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

Article abstract of DOI:10.3762/bjoc.12.244

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.

Full text of DOI:10.3762/bjoc.12.244

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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
Open Access
Address:
Beilstein J. Org. Chem. 2016, 12, 2495–2502.
1Department of Macromolecular Science, Graduate School of
Science, Osaka University, Toyonaka, Osaka 560-0043, Japan and
2JST-ImPACT, Chiyoda-ku, Tokyo 100-8914, Japan
doi:10.3762/bjoc.12.244
Received: 26 August 2016
Accepted: 08 November 2016
Published: 22 November 2016
Email:
Akira Harada* - harada@chem.sci.osaka-u.ac.jp
This article is part of the Thematic Series "Superstructures with
cyclodextrins: Chemistry and applications IV".
* Corresponding author
§ Current affiliation: Faculty of Pure and Applied Sciences, University
of Tsukuba.
Guest Editor: G. Wenz
Keywords:
© 2016 Koyanagi et al.; licensee Beilstein-Institut.
License and terms: see end of document.
cyclodextrin; radical polymerization; RAFT polymerization; substrate
recognition site; supramolecular catalyst
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 ex-
amined 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 pres-
ence 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 strate that the cylindrical cavities of enzymes can effectively
DNA, and specific substrate recognition by enzymes play im- recognize substrates to produce biological polymers [1-6].
portant roles in forming supramolecular structures, achieving Cyclodextrins (CDs) have been widely used as substrate-recog-
functions, and maintaining life [1-6]. The crystal structures of nition moieties in artificial enzymes [7-15], which have been
RNA polymerase, DNA polymerase, and λ-exonuclease demon- used in the hydrolysis of activated esters [16-19] and as phase-
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Beilstein J. Org. Chem. 2016, 12, 2495–2502.
transfer catalysts [20-28]. Moreover, via complex formation, between the initiating end group and the growing polymer
modern supramolecular catalysts [29-33] have been used to chain.
achieve various highly efficient and selective reactions, includ-
ing hydrolysis reactions [10-15], C–H bond activation [34-36], In this study, the monomer recognition site is introduced to a re-
olefin epoxidation [37-39], Diels–Alder reactions [40-42], 1,3- versible addition–fragmentation chain transfer (RAFT) poly-
dipole cycloadditions [43,44], and polymerizations [45-47], merization system [65-69]. We have synthesized a chain
among others. Selective substrate recognition and activation are transfer agent (CTA) bearing the CD moiety (CD-CTA) and
essential functions of supramolecular catalysts.
have investigated this agent’s polymerization behavior. The po-
lymerization rate constant decreased with the addition of
CD derivatives are widely used in radical polymerization to competitive molecules, indicating that complexation between
dissolve hydrophobic monomers in aqueous solutions [48-54] CD-CTA and the monomer plays an important role in deter-
and to control the aggregation of polymers [55-58]. Although mining polymerization rate.
supramolecular catalysts with CDs as monomer recognition
Results and Discussion
sites and catalytic active sites have been designed for polymeri-
zation reactions, relatively few reports have described a catalyt- Preparation of α-CD-CTA
ic design in which the catalytic active site does not leave the CD We designed a CTA reagent with α-CD or β-CD. Figure 1 illus-
monomer recognition site during the growing step. In a previous trates the preparation of α-CD-CTA. Mercaptopropionic acid
design of radical initiators with CDs, the radical-initiating end was reacted with benzyl bromide, K3PO4, and carbon bisulfide
group leaves the CD monomer recognition site [59,60]. With (CS2) in acetone to afford a trithiocarbonyl derivative, a CTA
this molecular design, an included monomer is distant from the with a carboxylic acid (CTA-COOH). α-CD-CTA was pre-
radical species and cannot be involved in the direct polymeriza- pared in 50% yield by the reaction of CTA-COOH and 3-NH2-
tion. Here, we will observe the effect of monomer recognition α-CD with N,N'-dicyclohexylcarbodiimide (DCC)/1-hydroxy-
of CD on polymerization if a supramolecular polymerization benzotriazole (HOBt) in DMF. The α-CD-CTA was purified
catalyst capable of inserting the monomer between the active using reverse-phase chromatography. β-CD-CTA was prepared
and binding sites can be designed. Based on this concept, we using the same method as α-CD-CTA in 45% yield (see Sup-
have reported that CDs can include and activate lactones to porting Information File 1). α-CD-CTA and β-CD-CTA can be
yield a polymer with a single CD at the end of the polymer dissolved in water. However, the solubility of β-CD-CTA in
chain [61-64]. Subsequently, we reported ring-opening metathe- water was significantly low, leading to the formation of precipi-
sis polymerization involving the use of a Ru complex with a tates. β-CD-CTA forms a self-inclusion complex or a supramo-
CD-derived monophosphine ligand [47]. In the design of the lecular dimer complex, which was characterized using
supramolecular polymerization catalysts, monomers are inserted 2D ROESY NMR (Supporting Information File 1, Figure S4).
