Spontaneous Amino-yne Click Polymerization: A Powerful Tool toward

Subscriber access provided by HACETTEPE UNIVERSITESI KUTUPHANESI

Article

Spontaneous Amino-Yne Click Polymerization: A Powerful Tool toward Regio-and Stereo-specific Poly(#-aminoacrylates) Benzhao He, Huifang Su, Tianwen Bai, Yongwei Wu, Shiwu Li, Meng Gao, Rongrong Hu, Zujin Zhao, Anjun Qin, Jun Ling, and Benzhong Tang J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b00929 • Publication Date (Web): 29 Mar 2017 Downloaded from http://pubs.acs.org on March 29, 2017

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Journal of the American Chemical Society is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 8

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Journal of the American Chemical Society

Spontaneous Amino-Yne Click Polymerization: A Powerful Tool toward Regio-and Stereo-specific Poly(β-aminoacrylates) Benzhao He,† Huifang Su,‡ Tianwen Bai,§ Yongwei Wu,† Shiwu Li,† Meng Gao,† Rongrong Hu,† Zujin Zhao,† Anjun Qin,*,† Jun Ling,*,§ and Ben Zhong Tang*,†,‡ †

Guangdong Innovative Research Team, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China. ‡

Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong, China.

§

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China. ABSTRACT: Efficient synthesis of poly(enamine)s has been a great challenge because of their poor stability, poor solubility and low molecular weights. In this work, a spontaneous amino-yne click polymerization for the efficient preparation of poly(enamine)s was established, which could proceed with 100% atom efficiency under very mild conditions without any external catalyst. Through systematical optimization of the reaction conditions, several soluble and thermally stable poly(β-aminoacrylates) with high molecular weights (Mw up to 64400) and well-defined structures were obtained in excellent yields (up to 99%). Moreover, the polymerization can perform in a regio-and stereo-specific fashion. Nuclear magnetic resonance (NMR) spectra analysis revealed that solely anti-Markovnikov additive products with 100% E-isomer were obtained. The reaction mechanism was well demonstrated under the assistance of density functional theory (DFT) calculation. In addition, by introducing the tetraphenylethene (TPE) moiety, the resulting polymers exhibit unique aggregation-induced emission (AIE) characteristics, and could be applied in explosives detection and bio-imaging. This polyhydroamination is a new type of click polymerization, and opens up enormous opportunities for preparing functional polymeric materials.

INTRODUCTION

reo-regular polymers with high molecular weights is highly desired.

Nowadays, polymeric materials are playing an increasingly important role in our society and daily lives. New polymers with new structures and functions rely on the development of new efficient and selective polymerizations. The click polymerization, developed based on the click reaction1, is an ideal candidate to be used for the preparation of polymers with unique properties due to their fascinating features, such as high efficiency, high selectivity, atom economy, simple product isolation and mild reaction conditions.

Recently, we successfully developed a spontaneous thiol-yne click polymerization. The aromatic diynes or triynes readily polymerize with dithiol monomers once they mixed together in THF at 30 oC, from which regio-specific poly(vinylene sulfide)s with high weight-average molecular weights (Mw) were produced.7 This polymerization greatly simplifies the experimental operation and is expected to be widely applied in functional polymer preparation. Generally, the spontaneous thiol-yne click polymerization belongs to the family of hydroXtion (X = thiola, amina, silyla, alkoxyla etc.), which inspires us to explore other spontaneous click polymerizations. Alone this line, one possibility is to develop the spontaneous click polymerization based on hydroamination of alkynes.

