Pathway complexity in supramolecular polymerization

Bioinspired, kinetically controlled seeded growth has been recently shown to provide length, dispersity, and sequence control on the primary structure of dynamic supramolecular polymers. However, command over the molecular organization at all hierarchical levels for the modulation of higher order structures of supramolecular polymers remains a formidable task. In this context, a surface-catalyzed secondary nucleation process, which plays an important role in the autocatalytic generation of amyloid fibrils and also during the chiral crystallization of small monomers, offers exciting possibilities for topology control in synthetic macromolecular systems by introducing secondary growth pathways compared to the usual primary nucleation-elongation process. However, mechanistic insights into the molecular determinants and driving forces for the secondary nucleation event in synthetic systems are not yet realized. Herein, we attempt to fill this dearth by showing an unprecedented molecular chirality control on the primary and secondary nucleation events in seed-induced supramolecular polymerization. Comprehensive kinetic experiments using in situ spectroscopic probing of the temporal changes of the monomer organization during the growth process provide a unique study to characterize the primary and secondary nucleation events in a supramolecular polymerization process. Kinetic analyses along with various microscopic studies further reveal the remarkable effect of stereoselective nucleation and seeding events on the (micro)structural aspects of the resulting multicomponent supramolecular polymers.

Open AccessCCS ChemistryRESEARCH ARTICLE18 May 2022In Situ Supramolecular Polymerization via Organometallic-Catalyzed Macromolecular Metamorphosis Xiwen Yang, Qianqian Ji, Jiaxiong Liu and Yiliu Liu Xiwen Yang South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, Guangzhou 510640 , Qianqian Ji South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, Guangzhou 510640 , Jiaxiong Liu South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, Guangzhou 510640 and Yiliu Liu *Corresponding author: E-mail Address: [email protected] South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, Guangzhou 510640 https://doi.org/10.31635/ccschem.022.202201936 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Integrating catalytic reactions with molecular assembly is a promising means of achieving controllable supramolecular polymerization. We report herein a novel and controllable method for in situ supramolecular polymerization via organometallic-catalyzed macromolecular metamorphosis. To this end, covalent polymers with polypentenamer backbones and pendant supramolecular motifs are designed and synthesized. By depolymerizing the polymers with Grubbs catalysts, the supramolecular motifs can be gradually released from the polymers to the solution. Supramolecular polymerization occurs when a critical concentration is reached. The supramolecular polymerization process was readily controlled by varying the rate of the depolymerization reaction. This work presents a novel approach that uses organometallic catalysis to transform covalent polymers into supramolecular polymers. It offers a new means of constructing complex molecular systems in a controllable manner. Download figure Download PowerPoint Introduction Supramolecular polymers, whose polymeric chains are formed by non-covalently connected monomers, hold great promise in developing functional materials with applications in optoelectronics, pharmaceutics, and recyclable plastics.1–6 The rational control of the supramolecular polymerization process is very important for the construction of supramolecular polymers with desired structures and functions. Therefore, the development of controllable supramolecular polymerization (CSP) methods is always a major focus of research in supramolecular polymer chemistry.7–11 Lately, a comprehensive understanding of molecular assembly processes, such as pathway selection and solvent effects, has greatly advanced the field of supramolecular polymerization.12–16 Several novel concepts, such as seeded living supramolecular polymerization,17–20 chain-growth supramolecular polymerization,21,22 supramolecular interfacial polymerization,23,24 and fuel-driven supramolecular polymerization,25–28 have been established. Nevertheless, compared with nature's ability to construct biological analogues of supramolecular polymers (e.g., microtubules and actin filaments), enormous challenges remain in the preparation of supramolecular polymers under precise temporal and spatial control.11,29 One powerful tool that nature utilizes is catalysis, which offers kinetic control over the assembly process to achieve emergent structures and functions.30–32 Therefore, integrating catalytic reactions with molecular assembly is legitimately considered a promising means of achieving CSP. For example, enzymatic catalysis has been successfully introduced to instruct the formation of transient supramolecular polymers in a controllable manner.32 Organometallic-catalyzed reactions that cover a broad range of catalysts and substrates, however, have still rarely been explored to drive or regulate supramolecular polymerization. Herein, we report a new method for in situ supramolecular polymerization via organometallic-catalyzed macromolecular metamorphosis. The basic concept utilizes organometallic-catalyzed depolymerization reactions to controllably transform covalent polymers into supramolecular polymers (Scheme 1). Generally, supramolecular motifs intended for supramolecular polymerization are modified on degradable covalent polymers as pendant groups. In this state, the supramolecular motifs remain unaggregated or ill-aggregated because of the structural constraints imposed by the polymer chains. Upon depolymerization, the supramolecular motifs are gradually released from the covalent polymers to the solution, where they form supramolecular polymers when a critical concentration is reached. The macromolecular metamorphosis from covalent polymers to supramolecular polymers can be readily tuned by varying the rate of depolymerization, thereby providing a means of kinetically controlling the supramolecular polymerization. Scheme 1 | Organometallic-catalyzed macromolecular metamorphosis: in situ transformation from covalent polymers to supramolecular polymers. Download figure Download PowerPoint Experimental Methods All reagents were purchased from commercial suppliers and used as received without further purification. 