Optically Active Helical Polyacetylene Self-Assembled into Chiral

Letter pubs.acs.org/macroletters

Optically Active Helical Polyacetylene Self-Assembled into Chiral Micelles Used As Nanoreactor for Helix-Sense-Selective Polymerization Biao Zhao,†,‡ Jinrui Deng,†,‡ and Jianping Deng*,†,‡ †

State Key Laboratory of Chemical Resource Engineering and ‡College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China S Supporting Information *

ABSTRACT: Chiral micelles have been drawing ever-increasing attention because of their potentials in mimicking the unique stereochemical effects of enzymes. This article reports on the first success in preparing chiral micelles through self-assembly of helical polyacetylene bearing cholic acid pendants. The micelles were further used as chiral nanoreactor, in which achiral acetylenic monomer smoothly underwent helix-sense-selective polymerization (HSSP). The HSSPs directly established optically active core/shell nanoparticles whose shell and core both were constructed by helical polymers. The shells (or micelles) provided a protective effect for the preferably induced one-handed helical polymer chains in the cores. The present work provides insights into the self-assembly of chiral helical polymers, and also provides a powerful strategy for constructing novel chiral polymer nanoarchitectures.

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macromolecules (e.g., DNA and collagens) in organisms. Furthermore, phenomena different from the usual polymerbased self-assemblies are also highly anticipated from the selfassembly systems of the kind. However, there have been only few reports on this research topic in literature.31−33 In this contribution, we report our exciting success in preparing chiral micelles by self-assembly of chiral helical polyacetylene with CA moieties. More importantly, the prepared micelles were further judiciously used as chiral nanoreactors in which helix-senseselective polymerizations (HSSPs) were achieved, directly providing optically active core/shell nanoparticles. Herein, it is worthy to be highlighted that the chiral micelles played triple roles (nanoreactor, chiral origin, and protective shell) in constructing the optically active core/shell structured nanoparticles. Scheme 1 outlines the strategy for preparing chiral micelles. A chiral substituted acetylene monomer with cholic acid group (ACA) was synthesized according to our previous report.34 ACA underwent solution polymerization in methanol in the presence of [Rh(nbd)Cl]2 and triethylamine (Et3N) catalytic complex. The obtained polymer (PACA) was first subjected to FT-IR spectroscopy. The FT-TR data are shown in Figure S1 in Supporting Information (SI, the same below). The disappearance of vibrational absorption peaks at 2100 cm−1 (CC group) confirmed the successful polymerization of

s a natural bile acid synthesized in liver, cholic acid (CA) possesses unique facial amphiphilicity and multiple functional group structures, which make it a significant building block for preparing biocompatible materials.1 Due to the structural rigidity and unusual structure of hydrophobic and hydrophilic regions, CA exhibits self-assembly property and can form distinctive supramolecular architectures with potential biological and medical applications. Depending on the type of CA-based polymers and self-assembly conditions, massive selfassembly aggregates with fascinating morphologies such as micellar structures,2−6 gel fibrils,7,8 tubules,9,10 wrinkled structures,11 and helical structures12,13 have been reported in recent years. Among these morphologies, CA-based micelles seem to be the most extensively explored type, as a promising class of drug delivery carriers due to their tunable physiochemical properties. Unfortunately, the chirality of CA has hardly been exploited yet. Moreover, despite the large number of CA-derived self-assemblies, synthetic helical polymers have not been involved in constructing the selfassemblies. The efforts along this direction may provide novel CA-based functional self-assembled architectures. As a proof-ofconcept work, the present article repots the first chiral micelles derived from helical polymer containing CA pendants. Chiral helical polymers have aroused much interest because of their intriguing optical activity.14−27 The unique property endows them with significant application in chiral related areas.28−30 We further hypothesize that self-assembly of synthetic helical polymers may create advanced functional architectures. The importance of such practices is more clearly demonstrated when considering the essential roles of biohelical © XXXX American Chemical Society

