Self-Accelerating Click Reaction for Cyclic Polymer - Macromolecules

Feb 9, 2017 - The comparative experiment was first performed with copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC) click reaction as intermole...
0 downloads 12 Views 2MB Size
Download PDF
Article pubs.acs.org/Macromolecules

Self-Accelerating Click Reaction for Cyclic Polymer Peng Sun,†,‡ Jiqiang Chen,† Jian’an Liu,† and Ke Zhang*,†,‡ †

State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, The Chinese Academy of Sciences, Beijing 100190, China ‡ University of Chinese Academy of Sciences, Beijing 100049, China S Supporting Information *

ABSTRACT: As the most straightforward synthetic strategy for cyclic polymers in theory, the traditional homodifunctional bimolecular ring-closure methods showed limited success for preparing pure cyclic polymers in practice even after several decades of development. A breakthrough was achieved in this paper to develop a successful homodifunctional bimolecular ring-closure method using a self-accelerating double strain-promoted azide− alkyne click reaction as the intermolecular and subsequent intramolecular coupling reactions. Because of the self-accelerating property of coupling reaction, this novel approach eliminated the usage of equimolar quantities between telechelic polymers and small molecule linkers, which was the prerequisite of traditional homodifunctional bimolecular ring-closure methods for pure cyclic polymers. More importantly, this approach could use an excess amount of small linkers to increase the intermolecular coupling reaction rate, further resulting in a significantly enhanced preparation efficiency of cyclic polymers.

■

INTRODUCTION Polymer topology played an important role in determining its physical properties and applications. Because of the endless molecular topology, cyclic polymers have demonstrated distinctly different physical properties compared to their linear counterparts, such as a smaller radius of gyration and hydrodynamic volume, lower melt viscosity, and higher thermostability.1−10 This endowed the functional materials from cyclic polymers with more advanced properties comparing to those from linear polymers, including the improved fluorescence and redox behavior,11 enhanced thermal stability of the self-assembled micelles,12 and increased gene transfection efficiency and reduced cell toxicity.13 The synthetic methods for cyclic polymers could be divided into two categories: the ringexpansion and ring-closure strategies.2−10 The ring-expansion techniques could produce cyclic polymers with high purity and large molecular weight in concentrated solution.14−21 However, it was usually hard to control the molecular weight and polydispersity of the resultant cyclic polymers.14−21 Alternatively, the ring-closure methods could prepare well-defined cyclic polymers with a medium and small molecular weight.11−13,22−33 In addition to simple monocyclic polymers, the ring-closure strategy could also facilitate to produce cyclic polymer derivatives with complex architectures, such as theta and eight shapes.22,24 Based on the coupling between α,ω-homodifunctional linear polymers and small molecule linkers, the homodifunctional bimolecular ring-closure strategy was the oldest and most straightforward method for preparing cyclic polymers.4,5,8−10 Even after several decades of development, however, most of the current homodifunctional bimolecular ring-closure methods © XXXX American Chemical Society

showed no success for the formation of pure cyclic polymers in practice. In this strategy, the homodifunctional linear polymers first reacted with the small linkers via intermolecular coupling to form the intermediate species, which was then intramolecularly ring-closed to produce the corresponding cyclic polymers. The traditional bimolecular ring-closure methods usually employed the same reactions to perform two-step coupling reactions. In this case, the accurate 1:1 stoichiometry was required between homodifunctional linear polymers and small linkers to guarantee the purity of resultant cyclic polymers, which was hardly achieved in practice considering the polymer molecular weight distribution. Even with 1:1 stoichiometry, it was still hard to produce the pure cyclic polymers since the intermolecular and intramolecular reactions required incompatible reaction concentrations. The efficient intermolecular coupling preferred a higher reaction concentration, but the selective intramolecular cyclization required an ultralow polymer concentration to avoid side reactions among the intermediate species. Two specific techniques have been tried to improve disadvantages of the traditional homodifunctional bimolecular ring-closure strategy. One was the electrostatic self-assembly and covalent fixation (ESA-CF) method,22−27 which used telechelic polymers with cyclic ammonium salt end groups and small linkers of dicarboxylate counteranions as the coupling reagents. In this approach, the electrostatic self-assembly temporarily locked the cationic end groups of telechelic Received: December 5, 2016 Revised: January 15, 2017