1H, 13C, and 19F NMR spectra were recorded with a JNM-ECZ500R 500 MHz NMR (JEOL, Tokyo, Japan) or Bruker Avance 400 MHz NMR spectrometer or Bruker Avance 500 MHz NMR spectrometer (Bruker, Switzerland. The high-resolution mass spectra were recorded on an Agilent1290/maXis impact high-resolution liquid chromatography mass spectrometer (LC-MS). Molecular weights and distributions were determined by gel permeation chromatography (GPC) with a Waters ACQUITY UPLC sample manager and a Waters ACQUITY differential refractive index detector; polystyrene was used as the standard. UV–vis absorption spectra in solution were recorded using a UV-3600Plus spectrophotometer (Shimadzu, Nakagyo-ku, Kyoto, Japan). The fluorescence spectra were recorded on an RF-6000 spectrofluorophotometer (Shimadzu, Nakagyo-ku, Kyoto, Japan). Atomic force microscopy (AFM) measurements were performed under ambient conditions using a Cypher VRS system operating in tapping mode in air (Oxford Instruments Asylum Research, Santa Barbara, California, United States). Silica cantilevers (AC200TS-R3, Oxford Instruments, Taiwan, China) with a resonance frequency of ∼150 kHz and a spring constant of ∼9 N m−1 were used. More experimental details are available in Supporting Information. Results and Discussion Polymer design and synthesis In our design, the covalent polymers (PCPs) was composed of a polypentenamer-based backbone functionalized with 3,6-di(thiophen-2-yl)-4,5-dihydropyrrolo[3,4-c]pyrrol-1(2H)-one (DPP) and polyoctahedral silsesquioxane (POSS) derivatives as pendant groups (Scheme 2). The polypentenamer-based backbone was chosen for its unique catalytic degradability by the ring-closing metathesis reaction.33–35 In particular, Kennemur and coworkers34 demonstrated that the polypentenamers can be transformed into other architectures through post-depolymerization reactions. The DPP derivative, which contains a planar π-conjugated core and hydrogen-bond-forming amide moieties, was chosen as the supramolecular motif.36–38 POSS-based pendant groups were introduced to endow the polymer with good solubility in low-polarity solvents.39,40 The steric structure of the POSS pendant groups was also thought to provide structural constraints that prevent the aggregation of the DPP moieties on the polymer chains. Scheme 2 | Polymer design: a polypentenamer backbone with DPP- and POSS-based pendant groups. Download figure Download PowerPoint The protocol of the organometallic-catalyzed macromolecular metamorphosis is described in Scheme 3. The PCP polymers are depolymerized continuously by ring-closing metathesis reactions catalyzed by the Grubbs catalysts. Thus, the cyclopentene-based monomers with different pendant groups, namely POSS-M and DPP-M, are gradually released from the polymeric chains into the solution. Without the structural constraints imposed by the polymer chains, the DPP-Ms are expected to undergo supramolecular polymerization in solution. Scheme 3 | Proposed protocol of the organometallic-catalyzed macromolecular metamorphosis. Download figure Download PowerPoint A post-polymerization modification strategy was used to synthesize the designed PCP polymers.41–43 This involves first synthesizing a precursor polypentenamer (PCP-0) that contains pentafluorophenyl ester moieties. Direct polymerization of the pentafluorophenyl ester containing cyclopentene monomer was infeasible; therefore, an indirect multistep synthetic route was employed instead. Polymerization of methyl cyclopent-3-ene-1-carboxylate, followed by hydrolysis of the methyl ester and esterification of the obtained carboxylic acid moieties with pentafluorophenyl trifluoroacetate, readily gave the desired PCP-0 (see Supporting Information Figure S4 for detailed synthetic procedure). Due to the high reactivity between pentafluorophenyl esters and amines, PCP-0 reacted efficiently with the amino-group containing DPP and POSS derivatives, straightforwardly producing the desired polymers PCP-1, PCP-2, and PCP-3 after dialysis (Figure 1). PCP-1 contained only POSS pendant groups, whereas PCP-2 and PCP-3 contained 5% and 20% DPP pendant groups, respectively. The GPC results of the PCP polymers are included in Table 1, and reveal that the molar mass dispersity values of all PCP polymers remained narrow after the post-polymerization modification of PCP-0. Because a low-polarity solvent was necessary for the proposed macromolecular metamorphosis, the solubility of the obtained PCP polymers in methyl cyclohexane (MCH) was determined first. To our delight, although these polymers contain many amide moieties alongside the polymer backbone, they solubilize well in MCH, most likely because of the solubilizing POSS pendant groups. Figure 1 | Synthesis of the polypentenamer-based covalent polymers (PCP-1, PCP-2, and PCP-3) via post-polymerization modification. Download figure Download PowerPoint Table 1 | Composition and GPC Characterization of the PCPs Polymer xa ya Mn,GPC (kDa)b Đb PCP-0 — — 37.4 1.07 PCP-1 1.00 — 42.0 1.04 PCP-2 0.95 0.05 39.2 1.05 PCP-3 0.80 0.20 36.4 1.07 aDetermined by 1H NMR analysis (in CDCl3). bMeasured by gel permeation chromatography in tetrahydrofuran. Organometallic-catalyzed depolymerization of the polypentenamer backbone Polypentenamers are known to undergo depolymerization by olefin metathesis catalyzed by the Grubbs catalysts.33 However, the depolymerization reaction is heavily dependent on several influencing factors, including the pendant groups, the catalysts, and the solvents.35 The depolymerization of PCP-1 was investigated first to determine the proper conditions for the subsequent macromolecular metamorphosis experiments (Figure 2a). Considering that the depolymerization must be performed in a low-polarity solvent, the 2nd generation Grubbs catalyst (G2) was chosen due to its decent solubility in MCH. In a test reaction, 0.20 equiv G2 (relative to the total olefin moieties) was added to a PCP-1 solution in MCH, and the reaction mixture was kept at 27 °C for 24 h. The reaction mixture was monitored by 1H NMR, GPC, and electrospray ionization mass spectroscopy (ESI-MS). As shown in Figure 2b, the GPC trace of PCP-1 in the high-molecular-weight region disappears after the reaction, suggesting that the polymers depolymerized into small molecules. 