Received: October 22, 2016 Accepted: December 13, 2016

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DOI: 10.1021/acsmacrolett.6b00808 ACS Macro Lett. 2017, 6, 6−10

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ACS Macro Letters

Scheme 1. Schematic Illustration for (A) Preparing Chiral Micelles by Self-Assembly of Helical Polyacetylene Bearing Pendent Cholic Acid Derivative (PACA) and (B) Helix-Sense-Selective Polymerization of Achiral Monomer (M) in the Chiral Micelles

vis absorption spectroscopies (Figure 2). Obvious CD signal around 325 nm was observed when the polymer was dissolved

ACA. The result indicates the successful preparation of PACA. The obtained PACA was then subjected to GPC measurement. The number-average molecular weight (Mn) of PACA is 29400 and the polydispersity (Mw/Mn) is 2.90. To acquire more understanding of the polymer, PACA was subjected to DSC (Figure S2) and TGA (Figure S3) analyses. The results show that PACA possesses good thermal performance. Based on the self-assembly property of cholic acid molecule, we subsequently preformed the self-assembly of PACA in methanol/water mixture solvent and obtained the PACA micelles. Transmission electron microscopy (TEM) image of the PACA micelle solution clearly demonstrates the formation of spherical micelles, as presented in Figure 1. It shows that

Figure 2. (A) CD and (B) UV−vis absorption spectra of PACA measured at 25 °C. Spectrum a, PACA solution (approximately 1 mmol/L by monomer units) in methanol; spectrum b, PACA micelle solution (diluted 2× with deionized water) in water.

in methanol (Figure 2A, spectrum a), which is in well agreement with our previous findings concerning PACA.34 Kuhn dissymmetry factor37−39 gabs (defined as Δε/ε) was also calculated to quantitatively estimate the degree of preferential helicity of PACA. The gabs of PACA at 325 nm is 7.1 × 10−4. According to our previous work regarding helical polyacetylenes and the nano- and microarchitectures,33−37 the above results indicate the formation of predominantly one-handed helical conformations in PACA chains. In Figure 2B (spectrum a), an UV−vis absorption peak is also found at 325 nm, similar to the corresponding CD spectrum. We further used CD and UV−vis techniques to investigate whether the helical conformations of PACA chains could be changed during the self-assembly process. The recorded spectra of PACA micelles are illustrated in Figure 2. In Figure 2A,B (spectrum b), intense CD and UV−vis signals can be found at 325 nm, just the same as the aforementioned pure PACA (spectra a in both Figure 2A and B). Therefore, we conclude that the helical structures of PACA chains were not changed during the self-assembly process. In other words, the selfassembled PACA micelles also possess optical activity. With the PACA micelles in hand, we further anticipate that the self-assembled PACA micelles may play triple roles: (1) The micelles serve as nanoreactors for performing catalytic

Figure 1. (A) TEM image of PACA micelles and (B) diameter distribution of PACA micelles measured by DLS. The inset (in A) presents the corresponding self-assembled PACA micelle solution.

PACA micelles with average diameter of approximately 140 nm were obtained. It should be noted that the reason for the formation of nonuniform micelles is because of the relatively wide molecular weight distribution of PACA prepared using [Rh(nbd)Cl]2 catalytic complex. We also characterized the PACA micelles by dynamic light scattering (DLS), as presented in Figure 1B. The DLS result is very consistent with the observations in TEM image. According to the studies from others23−28 and us,33−36 the macromolecular helical structures of helical polyacetylenes can be explored by circular dichroism (CD) and UV−vis absorption spectroscopy measurements. To investigate the predominant helicity of polymer PACA, we characterized it by CD and UV− 7

