Precisely Controlling Dimerization and Trimerization in Topochemical

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Precisely Controlling Dimerization and Trimerization in Topochemical Reaction Templated by Biomacromolecules Xiaoyong Jia,† Mingjie Zhu,† Qiao Bian,† Bingbing Yue,† Yaping Zhuang,† Bin Wu,† Lin Yu,† Jiandong Ding,† Junji Zhang,‡ and Liangliang Zhu*,† †

Macromolecules Downloaded from pubs.acs.org by UNIV OF SUNDERLAND on 10/03/18. For personal use only.

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, P. R. China ‡ Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science & Technology, Shanghai 200237, P. R. China S Supporting Information *

ABSTRACT: Topochemical reactions can be effectively conducted without additional reagents and solvation requirements. Hence, they are attractive in various fields of modern chemistry. However, there remains a lack of ways to precisely control the degree upon topochemical polymerization or oligomerization. As compared with yielded π-structured polymers, a slight difference in repeating unit of their oligomeric counterparts can normally connect to distinct visualized optoelectronic properties in the UV−vis region. Therefore, we herein report that the well-selected biomacromolecular templates were straightforwardly employed to attain a precise control of topochemical photooligomerization degree for a series of uniform oligomeric π-functional materials. A diphenyldiacetylene prototype was designed and electrostatically interacted with BSA (albumin from bovine serum), DNA (calf thymus), and HS (heparin sodium), and their binding constant exhibited a progressive order of magnitude. In this way, photooligomerization control for uniquely forming corresponding dimeric and trimeric oligodiacetylenes can be successfully achieved upon photoirradiation with the template optimized from the perspective of adjustable dynamic equilibrium. Furthermore, two of the oligodiacetylene species reveal blue and yellow fluorescence and therefore can be applied into selective and multichannel bioimaging with good biocompatibility on account of their biomacromolecular templates, featuring the advantage of obtaining species with repeating-unit difference for material applications.

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INTRODUCTION Molecular weight (MW) control is always an important issue in numerous cases of polymerization and oligomerization.1−3 In particular, it has drawn increasing attention in those topochemical reactions, since the chemistry can effectively work without additional reagents and solvation requirements and the related functionality-oriented products can accordingly perform promising applications in various fields.4−8 Unlike unimolecular behaviors with less stringent requirements to engineer reactivity with constrained media, topochemical transformations largely rely on preorganization of the reactive components to facilitate bond-making and bond-breaking through minimal atom displacement.9,10 To align the reactants, the past years have witnessed a series of ordered systems, such as crystals,11,12 self-assembly monolayers,13,14 porous materials,15−17 block copolymers,18,19 etc., to serve as templates for effectively directing diverse topochemical polymerizations and oligomerizations. However, to the best of our knowledge, polymerization and oligomerization degrees of such leading species remain out of precise control, probably due to the lack of smart and optimized intermolecular alignment fashions. © XXXX American Chemical Society

Interestingly, biomacromolecules including peptide or nucleotide structures can flexibly bind with well-defined chemical components through noncovalent interactions with different altitude.20−24 Thus, we sought to exploit the way of harnessing biomacromolecular templates to investigate the control of topochemical reaction degree through a preorganization design from the perspective of adjustable dynamic equilibrium. Among the variety of topochemical systems, diacetylene is a typical prototype with unique structural, photophysical, and electronic properties and thus can show talented potential in bioelectronic materials, optoelectronic devices, and sensors.25−35 Since Wegner reported the first example of diacetylene polymerization in the solid state,36 it has been well-known that molecular preorganization plays a key role in its topochemical 1,4-addition reaction by heating or UV irradiation to form ene−yne bond chains.37−43 Compared with the conventional diacetylene compounds, the aromatized Received: August 24, 2018 Revised: September 11, 2018

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DOI: 10.1021/acs.macromol.8b01824 Macromolecules XXXX, XXX, XXX−XXX