With the efforts paid by the polymer chemists, Cu(I)catalyzed azide-alkyne cycloaddition,2 thiol-yne reaction,3 thiol-ene reaction,4 Diels–Alder reaction,5 have been developed into robust click polymerizations for the preparation of functional polymers.6 However, most of these click polymerizations required transition-metal catalysts, elevated temperature or UV light irradiation etc. which complicates the experimental operation and restricts its application in certain degree. Therefore, development of new click polymerizations that can perform spontaneously at room temperature, and generate regio- and/or ste-

Hydroamination, the direct addition of an amine group to an unsaturated C-C bond, like ethynyl group, is an efficient method to direct synthesis nitrogen-containing compounds.8 Over the past few decades, many catalytic systems have been developed.9 Most of the hydroamination of alkynes generated imine and enamine derivatives. The former, however, are unstable in acidic conditions,

ACS Paragon Plus Environment


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

whereas, the latter always possess stereo-random vinyl bonds. Thus, it is a great challenge to explore a facile polymerization methodology to synthesize nitrogencontaining regio- and stereo-specific polymers. Although great progresses have been made in the development of hydroamination of alkynes,10 to the best of our knowledge, the polyhydroamination of alkynes is rarely reported besides our recent work on the Cu(I)catalyzed amino-yne click polymerization.11 This click polymerization undergoes in a regio- and stereo-selective fashion, and could produce polyenamines with high Mw in high yields. However, this click polymerization required CuCl as catalyst, and must be carried out at 140 oC, which slightly limit their further applications. During the experiments, we occasionally changed the internal alkyne monomer to external propiolate one, and found the polymerization readily occurred when this diyne mixed with aliphatic secondary diamine at room temperature, that is, this reaction undergoes spontaneously. More excitingly, solely anti-Markovnikov addition and 100% E-configuration products were obtained. These results agree well with previous reports that the Michael addition of amines to activated acetylenes could offer solely anti-Markovnikov additive products with 100% Econfiguration.10 Encouraged by these exciting results, we systematically investigated this polyhydroamination. As a result, a spontaneous polymerization of propiolates and amines, that is, the spontaneous amine-yne click polymerization, was successfully established, and a series of regio-and stereospecific poly(β-aminoacrylate)s with high Mw were produced in high yields (Scheme 1). It is worth noting that this click polymerization is functional tolerant, and functional moieties, such as tetraphenylethene (TPE) could be introduced to the polymers to offer them with aggregation-induced emission (AIE) characteristics and to be used to sensitively detect explosives. More importantly, thanks to the high efficiency, mild reaction conditions and simple experimental operation, this polymerization could also be applied in preparation biocompatible polymers to image the cells.12 Scheme 1. Syntheses of poly(β-aminoacrylates) by spontaneous click polymerization of dipropiolates and diamines.

RESULTS AND DISCUSSION Polymerization

Page 2 of 8

The monomers used in this work are readily available or could be prepared with ease (Scheme S1). Most importantly, they are all stable under ambient conditions. In order to obtain soluble poly(β-aminoacrylate)s with high Mw, we systematically investigated the polymerization conditions using 1a and 2a as monomers. The solvent, temperature, monomer concentrations, and reaction time were carefully investigated (Tables S1-S4, Supporting Information). It was found that the solvent and the temperature exerted little effect on the polymerization. While the monomer concentration played a crucial role for this polymerization. With increasing monomer concentration, the Mw increased gradually, and reached the maximum when the monomer concentration is 2 M. Moreover, the polymerization were so efficient that a polymer with Mw of 53 600 was obtained in high yield (98%) even after only 3 h (Table S4, entry 4). Considering the environmentalfriendliness and simple experimental operation, we chose monomer concentration of 2 M, solvent of dichloromethane (DCM), reaction time of 3 h, and room temperature as the optimal polymerization conditions for further investigation. Furthermore, the reaction atmosphere investigation showed that almost similar polymerization results could be obtained no matter the reaction was carried out under nitrogen or in air. (Table 1, entries 1 and 2). The oxygen and moisture tolerances of this polymerization will further simplify the reaction operation. Table 1. Spontaneous click polymerization of diynes 1 and diamines 2.a entry

monomers

yield (%)

Mwb

Ðb

1 2c 3d 4 5 6e 7f 8e 9

1a + 2a 1a + 2a 1a + 2b 1a + 2c 1a + 2d 1b + 2a 1b + 2b 1b + 2c 1b + 2d

98 99 96 98 99 97 96 99 88

53 600 52 800 64 400g 31 680 17 300 35 900g 48 600g 16 000 14 300

2.31 1.96 2.53g 1.91 1.51 1.87g 1.66g 1.93 1.40

a

Carried out under nitrogen in DCM at room temperature (rt) b for 3 h; [M]0 = 2 M. Determined by advanced polymer chromatography (APC) in THF on the basis of a linear polyc d styrene calibration. Conducted in air. Carried out under e nitrogen in DCM at rt for 3 h; [M]0 = 1 M. Carried out under f nitrogen in DCM at rt for 20 min; [M]0 = 1 M. Carried out g under nitrogen in DCM at rt for 1.5 h; [M]0 = 1 M. Determined by gel-permeation chromatography (GPC) in chloroform on the basis of a linear polystyrene calibration.

