Letter Cite This: ACS Macro Lett. 2017, 6, 1337-1341
pubs.acs.org/macroletters
Coenzyme-Catalyzed Electro-RAFT Polymerization Wei Sang,‡ Miaomiao Xu,‡ and Qiang Yan* State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China S Supporting Information *
ABSTRACT: Here we report an electrochemically switchable reversible addition− fragmentation chain transfer polymerization (eRAFT). A new family of biochemical coenzymes are discovered that can be used as highly efficient electroredox catalysts to mediate this polymerization. The oxidation of coenzyme, nicotinamide adenine dinucleotide (NADH), can promote the reduction of a chain transfer agent, triggering generation and propagation of polymer radicals. External potential can activate the reduction of the NAD+ oxidized state and pause the propagation. Tuning the applied potential to reversibly switch the catalyst between its reduced and oxidized states can toggle the polymerization between ON and OFF states. This new strategy is universal to a broad scope of monomers, and ppm-level coenzymes result in the desirable polymer structures with targeted molecular weight, dispersity, and excellent chain-end fidelity. We envisage that the bioorganic-based catalysts would open new directions of organocatalyzed electro-controlled polymerization and be of value in electrocatalysis for well-structured polymers. Scheme 1. (a) Previous Metal-Catalyzed eATRP Polymerization Mechanism and (b) Proposed CoenzymeCatalyzed Electro-Controlled RAFT Polymerization Mechanism Using NAD+ Coenzyme as Electroredox Catalyst
E
lectrochemistry as a classic technology with long history has reemerged, offering a powerful, sustainable, and atomeconomic method for redox transformation of molecules.1,2 It manifests vast potential in a range of research fields, particularly in organic synthesis and polymer science,3−6 because it allows us to manipulate the chemical reaction process in a remote, switchable, and programmed manner. Exploiting electrochemistry to synthesize polymers has been known for over a century;2,7 however, it has been rarely applied to construct polymers in a controlled and switchable fashion. A seminal work in this respect was derived from Matyjaszewski and co-workers, who have reported electrochemically mediated atom transfer radical polymerization (eATRP).8,9 This approach relies on metal catalyst as the redox-active center to transfer electrons by electrochemical stimuli for activating and deactivating the radical species (Scheme 1a).8 Reversible addition−fragmentation chain transfer (RAFT) is the other most used controlled radical polymerization.10 Recently, great efforts have been devoted to realizing external stimuli-regulated RAFT processes11 by using light,12−14 temperature,15 and even mechanic forces;16 however, RAFT polymerization controlled by electrochemistry has been rare.17 An important problem in developing electrochemically mediated RAFT polymerization is to seek suitable redox catalysts that can reversibly transfer electrons to generate the polymer radicals. Recently, photoredox catalysts (e.g., iridium, phenazine, and metalloporphyrins) have attracted great attention.12−14 Their triplet states excited by irradiation possess high reducing power (E0* < −2 V vs SCE), easily inducing the chain transfer agents (CTA) to form active radicals. However, the photochemical dyes are difficult to apply in an electro© XXXX American Chemical Society
catalyzed system since they are unable to form the triplet states under electrochemical stimuli. To address this challenge, we turn to focus on a large family of intracellular redox molecules, called coenzymes.18 Coenzymes can be considered as nonprotein “helper compounds” that play crucial roles in Received: November 10, 2017 Accepted: November 14, 2017
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DOI: 10.1021/acsmacrolett.7b00886 ACS Macro Lett. 2017, 6, 1337−1341
Letter