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Figure 1. Schematic representation of DPDA and its noncovalent bonding with indicated biomacromolecular templates, followed by photopolymerization to different degrees with a yield of uniquely dimeric or trimeric oligodiacetylenes, or probably coexisting after irradiation.

electrostatic force can ideally lead to various degrees of photooligomerization, resulting finally in oligodiacetylenes with dimerization and trimerization precisely controlled.

derivative named diphenyldiacetylene (DPDA) attracted a great deal of interest for its unique advantages, such as its extended π-conjunction and large intermolecular organization tendency, enabling more extensive luminescent properties and applications of cross-linked DPDA.44−51 In this work, we attempted to address the degree control of the photo-crosslinked DPDA and thus may apply the distinct luminescent properties of the leading oligodiacetylenes with repeating-unit difference into those precise and selective events of molecular sensing and labeling. To tackle the challenge of precisely controlling the topochemical reaction of DPDA, we employ a series of wellselected biomacromolecules to involve the noncovalent dynamic equilibrium in templating the reaction process. Additionally, a wide range of biomaterials with innate biocompatibility provide a rich choice for different designs and application purposes. Herein, we designed a DPDA derivative containing two quaternized imidazoles (DPDA, see synthetic route and details in the Supporting Information). It has a good solubility in aqueous media and can form electrostatic interaction with negatively charged species. As is known, the electrostatic interaction is a weak reversible force and is frequently connected with a dynamic equilibrium of formation and dissociation, which is similar to host−guest and π−π interactions.52−54 Three kinds of negatively charged biomacromolecular templates were optimized in this study. BSA (albumin from bovine serum) is an albumin in bovine serum containing a variety of amino acid residues, which makes BSA rich in negatively charged groups.55,56 DNA (calf thymus) is a doublehelix structure macromolecule with a phosphate backbone that can bind with cations.57−59 In addition, HS, namely heparin sodium, is a highly sulfated linear glycoaminoglycan and known as a most negatively charged biological macromolecule, bearing repeating units of 2-amino-2-deoxyglucopyranose residues and pyranosyluronic acid.60,61 Thus, monomer DPDA could be expected to form hybrid self-assemblies along with these biomacromolecular templates, followed by topochemical reaction under 254 nm irradiation. Because the three templates are composed of different negatively charged functional groups, the strength of the electrostatic force formed with DPDA would be different. The strength of the

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RESULTS AND DISCUSSION Study for Photooligomerization through Optical Properties. To explore the noncovalent interaction, the biomacromolecular templates were added into Tris-HCl buffer solution (10 mM, pH = 7.5) of DPDA with a fixed concentration (10 μM) progressively to yield three hybrid self-assembled materials named DPDA@BSA, DPDA@DNA, and DPDA@HS. For the emission spectra (Figure S1), the band around 415 nm increased slightly with addition of templates, whereas it became stationary when the amount of biomacromolecular templates reached a certain value, which was 24 μM for BSA, 18 μM for DNA, and 1.6 μM for HS (Figure S2). Therefore, we collected their UV−vis absorption spectra with stepwisely increasing the concentration of templates to the above value. The absorption signals of the band at 296, 316, and 338 nm decreased continuously, while those at 265 and 278 nm kept increasing until a relatively broad band formed (Figure S1). Through ITC, we calculated their binding constant as 49000, 8900, and 1100 M−1 for HS, DNA, and BSA, respectively. (Figure S3). Despite the fact that some other noncovalent interactions may exist, we believe the gradient binding constants were dominantly caused by electrostatical forces between quaternized imidazole of DPDA and different negatively charged groups in these biomacromolecules. Upon the establishment of these hybrid materials, we turned to investigate the template effect toward the topochemical reaction of DPDA in aqueous solution. As the luminescent signal of the ene−yne structures is sensitive to π-conjugation length, we analyzed the emission spectra to illustrate the reaction progress first. Derivatives of diaryldiacetylenes usually show a clear transition from weak/no fluorescence to strong fluorescence owing to the enlargement of the π-conjugated skeleton. No apparent change on the emission band of DPDA in buffer solution was recorded before and after photoirradiation at 254 nm for 30 min, which indicated that the topochemical reaction of the free DPDA monomer cannot proceed appreciably without preorganization (Figure S4a). In B