A

DOI: 10.1021/acs.macromol.6b02614 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Scheme 1. Preparation of Monocyclic and Multicyclic PS Based on the Combination of ATRP and DSPAAC, Where One Isomer Was Used To Demonstrate the Molecular Structures of Bicyclic and Tricyclic PS, Respectively

byproducts functionalized by linkers at both ends. In this case, the usage of excess linkers could increase the intermolecular coupling reaction rate between polymers and linkers due to the higher concentration of linkers. This increased the formation efficiency of linear intermediate species, further resulting in the enhanced total preparation efficiency of cyclic polymers. Although only two bimolecular ring-closure techniques were developed based on above theory to date, both of them had obvious disadvantages.28−33 The first one focused on the synthesis of cyclic polyethers such as poly(ethylene oxide) (PEO) by the Williamson reaction, in which the homodifunctional polyethers with hydroxyl end groups were cyclized by reacting with dichloromethane in the presence of potassium hydroxide.28−30 Because of the high reactivity of the chloroether intermediates formed from intermolecular coupling, the following intramolecular cyclization could produce cyclic polyethers even with dichloromethane as solvent. Although the cyclization reaction was performed in a highly dilute solution, the intermolecular coupling byproducts with high molecular weight could not be avoided in this approach. The fractional precipitation was required to remove the byproducts for purifying cyclic polyethers. In addition, the requirement of potassium hydroxide also limited this method to prepare varied cyclic polymers containing chemical bonds liable to hydrolysis such as esters or amides. The second method was based on the intramolecular radical trap-assisted atom transfer radical coupling reaction (RTA-ATRC).31−33 In this approach, one end group of the dihalogenated polymer from atom

polymers by anionic dicarboxylate linkers to form cyclic intermediates of ionic complex in dilute solution. The precursor solution was then heated to induce the ring-opening reaction of the cyclic ammonium groups by the carboxylate counterions and produce the covalent cyclic polymers. In the ESA-CF method, the almost 1:1 stoichiometry was ingeniously achieved by electrostatic self-assembly by virtue of the balance of electric charges. In addition, the possible trace amount of linear contaminants could be easily removed by preparative thin-layer chromatography due to their ionic characteristics. Resultantly, the ESA-CF bimolecular ring-closure method has been used to successfully fabricate varied cyclic polymer topology. The other technique employed the self-accelerating reaction to couple the homodifunctional linear polymers and small molecule linkers.28−33 In this approach, the intermolecular coupling reaction between a small linker and one end group of a polymer chain in situ activated the second reactive moiety of the linker. It gained a much larger rate constant to react with the other end group of the polymer chain under dilute solution, facilitating the intramolecular cyclization and the formation of cyclic polymers as well. In contrast to the same reaction used for intermolecular and intramolecular coupling in traditional bimolecular ring-closure methods, the self-accelerating coupling reaction allowed the novel techniques to produce pure cyclic polymers in the presence of an excess amount of small linkers. This was because the accelerated intramolecular cyclization reaction could compensate for the side effects of the presence of excess linkers and avoid the formation of linear polymer B

DOI: 10.1021/acs.macromol.6b02614 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 1. (A) GPC curves of N3-PS23-N3 (black) and the corresponding PS cyclized from CuAAC with PS concentration of 1 × 10−4 M (red). (B) GPC curves of N3-PS23-N3 (black, Mn = 2870 and PDI = 1.06) and the corresponding cyclic PS from DSPAAC with PS concentration of 1 × 10−4 M (red) and 2 × 10−5 M (blue, Mn = 2230 and PDI = 1.06). (C) GPC curves of N3-PS23-N3 (black) and the corresponding PS cyclization results from DSPAAC with alkyne to azide molar ratio of 10/1 at varied reaction time of 24 h (red), 48 h (blue), and 72 h (dark cyan). (D) GPC curves of N3PS23-N3 (black) and the corresponding PS cyclization results from DSPAAC with alkyne to azide molar ratio of 100/1 at varied reaction time of 2 h (red), 4.5 h (blue), and 6 h (dark cyan). THF was used as the eluent, and PS standards were used for the calibration.

■ ■

transfer radical polymerization (ATRP) was activated via ATRC process under dilute solution by a radical trap. It was then efficiently reacted with the radical at the other polymer chain end to cyclize the linear polymer chain. Although the well-defined cyclic polystyrene (PS)31 was prepared from this RTA-ATRC ring-closure method, it indeed showed limited success for the formation of cyclic poly(methyl acrylate)32 and poly(methyl methacrylate).33 A significant amount of intermolecular coupling byproducts with higher molecular weight was obtained in these two cases. In addition, another disadvantage of this method lied in the fact that the cyclization process should be performed under inert gas in the presence of metal catalyst. Recently, a double-strain-promoted azide−alkyne click reaction (DSPAAC) was reported in organic chemistry using sym-dibenzo-1,5-cyclooctadiene-3,7-diyne (DBA) and azides as reagents.34−36 The cycloaddition of the first alkyne with azide increased the DBA ring strain and significantly activated the second alkyne, which reacted with azide much faster than the original DBA alkyne groups. It has been demonstrated that the mono-cycloadduction intermediate was neither isolated nor detected by reacting DBA with less amount of azides. This strongly indicated the self-accelerating reaction property.34,35 Although DSPAAC has been employed in biochemistry for modifying biomolecules,34,36 it has never been employed in polymer chemistry for fabricating polymer topology as far as we know. Herein, we explored this chemistry for the formation of cyclic polymers for the first time. Scheme 1 details the preparation of monocyclic and multicyclic PS exemplified by the combination of ATRP and DSPAAC.