ACS Macro Letters biochemical transformations.18 In general, they have electroswitchable redox states featuring mild redox ability and rapid electron transfer, which is highly desired for electrocatalyzed polymerization. For example, nicotinamide adenine dinucleotide (NAD+) is one of the most pivotal and ubiquitous coenzymes in cells, which can mediate many biochemical transformations via a reversible eletroredox process (NAD+ + H+ + e− ↔ NADH).19,20 Taking inspiration from the nature of coenzymes and emulating their redox pathways, we postulated that using NAD+ as an electroredox catalyst could invoke polymerization. Our design is coupling this electro-switchable catalyst to a RAFT process. In the presence of mild reducing potential, NAD+ can be reduced to NADH, and the latter reacts with the chain transfer agents to yield a polymer radical for chain propagation. Reversibly, changing the external potential to oxidize the NADH to the initial NAD+ species, the ongoing polymerization could be cessation. Regulating the potential to change the redox form of the catalyst between NADH and NAD+ can toggle the RAFT polymerization between the “ON” and “OFF” state (Scheme 1b). This is a universal strategy applicable to various monomers. We envisaged that this new electro-RAFT strategy would enrich the repertoire of electrochemically mediated radical polymerization, and the coenzyme catalysts would open up a new avenue to organic electrocatalysis. To test our idea, the polymerization of methyl methacrylate (MMA) was performed by using 4-cyano-4-(phenyl- carbonothioylthio) pentanoic acid (termed as CPAD) as a typical CTA and NAD+ as a catalyst. For precise regulation of the redox states of reactants, we used cyclic voltammetry (CV) to determine the half-wave potential of catalyst and CTA. The reduction potential of the NAD+/NADH pair was E = −0.54 V (vs Ag+/Ag), close to the reported result,21 while the redox potential of CPAD (E = −0.4 V vs Ag+/Ag) was higher than that of NAD+ (Figure S1).22 This allows NADH to reduce CPAD with a concomitant electron transfer to form a radical. To convert deactivated NAD+ to activated NADH species, we provided a −0.65 V of reducing potential. Encouragingly, preliminary experiments employing 4000 ppm catalyst did afford polymer; however, the reaction was incontrollable, with an Mw/Mn of 2.74 (Table 1, entry 1). The main reason was that the reduced NADH is highly active, leading to the production of a high concentration of radicals in the electrode. We found that remarkably decreasing the catalyst loading to initial 1/10 (400 ppm) obtained well-defined polymer with narrow dispersion of 1.32 (Table 1, entry 2). Further optimization showed that the lowest content of the catalyst to maintain this polymerization was 40 ppm (Table 1, entries 3−7). To confirm the proposed mechanism, control experiments proceeded in the absence of the catalyst or potential, but neither afforded the polymer (Table 1, entries 9 and 10). This means that both coenzyme and electrochemical stimulus are necessary for this electrochemically controlled polymerization. Investigating the polymerization kinetics under the optimized conditions (E = −0.65 V, 40 ppm catalyst) revealed that this polymerization had a short induction period (∼3 min) followed by a rapid monomer consumption, finally reaching over 90% conversion within 6 h (Figure 1a, green circle). The numberaverage molecular weight (Mn) correlated linearly with the conversion (Figure 1b, green circle) and coincided well with the theoretical values (Figure 1b, dash line). The Mw/Mn value tended to decrease from 1.37 to 1.08 as the reaction progressed (Figure 1b, green open circle). These findings satisfied the
Table 1. Electro-Controlled RAFT Polymerization of MMA Using NAD+ Redox Catalyst
entry [NADI+]a(ppm) 1 2 3 4 5 6 7 8d 9e
4000 400 40 40 40 40 40 0 40
time (h)
conv. (%)
Mn,GPCb (kg/mol)
Mn,thc (kg/mol)
Mw/Mn
6 4 6 4 2.5 1.5 1.0 4 4
82 80 85 76 39 30 25 0 0
49.1 42.3 43.1 39.4 23.8 17.6 13.9 0 0
41.2 40.2 42.6 38.5 19.7 15.4 12.8 -
2.74 1.32 1.07 1.09 1.13 1.21 1.27 -
a Reaction conditions: [MMA]/[CPAD]/[NAD+] = 500/1/0.002−0.2 in acetonitrile (0.2 mL/mmol of MMA). bCharacterized by GPC in THE using standard PMMA for calibration. cCalculated on the basis of Mn,th = McPAD + 500 × conversion × MMMA. dThe reaction was run in the absence of NAID+. eThe reaction was run in the absence of applied potential.