With the optimized polymerization conditions in hand, various types of monomers were examined to test the robustness and universality of this polymerization. The polymerization results showed that all the polymerizations performed spontaneously, readily producing polymers with high Mw (up to 64 400) in high yields (up to 99%) (Table 1). These results manifest the universality of this powerful and efficient polymerization.


Page 3 of 8

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Moreover, we also tried to polymerize other type amines with 1a to investigate their scope. The results showed that the aliphatic primary amines could also be polymerized with 1a under the optimized polymerization conditions. For example, the polymerization of 1,6diaminohexane (2e) with 1a (Scheme S2) propagated smoothly, and P1a2e with high molecular weight (34200) was obtained in 99% yield after 3 h (Table S5). In addition, aromatic amines could not spontaneously react with 1a under our optimized conditions probably due to the p-π conjugation between the lone pair electrons of amine with aromatic rings, which reduced the electrophilic properties of amines. Most of the resultant polymers are soluble in commonly used organic solvents, such as tetrahydrofuran (THF), DCM, chloroform, and N,N-dimethylformamide (DMF), whereas, P1a2b, P1b2a and P1b2b could only be dissolved in DCM and chloroform. The thermal properties of the polymers were evaluated by thermogravimetric analysis (TGA), and the results indicated that the 5% weight loss temperatures (Td) of them are in the range of 265-357 oC (Figure S1), suggesting that they are thermally stable.

A

B

The 13C NMR spectra further confirmed the success of the amino-yne click polymerization. As shown in Figure 3,

C=O

NH2

C C=OC=C

D C=O C=C

4000

3000

2000

1600

1200

800

400

-1

Wavenumber (cm )

Figure 1. FT-IR spectra of (A) monomer 1a, (B) monomer 2a, (C) model compound 4 and (D) polymer P1a2a. O

A

O

O

a

a

Structural Characterization The structural of the as-prepared polymers were characterized by FT-IR and NMR spectra. To facilitate the structural characterization of the polymers, model compound 4 was prepared by the hydroamination between 1a and diethylamine (Scheme S3) under the same reaction conditions. The FT-IR, 1H and 13C NMR spectra of polymer P1a2a, model compound 4 and their corresponding monomers 1a and 2a are given as examples. In the FT-IR spectra (Figure 1), the ≡C-H and C≡C stretching vibrations of 1a and the N-H stretching vibration of 2a occur at 3231, 2113 and 3300 cm-1, respectively. These peaks could not be observed in the spectra of P1a2a and 4. Meanwhile, a new peak associated with C=C stretching vibrations appeared at 1610 cm-1, revealing the occurrence of the polymerization. Similar results were obtained in the FT-IR spectra of other polymers (Figure S2). The NMR spectroscopy could provide more detailed information about the polymer structures. In the 1H NMR spectra, the ethynyl proton of 1a, the NH proton and the CH2 protons of 2a resonate at δ 2.88, 1.14, 2.69, and 2.60, respectively, which could not be found in the spectra of 4 and P1a2a (Figure 2). Meanwhile, four new peaks at δ 7.37, 4.56, 3.26 and 3.17, assignable to the resonances of the HC=CH group and CH2 group next to N atom, respectively, appeared in the spectra of P1a2a. The coupling constant of HC=CH group is 13 Hz, confirming the existing of E-isomers in P1a2a.13 Moreover, from the spectra, we could not find the resonant peaks associated with the branched and Z-isomers, indicating that the polymerization proceeds in regio-and stereo-specific fashion and is a new kind of spontaneous amino-yne click polymerization.