EXPERIMENTAL SECTION

All experimental details are given in the Supporting Information.

RESULTS AND DISCUSSION

Evaluation of Self-Accelerating Double-Strain-Promoted Azide−Alkyne Click Reaction. Although DSPAAC has been used in biochemistry as a self-accelerating reaction, the important factor of rate constant ratio (K = k2/k1) between the second (k2) and first (k1) azide−alkyne cycloaddition reactions has not been estimated to quantify its self-accelerating property. A model reaction was selected using DBA and benzyl azide as reactants to calculate the K value. The detailed reaction scheme and calculation process are shown in the Experimental Section of the Supporting Information and Figures S1 and S2, in which the reaction was conveniently performed at room temperature opening in air. Figure S1E shows the 1H NMR spectrum of the reaction mixture in 7 min, where all of the peak signals could be assigned to the starting materials of DBA (Figure S1A) and benzyl azide (Figure S1B) and the resultant bis-cycloaddition products (Figure S1C,D). In addition, no any other extra peak was observed for the presumed mono-cycloaddition intermediate, which corresponded well with the reported results34,35 and clearly indicated a significantly larger k2 than k1. According to the theory from the literature,37,38 the rate constant ratio K (k2/k1) was determined as 185 for this model reaction based on the time-dependent consumption of DBA from 1H NMR characterization (Figure S2A−C). In addition, the k1 could be further calculated as 5.84 × 10−2 M−1 s−1 (Figure S2D), correlating well with the reported values in the literature.34 C

DOI: 10.1021/acs.macromol.6b02614 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 2. MALDI-TOF MS of N3-PS23-N3 linear precursor (A) and the resultant monocyclic PS (B).

Preparation of Monocyclic Polymers. Since azide endfunctionalized polymers could be conveniently obtained by ATRP, the first example for the preparation of monocyclic polymers was developed by combining ATRP and DSPAAC (Scheme 1). The preparation of linear precursor of homodifunctional PS with azide end groups (N3-PS-N3) was detailed in the Experimental Section of the Supporting Information and Figure S3. In short, the well-defined homodifunctional PS with terminal bromine atoms (Br-PS-Br) was prepared by ATRP with a commercial available 1,4-bis(bromomethyl)benzene as initiator. The N3-PS-N3 was then prepared by substituting the terminal bromine atom of Br-PS-Br with an azide moiety in the presence of sodium azide. Figure 1A (black curve) shows the GPC characterization of N3-PS-N3, in which a monomodal and symmetrical peak shape was observed. The corresponding Mn and PDI were calculated as 2870 and 1.06, respectively. The comparative experiment was first performed with copper(I)-catalyzed alkyne−azide cycloaddition (CuAAC) click reaction as intermolecular and intramolecular coupling reaction, which has been widely used for the formation of cyclic polymers. The same reaction rate constant was achieved between the intermolecular and intramolecular couplings by employing 1,7-octadiyne as small linkers to cyclize N3-PS-N3. Using a molar ratio of 100 between 1,7-octadiyne and N3-PSN3, the CuAAC cyclization reaction was then performed with a PS concentration of 1 × 10−4 M in toluene under N2 at 50 °C for 24 h. The combination of CuBr/PMDETA/ascorbic acid was used as catalyst system. Figure 1A (red curve) shows the GPC characterization of the resultant PS, in which the peak

position kept its original position but the monomodal peak shape became much broader compared to that (black) of N3PS-N3. This clearly indicated that the pure monocyclic PS could not be produced using the same CuAAC reaction for intermolecular and intramolecular coupling in the presence of excess linkers. In addition, the broader peak shape demonstrated that the resultant PS in this case was mostly a mixture of monocyclic PS and telechelic PS terminated by 1,7-octadiyne at both ends. Figure S4A shows the corresponding FT-IR spectrum (red curve) of the resultant PS, in which the characteristic peak of azide completely disappeared at 2100 cm−1 compared to that (black curve) of N3-PS-N3. This indicated a complete consumption of azide groups in the used reaction condition. The self-accelerating DSPAAC was then employed to cyclize N3-PS-N3 by replacing CuAAC. As a contrast, the molar ratio between DBA and N3-PS-N3 and the PS concentration were kept as the same values of 100 and 1 × 10−4 M, respectively. The cyclization reaction was conveniently performed at room temperature in air for 24 h using lower boiling point THF as solvent. Figure 1B (red curve) shows GPC characterization of the resultant PS, in which two peak distributions were observed. The major symmetrical and narrow peak distribution with a content ca. 92% at lower molecular weight direction was contributed by the well-defined monocyclic PS. Compared to that (black curve) of N3-PS-N3 precursor, the peak position of monocyclic PS shifted to lower molecular direction, indicating a smaller hydrodynamic radius of the cyclic polymer topology. The minor broad distribution with a content less than 8% at higher molecular weight direction was from the multiblock PS D

