer-material composites stemming from MCRs are introduced, and the preliminary applications of these composites are also discussed.

High Throughput Preparation of UV-Protective Polymers from Essential Oil Extracts via the Biginelli Reaction

A high throughput (HTP) system has been developed to exploit new functional polymers. We synthesized 25 monomers in a mini-HTP manner through the tricomponent Biginelli reaction with high yields. The starting materials were five aldehydes extracted from essential oils. The 25 corresponding polymers were conveniently prepared via mini-HTP radical polymerization initially realizing the benefit of HTP methods to quickly fabricate sample libraries. The distinct radical scavenging ability of these Biginelli polymers was evaluated through a HTP measurement to choose the three best radical scavengers. This confirms the superiority of the HTP strategy to rapidly collect and analyze data. The selected polymers have been upgraded and screened according to different requirements for biomaterials and offer water-soluble and biocompatible copolymers that effectively protect cells from the fatal UV damage. This research is a straightforward way to establish new libraries of monomers with abundant diversity. It offers polymers with interesting functionalities. This suggests that a broader study of multicomponent reactions and HTP methods might be useful in many interdisciplinary fields. To the best of our knowledge, this is the first report of a HTP study of the Biginelli reaction to develop a promising polymeric biomaterial, which might have important implications for the organic chemistry and polymer communities.