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Figure 2. Template photooligomerization monitored by optical signal in Tris-HCl buffer solution (10 mM, pH = 7.5). The emission spectra of DPDA (3.0 × 10−5 M) containing (a) BSA (7.2 × 10−5 M), (b) DNA (5.4 × 10−5 M), and (c) HS (0.48 × 10−5 M) and the UV−vis absorption spectra containing (d) BSA (7.2 × 10−5 M), (e) DNA (5.4 × 10−5 M), and (f) HS (0.48 × 10−5 M) after photoirradiation for 5 min.

Figure 3. Characterization of the products after photooligomerization: (a) TEM images of DPDA, DPDA-D@BSA, DPDA-DT@DNA, and DPDA-T@HS prepared from their corresponding aqueous solutions. (b) Photograph of DPDA-D@BSA, DPDA-DT@DNA, and DPDA-T@HS under a 365 nm UV lamp (top) and sunlight (bottom).

contrast, notable changes were seen in the emission spectra of the solutions containing biomacromolecular templates. These hybrid systems involved fast reaction, and the reaction process could be expected to be completed in 5 min until the spectral variations became saturated (Figure S5). In the case of DPDA@BSA, a strong emission band around 415 nm (Figure 2a) corresponding to blue fluorescence (Figure 3b) was observed after photoirradiation, while a strong band around 540 nm (Figure 2c) corresponding to yellow fluorescence (Figure 3b) appeared in the case of DPDA@HS. Simultaneously, two strong emission bands which lay around 415 and 540 nm appeared in the spectrum of DPDA@DNA after photoirradiation (Figure 2b) and showed their mixed luminescent color of light white (Figure 3b). By collecting their absorption spectra before and after 254 nm irradiation, we observed a similar tendency of the template photooligomerization. The absorption spectra of free DPDA

monomer just displayed negligible change after photoirradiation (Figure S4b). In contrast, the absorption spectral variations of the hybrid systems became saturated after photoirradiation for 5 min (Figure S6). The broad absorption band from 350 to 500 nm emerged while the peaks around 335, 315, 300, and 260 nm underwent a significant decrease after photoirradiation of 5 min. Whereas three templates led to the different intensity of newly emerged absorption band, and the absorbance reached 0.103, 0.165, and 0.332 for BSA, DNA, and HS. This phenomenon has been observed in other similar DPDA derivatives.62−64 An apparent color change from colorless to yellow after photoirradiation was also observed in the solution of these hybrids (Figure 3b). We also acquired the circular dichroism (CD) spectra to further confirm the interaction between DPDA and these templates. The Cotton effect appearing at wavelengths in accordance with the absorption band of DPDA (300−360 nm) undoubtedly C

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Figure 4. MW study of photooligomerization: (a) MALDI-TOF MS spectrum of dimer obtained from DPDA-D@BSA, (b) MALDI-TOF MS spectrum of trimer obtained from DPDA-T@HS, (c) GPC traces of the DPDA and templates samples after UV irradiation, and (d) a proposed mechanism for indicating the influence of electrostatic interaction with a dimer intermediate.