DOI: 10.1021/acs.macromol.6b02614 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 3. (A) 1H NMR spectrum of monocyclic PEO. (B) GPC curves of N3-PEO45-N3 (black, Mn = 3430 and PDI = 1.03) and the resultant monocyclic PEO (red, Mn = 2430 and PDI = 1.03), where THF was used as the eluent and PS standards were used for the calibration.

formation efficiency of linear intermediate species by increasing the intermolecular coupling reaction rate between linkers and polymers. To confirm this, two molar ratios of 10 and 100 were used between DBA and N3-PS-N3 for the formation of monocyclic PS, in which the comparative cyclization reactions were all performed in air at room temperature with a PS concentration of 2 × 10−5 M. Three parallel experiments were performed in each molar ratio group. After the designed reaction time, the ring-closing reactions were stopped separately by concentrating the dilute cyclization solution for further GPC characterization. During the concentrating process, the intermolecular coupling happened among the unreacted linear N3-PS-N3 and produced the multiblock PS due to the increased polymer concentration and self-accelerating property of DSPAAC. In this case, the content ratio of the resultant monocyclic PS and multiblock PS could be used to quantify the cyclization efficiency at different reaction time for the given molar ratio of DBA and N3-PS-N3. Figure 1C shows the GPC characterization of the resultant PS from three parallel experiments with different reaction time using the molar ratio of 10 between DBA and N3-PS-N3, where two peak distributions were observed for all cases. The narrow and symmetrical distribution with lower molecular weight was assigned to the monocyclic PS, since its peak position completely shifted to the lower molecular weight direction compared to that (black curve) of linear N3-PS-N3. The broad distribution with higher molecular weight was ascribed to the multiblock PS formed in concentrating process, whose existence clearly indicated that linear N3-PS-N3 could not be completely cyclized even after 72 h at this condition. The peak area ratio between these two distributions could be used to quantify the cyclization efficiency. With increasing the cyclization time from 24 to 48 h again to 72 h, the cyclization efficiency increased from 64% to 83% again to 92%. Figure 1D shows the GPC characterization of the corresponding PS resulted from three parallel experiments with different reaction time using the molar ratio of 100 between DBA and N3-PS-N3. It indicated the content of monocyclic PS also increased with increasing the reaction time. In addition, the broad distribution of multiblock PS completely disappeared at higher molecular weight direction after only 6 h in this case. Resultantly, the usage of 10 times more DBA significantly increased the efficiency of N3-PS-N3 cyclization, in which the complete cyclization time decreased from more than 72 h to less than 6 h. Inspired by the successful formation of monocyclic PS, the universality of this novel bimolecular ring-closure method has

byproducts formed by intermolecular coupling among N3-PSN3. It could be conveniently removed by decreasing the PS concentration for cyclization. To demonstrate this, the cyclization reaction was then performed with a PS concentration of 2 × 10−5 M while keeping other conditions constant. Figure 1B (blue curve) shows the corresponding GPC characterization. The multiblock PS byproducts almost disappeared at higher molecular weight direction compared to that (red curve) from higher PS concentration. In addition, a monomodal peak shape was obtained completely overlapping with that (red curve) of monocyclic PS from higher PS concentration. The integration of GPC curves produced a similar PDI of 1.06 and a 0.78 times smaller Mn (2230 for monocyclic PS vs 2870 for linear PS) between monocyclic PS (blue curve) and N3-PS-N3 precursor (black curve). Figure S4B shows the corresponding FT-IR spectrum (red curve) of the monocyclic PS, in which the characteristic peak of azide completely disappeared at 2100 cm−1 compared to that (black curve) of N3-PS-N3. This indicated the complete consumption of azide groups in these DSPAAC ring-closing reaction conditions. Figure 2 shows the MALDI-TOF MS of linear N3-PS-N3 (A) and the monocyclic PS (B) from PS concentration of 2 × 10−5 M. As shown in the full spectra (left), the absolute molecular weights were similar for both cases expanding from 2000 to 3750. Compared to the apparent Mn ratio of 0.78 between monocyclic PS and linear N3-PS-N3 from GPC characterization, similar absolute molecular weight indicated a more compact molecular structure for monocyclic PS and confirmed the successful formation of the cyclic topology. From the expanded spectra (right), the peak distribution of linear N3-PS-N3 could be accurately assigned to N3-PS-N3 with elimination of 2N2 ionized with Ag+. For the monocyclic PS, the peak distribution was precisely ascribed to the monocyclic PS ionized with Ag+. A regular m/z interval of ca. 104 was observed between the neighboring peaks in the distribution for both cases, which corresponded to the molar mass of the St monomer unit. As a result, different from traditional bimolecular ring-closure methods having same intermolecular and intramolecular coupling reactions, this novel approach from self-accelerating DSPAAC could conveniently produce well-defined cyclic polymers without requiring accurate 1:1 stoichiometry between homodifunctional linear polymers and small linkers. As a matter of fact, the usage of excess small linkers could significantly improve the preparation efficiency of cyclic polymers. This was because the higher concentration of linkers could enhance the E