1H NMR analysis revealed that the broadened olefin proton signal of PCP-1 became sharp and moved from 5.62 to 5.51 ppm after the reaction (Figure 2c). This indicates the quantitative conversion of the PCP-1 into POSS-M. ESI-MS revealed an m/z signal at 990.3473 corresponding to [(POSS-M)+Na]+, further confirming that the depolymerization had proceeded smoothly ( Supporting Information Figure S16). In summary, these experiments confirmed that the PCP polymer can be readily depolymerized by using the 2nd generation Grubbs catalyst at 27 °C in MCH solution. Figure 2 | Depolymerization of PCP-1 by G2 in MCH solution: (a) scheme of the depolymerization reaction; (b) GPC traces of PCP-1 (red) and PCP-1 after the reaction (blue); (c) stacked 1H NMR spectra (benzene-d6) of PCP-1 (red), PCP-1 after the reaction (blue) and POSS-M (black). Download figure Download PowerPoint DPP-based supramolecular motif According to our protocol, DPP-based supramolecular motifs were released from the polymers in the form of DPP-M upon depolymerization. Therefore, the intrinsic supramolecular polymerization property of DPP-M was carefully investigated prior to the macromolecular metamorphosis experiments. The detailed procedure for the synthesis of DPP-M is included in the Supporting Information Figure S1. It was thought DPP-M forms supramolecular polymers via the joint force of π–π stacking and intramolecular hydrogen bonds (Figure 3a). First, solutions of DPP-M in dichloromethane (DCM) or MCH were studied by UV–vis and fluorescence spectroscopy. As shown in Figure 3b, the solution of DPP-M in DCM was orange and produced an absorption peak at approximately 547 nm, whereas the solution of DPP-M in MCH was purple and produced an absorption maximum peak at 586 nm. We rationalized this profound difference in absorption stems from the different aggregation states of DPP-M. The DPP-M is molecularly dissolved in DCM, thereby showing the characteristic absorption of the DPP chromophore. In the low-polarity solvent MCH, DPP-M underwent supramolecular polymerization in a J-aggregated manner, which led to the observed bathochromic shift in absorption. This was further confirmed by the fluorescence spectroscopy results. As shown in Figure 3b, DPP-M fluoresced strongly in DCM, whereas it negligibly fluoresced in MCH. This indicates that DPP-M was strongly aggregated in MCH, which led to severe fluorescence quenching. The morphology of the DPP-M based supramolecular polymers was studied by AFM. Multi-micrometer-long fibers with an approximate height of 3.5 nm, which were presumably single-stranded supramolecular polymers formed by stacked DPP-M molecules, were found (Figure 3c). Figure 3 | Supramolecular polymerization behavior of DPP-M: (a) molecular structure of DPP-M; (b) UV–vis spectra (solid lines) and fluorescence spectra (dashed lines) of DPP-M in DCM (red) or MCH (blue); (c) AFM height image of a sample prepared from an MCH solution of DPP-M. Download figure Download PowerPoint Temperature-dependent UV–vis spectroscopy was further employed to elucidate the mechanism by which the supramolecular polymerization of DPP-M occurs. The solution of DPP-M in MCH was first heated to 75 °C, then slowly cooled to 10 °C at a cooling rate of 0.5 °C/min. As shown in Figure 4a, the absorption maximum of DPP-M at high temperatures peaked at 547 nm, then it underwent a bathochromic shift to 586 nm upon cooling to certain temperatures. A plot of the absorption at 586 nm against temperature reveals curves with non-sigmoidal transition, which is indicative of a cooperative nucleation–elongation of supramolecular polymerization mechanism (Figure 4b).44–48 Fitting the non-sigmoidal transition by applying the cooperative nucleation–elongation model introduced by Meijer and co-workers gives a critical elongation temperature (Te) of 291.8 K and an elongation enthalpy (ΔHe) of −171.9 kJ mol−1 at the DPP-M concentration of 20.0 μM ( Supporting Information Figure S12). Moreover, the Te is positively correlated with the concentration of the DPP-M solution; DPP-M concentrations of 20.0, 40.0, and 60.0 μM correspond to Te values of 291.8, 302.1, and 306.0 K, respectively. This also suggests that, to guarantee supramolecular polymerization at room temperature, the total concentration of the DPP moiety ([DPP]tot.) needs to be >40.0 μM. Figure 4 | (a) Temperature-dependent UV–vis spectra of a 40.0 μM solution of DPP-M in MCH; (b) plots of the absorption at 586 nm against temperature of MCH solutions of DPP-M of various concentrations (black, 20.0 μM; red, 40.0 μM; blue, 60.0 μM). Download figure Download PowerPoint In situ supramolecular polymerization via macromolecular metamorphosis With the aforementioned information in hand, the catalytic macromolecular metamorphosis of PCP-2 was performed. A MCH solution of PCP-2 with [DPP]tot. of 60.0 μM was used for all experiments. Notably, the UV–vis spectra of the PCP-2 solution had a similar absorption profile to that of the DCM solution of DPP-M, without noticeable absorption at approximately 586 nm. This suggests that the DPP motifs on the polymer chain were not J-aggregated, most likely due to the structural constrains imposed by the POSS-based polymer chains. Immediately after the addition of G2, the PCP-2 solution was continuously monitored by UV–vis spectroscopy. The time-dependent UV–vis spectra obtained from the sample with 0.20 equiv G2 is shown in Figure 5a. Interestingly, the changes in the absorption profile can be divided into two distinct stages. In the first stage, before approximately 120 min, there was no profound change in the absorption profile, only a small hypochromic shift of the absorption maximum from 550 nm to 547 nm was found (Figure 5c). Starting at 120 min after the addition of G2, the intensity of the