C≡C

≡C-H

O

*

B

c

H N

e

N H

b

e b

d c d

*

C

O

f

h

N

O

O

g

N O

f

g

h

* O

f

i

D

N

g

O

O

N n O

i

h

h

g f

*

8

7

6

5

4

3

2

1

Chemical shift (ppm) 1

Figure 2. H NMR spectra of (A) monomer 1a, (B) monomer 2a, (C) model compound 4 and (D) polymer P1a2a in CDCl3. The solvent peaks are marked with asterisks.

the ethynyl carbons of 1a resonated at δ 74.71 and 74.85, and those of 2a at δ 49.60, 44.27 and 15.45 are absent in the 13C NMR spectra of 4 and P1a2a. Meanwhile, the resonance peak of carbonyl carbons of 1a at δ 152.91 was shifted to δ 170.12 in 4 and P1a2a. Furthermore, two new peaks associated with the resonances of vinyl carbons appeared at δ 150.92 and 83.39 in P1a2a. Similar conclusions could be drawn by analysis of the NMR spectra of other polymers (Figures S3 and S4).


Journal of the American Chemical Society O

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

b

A

O

c O

a

*

O

a b c 75.5

75.0

74.5

74.0

% (?X)

B

e

f N H

d

H N f e

d

*

N

In the first step, the lone pair electrons of amine attack the end carbon of the ethynyl group, forming transition states (TS) of zwitterionic precursors to Z/E configuration intermediates. The addition step exhibits weak selectivity of different configuration since only 1.0 kcal/mol difference in Gibbs free energy barrier and 2.0 kcal/mol differences between two generated intermediates are observed. Moreover, a configuration exchange is also possible between two intermediates with an energy barrier of 24.1 kcal/mol.

O

g

C

Page 4 of 8

h

O

i O

N O

g

h *

i

O

g

D N

h

O

i O

n

g

*

i

180

N O

h 160

140

120

100

80

60

40

20

Chemical shift (ppm) 13

Figure 3. C NMR spectra of (A) monomer 1a, (B) monomer 2a, (C) model compound 4 and (D) polymer P1a2a in CDCl3. The solvent peaks are marked with asterisks.

Interestingly, the structural characterization of P1a2e by 1H and 13C NMR spectra showed that it is regio-regular but stereo-random (Figures S5 and S6). This result could ascribe to the formation of a pseudo six-membered rings by the intramolecular hydrogen bond between the N–H and C=O groups during the polymerization process. Although it is not perfect stereo-specificity, the reaction of primary amine and propiolate monomer could also be regarded as a new spontaneous amino-yne click polymerization due to its regio-selectivity and high efficiency. Mechanism Research Theoretically, the hydroamination reaction can not only proceed through Markovnikov addition route to yield branched adducts, but also perform by anti-Markovnikov addition way to furnish linear products with E and/or Z conformations.9b,9c Delightfully, our developed spontaneous amino-yne click polymerization possesses excellent regio- and stereo-selectivity. To understand the underneath reaction mechanism, we performed the theoretical simulation. Herein, we used methyl propiolate and diethylamine as model reaction molecules to simplify the calculation, and employed the powerful density functional theory (DFT) to analyze the mechanism of the profile of this reaction.14 In theory, it consists of two elementary reactions: one is nucleophilic addition and the other is proton transfer. Moreover, two transformation pathways between zwitterionic and stable intermediates were observed. These routes are demonstrated in Figure 4 with selected 3D geometries (Figure S7) and coordinates in Supporting Information.