DOI: 10.1021/acs.macromol.6b02614 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 4. MALDI-TOF MS of N3-PEO45-N3 linear precursor (A) and the resultant monocyclic PEO (B).

PEO expanded from 2000 to 2800, which was higher than that of linear counterparts expanding from 1800 to 2600. This was reasonable because one DBA molecule was coupled with N3PEO-N3 precursor to form one monocyclic PEO, and the molecular weight of DBA was around 4.5 times more than that of EO monomer unit. From the expanded spectra (right), the peak distribution of the linear N3-PEO-N3 could be accurately assigned to N3-PEO-N3 ionized with Na+. For the monocyclic PEO, the peak distribution was precisely ascribed to the monocyclic PEO ionized with Na+. In addition, a regular m/z interval of ca. 44 was observed between the neighboring peaks in the distribution for both cases, which corresponded to the molar mass of EO monomer unit. Preparation of Multicyclic Polymers. After the successful fabrication of monocyclic polymer topology, the DSPAAC was further explored to prepare multicyclic polymers with advanced cyclic topologies. The fabrication of bicyclic and tricyclic structures was demonstrated as examples (Scheme 1). To perform this, the star PS precursors with 4 and 6 linear arms were prepared bearing azide end groups. Their preparation processes were detailed in the Experimental Section of the Supporting Information and Figures S6 and S7. Using commercially available 1,2,4,5-tetrakis(bromomethyl)benzene and hexakis(bromomethyl)benzene as ATRP initiators, the well-defined star PS was synthesized to have 4 and 6 bromineterminated linear arms. The following substitution of terminal bromine atom by azide moiety produced the corresponding star PS precursors with azide-terminated 4 and 6 linear arms. Figure

been further extended to prepare other monocyclic polymers like monocyclic PEO. The homo-difunctional PEO with azide end groups (N3-PEO-N3) was prepared by end-functionalizing commercial available homo-difunctional PEO with hydroxyl end groups (HO-PEO-OH). The preparation process was detailed in the Experimental Section of the Supporting Information and Figure S5. Using a molar ratio of 100 between DBA and N3-PEO-N3 and a PEO concentration of 2 × 10−5 M in THF, the cyclization reaction was conveniently performed at room temperature in air for 24 h. Figure 3B shows the corresponding GPC characterization, in which the GPC curve (red) of monocyclic PEO preserved the well-defined monomodal and symmetric peak shape, but the peak position completely shifted to lower molecular weight direction compared to that (black curve) of the linear precursor. The integration of GPC curves showed a similar PDI of 1.03 and a 0.71 times smaller Mn (2430 for monocyclic PEO vs 3430 for linear PEO) between monocyclic (red curve) and linear PEO (black curve). This resulted from the characteristic smaller hydrodynamic volume of cyclic polymers than that of linear counterparts, strongly indicating the successful formation of monocyclic PEO. Figure 3A shows the 1H NMR spectrum of the resultant monocyclic PEO, in which the area ratio of 1/2 was obtained between peak a from PEO and peaks b and c from DBA linker. This clearly indicated the quantitative formation of monocyclic PEO. Figure 4 shows the MALDI-TOF mass spectra of linear (A) and monocyclic PEO (B). From the full spectra (left), the absolute molecular weights of the monocyclic F

DOI: 10.1021/acs.macromol.6b02614 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 5. (A) GPC curves of star PS precursors with 4 linear arms (black, Mn = 5000 and PDI = 1.06) and the resultant bicyclic PS (red, Mn = 4300 and PDI = 1.06). (B) GPC curves of star PS precursors with 6 linear arms (black, Mn = 5760 and PDI = 1.05) and the resultant tricyclic PS (red, Mn = 4950 and PDI = 1.05). THF was used as the eluent, and polystyrene standards were used for the calibration.

Figure 6. MALDI-TOF MS of star PS precursors with 4 linear arms (A) and the resultant bicyclic PS (B), where one isomer was used to demonstrate the molecular structures of bicyclic PS.

of tricyclic PS. Figure 5 (red curves) shows the GPC characterization of the resultant bicyclic and tricyclic PS. Compared to those (black curves) of the respective precursors, the well-defined monomodal and symmetric peak shapes were all preserved, but the peak positions completely shifted to lower molecular weight direction for both cases. This was resulted from the characteristic smaller hydrodynamic volume of cyclic polymers than that of linear counterparts, strongly indicating the successful formation of cyclic topologies.