absorption peak at 547 nm underwent a significant reduction. An emergent shoulder absorption peak at 586 nm grew rapidly and reached a plateau after approximately 6 h (Figure 5d). The two different stages are also reflected in the appearance of the solution (Figure 5b). The solution gradually turned from reddish to orange, with fluorescence detectable by the naked eye in the first stage, and then turned purple in the second stage. A plot of the changes in absorption at 586 nm against reaction time is shown in Figure 6, together with a schematic rationale of the results. During the first stage, the depolymerization of PCP-2 catalyzed by G2 proceeds, and the DPP-M is gradually released from the polymer chains to the solution phase. Upon reaching a critical point, the DPP-M starts to nucleate, then undergoes elongation to form J-aggregated supramolecular polymers. Figure 5 | Time-dependent UV–vis spectra of the PCP-2 solution with 0.2 equiv G2, (a) the full spectra; (c) stage I; (d) stage II; (b) color of the reaction mixture at various stages. Download figure Download PowerPoint Because the process of supramolecular polymerization directly correlates with the concentration of DPP-M released from PCP-2, we supposed that kinetic control over the supramolecular polymerization can be realized by varying the rate of the depolymerization reaction. To this end, experiments on the depolymerization of PCP-2 using various amounts of G2 were performed. The plots of absorption at 586 nm against time for all the experiments are shown in Figure 7a. All the obtained curves have similar profiles that comprise two stages, but with different transition times. For example, the transition starts at 70 min in the sample with 1.0 equiv G2, which is much sooner than in the sample with 0.20 equal G2. As the amount of catalyst decreases, the transition starts later: 170 min for the sample with 0.10 equiv G2 and over 300 min for the sample with 0.05 equiv G2. Notably, although the transition times are different, the maximum of absorption at 586 nm reaches a plateau with similar values after 24 h in all cases. Figure 6 | The macromolecular metamorphosis of PCP-2. Download figure Download PowerPoint Figure 7 | Plots of the absorption at 586 nm against reaction time: (a) PCP-2 solutions ([DPP]tot. = 60.0 μM) with various amounts of the G2 (brown, 0.05 equiv; green, 0.10 equiv; red, 0.20 equiv; blue, 1.0 equiv); (b) PCP-3 solutions at various concentration ([DPP]tot.: 60.0 μM, black; 80.0 μM, red; 120.0 μM, blue) with the same amount of G2 (120.0 μM). Download figure Download PowerPoint The depolymerization of PCP-3, which contains a higher content of DPP-based pendant groups, was performed as well. In the depolymerization experiments of PCP-3, the G2 catalysts were set at 120.0 μM but the concentration of PCP-3 varied. The plots of the absorption at 586 nm against reaction time are shown in Figure 7b. With identical [DPP]tot. of 60.0 μM and G2 catalyst of 120.0 μM, the transition in the PCP-3 reaction mixture started at 140 min, sooner than in PCP-2, which started at 170 min. In addition, the time of transition decreased with the increase of the concentration of PCP-3. These results indicate that, besides varying the amount of G2 catalyst, the supramolecular polymerization process can also be controlled by tuning the composition and the concentration of the precursor PCP polymers. As with PCP-1, the GPC and 1H NMR measurements confirmed the quantitative depolymerization of PCP-2 and PCP-3 in all cases (see Supporting Information). The solutions of the reaction mixture were spin-coated onto silicon wafers and investigated by AFM (Figure 8). Micrometer-long fibers were found in the samples from the depolymerized PCP-3 with [DPP]tot. of 60.0 and 80.0 μM (Figure 8a and Supporting Information Figures S34–S35). The height of the obtained fibers is in the range of 3.0–4.0 nm, which is consistent with the supramolecular polymers formed directly by DPP-M. This confirms the successful in situ transformation of the covalent PCP polymers into DPP-M based supramolecular polymers. Furthermore, in the samples from the depolymerized PCP-2 ([DPP]tot. = 60.0 μM, Figure 8b, Supporting Information Figures S23–S26) or the depolymerized PCP-3 with higher concentration ([DPP]tot. = 120.0 μM, Supporting Information Figure S36), fibers and some large-size aggregates co-existed. These large-size aggregates were identified as assemblies formed by POSS-M as "side products" by comparing with the samples from the depolymerized PCP-1 ( Supporting Information Figure S15). This is attributed to the relatively high concentration of the formed POSS-M in these samples that exceeds its critical aggregation concentration (CAC), thus aggregating. It suggests that, to prepare neat supramolecular polymers in situ, the solubilizing pendant groups should have a high CAC value or be kept at a relative low concentration. Figure 8 | AFM height image of a sample prepared from (a) the PCP-3 solution ([DPP]tot. = 60.0 μM) after depolymerization; (b) the PCP-2 solution ([DPP]tot. = 60.0 μM) after depolymerization. Download figure Download PowerPoint Conclusions Here, we describe a new approach to controlling supramolecular polymerization through organometallic-catalyzed macromolecular metamorphosis. Polypentenamers functionalized with DPP-based supramolecular motifs and POSS pendant groups were synthesized. The POSS pendant groups endow the polymers with greater solubility in the low-polarity solvent MCH and provide structural constraints to prevent the aggregation of DPP-based supramolecular motifs. The polypentenamers can be readily depolymerized at room temperature using the second-generation Grubbs catalyst in MCH. Upon depolymerization, the DPP-based supramolecular motifs are gradually released from the covalent polymers and transformed into supramolecular polymers. This unique macromolecular metamorphosis approach takes advantage of an organometallic-catalyzed reaction to provide kinetic control of the supramolecular polymerization. The technique, which catalytically transforms covalent polymers into supramolecular polymers, is potentially useful as a new effective method for fabricating complex supramolecular