Figure 4. DFT calculated profiles of addition and proton transfer steps of E- (black) and Z-configuration pathways (red), as well as the transformations between zwitterionic intermediates (blue) and vinyl products (olive). All numbers are given as relative Gibbs free energy in kcal/mol. The second step, i.e. proton transfer, is also investigated in DFT calculations. The proton transfer includes intramolecular and intermolecular pathways. As an intramolecular pathway, E-intermediate undergoes a fourmember ring TS with the Gibbs energy barrier of 26.1 kcal/mol (show as the black line in Figure 4). On the contrary, due to the hindrance of ester group, intramolecular proton transfer in Z-intermediate is suppressed and shows no reaction pathway to fulfill (dash line with a cross in Figure 4). This simulation indicates that the Econfiguration will be the dominant isomeric units in the polymers. For the intermolecular proton transfer, when triethylamine (TEA) was used as proton accepter (medium), both E- and Z-isomer containing products can be produced, where no energy barrier can be located. It is worth pointing out that our polymers contain tertiary amine repeating units, which could act as the intermolecular proton transfer medium to facilitate the formation of Z-products. Indeed, we observed this in our control experiments. When the polymerization of 1a and 2a was carried out at 0 oC for 3 h, 9% fraction of Z-isomeric units in the product were recorded, whereas, when 0.05 equivalents of TEA was used as media reagent, the fraction of Z-isomeric units in the product further increased to 13% (Figure S8A and 8C).


Page 5 of 8

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


The E-isomers are more stable than the Z-isomers with an energy difference of 5.4 kcal/mol. The transformation between two vinyl products (olive line) takes place via one TS of “nitrogen-activated double bond rotation” The Gibbs energy barrier of transformation of vinyl spices (34.3 kcal/mol) is higher than that of addition steps (20.6 or 21.6 kcal/mol), indicating that transformation from Zto E-isomeric units should be more difficult to take place. This theoretical calculation agrees well with our experimental results. As aforementioned, when the polymerization of 1a and 2a proceeded at 0 oC, 9% Z-isomeric units in the product was obtained. However, when the product with Mw of 18000 was allowed to stand at room temperature for 4 h, the Z- configuration totally transferred to Eone as indicated in the 1H NMR spectra (Figure S8A and S8B). Photoluminescence (PL) Properties and Applications The incorporation of the typical AIE-active TPE moiety into the polymer skeletons of P1a2d and P1b2d make them AIE-active too. We thus systematically investigated their emission behaviors in THF/water mixtures with different fw (Figure 5A). The PL curves of their THF solution are almost a flat line parallel to the abscissa, indicating that the polymers are virtually non-luminescent. With the addition of water, a poor solvent for them, the emission intensity slowly increased. From the photographs of P1a2d taken in THF and THF/water mixture with water fraction (fw) of 90% (insets of Figure 5B), we can see that the THF solutions are almost non-emissive, while the THF/water mixtures fluoresce intensely. The highest fluorescence intensity was reached at the fw of 90%, which are 79 and 29-fold higher than that of their THF solution for P1a2d and P1b2d, respectively (Figures 5B and S9). Such PL behaviors further confirmed that P1a2d and P1b2d are AIE-active. The fluorescence enhancement of P1a2d is higher than that of P1b2d, which could be attributed to the spring-like architectures with flexible spacers P1a2d.15 When P1a2d dissolved in good solvents, the large free volumes enable the phenyl rings of the TPE units to rotate freely, making it non-emissive. However, the P1b2d

Figure 5. (A) PL spectra of P1a2d in THF and THF/water mixtures. Concentration: 10 μM; λex: 322 nm. (B) Plot of relative PL intensity versus water fraction in THF/water mixtures, where I = peak intensity in water mixtures and I0 = peak intensity in pure THF. Inset in panel B: photographs of P1a2d in pure THF and a THF/water mixture with 90% water.