5 (black curves) shows the GPC characterization, in which monomodal and symmetrical peak shapes were observed for both cases. The integration produced Mn = 5000 and PDI = 1.06 for 4-arm star PS precursor and Mn = 5760 and PDI = 1.05 for 6-arm star PS precursor, respectively. The subsequent cyclization reactions were all performed at room temperature in air for 24 h using THF as solvent. The polymer concentration and alkyne to azide molar ratio were used as 2 × 10−6 M and 375 for preparing bicyclic PS, while they were optimized as 1.6 × 10−6 M and 312 for the formation G

DOI: 10.1021/acs.macromol.6b02614 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 7. MALDI-TOF MS of star PS precursors with 6 linear arms (A) and the resultant tricyclic PS (B), where one isomer was used to demonstrate the molecular structures of tricyclic PS.

tricyclic PS, the peak distribution was precisely ascribed to the tricyclic PS ionized with Ag+. In addition, a regular m/z interval of ca. 104 was observed between the neighboring peaks in the distribution for all cases (Figures 6 and 7), which corresponded to the molar mass of St monomer unit. This again clearly indicated the successful fabrication of muticyclic polymer topology based on the combination of ATRP and selfaccelerating DSPAAC.

Figure 6 shows the MALDI-TOF mass spectra of 4-arm star PS precursor (A) and bicyclic PS (B). From the full spectra (left), the absolute molecular weights of the bicyclic PS expanded from 4750 to 7000, which was higher than that of 4arm star PS precursor expanding from 4250 to 6500. This was reasonable because two DBA molecules were coupled with 4arm star PS precursor to form one bicyclic PS, leading to the clearly increased molecular weight. From the expanded spectra (right), the peak distribution of the 4-arm star PS precursor could be accurately assigned to 4-arm star PS with elimination of 4N2 ionized with Ag+. For the bicyclic PS, the peak distribution was precisely ascribed to the bicyclic PS ionized with Ag+. Figure 7 shows the corresponding MALDI-TOF mass spectra of 6-arm star PS precursor (A) and the resultant tricyclic PS (B). From the full spectra (left), the absolute molecular weights of the tricyclic PS increased compared to that of linear precursor. This was caused by the coupled DBA molecule in the formation of tricyclic PS. From the expanded spectra (right), the peak distribution of the 6-arm star PS precursor could be accurately assigned to 6-arm star PS precursor with an elimination of 6N2 ionized with Ag+. For the

■

CONCLUSIONS A novel homodifunctional bimolecular ring-closure method was developed to successfully fabricate the well-defined cyclic polymers and their derivatives based on the self-accelerating double strain-promoted azide−alkyne click reaction. This method not only rejuvenated the bimolecular ring-closure strategy for the formation of pure cyclic polymers but also demonstrated several distinct advantages. Because of the selfaccelerating property of the ring-closing reaction, this method eliminated the requirement of precise 1:1 stoichiometry between the complementary reaction groups from the linear polymer precursors and small linkers. As a matter of fact, the H

DOI: 10.1021/acs.macromol.6b02614 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