architectures. In our method, the precursor polymers act as a reservoir to provide monomers for supramolecular polymerization in situ, which provides a unique alternative to the popular "combination of good solvent and poor solvent" approach. Our current efforts are directed toward the application of this method in living supramolecular polymerization to fabricate complex supramolecular structures, for example multi-block supramolecular polymers.49–51 Supporting Information Supporting Information is available and includes experimental details, synthesis of chemical compounds, and other supplementary results. Conflicts of Interest The authors declare no competing interests. Acknowledgments We gratefully acknowledge the financial support from National Key R&D Program of China (grant no. 2021YFA1501600), National Natural Science Foundation of China (grant no. 21901077), Natural Science Foundation of Guangdong Province (grant no. 2016ZT06C322), Open Project of State Key Laboratory for Supramolecular Structure and Materials (grant no. SKLSSM2021012) and the Research Fund Program of Guangdong Provincial Key Laboratory of Functional and Intelligent Materials and (grant no. Meijer Meijer Supramolecular 3. of Materials with Supramolecular Polymer to Functional Supramolecular Liu by Supramolecular 1, Meijer Polymerization through and to Supramolecular Polymerization from to Supramolecular Meijer in Supramolecular Meijer in Supramolecular as a Meijer in Supramolecular and Molecular the of Supramolecular Supramolecular Polymerization under and Supramolecular Polymerization through a 6, of and Supramolecular Polymerization of Supramolecular in in Supramolecular for the of Supramolecular Supramolecular Polymerization via a A of Supramolecular of Materials by a and Supramolecular Supramolecular Polymerization by 1, in Supramolecular from for and Molecular Yang Synthesis and via Supramolecular Kennemur and Kennemur of Polypentenamers and Macromolecular Liu Yang of via Functional Supramolecular Materials for of on Supramolecular and of the of Liu Liu and on Yang Liu Molecular for with and and for the of Functional Liu Meijer for the of Functional to Liu Meijer at from Meijer to from Supramolecular Meijer into the of The of and Supramolecular Polymerization of a into Liu Supramolecular Polymerization of for Supramolecular and of Molecular on Supramolecular Synthesis in Polymerization of 1, and Supramolecular via Information situ gratefully acknowledge the financial support from National Key R&D Program of China (grant no. 2021YFA1501600), National Natural Science Foundation of China (grant no. 21901077), Natural Science Foundation of Guangdong Province (grant no. 2016ZT06C322), Open Project of State Key Laboratory for Supramolecular Structure and Materials (grant no. SKLSSM2021012) and the Research Fund Program of Guangdong Provincial Key Laboratory of Functional and Intelligent Materials and (grant no. times

SummaryThe precise sequence control of polymer chain is an important research topic of polymer chemistry. Although some methods such as iterative synthesis and supramolecular polymerization have been developed to fabricate sequence-controllable polymer, it is still a great challenge to consecutively prepare multiple supramolecular polymers with different sequence structures. In this work, through the reasonable utilization of assembly motifs, we integrated multiple host-guest recognitions and metal coordination interactions to prepare different sequence-controlled supramolecular polymers by a multistep assembly strategy. This research provides inspiration for the design and preparation of supramolecular polymers with different sequence structures.

The synthesis of supramolecular polymers with controlled architecture is a grand challenge in supramolecular chemistry. Although living supramolecular polymerization via primary nucleation has been extensively studied for controlling the supramolecular polymerization of small molecules, the resulting supramolecular polymers have typically exhibited one-dimensional morphology. In this report, we present the synthesis of intriguing supramolecular polymer architectures through a secondary nucleation event, a mechanism well-established in protein aggregation and the crystallization of small molecules. To achieve this, we choose perylene diimide with 2-ethylhexyl chains at the imide position as they are capable of forming dormant monomers in solution. Activating these dormant monomers via mechanical stimuli and hetero-seeding using propoxyethyl perylene diimide seeds, secondary nucleation event takes over, leading to the formation of three-dimensional spherical spherulites and scarf-like supramolecular polymer heterostructures, respectively. Therefore, the results presented in this study propose a simple molecular design for synthesizing well-defined supramolecular polymer architectures via secondary nucleation.

Kinetically formed metastable molecular assemblies have attracted increasing interest especially in the field of supramolecular polymers. In most cases, metastable assemblies are ensemblies of aggregates based on the same supramolecular motif but with different lengths or sizes, and therefore their kinetic stabilities are experimentally indistinguishable. Herein, we demonstrate a topological effect on kinetic stabilities in a complex mixture of metastable supramolecular polymers. Our azobenzene-incorporated monomer upon heating in nonpolar solvent at ambient temperature kinetically forms complex mixtures of supramolecular polymers with cyclized and open-ended randomly coiled topologies. Upon further heating, we obtained thermodynamically stable twisted fibrils organizing into crystalline fibers. Through the direct visualization of the complex supramolecular polymer mixtures by atomic force microscopy, we demonstrate that the cyclized supramolecular polymer has superior kinetic stability compared to the open-ended species toward the thermal transformation into twisted fibrils. Since the superior kinetic stability of the cyclized species can be attributed to the absence of aggregate termini, we could convert them fully into the thermodynamic species through photoinduced opening of the cyclized structures.