Figure 1: Preparation scheme of α-CD-CTA.
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Beilstein J. Org. Chem. 2016, 12, 2495–2502.
We focused on the polymerization activity of α-CD-CTA dimeric structure in the crystal. Figure S5b shows a schematic
because the β-CD cavity of β-CD-CTA was capped by the CTA diagram of the crystal structure of β-CD/DMA. The stoichiome-
unit, inhibiting the molecular recognition property.
try of β-CD and encapsulated DMA was 2:3. For two of the
DMA molecules, the N,N-dimethylamino and the vinyl groups
were located at the wider and the narrower rims of the β-CD
cavity, respectively. The other one of the DMA molecules was
Crystal structure of the α-CD-DMA and β-CD-
DMA complexes
We chose N,N-dimethylacrylamide (DMA), acrylic acid (AA), packed between the two β-CD molecules in an equatorial plane.
and acrylamide (AAm) as water-soluble vinyl monomers for
radical polymerization. Prior to studying the polymerization of When mixing α-CD and AA in water, we obtained a powder
vinyl monomers, we investigated the complex formation of CDs precipitate of a complex between α-CD and AA, although the
with vinyl monomers. When mixing α-CD and DMA, we ob- crystal structure of α-CD and AA was not solved. The forma-
tained single crystals suitable for X-ray crystallography analy- tion of precipitate implied the formation of a host-guest com-
sis. The X-ray crystallography analysis is important to under- plex between them. A mixture of CDs (α-CD, β-CD and γ-CD)
stand the complex in the condensed phase. Figure 2a shows the and AAm did not result in a precipitate, indicating that the
crystal structure of α-CD with DMA. α-CD formed a head-to- affinities of the CDs for AAm were low.
tail channel structure in the crystal. Figure 2b shows the
Polymerization of vinyl monomers mediated
by α-CD-CTA
schematic diagram of the crystal structure of α-CD/DMA. The
stoichiometry of α-CD and encapsulated DMA was 1:1.
α-CD-CTA-mediated polymerizations of water-soluble vinyl
The N,N-dimethylamino group was located at the wider rim monomers were performed in aqueous media, where the strong
(secondary hydroxy group) of the α-CD cavity and the vinyl molecular recognition property of α-CD is expected due to the
group was pointed toward the opposite direction. Based on the hydrophobic effect. As a water-soluble radical initiator, we
crystal structure, it is speculated that the modification of the selected 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochlo-
wider rim of α-CD with the CTA group would bring the vinyl ride (VA-044). Two hundred equivalents (equiv) of monomers,
group of DMA and reactive radical species close together 1 equiv of α-CD-CTA, and 0.4 equiv of VA-044 were mixed in
during the course of RAFT polymerization.
water (monomer: 1 mol/kg). After the reactants were mixed and
degassed, the sample tube was heated at 45 °C in an Ar atmo-
Figure S5a (Supporting Information File 1) shows the crystal sphere. After 24 hours, the polymer solution was lyophilized.
structure of β-CD with DMA. β-CD formed a head-to-head The resulting polymers were dissolved in 8 mL MeOH or
Figure 2: Crystal structure of α-CD with N,N-dimethylacrylamide (DMA). (a) The structure of an 1:1 inclusion complex between α-CD and DMA. One
of the disordered pattern of DMA is shown. DMA molecules outside the α-CD, hydrogen atoms, and water molecules are omitted for clarity. Colors of
the atoms are based on CPK coloring. DMA, space-filling model; CD, stick model. (b) A schematic diagram of the inclusion complex of α-CD/DMA.
