Fluorescent Cell-Conjugation by a Multifunctional Polymer: A New Application of the Hantzsch Reaction

Abstract

Multicomponent reactions (MCRs) can form unique structures with interesting functions, therefore, multifunctional polymers might be simply prepared using MCRs as coupling tools to simultaneously link and generate different functional groups. To verify this concept, a new fluorescent polymer containing phenylboronic acid has been facilely prepared via a one pot method by combining the Hantzsch reaction with reversible addition−fragmentation chain transfer (RAFT) polymerization. The Hantzsch-RAFT system has been found robust to smoothly achieve predesigned multifunctional polymer, which can be used for cell conjugation through the interaction between phenylboronic acid and glycoprotein on cell membrane. The conjugated cells could be directly observed due to the fluorescent Hantzsch moiety in the polymer chain, demonstrating a new application of the old Hantzsch reaction (>130 years) outside organic chemistry. Meanwhile, the conjugated cells remained excellent dispersity in the presence of coagulation protein (lectin), implying that multifunctional polymer a possible anticoagulant for cell separation. We believe that the current research paves a new way to exploit new applications of MCRs in interdisciplinary fields and might prompt the development of other multifunctional polymers based on different MCRs.

Similarity and Competition between Biginelli and Hantzsch Reactions: an Opportunity for Modern Medicinal Chemistry

“…Since then, it entered the global market and went on to become the second most sold drug from Bayer in the1980s. [23] Besides their classical applications in medicinal chemistry, the 1,4-DHPs have been recently proposed as antioxidant agents in food and biological systems, [24] monomers of multifunctional fluorescent polymers, [25] and H-transfer agents in the redox and photoredox organic synthesis. [26,27] The Hantzsch reaction was announced in 1882 by Arthur Hantzsch as a one pot, four-component reaction (4CR) between ammonia, aromatic aldehyde and two molecules of -keto ester, without the intervention of any other reagents (Scheme 1).…”

Using One Photoredox Catalyst to Simultaneously Mediate Two Different Polymerizations for Photo‐Triggered Multi‐Component Orthogonal Polymerizations

“…Because multiple components are able to react in one‐step to high‐efficiently generate predictable architectures and functionalities under mild reaction conditions. [ 1–8 ] Noteworthy, the key for successful MCRs is to seek highly efficient “click reaction” (Passerini reaction, [ 9 ] Ugi reaction, [ 10,11 ] Biginelli reaction, [ 12,13 ] and Kabachnik‐Fields reaction [ 14 ] ) that can be carried out in one‐step and one‐pot without the generation of side products. Therefore, MCRs also exhibit unique click properties as the typical Cu(I)‐catalyzed azide‐alkyne cycloaddition (CuAAC) reaction, [ 15–17 ] such as high atom economy and simple procedure.…”

The Hantzsch Reaction in Polymer Chemistry: From Synthetic Methods to Applications

“…In 2011, pioneering research by Meier and coworkers led to the use of natural products as starting materials for the preparation of polycondensates through the tri‐component Passerini reaction. [ 7 ] Afterward, many MCRs, such as the Passerini, [ 8 ] Biginelli, [ 9 ] Kabachnik‐Fields (KF), [ 10 ] Ugi, [ 11 ] and Hantzsch reactions, [ 12 ] as well as alkyne‐based [ 13 ] and metal catalyzed MCRs, [ 14 ] have been used to develop novel functional polymers. After around 10‐years of development, preparation of functional polymers via MCRs has become a vibrant new branch of polymer chemistry; MCRs have been recognized as a power tool for enriching the functionality, properties, topology, and diversity of polymers.…”

“…These polymeric FA probes are found to be biocompatible for the in vivo experiments; an optimized polymeric FA probe was found to be successful in the detection of endogenous FA in zebrafish via the Hantzcsh reaction ( Figure ). [ 12b ] For the blank larvae's internals, a weak fluorescence signal was observed (Figure 8a). After incubating the larvae with methanol (MeOH, source compound of FA) and FA fluorescent probe (P1), clear fluorescent signals were observed in the head and tail of larvae (Figure 8b).…”

“…prepared a monomer (M1) containing the fluorescent phenylboronic acid (PBA) via Hantzsch reaction, and used this monomer to prepare a water‐soluble copolymer (P1) containing both the PBA and fluorescent 1,4‐DHP groups ( Figure a). [ 12e ] Effective linking of curcumin with P1 due to the dynamic covalent bonding between the PBA group in P1 and the 1,3‐diketone group in curcumin led to dramatic improvement of the water solubility of curcumin. The curcumin–P1 conjugate is stable under neutral conditions (pH = 7.4) while decomposing quickly under acidic condition (pH = 5.5) (Figure 9b).…”