CONSPECTUS: Supramolecular polymers, fabricated via the combination of supramolecular chemistry and polymer science, are polymeric arrays of repeating units held together by reversible, relatively weak noncovalent interactions. The introduction of noncovalent interactions, such as hydrogen bonding, aromatic stacking interactions, metal coordination, and host-guest interactions, endows supramolecular polymers with unique stimuli responsiveness and self-adjusting abilities. As a result, diverse monomer structures have been designed and synthesized to construct various types of supramolecular polymers. By changing the noncovalent interaction types, numbers, or chemical structures of functional groups in these monomers, supramolecular polymeric materials can be prepared with tailored chemical and physical properties. In recent years, the interest in supramolecular polymers has been extended from the preparation of intriguing topological structures to the discoveries of potential applications as functional materials. Compared with traditional polymers, supramolecular polymers show some advantages in the fabrication of reversible or responsive materials. The development of supramolecular polymers also offers a platform to construct complex and sophisticated materials with a bottom-up approach. Macrocylic hosts, including crown ethers, cyclodextrins, calixarenes, cucurbiturils, and pillararenes, are the most commonly used building blocks in the fabrication of host-guest interaction-based supramolecular polymers. With the introduction of complementary guest molecules, macrocylic hosts demonstrate selective and stimuli-responsive host-guest complexation behaviors. By elaborate molecular design, the resultant supramolecular polymers can exhibit diverse structures based on the self-selectivity of host-guest interactions. The introduction of reversible host-guest interactions can further endow these supramolecular polymers with interesting and fascinating chemical/physical properties, including stimuli responsiveness, self-healing, and environmental adaptation. It has been reported that macrocycle-based supramolecular polymers can respond to pH change, photoirradition, anions, cations, temperature, and solvent. Macrocycle-based supramolecular polymers have been prepared in solution, in gel, and in the solid state. Furthermore, the solvent has a very important influence on the formation of these supramolecular polymers. Crown ether- and pillararene-based supramolecular polymers have mainly formed in organic solvents, such as chloroform, acetone, and acetonitrile, while cyclodextrin- and cucurbituril-based supramolecular polymerizations have been usually observed in aqueous solutions. For calixarenes, both organic solvents and water have been used as suitable media for supramolecular polymerization. With the development of supramolecular chemistry and polymer science, various methods, such as nuclear magnetic resonance spectroscopy, X-ray techniques, electron microscopies, and theoretical calculation and computer simulation, have been applied for characterizing supramolecular polymers. The fabrication of macrocycle-based supramolecular polymers has become a currently hot research topic. In this Account, we summarize recent results in the investigation of supramolecular polymers constructed from macrocycle-based host-guest molecular recognition motifs. These supramolecular polymers are classified based on the different macrocycles used in them. Their monomer design, structure control, stimuli-responsiveness, and applications in various areas are discussed, and future research directions are proposed. It is expected that the development of supramolecular polymers will not only change the way we live and work but also exert significant influence on scientific research.

Review: 56 refs.

Spatiotemporal segregation of chiral supramolecular polymers

Controlling the nanoscale orientation of π-conjugated systems remains challenging due to the complexity of multiple energy landscapes involved in the supramolecular assembly process. In this study, we have developed an effective strategy for programming the pathways of π-conjugated supramolecular polymers, by incorporating both electron-rich methoxy- or methanthiol-benzene as donor unit and electron-poor cyano-vinylenes as acceptor units on the monomeric structure. It leads to the formation of parallel-stacked supramolecular polymers as the metastable species through homomeric donor/acceptor packing, which convert to slip-stacked supramolecular polymers as the thermodynamically stable species facilitated by heteromeric donor-acceptor packing. By further investigating the external seed-induced kinetic-to-thermodynamic transformation behaviors, our findings suggest that the donor-acceptor functionality on the seed structure is crucial for accelerating pathway conversion. This is achieved by eliminating the initial lag phase in the supramolecular polymerization process. Overall, this study provides valuable insights into designing molecular structures that control aggregation pathways of π-conjugated nanostructures.

Structure to Function in Supramolecular Polymers and Materials.

Controlling the nanoscale orientation of π‐conjugated systems remains challenging due to the complexity of multiple energy landscapes involved in the supramolecular assembly process. In this study, we have developed an effective strategy for programming the pathways of π‐conjugated supramolecular polymers, by incorporating both electron‐rich methoxy‐ or methanthiol‐benzene as donor unit and electron‐poor cyano‐vinylenes as acceptor units on the monomeric structure. It leads to the formation of parallel‐stacked supramolecular polymers as the metastable species through homomeric donor/acceptor packing, which convert to slip‐stacked supramolecular polymers as the thermodynamically stable species facilitated by heteromeric donor‐acceptor packing. By further investigating the external seed‐induced kinetic‐to‐thermodynamic transformation behaviors, our findings suggest that the donor‐acceptor functionality on the seed structure is crucial for accelerating pathway conversion. This is achieved by eliminating the initial lag phase in the supramolecular polymerization process. Overall, this study provides valuable insights into designing molecular structures that control aggregation pathways of π‐conjugated nanostructures.