to a moderate electrostatic force between DPDA and templates such as DNA. Finally, the MS spectrum of DPDA-T@HS shows a signal around m/z 1356 (Figure 4b), which corresponds to the trimer of the oligodiacetylenes without the signal from dimer. It suggests that trimer could be formed uniformly after photoirradiation upon a relatively strong electrostatic force between DPDA and templates such as HS. No signal from a species of higher polymerization degree could be observed in these spectra (Figure S11), signifying that a clear photooligomerization with distinct MW control was achieved. In this way, the emission spectra can be correspondingly associated with these spectral data, and we can unambiguously conclude that the emission band around 415 nm originated from the dimericoligodiacetylene while the emission band around 540 nm originated from the trimeric species, as illustrated in Figure 2. On the basis of these results, we turned to carry out their gel permeation chromatography (GPC) to prove an overall scheme of the photooligomerization degree. Figure 4c shows the GPC chromatograms of reacted DPDA with template photooligomerization. As DPDA monomer shows one peak only at retention time 42.20 min, we can see that DPDA-D@ BSA shows one peak around the retention time 41.10 min and another one at the retention time 42.20 min, corresponding to dimer and the monomer according to the calculated MW (Table S1), respectively. The DPDA-DT@DNA shows three peaks around retention times 42.20, 41.10, and 39.25 min, and they can be assigned to monomer, dimer, and trimer, respectively. The DPDA-T@HS shows two peaks at retention times 42.20 and 39.25 min, corresponding to monomer and trimer, respectively. It should be emphasized that these biomacromolecular templates have been removed by column chromatography for the GPC characterization, featuring an isolatable template synthesis method owing to the dynamic characteristic of the electrostatic interaction. This is consistent with the DLS data (Figure S8). As mentioned above, the BSA, DNA, and HS have different strengths of electrostatic interaction with DPDA, which always keep a certain dynamic equilibrium between self-assembly and

suggests a successful formation of the hybrid systems (Figure S7). TEM images showed that the morphology of DPDA species could be greatly affected upon these template reactions. The DPDA self-assembled in a scattered state without biomacromolecular templates. However, with the addition of the templates, DPDA monomers can be arranged along these templates. Thus, after irradiation, these leading structures displayed morphology similar to their corresponding biomacromolecular templates (Figure 3a). The size change of the assembled structures can be well distinguished by dynamic light scattering (DLS, see Figure S8). Study for Photooligomerization Degree. With all these results above, we can assume that different photooligomerization degrees can be reached by altering these biomacromolecular templates, as ene−yne structures with more repeating units (i.e., longer π-conjugated backbone) normally bring in bathochromically shifted absorption/emission bands. From the binding constant calculated from ITC, we speculated that the strength of the binding interaction might profoundly affect the topochemical reaction degree of DPDA. Through the emission spectra, we can infer that oligodiacetylenes with different MWs formed using these templates after photoirradiation. To validate this hypothesis, the molecular weight of these leading products was measured by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF). The MS spectrum of theDPDA monomer shows a signal around m/z 452 (Figure S9). By measuring the MALDI-TOF MS spectra of DPDA-D@BSA, a main signal around m/z 904 is observed (Figure 4a), which corresponds to the dimer of the oligodiacetylenes. No trimer or other oligodiacetylene signals with more repeating units were detected, implying that dimer formed uniformly after photoirradiation because of a relatively weak electrostatic interaction between DPDA and templates such as BSA. Simultaneously, the MS spectrum of DPDA-DT@DNA displays two signals around m/z 904 and 1356 (Figure S10), which correspond to the dimer and the trimer of the oligodiacetylenes, respectively. This result indicates that both dimer and trimer could be formed after photoirradiation owing D

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investigate the cellular imaging behavior of three photocross-linked DPDA in the hybrid systems using confocal laser scanning microscopy (CLSM). As the control of photooligomerization degree of DPDA resulted in distinct luminescent property, these leading systems would show channel selective imaging effect when taken up by cells. We employed human mesenchymal stem cells (hMSCs) as the model cells, which are very important in tissue engineering and regenerative medicine.67 After incubation of DPDA-D@BSA with hMSCs, a laser excitation gave rise to an emission only observed at the 408 nm channel (Figure 5a),