(9) Laurent, B. A.; Grayson, S. M. Synthetic Approaches for the Preparation of Cyclic Polymers. Chem. Soc. Rev. 2009, 38, 2202−2213. (10) Endo, K. Synthesis and Properties of Cyclic Polymers. Adv. Polym. Sci. 2008, 217, 121−183. (11) Zhu, X.; Zhou, N.; Zhang, Z.; Sun, B.; Yang, Y.; Zhu, J.; Zhu, X. Cyclic Polymers with Pendent Carbazole Units: Enhanced Fluorescence and Redox Behavior. Angew. Chem., Int. Ed. 2011, 50, 6615− 6618. (12) Honda, S.; Yamamoto, T.; Tezuka, Y. Tuneable Enhancement of the Salt and Thermal Stability of Polymeric Micelles by Cyclized Amphiphiles. Nat. Commun. 2013, 4, 1574−1583. (13) Cortez, M. A.; Godbey, W. T.; Fang, Y. L.; Payne, M. E.; Cafferty, B. J.; Kosakowska, K. A.; Grayson, S. M. The Synthesis of Cyclic Poly(ethylene imine) and Exact Linear Analogues: An Evaluation of Gene Delivery Comparing Polymer Architectures. J. Am. Chem. Soc. 2015, 137, 6541−6549. (14) Roland, C. D.; Li, H.; Abboud, K. A.; Wagener, K. B.; Veige, A. S. Cyclic Polymers from alkynes. Nat. Chem. 2016, 8, 791−796. (15) Asenjo-Sanz, I.; Veloso, A.; Miranda, J. I.; Alegría, A.; Pomposo, J. A.; Barroso-Bujans, F. Zwitterionic Ring-Opening Copolymerization of Tetrahydrofuran and Glycidyl Phenyl Ether with B(C6F5)3. Macromolecules 2015, 48, 1664−1672. (16) Piedra-Arroni, E.; Ladavière, C.; Amgoune, A.; Bourissou, D. Ring-Opening Polymerization with Zn(C6F5)2-Based Lewis Pairs: Original and Efficient Approach to Cyclic Polyesters. J. Am. Chem. Soc. 2013, 135, 13306−13309. (17) Zhang, K.; Zha, Y. P.; Peng, B.; Chen, Y. M.; Tew, G. N. Metallo-Supramolecular Cyclic Polymers. J. Am. Chem. Soc. 2013, 135, 15994−15997. (18) Zhang, K.; Lackey, A. M.; Wu, Y.; Tew, G. N. Universal Cyclic Polymer Templates. J. Am. Chem. Soc. 2011, 133, 6906−6909. (19) Culkin, D. A.; Jeong, W.; Csihony, S.; Gomez, E. D.; Balsara, N. P.; Hedrick, J. L.; Waymouth, R. M. Zwitterionic Polymerization of Lactide to Cyclic Poly(Lactide) by Using N-Heterocyclic Carbene Organocatalysts. Angew. Chem., Int. Ed. 2007, 46, 2627−2630. (20) Bielawski, C. W.; Benitez, D.; Grubbs, R. H. An “Endless” Route to Cyclic Polymers. Science 2002, 297, 2041−2044. (21) Kricheldorf, H. R.; Lee, S. Polylactones. 35. Macrocyclic and Stereoselective Polymerization of β-D,L-Butyrolactone with Cyclic Dibutytin Initiators. Macromolecules 1995, 28, 6718−6725. (22) Oike, H.; Imaizumi, H.; Mouri, T.; Yoshioka, Y.; Uchibori, A.; Tezuka, Y. Designing Unusual Polymer Topologies by Electrostatic Self-Assembly and Covalent ixation. J. Am. Chem. Soc. 2000, 122, 9592−9599. (23) Tezuka, Y.; Oike, H. Topological Polymer Chemistry: Systematic Classiscation of Nonlinear Polymer Topologies. J. Am. Chem. Soc. 2001, 123, 11570−11576. (24) Tezuka, Y.; Fujiyama, K. Construction of Polymeric δ-Graph: A Doubly Fused Tricyclic Topology. J. Am. Chem. Soc. 2005, 127, 6266− 6270. (25) Sugai, N.; Heguri, H.; Ohta, K.; Meng, Q. Y.; Yamamoto, T.; Tezuka, Y. Effective Click Construction of Bridged- and SpiroMulticyclic Polymer Topologies with Tailored Cyclic Preolymers (kyklo-Telechelics). J. Am. Chem. Soc. 2010, 132, 14790−14802. (26) Sugai, N.; Heguri, H. Y.; Yamamoto, T.; Tezuka, Y. A Programmed Polymer Folding: Click and Clip Construction of Doubly Fused Tricyclic and Triply Fused Tetracyclic Polymer Topologies. J. Am. Chem. Soc. 2011, 133, 19694−19697. (27) Heguri, H.; Yamamoto, T.; Tezuka, Y. Folding Construction of a Pentacyclic Quadruply fused Polymer Topology with Tailored kykloTelechelic Precursors. Angew. Chem., Int. Ed. 2015, 54, 8688−8692. (28) Yan, Z. G.; Yang, Z.; Price, C.; Booth, C. Cyclisation of Poly(ethylene glycol)s and Related Block Copolymers. Makromol. Chem., Rapid Commun. 1993, 14, 725−732. (29) Yu, G. E.; Sinnathamby, P.; Price, C.; Booth, C. Preparation of Large Cyclic Poly(oxyethylene). Chem. Commun. 1996, 1, 31−32. (30) Yu, G. E.; Sinnathamby, P.; Sun, T.; Heatley, F.; Price, C.; Booth, C. Preparation and Characterization of Cyclic Poly(oxypropylene). Macromol. Rapid Commun. 1997, 18, 1085.

employment of excess amounts of small linkers could increase the intermolecular coupling reaction rate between linear polymer precursors and linkers. This increased the formation efficiency of linear intermediate species, further resulting in the enhanced total preparation efficiency of cyclic polymers. Because of the convenient reaction conditions of doublestrain-promoted azide−alkyne cyclization, this method could efficiently produce cyclic polymers in air at room temperature in regular low boiling point solvents without requiring any catalysts or chemical stimuli. Since the azide end-functionalized linear polymer precursors could be easily obtained from varied living polymerization techniques such as ATRP, ring-opening polymerization, and reversible addition−fragmentation chain transfer polymerization, this method could be used to prepare all kinds of cyclic polymers with varied structures and functionalities in theory. Resultantly, it is expected that this novel bimolecular ring-closure method should become one of the basic tools for the formation of well-defined cyclic polymers.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.6b02614. Experimental Section and Figures S1−S7 (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (K.Z.). ORCID

Ke Zhang: 0000-0001-5972-5127 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS Generous support was primarily provided by National Science Foundation of China (21622406 and 21604089) and Ministry of Science and Technology of China (2014CB932200). K.Z. thanks the Bairen project from The Chinese Academy of Sciences for support.