Open AccessCCS ChemistryRESEARCH ARTICLE3 Oct 2022Supramolecular Polymerization Powered by Escherichia coli: Fabricating a Near-Infrared Photothermal Antibacterial Agent in Situ Zihe Yin, Yuchong Yang, Jinpeng Yang, Guobin Song, Hao Hu, Peng Zheng and Jiang-Fei Xu Zihe Yin Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084 Google Scholar More articles by this author , Yuchong Yang Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084 Google Scholar More articles by this author , Jinpeng Yang Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084 Google Scholar More articles by this author , Guobin Song State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023 Google Scholar More articles by this author , Hao Hu Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084 Google Scholar More articles by this author , Peng Zheng State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023 Google Scholar More articles by this author and Jiang-Fei Xu *Corresponding author: E-mail Address: [email protected] Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084 Google Scholar More articles by this author https://doi.org/10.31635/ccschem.021.202101490 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail An Escherichia coli reduction-powered supramolecular polymerization is reported, leading to the fabrication of a near-infrared (NIR) photothermal antibacterial agent in situ. To this end, a bifunctional monomer containing two viologen moieties was designed. When incubating E. coli with the bifunctional monomer and cucurbit[8]uril, viologen moieties were reduced to viologen cation radicals by E. coli, and a supramolecular polymer with supramolecular dimers of viologen cation radicals integrated into the main chain was fabricated on the surface of E. coli. The NIR photothermal conversion property of the supramolecular dimer of viologencation radicals endowed the supramolecular polymer with photothermal antibacterial ability, and this performance was further improved by the local enrichment effect of supramolecular polymers and their enhanced adsorption onto the bacteria surface. Moreover, only certain bacteria, such as E. coli, possess the reducing ability to power supramolecular polymerization, whereas many other bacteria, such as Bacillus subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus, do not possess this ability. Therefore, the supramolecular polymer exhibits outstanding bacterial inhibition efficiency (>99.9%) with high specificity toward E. coli under 1064 nm NIR irradiation. It is anticipated that this biologically powered in situ supramolecular polymerization strategy presents great potential in fabricating smart biomedical supramolecular materials with adaptivity and programmability. Download figure Download PowerPoint Introduction In an out-of-equilibrium biological system, many metabolic activities and physiological functions are energy-consuming processes. For bacteria, a transmembrane redox potential generated by procaryote respiration not only supports biological functions,1,2 but also can be employed as an energy source for various artificial applications, such as bioelectrosynthesis, initiation of polymerization, and microbial fuel cells.3–10 Notably, the reducing ability of bacteria originating from this redox potential has been applied to the in situ fabrication of biomedical materials at the places where they function.7,8,11 Compared with conventional biomedical materials, which are generally readily constructed and then transported to the working area, in an in situ fabrication strategy, the targeting ability could be realized, and then the transporting process could be omitted, thus improving the specificity and adaptivity of biomedical materials.12–17 As an integration of polymer science and supramolecular chemistry, supramolecular polymers exhibit superiority in various biomedical applications18–25 such as drug delivery,26–30 bioimaging and diagnosis,31,32 phototherapy,33–35 and tissue engineering.36–38 If supramolecular polymerization could be implemented in biological environments, biodegradability and stimuli-responsiveness originating from the dynamic and reversible noncovalent interactions may be imparted to the supramolecular biomedical materials that are fabricated in situ. Therefore, we wondered whether the reducing ability of bacteria could be utilized to power a supramolecular polymerization process. Our design idea arises from the fact that some electron-deficient dyes with large π-conjugated structures can be reduced to organic free radicals in a local reducing environment produced by some facultative anaerobic bacteria such as Escherichia coli.11,39,40 On the one hand, the self-assembly of these organic free radicals into supramolecular free radicals may serve as the driving force for supramolecular polymerization.41–50 On the other hand, supramolecular free radicals are expected to possess remarkable near-infrared (NIR) absorption,51–54 which may endow the supramolecular polymers with an outstanding photothermal conversion property and photothermal antibacterial performance. Therefore, by integrating the formation of NIR photothermal conversion motifs into a bacteria-powered supramolecular polymerization process, NIR photothermal antibacterial supramolecular polymers are hopeful to be constructed. Such an antibacterial agent would be selectively activated by the reduction with E. coli, whereas it could exactly kill thebacteria that induced the activation before. Such a “suicide” process of the bacteria may impart high antibacterial specificity to the agent. To this end, we designed and synthesized a bifunctional monomer named isviologen-diazabicyclo[2.2.2]octane-viologen (VDV), which contained two viologen moieties as end groups linked by a rigid and positively charged 1,4-diazabicyclo[2.2.2]octane unit. It was discovered that E. coli possessed the ability for reducing viologen into viologen cation radical under anaerobic conditions. As shown in Schemes 1a and 1b, when incubating E. coli with equimolar amounts of VDV and cucurbit[8]uril (CB[8]), the viologen moieties could be reduced to viologen cation radicals, and an in situ supramolecular polymerization could occur driven by the 2:1 host–guest complexation between viologen cation radicals and CB[8], generating a supramolecular polymer (VR-SP) with supramolecular dimers of viologen cation radicals integrated into the main chain. Moreover, the supramolecular dimer of viologen cation radicals exhibited absorption at the NIR biowindow, which might endow the VR-SP with photothermal antibacterial activity. By forming such an NIR photothermal antibacterial agent, E. coli could be killed by the local increase in temperature under NIR irradiation. This photothermal therapy is a powerful antimicrobial method with high penetration depth, few side effects, and low risk in generating drug resistance.55–71 Furthermore, the photothermal antibacterial efficiency could be enhanced significantly by the local enrichment effect