Radical polymerization by a supramolecular catalyst: cyclodextrin with a RAFT reagent

Radical polymerization by a supramolecular catalyst: cyclodextrin with a RAFT reagent Kohei Koyanagi1, Yoshinori Takashima1, Takashi Nakamura1,§, Hiroyasu Yamaguchi1 and Akira Harada*1,2 Full Research Paper Address: 1Department of Macromolecular Science, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan and 2JST-ImPACT, Chiyoda-ku, Tokyo 100-8914, Japan Email: Akira Harada* - * Corresponding author § Current affiliation: Faculty of Pure and Applied Sciences, University of Tsukuba. Keywords: cyclodextrin; radical polymerization; RAFT polymerization; substrate recognition site; supramolecular catalyst Open Access Beilstein J. Org. Chem. 2016, 12, 2495–2502. doi:10.3762/bjoc.12.244 Received: 26 August 2016 Accepted: 08 November 2016 Published: 22 November 2016 This article is part of the Thematic Series "Superstructures with cyclodextrins: Chemistry and applications IV". Guest Editor: G. Wenz © 2016 Koyanagi et al.; licensee Beilstein-Institut. License and terms: see end of document. Abstract Supramolecular catalysts have received a great deal of attention because they improve the selectivity and efficiency of reactions. Catalysts with host molecules exhibit specific reaction properties and recognize substrates via host–guest interactions. Here, we examined radical polymerization reactions with a chain transfer agent (CTA) that has α-cyclodextrin (α-CD) as a host molecule (α-CD-CTA). Prior to the polymerization of N,N-dimethylacrylamide (DMA), we investigated the complex formation of α-CD with DMA. Single X-ray analysis demonstrated that α-CD includes DMA inside its cavity. When DMA was polymerized in the presence of α-CD-CTA using 2,2'-azobis[2-(2-imidazolin-2-yl)propane dihydrochloride (VA-044) as an initiator in an aqueous solution, poly(DMA) was obtained in good yield and with narrow molecular weight distribution. In contrast, the polymerization of DMA without α-CD-CTA produced more widely distributed polymers. In the presence of 1,6-hexanediol (C6 diol) which works as a competitive molecule by being included in the α-CD cavity, the reaction yield was lower than that without C6 diol. Introduction The folding of proteins in biological systems, the replication of DNA, and specific substrate recognition by enzymes play important roles in forming supramolecular structures, achieving functions, and maintaining life [1-6]. The crystal structures of RNA polymerase, DNA polymerase, and λ-exonuclease demon- strate that the cylindrical cavities of enzymes can effectively recognize substrates to produce biological polymers [1-6]. Cyclodextrins (CDs) have been widely used as substrate-recognition moieties in artificial enzymes [7-15], which have been used in the hydrolysis of activated esters [16-19] and as phase- 2495 Beilstein J. Org. Chem. 2016, 12, 2495–2502. transfer catalysts [20-28]. Moreover, via complex formation, modern supramolecular catalysts [29-33] have been used to achieve various highly efficient and selective reactions, including hydrolysis reactions [10-15], C–H bond activation [34-36], olefin epoxidation [37-39], Diels–Alder reactions [40-42], 1,3dipole cycloadditions [43,44], and polymerizations [45-47], among others. Selective substrate recognition and activation are essential functions of supramolecular catalysts. CD derivatives are widely used in radical polymerization to dissolve hydrophobic monomers in aqueous solutions [48-54] and to control the aggregation of polymers [55-58]. Although supramolecular catalysts with CDs as monomer recognition sites and catalytic active sites have been designed for polymerization reactions, relatively few reports have described a catalytic design in which the catalytic active site does not leave the CD monomer recognition site during the growing step. In a previous design of radical initiators with CDs, the radical-initiating end group leaves the CD monomer recognition site [59,60]. With this molecular design, an included monomer is distant from the radical species and cannot be involved in the direct polymerization. Here, we will observe the effect of monomer recognition of CD on polymerization if a supramolecular polymerization catalyst capable of inserting the monomer between the active and binding sites can be designed. Based on this concept, we have reported that CDs can include and activate lactones to yield a polymer with a single CD at the end of the polymer chain [61-64]. Subsequently, we reported ring-opening metathesis polymerization involving the use of a Ru complex with a CD-derived monophosphine ligand [47]. In the design of the supramolecular polymerization catalysts, monomers are inserted between the initiating end group and the growing polymer chain. In this study, the monomer recognition site is introduced to a reversible addition–fragmentation chain transfer (RAFT) polymerization system [65-69]. We have synthesized a chain transfer agent (CTA) bearing the CD moiety (CD-CTA) and have investigated this agent’s polymerization behavior. The polymerization rate constant decreased with the addition of competitive molecules, indicating that complexation between CD-CTA and the monomer plays an important role in determining polymerization rate. Results and Discussion Preparation of α-CD-CTA We designed a CTA reagent with α-CD or β-CD. Figure 1 illustrates the preparation of α-CD-CTA. Mercaptopropionic acid was reacted with benzyl bromide, K3PO4, and carbon bisulfide (CS2) in acetone to afford a trithiocarbonyl derivative, a CTA with a carboxylic acid (CTA-COOH). α-CD-CTA was prepared in 50% yield by the reaction of CTA-COOH and 3-NH2α-CD with N,N'-dicyclohexylcarbodiimide (DCC)/1-hydroxybenzotriazole (HOBt) in DMF. The α-CD-CTA was purified using reverse-phase chromatography. β-CD-CTA was prepared using the same method as α-CD-CTA in 45% yield (see Supporting Information File 1). α-CD-CTA and β-CD-CTA can be dissolved in water. However, the solubility of β-CD-CTA in water was significantly low, leading to the formation of precipitates. β-CD-CTA forms a self-inclusion complex or a supramolecular dimer complex, which was characterized using 2D ROESY NMR (Supporting Information File 1, Figure S4). Figure 1: Preparation scheme of α-CD-CTA. 2496 Beilstein J. Org. Chem. 2016, 12, 2495–2502. We focused on the polymerization activity of α-CD-CTA because the β-CD cavity of β-CD-CTA was capped by the CTA unit, inhibiting the molecular recognition property. Crystal structure of the α-CD-DMA and β-CDDMA complexes We chose N,N-dimethylacrylamide (DMA), acrylic acid (AA), and acrylamide (AAm) as water-soluble vinyl monomers for radical polymerization. Prior to studying the polymerization of vinyl monomers, we investigated the complex formation of CDs with vinyl monomers. When mixing α-CD and DMA, we obtained single crystals suitable for X-ray crystallography analysis. The X-ray crystallography analysis is important to understand the complex in the condensed phase. Figure 2a shows (...truncated)