dissociation. The stronger electrostatic force normally makes a stronger self-assembly and a weaker dissociation. Hence, we can resolve the total reaction process like this: The three hybrid systems performed similarly under photoirradiation for a few seconds and the emission band around 415 nm emerged, implying that the dimer formed first (Figure S5). With the prolonged irradiation, the emission spectra of DPDA@BSA around 415 nm gradually increased without generating a new emission band, indicating only the dimer formed in DPDA@ BSA. While in DPDA@DNA, a new emission band around 540 nm emerged, suggesting that the trimer started to form until equilibrium was reached between the trimeric and dimeric species. For DPDA@HS, however, the dimer emission band gradually disappeared with the emerging and increasing of the trimer emission band, which is in accordance with the fact that only the trimer could be formed in DPDA@HS. We could assume that a stronger electrostatic force can lead to a larger local molecular concentration of DPDA, which is favorable for the formation of the trimer rather than the dimer. DPDA monomers can form an orderly arrangement after biomacromolecules are added in. The electrostatic interaction between DPDA and biomacromolecules is always kept in a certain dynamic equilibrium between self-assembly and dissociation. Then under irradiation for a few seconds, dimers formed first. When the electrostatic force is weak such as BSA to DPDA, it is easy to dissociate after the formation of dimers, and it will be insufficient to form trimers along with the dissociation. On the other hand, when the electrostatic force is strong such as HS to DPDA, it is hard to dissociate after the formation of dimers, and it will successively form trimers rather than dissociation. The formed dimers also kept an orderly arrangement with surrounding monomers to enable the trimer generation (Figure 4d). For the BSA system after the formation of dimers, it will have a fast dissociation speed and cannot form an orderly arrangement between the monomers and dimers because of the weak electrostatic force; thus, the trimers cannot form. For the HS system, it has a stronger electrostatic force than the BSA system, and trimers can form in that case. After the formation of the trimers, the electrostatic force will not be strong enough to keep the trimers and monomers in an orderly arrangement, and further reaction will stop. To further support this mechanism, the study for the ratio change between the templates (even some synthetic polymer templates) and DPDA was performed (Figures S12 and S13). These results suggest that the noncovalent interaction strength should be the key factor for this topochemical reaction, since the molecular chain was kept in a relatively free state in water solution and the structural effect of the biomacromolecules can be minimized. Photooligomerization Application in Cell Imaging Study. As tunable molecular photoluminescence property has become crucial in diverse needs of bioimaging and labeling,65,66 we turned to seek the application of their individual and complementary luminescent properties at the cellular level upon precisely controlling the dimeric and trimeric oligodiacetylene formation. Cytotoxicity evaluation is an important parameter to be considered for developing a new biomaterial system. In this work, accounting kit-8 (CCK8) assay was conducted to test whether cytotoxicity effects would emerge in our materials. Through cell viability examination, no obvious cytotoxicity was observed at low concentration from 1 to 10 μM after 24 h incubation (Figure S14), reflecting an excellent biocompatibility in aqueous media. Then, we turned to

Figure 5. Multichannel selective bioimaging: CLSM images of hMSCs in the presence of (a) DPDA-D@BSA, (b) DPDA-DT@ DNA, and (c) DPDA-T@HS at channels of 408 and 564 nm and merged image. The scale bars refer to 100 μm.

while the cells incubated with DPDA-T@HS reveal brightness at the 564 nm channel only (Figure 5c). When the cells were incubated with DPDA-DT@DNA, a duplexed luminescence from both channels of 408 and 564 nm (Figure 5b) is exhibited. These phenomena are in agreement with their emission property discussed above. Their merged cell images show comparable performance with their luminescent pictures in solution. Thus, through precise control of the MW of the oligodiacetylenes upon the template reaction, we have achieved the selectivity of luminescence imaging with different channels at the cellular level.

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CONCLUSIONS In summary, a biomacromolecular template strategy described here has enabled us to effectively regulate the topochemical photooligomerization degree. This strategy takes advantage of electrostatic interactions between DPDA and negatively charged biological templates for realizing the dimerization and trimerization control of oligodiacetylenes. Dimer can be uniquely formed after photoirradiation in the presence of BSA while the electrostatic force is relatively weak, while dimer and trimer can both be yielded along with an enhanced electrostatic interaction templated by DNA. Further strengthening the electrostatic force by using HS as template, we can find only trimer was yielded upon irradiation. The distinct luminescent properties of the dimeric and trimeric oligodiacetylenes are accompanied by an individual and complemenE