DOI: 10.1021/acsmacrolett.6b00808 ACS Macro Lett. 2017, 6, 6−10

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ACS Macro Letters emulsion polymerizations, hereby directly constructing core/ shell polymer nanoparticles; (2) The chiral micelles provide a chiral origin to induce helix-sense-selective polymerization (HSSP) of achiral substituted acetylene monomers; (3) The PACA micelles act as a protective shell to improve the stability of the induced optically active polymer core due to its good thermal performance. Based on the above hypothesis, we further designed and carried out HSSP of achiral substituted acetylene monomer (M) in PACA micelles. The underlying strategy for HSSP is illustrated in Scheme 1B. First, achiral monomer (M, dissolved in tetrahydrofuran, THF) was added into the PACA micellar solution to prepare the monomer emulsion. Then Rh catalyst (dissolved in THF) was added to initiate the polymerization. After polymerization, core/shell structured nanoparticles were obtained, which were clearly confirmed by TEM images (Figure 3A,B). SEM image of the

Figure 4. (A) CD and (B) UV−vis absorption spectra of polymer emulsion measured at 25 °C. Spectrum a and b, core/shell nanoparticles emulsion and PACA micelle solution (both diluted 50 times with deionized water), respectively; spectrum c, polyM (the polymer derived from achiral monomer M) emulsion by using achiral emulsifier. (C) CD and (D) UV−vis spectra of core/shell nanoparticles solution under varied temperatures.

4A), which is due to the ultralow concentration of PACA micelle solution under the test conditions. Thus, we concluded that the Cotton effect observed in core/shell nanoparticles (λmax, 350 nm) cannot arise from PACA micelles, but from the induced preferential helical structures in polyM chains. To further confirm our assumption, we subsequently prepared polyM (the polymer derived from achiral monomer M) emulsion by emulsion polymerization using a typical achiral emulsifier Triton X-100. More details are placed in Experimental Section in SI. The Mn of polyM was found to be 8000, which convincingly confirm the successful polymerization of the monomer. Polymer nanoparticles were also obtained in this case and their average diameter was found to be approximately 100 nm (Figure S6). We further characterized the optical activity of the obtained polyM emulsion, as placed in Figure 4. No Cotton effect is observed around 350 nm in this control sample (Figure 4A, spectrum c). However, an obvious absorption peak is still found at about 350 nm in the UV−vis spectrum of the control polyM emulsion (Figure 4B, spectrum c). The observations demonstrate that in the control polyM sample, polyM adopted helical conformations; however, they were racemic helices, leading to no optical activity observed.41,42 We also blended the chiral PACA micelles with polyM (prepared in achiral conditions). The major process is presented in SI. However, no CD signal is found at 350 nm in this case either (Figure S7). The above results further indicate that chiral PACA micelles played a decisive role for constructing optically active core/shell nanoparticles by starting from achiral monomer through the HSSP process as presented in Scheme 1B. To acquire pure polyM cores, we next attempted to remove the shells by washing with methanol due to the different solubility of the core and shell. However, we found it difficult to exclude the shells completely because the core and shell both were constructed by substituted polyacetylenes. The obtained polyM core was characterized by TEM (Figure S8). No obvious

Figure 3. (A) TEM image of core/shell nanoparticles. (B) Magnified TEM image. The inset (in A) indicates the corresponding core/shell nanoparticles emulsion.

prepared core/shell nanoparticles is presented in Figure S4. DLS result shows that the average size of the core/shell nanoparticles was approximately 224 nm. Besides, we found no direct correlation occurring between the diameter of the particles and polymer yield, due to the wide size distribution of the PACA micelles. FT-IR spectra analysis was shown in Figure S5 in SI. A new peak appeared at 698 cm−1, which is assigned to the benzene ring moieties in polyM chains. The result further supported the successful fabrication of core/shell nanoparticles. To justify whether the chiral PACA micelles efficiently induced HSSP of the achiral monomer M, the obtained core/ shell nanoparticles were characterized by CD and UV−vis measurements, as presented in Figure 4. Pronounced positive CD signal is found around 350 nm for core/shell nanoparticles (spectrum a in Figure 4A). Meanwhile, strong UV−vis signal is also found around 350 nm (spectrum a in Figure 4B). Based on our previous series of work on helical polyacetylenes,33−37 the results (Figure 4, spectra a) indicate that the as-formed core/ shell nanoparticles possessed optical activity. Referring to our previous research,40 we found that the emulsion concentration had a big influence on the intensity of CD signal. In more detail, CD signal cannot be detected when the examined optically active polymer emulsion was diluted to an ultralow concentration. From Figure 2 we know that both PACA and its micelles exhibited Cotton effect and UV−vis absorption at a λmax of 325 nm. For a further comparison, we diluted the PACA micelles with deionized water to the same concentration of core/shell nanoparticles emulsion for CD and UV−vis techniques. However, no obvious CD signal can be observed at the wavelength range 300−500 nm (spectrum b in Figure 8