Figure 1. (a) Monomer conversion plotted versus reaction time and (b) number-average molecular weight (Mn) and Mw/Mn with respect to conversion as a function of applied potential. Polymerizations were conducted in acetonitrile and [MMA]:[CPAD]:[NAD + ] = 500:1:0.002.
characteristics of living chain growth. To further regulate the rate of electro-controlled RAFT, we intended to fluctuate the potential over a range of 100 mV. A reaction acceleration was observed at a more negative potential (E = −0.75 V), whereas a more positive potential (E = −0.55 V) caused a slower rate (Figure 1a, red and blue circle). Evaluating the slopes of these kinetic curves, the rate of polymerization had a 2.6-fold increase by adjusting the potential from −0.55 V to −0.75 V (Figure S2). Moreover, the features of living polymerization were kept regardless of external potential alteration (Figure 1b). Next, we targeted to probe the feasibility of electrocontrolled polymerization through modulating the redox states of NAD+ in situ. For this, we examined the electrochemical conversion mechanism of the NAD + /NADH pair by fluorescent spectroscopy. In the absence of stimulus, the monomer with NAD+ showed no fluorescence (excitation wavelength is fixed at 390 nm); in contrast, upon addition of a reducing potential (−0.65 V), a fluorescence at 447 nm ascribed to the characteristic emission of NADH appeared and enhanced gradually, which indicated the in situ generation of NADH species.23 Shifting the potential from −0.65 V to −0.40 V to inhibit the reduction of NAD+, the fluorescence was silent again, corresponding to a reversible regeneration of NAD+ form (Figure S3). With this result in hand, we applied an intermittent potential (E = −0.65 V/−0.40 V) to the system 1338
DOI: 10.1021/acsmacrolett.7b00886 ACS Macro Lett. 2017, 6, 1337−1341
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ACS Macro Letters
goal: tuning the applied potential to convert the catalyst between reduced NADH form and oxidized NAD+ form provides a possible method for temporal control of the polymer chain propagation between the active and dormant state. We desired that this electrochemically mediated RAFT method was applicable to a broad range of monomers, especially those monomers that are intractable in classical RAFT formulation, such as vinyl acetate (VAc) and acrylonitrile (AN).24−26 First we chose five types of monomers to represent the usual “more-activated” monomer (MAM) families: styrene (St, representing styrene-based monomers), nbutyl methacrylate (n-BMA, representing methacrylate monomers), acrylic acid (AA, representing acidic monomers), N,Ndimethyl acrylamide (DMA, representing acrylamide monomers), and 2-hydroxypropyl methacrylate (HPMA, representing monomers with active group). Using CPAD as the CTA, electrochemical polymerizations showed good living control over these five types of monomers (Table 2, entries 1−15). The polymerizations for most of the monomers attained over 90% monomer conversions within 6 h and favorable dispersities (Mw/Mn < 1.30). However, for the case of St, the conversion can only reach moderate levels (400 ppm) and improving the reducing potential (20 000 g/mol for AN) can be successfully obtained (Table 2, entries 20−25). To further validate the advantages of coenzymecatalyzed electro-controlled RAFT polymerization, a panel of control experiments were designed and carried out using the CuIIBr2 metal-catalyst system in eATRP protocol. However, it only allowed the polymerization of St and n-BMA monomers, but for other monomers (DMA, HPMA, AA, VAc, and AN) the reactions failed (Figure S5). From these, it can be drawn that our strategy can settle the functional group tolerance and manifest better chemical versatility. Finally, we wanted to survey the chain-end fidelity of this polymerization method. To this end, we attempted to synthesize a block copolymer by the sequential electro-RAFT process. To our best knowledge, the synthesis of PAA-b-PVAc diblock copolymer via a single polymerization has been an arduous task because the RAFT method makes it hard to copolymerize the less activated and more activated monomers.27 A compromising way was using click chemistry or reaction mechanism transformations.28−30 However, these involved tedious synthesis and multiple steps. For this, we adopted our electro-controlled RAFT route to overcome this dilemma. Utilizing standard conditions (40 ppm catalyst and −0.65 V) with CPBD as the CTA, the PAA block can be first afforded with Mn,PAA = 1.4 kg/mol (conversion: 85%, Figure 3a,
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsmacrolett.7b00886. Experimental procedures for synthesis of all polymer samples and supporting characterization data (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Qiang Yan: 0000-0001-5523-2659 Author Contributions ‡
W.S. and M.X. contributed equally.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (21674022 and 51703034) and Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences.
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Figure 3. (a) Electro-RAFT synthetic route and GPC traces of PAA and PAA-b-PVAc diblock copolymer. (b) Self-assembly structure of PAA-b-PVAc diblock copolymers.
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