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(CCK-8) assays. Huma mesenchymal stem cells (hMSCs) were obtained from the Cell Bank of the Chinese Academy of Sciences (Shanghai, China) and were seeded into a 96-well plate at a density of 1 × 10−4 cells per well in Dulbecco’s modified Eagle medium (DMEM) containing 10% fetal bovine serum (FBS) under 5% CO2 at 37 °C. After the cells grew for 12 h, the medium was changed into a new medium (200 μL/well) containing materials at 1, 2, 5, 10, and 20 μM concentrations. After the cells were incubated with the sample for 24 h, the medium was replaced with 100 μL of fresh medium. Subsequently, 10 μL of CCK-8 was added to each well and homogeneously mixed, followed by incubation in a CO2 incubator at 37 °C for 4 h, and finally, 80 μL of the solutions was put into a new 96-well plate. After incubation for 3 h, the absorbance at 450 nm in each well was determined using a microplate reader (Multiskan Mk3). The relative cell viability was calculated to quantify the cytotoxicity. Confocal Microscopic Images. HMSC cells were seeded in 35 mm plastic-bottomed m-dishes and grown in DMEM medium for 24 h. Then the cells were treated with materials (10 μM) for another 4 h. The cells were washed with a phosphate buffer saline (PBS) solution (pH 7.4) three times and fixed with polyformaldehyde at 4 °C for 15 min. The luminescence images of the cells were captured using a Nikon laser scanning confocal microscope. Association Constant K between the DPDA and Biological Templates. The association constant between DPDA and the three biological templates in Tris buffer solution was determined by ITC (isothermal titration calorimetry). All ITC measurements were performed in triplicate using a Microcal PeaQ- ITC with a 200 μL sample cell, 40 μL titration syringe, 1−5 μL injection volumes, and 240−600 s interval between injections, as dictated by the experiment. In the figures of ITC measurements, the top panel shows the raw ITC data (power vs time), where each spike represents the injection of titrant into the cell, and the bottom panel shows the integrated and normalized heat plotted vs the molar ratio of titrant (syringe) to titrand (cell). Data were fit using the Origin software from MicroCal. The concentration of DPDA was added to the cell, and it was kept at 1.0 × 10−4 M; the volume was 200 μL. The templates were added to the syringe; concentration for the BSA, DNA, and HS was 2.0 × 10−3, 2.0 × 10−3, and 2.0 × 10−3 M, and the volume was 40 μL. The injection volume was 2 μL each time.

tary spectral region coverage as well as an excellent biocompatibility complexed with the biomacromolecular templates, which together make the hybrid system suitable for selective and multichannel bioimaging. We believe that the interdisciplinary strategy demonstrated in this study is valuable for applying in other topochemical reactions that can be related to versatile material functions.