DOI: 10.1021/acsmacrolett.6b00808 ACS Macro Lett. 2017, 6, 6−10

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core/shell structure can be found in Figure S8 after washing with methanol. NMR data of the as-obtained polyM core are presented in Figure S9, confirming the formation of polyM core. CD and UV−vis results of the obtained polyM core are shown in Figure S10. In Figure S10A, a powerful CD signal is found around 350 nm, similar to the CD spectrum of core/shell nanoparticles (Figure 4A, spectrum a). It further demonstrates that the induced helicity in the polyM cores can be retained even after removing PACA shells. The above results definitely confirmed that HSSP successfully took place inside the PACA micelles. The chiral micelles provided the chiral source. When the achiral monomer was charged in the micellar solution, hydrogen bonds were formed between the chiral micelles and achiral monomer, which endowed the original achiral monomer with pseudochirality. In the course of polymerization, helical polymer with predominantly helicity was formed, resulting in optically active core/ shell nanoparticles. Herein it is noteworthy that after adjusting the diameter and concentration of chiral micelles, optically active core/shell nanoparticles with different sizes are anticipated in future. We tested another achiral monomer (M1, structurally presented in Figure S11) to undergo HSSP in the PACA micelles. However, no Cotton effect is observed in the wavelength range 300−500 nm in this sample (Figure S11), which may be due to the relatively less bulky pendant group in this monomer when compared with monomer M. In more detail, monomers with appropriate pendant group are needed to successfully undergo HSSP in the chiral micelles. After successfully preparing the core/shell nanoparticles, we subsequently researched the thermal stability of the induced predominantly helices of the polyM cores by CD and UV−vis measurements, as presented in Figure 4C,D. The CD and UV− vis signals hardly changed when temperature increased from 20 to 80 °C, indicating high thermal stability of the induced preferentially helical structures in polyM. Furthermore, the CD signal can remain stable at room temperature even for five months. As a control, we also performed HSSP of achiral monomer M by using achiral emulsifier Triton X-100 and (R)-(+)-phenethylamine according to our previous work.43 The detailed processes are presented in the SI. Figure S12 illustrates the TEM image of the prepared polyM nanoparticles. The Mn of polyM in this case was 8100. For comparison, we present in Figure S13 the temperature dependence of CD and UV−vis spectra of the obtained polyM emulsion. Obvious decrease takes place in CD and UV−vis signals when temperature increased to 80 °C. By comparing Figure 4 with Figure S13, we can conclude that the outside PACA shells dramatically improved the stability of the induced predominately macromolecular helices. The results further confirmed our hypothesis that PACA micelles can offer protection for the inside cores. In conclusion, novel chiral micelles were prepared for the first time by self-assembly of helical polyacetylene with cholic acid pendent groups. The micelles were further used as chiral nanoreactors to induce helix-sense-selective polymerization of achiral monomer, directly constructing optically active core/ shell nanoparticles. The micelles also provided a protective shell for the induced preferential structures in the cores. The present study largely extends our understanding on the self-assembly of synthetic helical polymer. Inspired by the strategy established in this work, more chiral self-assembly systems with complex morphologies and multifunctions can be expected in future.

Letter

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsmacrolett.6b00808.

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Materials, experimental details, and supplementary data (PDF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Jianping Deng: 0000-0001-9892-0654 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS

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REFERENCES

This work was supported by the National Natural Science Foundation of China (21474007, 21274008, 21174010) and the Funds for Creative Research Groups of China (51521062).

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