has more rigid structure, and has a weak fluorescence when dissolved in good solvents. Thanks to their AIE feature, the aggregates of P1a2d and P1b2d could be used to sensitively detect explosives, which is important for homeland security and antiterrorism.16 The commercially available picric acid (PA) was used as a model explosive, and the nano-aggregates of polymers in THF/water mixtures with fw of 90% were utilized as probe. With gradual addition of PA into the aqueous solution, the PL intensities of the aggregates of P1a2d and P1b2d were progressively decreased, but the PL spectral profile maintains unchanged (Figure S10A and 10C). The quenching constants of P1a2d and P1b2d were deduced to be 67 900 and 691 010 M-1 from the SternVolmer plots, respectively (Figure S10B and 10D). The limits of detection (LOD) of P1a2d and P1b2d was thus calculated to be 3.87 × 10−6 and 1.28 × 10−7 M according to the equation of LOD = 3SB/m,17 respectively. In this equation, SB represents the standard deviation of the blank measurements and m is the slope of intensity versus sample concentration. These LOD values are comparable to those in the previous reports.18 Besides using the “wet” method, the detection of the PA detection could also work in the solid state. As shown in Figure S11, the test strips of P1a2d and P1b2d, fabricated by adsorbing the polymers onto filter papers according to the literature methods,19 display strong PL upon photo-excitation after dipping into their nonsolvent of toluene, while become non-emissive after dipping into the toluene solution of PA (50 µg/mL). This demonstrates a prototype device using the AIE polymers for detecting explosives in real-world applications. Since this amino-yne click polymerization performs spontaneously under very mild reaction conditions, it is envisioned promising in preparation polymeric materials for biological applications. To demonstrate the possibility, amino group-terminated TPE-containing poly(βaminoacrylate)s with Mw of 4580, namely P-TPE was prepared in excellent yield by this click polymerization (Scheme S4). The cytotoxicity of P-TPE was first evaluated using standard MTT cell-viability assay. The results showed that the cell viabilities remain over 80% at a PTPE concentration of 30 μg/mL for both normal and cancer cells (Figure S12), indicative of its low cytotoxicity. Moreover, P-TPE possesses excellent photo-stability. As shown in Figure S13, its fluorescence intensity in HeLa cells remained almost unchanged even after 15 min of continuous irradiation with excitation at 405 nm, making it applicable in long-term cell tracking. Taking the advantage of low cytotoxicity, excellent photo-stability and AIE feature of P-TPE, we then applied it in cell imaging. The amino-terminated P-TPE has a weak alkaline, which may specifically labeled lysosomes. We also used a commercial lysosome specific dye, LysoTracker Red DND-99 (LTR), to co-stain the HeLa cells. The colocalization images indicated that P-TPE with concentration of 20 µM could selectively label lysosomes (Figure 6) although the efficiency should be further enhanced.



Page 6 of 8

Notes

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The authors declare no competing financial interest.

ACKNOWLEDGMENT This work was financially supported by the National Natural Science Foundation of China (21525417 and 21490571); the key project of the Ministry of Science and Technology of China (2013CB834702); The National Program for Support of TopNotch Young Professionals; the Fundamental Research Funds for the Central Universities (2015ZY013) and the Innovation and Technology Commission of Hong Kong (ITCCNERC14S01). A.J.Q. and B.Z.T. thank the support from Guangdong Innovative Research Team Program (201101C0105067115).

REFERENCES

Figure 6. Colocalization images of HeLa cells incubated with P-TPE (20 μM, 3 h) and LysoTracker Red (LTR, 50 nM, 10 min). (A) Bright-field image. (B) P-TPE (λex = 405 nm, λem = 450-500 nm). (C) LTR (λex = 543 nm, λem = 560-650 nm). (D) The merged image of (A), (B) and (C). All images share the same scale bar: 20 μm.

CONCLUSION In summary, we successfully developed a simple and powerful spontaneous amino-yne click polymerization for the first time. This polymerization can proceed in a regioand stereo-specific fashion under very mild conditions, producing poly(β-aminoacrylate)s with high molecular weights in excellent yields. 1H NMR spectra analysis revealed that solely anti-Markovnikov additive products with 100% E-isomer were obtained. DFT calculation has well unveiled the underneath reaction mechanism of this amino-yne click polymerization. Furthermore, the resultant polymers possess good solubility and high thermal stability. Thanks to its excellent function tolerance, this polymerization could generate polymers bearing AIEactive TPE moieties in their main-chains, making them AIE-active and be applicable in explosive sensing and specific lysosome labelling. The robustness and efficiency of this spontaneous amino-yne click polymerization enable it to be widely applied in diverse areas.

ASSOCIATED CONTENT Supporting Information Experimental details, reaction condition optimization parameters, characterization data (TGA, FT-IR, NMR, etc.), application data (explosives detection and cytotoxicity evaluation), 3-D geometries and coordinates of the calculated model compounds. This material is available free of charge on the ACS Publications website.