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Beilstein J. Org. Chem. 2016, 12, 2495–2502.
chloroform, then reprecipitated into 80 mL diethyl ether. This the presence of the α-CD-CTA or the competitive C6 diol guest.
cycle repeated twice to remove monomer. The structures of the The polymerization of AAm mediated by α-CD-CTA gave
obtained polymers were characterized by 1H NMR spectrosco- polymers with slightly narrower distributions. From the series
py (Figure S6, Supporting Information File 1). The 1H NMR of experiments, it was demonstrated that the molecular recogni-
signals of the benzyl group and those of the CD moiety of tion property of α-CD-CTA effectively affected the chain
α-CD-CTA were both observed in the obtained polymer, which transfer step.
indicates that both groups did not leave the polymer main chain
Rate and mechanism of α-CD-CTA-medi-
after the radical polymerization and that α-CD-CTA functioned
as a good chain transfer agent. Some end groups are formed ated polymerization
from the VA 044 initiator. We investigated the polymerization rate of DMA mediated by
α-CD-CTA and the effect of the competitive molecule in water.
Table 1 shows results for VA-044-initiated polymerizations of A mixture of DMA (200 equiv), α-CD-CTA (1 equiv), and
DMA, AA and AAm. Polymers’ molecular weights and distri- VA-044 (0.4 equiv) in D2O (0.25 mol/kg) was degassed and
butions were determined by gel permeation chromatography heated at 45 °C in an Ar atmosphere. When a concentration of
(GPC). The polymerization of DMA and AA mediated by 1 mol/kg was used, the polymerization rate was too fast to trace
α-CD-CTA gave polymers with similar molecular weights (12.8 during the initial stages of polymerization. Therefore, we chose
and 14.8 kDa) and narrow distributions in good yields to utilize a concentration of 0.25 mol/kg because this concentra-
(85–88%) (Table 1, entries 2 and 5). In contrast, in the absence tion allowed the polymerization rate to be easily followed. At
of α-CD-CTA, free radical polymerization with VA-044 gave regular time intervals, a 0.6 mL sample was collected and
polymers with higher molecular weights and wider distribu- analyzed using 1H NMR spectroscopy. The conversions were
tions (Table 1, entries 1 and 4). In order to investigate the effect calculated using the ratio between the integral values for
of encapsulation of monomer by α-CD moiety, the reactions in the polymer main chain and the vinyl group of the DMA mono-
the presence of 1,6-hexanediol (C6 diol) as a competitive guest mer.
molecule were also investigated. C6 diol was selected as a non-
ionic molecule with a high association constant to α-CD Figure 3a, b and c shows time-conversion curves, kinetic plots,
(Ka = 134 M−1 ) [70]. In the presence of C6 diol, the reaction and Mn-conversion for the polymerization of DMA mediated by
yields dropped to 63–72%, whereas the molecular weights of α-CD-CTA. The time-conversion plots indicate the induction
the polymers increased (22.9 and 19.4 kDa in entries 3 and 6, period in the presence and absence of C6 diol. Kinetic rates
respectively). It is considered that by inhibiting the molecular were determined using the least-square method after the induc-
recognition of α-CD, the inclusion complexation ratio between tion period. The presence of C6 diol made a clear difference in
the monomer and α-CD-CTA was decreased, which lead to the polymerization rate by α-CD-CTA. The kinetic rate was
lower yields and higher molecular weight of the resulting poly- faster for α-CD-CTA (k = 2.2 h−1) than for α-CD-CTA/C6 diol
mers due to preceding free radical polymerization. In the reac- (k = 1.7 h−1). This finding supports that C6 diol inhibits mono-
tion of AAm monomer, which has a low affinity with α-CD, the mer recognition by the α-CD cavity, which was also indicated
properties of the obtained polymers were similar regardless of by the series of experiments in Table 1.
Table 1: Polymerizations of water-soluble vinyl monomers, mediated by α-CD-CTAa.
Entry
CTAb
Monomerb
Competitorc
Mn / 103 d
Mw / Mnd
Yield%
1
2
–
DMA
DMA
DMA
AA
–
9679
12.8
22.9
45.9
14.8
19.4
3841
10.4
9.9
>10
1.2
1.3
>10
1.2
1.2
>10
1.3
1.4
96
85
63
98
88
72
98
98
99
α-CD-CTA
α-CD-CTA
–
–
3
C6 diol
4
–
5
α-CD-CTA
α-CD-CTA
–
AA
–
C6 diol
–
6
AA
7e
8e
9e
AAm
AAm
AAm
α-CD-CTA
α-CD-CTA
–
C6 diol
aPolymerization was performed at 45 °C for 24 h, with VA-044 as an initiator. b[Monomer]0/[CTA]0/[I]0 = 200/1/0.4 ([Monomer]0 = 1 M).
c[Competitor]0/[CTA]0 = 50/1. dMn and Mw/Mn were determined by GPC using polystyrene sulfonate sodium salt (PSSNa) or polyacrylamide (PAAm)
as references. ePolymerization of AAm was performed in acetate buffer [71,72].
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