■

REFERENCES

(1) Yamamoto, T.; Tezuka, Y. Cyclic Polymers Revealing Topology Effects upon Self-Assemblies, Dynamics and Responses. Soft Matter 2015, 11, 7458−7468. (2) Williams, R. J.; Dove, A. P.; O’Reilly, R. K. Self-Assembly of Cyclic Polymers. Polym. Chem. 2015, 6, 2998−3008. (3) Zhang, K.; Tew, G. N. Cyclic Polymers as a Building Block for Cyclic Brush and Gels. React. Funct. Polym. 2014, 80, 40−47. (4) Jia, Z. F.; Monteiro, M. J. Synthesis of Cyclic Polymers vias Ring Closure. Adv. Polym. Sci. 2013, 262, 295−328. (5) Jia, Z. F.; Monteiro, M. J. Cyclic Polymers: Methods and Strategies. J. Polym. Sci., Part A: Polym. Chem. 2012, 50, 2085−2097. (6) Hoskins, J. N.; Grayson, S. M. Cyclic Polyesters: Sythetic Approaches and Potential Applications. Polym. Chem. 2011, 2, 289− 299. (7) Yamamoto, T.; Tezuka, Y. Topological Polymer Chemistry: a Cyclic Approach toward Novel Polymer Properties and Functions. Polym. Chem. 2011, 2, 1930−1941. (8) Kricheldorf, H. R. Cyclic Polymers: Synthetic Strategies and Physical Properties. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 251− 284. I

DOI: 10.1021/acs.macromol.6b02614 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules (31) Andrew, F. V.; Tillman, E. S.; Findeis, P. M.; Radzinski, S. C. Synthesis of Macrocyclic Polymers Formed via Intramolecular Radical Trap-Assisted Atom Transfer Radical Coupling. ACS Macro Lett. 2012, 1, 1066−1070. (32) Blackburn, S. C.; Myers, K. D.; Tillman, E. S. Macrocyclic Poly(methyl acrylate) and Macrocyclic Poly(methyl acrylate-blockstyrene) Synthesized by Radical Trap-Assisted Atom Transfer Racical Coupling. Polymer 2015, 68, 284−292. (33) Blackburn, S. C.; Tillman, E. S. Synthesis of Cyclic Poly(methyl methacrylate) Directly from Dihalogenated Linear Precursors. Macromol. Chem. Phys. 2015, 216, 1282−1290. (34) Kii, I.; Shiraishi, A.; Hiramatsu, T.; Matsushita, T.; Uekusa, H.; Yoshida, S.; Yamamoto, M.; Kudo, A.; Hagiwara, M.; Hosoya, T. Starin-Promoted Double-Click Reaction for Chemical Modification of Azido-Biomolecuels. Org. Biomol. Chem. 2010, 8, 4051−5055. (35) Wang, L. F.; Dai, C. F.; Chen, W. X.; Wang, S. L.; Wang, B. H. Facile Derivatization of Azide Ions Using Click Chemistry for Their Sentitive Detection with LC-MS. Chem. Commun. 2011, 47, 10377− 10379. (36) Tanaka, K.; Nakamoto, Y.; Siwo, E. R.; Praditpa, A. R.; Morimoto, K.; Fujiwara, T.; Yoshida, S.; Hosoya, T.; Tamura, Y.; Hirai, G.; Sodeoka, M.; Fukase, K. Development of Bis-Unsaturated Ester Alderhydses as Amino-Glue Probes: Sequential Double Azaelectrocyclization as A Promising Strategy for Bioconjugation. Org. Biomol. Chem. 2013, 11, 7326−7333. (37) Kihara, N.; Komatsu, S. I.; Takata, T.; Endo, T. Significance of Stoichiometric Imbalance in Step Polymerization via Reactive Intermediate. Macromolecules 1999, 32, 4776−4783. (38) Iimori, H.; Shibasaki, Y.; Ando, S.; Ueda, M.; Nonstoichiometric Polycondensation, I. Synthesis of Polythioether from Dibromomethane and 4,4 ′-Thiobisbenzenethiol. Macromol. Symp. 2003, 199, 23−36.

J

DOI: 10.1021/acs.macromol.6b02614 Macromolecules XXXX, XXX, XXX−XXX