AUTHOR INFORMATION Corresponding Author * [email protected] (A.J.Q.) * [email protected] (J.L.) * [email protected] (B.Z.T.)

(1) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem. Int. Ed. 2001, 40, 2004-2021. (2) (a) Qin, A.; Liu, Y.; Tang, B. Z. Macromol. Chem. Phys. 2015, 216, 818-828; (b) Li, H. K.; Sun, J. Z.; Qin, A. J.; Tang, B. Z. Chin. J. Polym. Sci. 2012, 30, 1-15; (c) Wu, W.; Ye, C.; Yu, G.; Liu, Y.; Qin, J.; Li, Z. Chem. Eur. J. 2012, 18, 4426-4434; (d) Lo, C. N.; Hsu, C. S. J. Polym. Sci., Part A: Polym. Chem. 2011, 49, 3355-3365; (e) Qin, A.; Lam, J. W. Y.; Tang, B. Z. Chem. Soc. Rev. 2010, 39, 2522-2544; (f) Iha, R.K., Wooley, K.L., Nystrom, A.M., Burke, D.J., Kade, M.J. and Hawker, C.J. Chem. Rev. 2009, 109: 5620-5686; (g) Lee, J. W.; Kim, J. H.; Kim, H. J.; Han, S. C.; Kim, J. H.; Shin, W. S.; Jin, S.-H. Bioconjugate Chem. 2007, 18, 579-584; (h) Zhou, L.; Geng, J.; Wang, G.; Liu, J.; Liu, B. ACS Macro Letters 2012, 1, 927-932. (i) Shi, Y.; Graff, R. W.; Cao, X. S.; Wang, X. F.; Gao, H. F. Angew. Chem. Int. Ed. 2015, 54, 7631-7635; (j) Wu, H.; Dong, W. H.; Wang, Z. T.; Yao, B. C.; Chen, M.; Sun, J. Z.; Qin, A. J.; Tang, B. Z. Sci. China Chem. 2015, 58, 1748-1752. (3) (a) Yao, B.; Sun, J.; Qin, A.; Tang, B. Z. Chin. Sci. Bull. 2013, 58, 2711-2718; (b) Zhao, B.; Zheng, Y.; Weng, Z.; Cai, S.; Gao, C. Polym. Chem. 2015, 6, 3747-3753; (c) Han, J.; Zhao, B.; Gao, Y.; Tang, A.; Gao, C. Polym. Chem. 2011, 2, 2175-2178. (d) Lowe, A. B.; Hoyle, C. E.; Bowman, C. N. J. Mater. Chem. 2010, 20, 4745-4750. (4) (a) Lowe, A. B. Polym. Chem. 2010, 1, 17-36; (b) Lowe, A. B. Polym. Chem. 2014, 5, 4820-4870. (c) Robb, M. J.; Hawker, C. J. ‘Click’ Chemistry in Polymer Science: CuAAC and Thiol– Ene Coupling for the Synthesis and Functionalization of Macromolecules. In Synthesis of Polymers: New Structures and Methods; Schlüter, A. D., Hawker, C. J., Sakamoto, J., Eds.; Wiley-VCH: Weinheim, Germany, 2012 Vol. 2, 923–971. (5) (a) Gandini, A. Prog. Polym. Sci. 2013, 38, 1-29; (b) Tasdelen, M. A. Polym. Chem. 2011, 2, 2133-2145. (6) (a) Kempe, K.; Krieg, A.; Becer, C. R.; Schubert, U. S. Chem. Soc. Rev. 2012, 41, 176-191; (b) Liu, Y.; Lam, J. W. Y.; Tang, B. Z. Natl. Sci. Rev. 2015, 2, 493-509. (7) (a) Yao, B.; Mei, J.; Li, J.; Wang, J.; Wu, H.; Sun, J. Z.; Qin, A.; Tang, B. Z. Macromolecules 2014, 47, 1325-1333; (b) Yao, B.; Hu, T.; Zhang, H.; Li, J.; Sun, J. Z.; Qin, A. J.; Tang, B. Z. Macromolecules, 2015, 48, 7782–7791. (8) (a) Müller, T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. Chem. Rev. 2008, 108, 3795-3892; (b) Yim, J. C. H.; Schafer, L. L. Eur. J. Org. Chem. 2014, 2014, 6825-6840. (9) (a) Huang, L.; Arndt, M.; Gooßen, K.; Heydt, H.; Gooßen, L. J. Chem. Rev. 2015, 115, 2596-2697; (b) Severin, R.; Doye, S. Chem. Soc. Rev. 2007, 36, 1407-1420; (c) Pohlki, F.; Doye, S. Chem. Soc. Rev. 2003, 32, 104-114. (10) (a) Zeng, R.; Sheng, H.; Rao, B.; Feng, Y.; Wang, H.; Sun, Y.; Chen, M.; Zhu, M. Chem. Res. Chin. Univ. 2015, 31, 212-217. (b)