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EXPERIMENTAL SECTION

General. 1H NMR and 13C NMR spectra were measured on a Bruker 400L spectrometer. High-resolution mass spectrometry (HRMS) data were measured by a matrix-assisted laser desorption ionization-time-of-flight/time-of-flight mass spectrometer (5800). The UV−vis absorption spectra were recorded on a Shimadzu 1800 spectrophotometer. The emission spectra were recorded on a Shimadzu RF-5301. The photoirradiation was performed using a hand-held UV lamp with the irradiation wavelength of 254 nm in a sealed 10 mm quartz cell. Transmission electron microscopy (TEM) was performed on a Jeol JEM 2100 with an accelerating voltage of 200 kV. The confocal microscopic images were captured by Nikon C2+ confocal microscope. The polymeric species were analyzed with an Agilent 1260 gel permeation chromatograph (GPC) equipped with a UV detector and calibrated with polystyrene standard samples. All isothermal titration calorimetry (ITC) measurements were performed in triplicate using a Microcal PeaQ- ITC. See the Supporting Information for the scheme pertaining to the compound labels below. Synthesis of Compound 1. The preparation for this compound was according to a similar procedure described in the literature.68 Synthesis of Compound 2. A solution of compound 1 (0.4653 g, 2 mmol) in anhydrous acetone (15 mL) was added dropwise into the mixture of dibromoethane (3.5 mL, 40 mmol) and potassium carbonate (2.7865 g, 20 mmol) in anhydrous acetone (15 mL). The mixture was allowed to reflux overnight under N2. The solvent was removed by a rotary evaporator, and the residue was purified by silica gel chromatography (petroleum ether/dichloromethane = 10:1) to afford pale yellow compound 2 (0.7562 g, 84.9%). 1H NMR (400 MHz, CDCl3, 298 K): δ 7.49−7.43 (m, 4H), 6.89−6.84 (m, 4H), 4.30 (t, J = 6.3 Hz, 4H), 3.64 (t, J = 6.3 Hz, 4H). 13C NMR (100 MHz, CDCl3, 298 K): δ 157.68, 133.12, 113.79, 113.67, 80.06, 72.11, 66.80, 27.68. MS (Maldi-Tof): calcd for [M + H]+ m/z = 448.9; found m/z: 448.1. Synthesis of Compound 3. Compound 2 (0.2260 g, 0.05 mmol) was added into the mixture of imidazole (0.3591 g, 5.2 mmol) and KOH (0.2891 g, 5.1 mmol) in acetonitrile (30 mL). The mixture was stirred at 80°C for 8 h and cooled to room temperature. After a flash column chromatography (ethyl acetate/methanol = 9:1), the crude product was further washed with deionized water (10 mL) and dried under vacuum to obtain the white compound 3 (0.1697 g, 79.6%). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 7.79 (s, 2H), 7.56−7.49 (m, 4H), 7.29 (t, J = 1.1 Hz, 2H), 7.02−6.97 (m, 4H), 6.95 (s, 2H), 4.42−4.36 (m, 4H), 4.34−4.29 (m, 4H). 13C NMR (100 MHz, CDMSO-d6, 298 K): δ 159.52, 138.09, 134.56, 128.79, 120.16, 115.63, 113.28, 81.96, 73.24, 67.83, 45.85. MS (Maldi-ToF): calcd for [M + H]+ m/z = 423.2; found m/z: 423.3. Synthesis of Compound DPDA. Compound 3 (0.1577 g, 0.37 mmol) was dissolved in iodomethane (20 mL) and refluxed overnight. After cooling to room temperature, iodomethane was removed by a rotary evaporator, and the residue was washed by anhydrous tetrahydrofuran (20 mL) and dichloromethane (20 mL) to obtain an orange solid (0.1815 g, 68.8%). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 9.17 (s, 2H), 7.81 (t, J = 1.8 Hz, 2H), 7.72 (t, J = 1.8 Hz, 2H), 7.60−7.49 (m, 4H), 7.07−6.98 (m, 4H), 4.65−4.56 (m, 4H), 4.45−4.36 (m, 4H), 3.87 (s, 6H). 13C NMR (100 MHz, CDMSO-d6, 298 K): δ 159.19, 137.51, 134.59, 124.02, 123.26, 115.76, 113.59, 81.93, 73.29, 66.45, 48.78, 36.34. MS (Maldi-ToF): calcd for [M − 2I−]+ m/z = 452.2; found m/z: 452.2. In Vitro Cytotoxicity Assay. The cell viability of DPDA oligomers was quantitatively determined by the cell counting kit-8

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.8b01824. Experimental data of synthetic scheme, UV−vis spectra, emission spectra, ITC, HRMS, GPC data, DLS and CD spectra (PDF)

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AUTHOR INFORMATION

Corresponding Author

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

Lin Yu: 0000-0001-7660-3367 Jiandong Ding: 0000-0001-7527-5760 Junji Zhang: 0000-0003-2823-4637 Liangliang Zhu: 0000-0001-6268-3351 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the NSFC/China (21628401) and partially from the Program of Thousand Young Talents of China. We thank Mr. C.-D. Gao for assistance with the ITC measurements. F

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DOI: 10.1021/acs.macromol.8b01824 Macromolecules XXXX, XXX, XXX−XXX