Page 7 of 8

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Huisgen, R.; Giese, B.; Huber, H. Tetrahedron Lett. 1967, 8, 1883-1888. (c) Um, I.-H.; Lee, E.-J.; Seok, J.-A.; Kim, K.-H. J. Org. Chem. 2005, 70, 7530-7536. (d) Choudhary, G.; Peddinti, R. K. Green Chem. 2011, 13, 3290-3299. (e) Truce, W. E.; Brady, D. G. J. Org. Chem. 1966, 31, 3543-3550. (11) He, B.; Zhen, S.; Wu, Y.; Hu, R.; Zhao, Z.; Qin, A.; Tang, B. Z. Polym. Chem. 2016, 7, 7375-7382. (12) (a) Mei, J.; Leung, N. L. C.; Kwok, R. T. K.; Lam, J. W. Y.; Tang, B. Z. Chem. Rev. 2015, 115, 11718-11940; (b) Zhang, X.; Wang, K.; Liu, M.; Zhang, X.; Tao, L.; Chen, Y.; Wei, Y. Nanoscale 2015, 7, 11486-11508; (c) Hu, R.; Kang, Y.; Tang, B. Z. Polym. J. 2016, 48, 359-370; (d) Qin, A.; Lam, J. W. Y.; Tang, B. Z. Prog. Polym. Sci. 2012, 37, 182-209. (13) Dolfini, J. E. J. Org. Chem. 1965, 30, 1298-1300. (14) (a) Liu, J.; Ling, J. J. Phys. Chem. A 2015, 119, 7070-7074. (b) Ling, J.; Huang, Y. Macromol. Chem. Phys. 2010, 211, 1708-1711. (15) Wang, J.; Mei, J.; Yuan, W.; Lu, P.; Qin, A.; Sun, J.; Ma, Y.; Tang, B. Z. J. Mater. Chem. 2011, 21, 4056-4059. (16) Salinas, Y.; Martínez-Mañez, R.; Marcos, M. D.; Sancenon, F.; Costero, A. M.; Parra, M.; Gil, S. Chem. Soc. Rev. 2012, 41, 1261-1296. (17) IUPAC, N.; Symbols, U. Pure Appl. Chem 1976, 45, 105. (18) (a) Ma, H.; He, C.; Li, X.; Ablikim, O.; Zhang, S.; Zhang, M. Sensors Actuators B: Chem. 2016, 230, 746-752; (b) Ma, Y.; Li, H.; Peng, S.; Wang, L. Anal. Chem. 2012, 84, 8415-8421. (c) Pinrat, O.; Boonkitpatarakul, K.; Paisuwan, W.; Sukwattanasinitt, M.; Ajavakom, A. Analyst 2015, 140, 18861893. (19) (a) Wu, W.; Ye, S.; Tang, R.; Huang, L.; Li, Q.; Yu, G.; Liu, Y.; Qin, J.; Li, Z. Polymer 2012, 53, 3163-3171. (b) Qin, A.; Lam, J. W. Y.; Tang, L.; Jim, C. K. W.; Zhao, H.; Sun, J.; Tang, B. Z. Macromolecules 2009, 42, 1421-1424.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Table of Contentsk


Page 8 of 8

Spontaneous Amino-yne Click Polymerization: A Powerful Tool toward

Recommend Documents