of supramolecular polymers and their enhanced adsorption onto the surface of bacteria, since the positively charged VR-SP would exhibit strong interactions with the negatively charged surface of the bacteria. In addition, after completely inhibiting E. coli, VR-SP would be spontaneously degraded, as the viologen cation radicals are easily oxidized (commonly by oxygen) without the continuous reduction powered by living bacteria, thus turning off the antibacterial activity automatically. We therefore envisioned that, based on the supramolecular polymerization powered by E. coli, an NIR photothermal antibacterial agent with high antibacterial efficiency, specificity, and degradability could be fabricated in situ. Scheme 1 | (a) Chemical structures of the bifunctional monomer VDV, CB[8], and the supramolecular dimer of viologen cation radicals, and a graphic representation of the photothermal antibacterial supramolecular polymer VR-SP. (b) A schematic representation for the photothermal therapy using an NIR photothermal antibacterial agent fabricated through in situ supramolecular polymerization powered by E. coli. Download figure Download PowerPoint Experimental Method Unless otherwise noted, materials were obtained from commercial suppliers and were used without further purification. All types of bacteria were grown in Luria–Bertani (LB) culture medium at 37 °C for 8 h before further application. The detailed synthetic routes of VDV and 1-methyl-1′-(3-(trimethylammonio)propyl)-viologen tribromide (VMA), as well as detailed experimental methods are shown in Supporting Information. UV–vis spectra were measured using a HITACHI UH4150 spectrophotometer (Hitachi, Ltd., Tokyo, Japan) or a GE Ultrospec9000 spectrophotometer (General Electric Company, Boston, Massachusetts, United States). VDV (0.20 mM), or VDV (0.20 mM) and CB[8] (0.20 mM) were dissolved in LB medium. Then, 3.5 mL LB medium with dissolved agent was transferred into a quartz cuvette (1.00 cm). Then 100 μL of the suspension of bacteria (E. coli, Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, or Pseudomonas aeruginosa) was added. The samples were sealed and incubated at 37 °C for 20 h, and then the UV–vis spectra were recorded. Electron paramagnetic resonance (EPR) spectra were obtained using a JEOL JES-FA200 spectrometer. VDV (0.20 mM), or VDV (0.20 mM) and CB[8] (0.20 mM) were dissolved in LB medium. Then 100 μL of the suspension of bacteria (E. coli or B. subtilis) was added into 3.5 mL LB medium with dissolved agent. The medium was blown by a pipette and transferred into a capillary tube (Φ = 0.5 mm). After being filled with the medium, the capillary tube was sealed by melted paraffin. The samples were incubated at 37 °C for 40 h and then measured with the EPR spectrometer. The redox potential of VDV and VDV-CB[8] was measured by differential pulse voltammetry. The differential pulse voltammetry measurements were carried out with the three-electrode system using a CHI660E electrochemical workstation (CH Instruments, Inc., Austin, Texas, United States). A glass carbon disk (0.07 cm2) was applied as the working electrode with a Pt counter electrode and a saturated Ag/AgCl electrode (KCl saturated) reference electrode. The working electrode was polished with 0.3 and 0.05 μm alumina (Al2O3) successively and washed with deionized water before use. NaCl solution (50 mM) was used as supporting electrolyte. After degassing by passing N2 through the solution for at least 30 min, differential pulse voltammetry measurements were conducted on VDV (0.20 mM), or VDV (0.20 mM) and CB[8] (0.20 mM) solution. The redox potential of the bacterial cultural medium was measured using a hand-held ORP probe (Shanghai Sanxin SX712). The E. coli suspension (15 μL) was added into a cuvette containing LB medium (2 mL). The composite electrode of the ORP probe (using saturated Ag/AgCl electrode as reference electrode) was also immersed in the medium to monitor redox potential changes. The cuvette was sealed to prevent interference from air, and the bacteria were then incubated at 37 °C for 12 h. After that, the redox potential of the medium of E. coli was detected. For E. faecalis, S. aureus, B. subtilis, and P. aeruginosa, the redox potential was measured with the same method. A Nanowizard 4 atomic force microscopy (AFM; JPK, Berlin, Germany) coupled to an inverted microscope (Olympus IX73, Olympus Corporation, Tokyo, Japan) was used to perform the AFM imaging on live E. coli. The AFM was equipped with a cell-culture chamber to keep the temperature appropriate for E. coli (37 ± 1 °C). And a poly-d-lysine-coated mica disc was used as the substrate for E. coli immobilization and subsequent imaging. A PFQMN-Lc-A-CAL AFM cantilever (Bruker Corporation, Billerica, Massachusetts, United States) with a nominal spring constant of 0.1 N/m was used. For detailed scanning parameters and sample preparation procedures, please refer to Supporting Information. An FC-1064-3000-MM Laser Light Source (Wavicle Laser) was applied to produce a 1064 nm NIR laser in the photothermal therapy under NIR irradiation, and the NIR laser-induced heat experimental phenomenon was recorded by a Fluke Ti450 Infrared Camera. VDV (0.20 mM), or VDV (0.20 mM) and CB[8] (0.20 mM), or VMA (0.40 mM) and CB[8] (0.20 mM) were dissolved in LB medium, and 3.5 mL LB medium with dissolved agents was transferred into a quartz cuvette (for control group, LB medium without dissolved agent was applied). Then 30 μL of the suspension of bacteria (E. coli or B. subtilis) was added. The samples were sealed and incubated at 37 °C for 20 h. After incubation, the samples were irradiated by a 1064 nm NIR laser (2.0 W/cm2) for 12.5 min at 37 °C, and the temperature of the cuvette was recorded by Fluke Ti450 Infrared Camera every 2.5 min. The inhibition ratio was determined by calculating the number of colony-forming units (CFUs). The cell viability of both BEAS-2B and NCM460 cells was measured in vitro by the Cell Counting Kit-8 (CCK-8) assay. The cells were planted in 96-well plates with a density of about 5 × 103–8 × 103 cells per well for 24 h. Then the cells were treated with the medium containing equimolar amounts of VDV and CB[8] or VDV alone ranging from 0.10 to 0.40 mM for 24 h. After that, the cells were treated with fresh medium containing CCK-8 for 1 h to replace the previous medium. A microplate reader (EnVision, PerkinElmer, Inc., Waltham, Massachusetts, United States) was used for the measurement of absorbance at 450 nm, which was applied to calculate the cell viability. For detailed cell culture conditions, please refer to Supporting Information. Results and Discussion The formation of viologen cation radicals from VDV by E. coli reduction was characterized by UV–vis spectroscopy. As shown in Figure 1a, when incubating E. coli with VDV or equimolar amounts of VDV and CB[8] for 12–20 h, the color of the solution changed from light yellow to blue or dark violet, which are the characteristic colors of viologen cation radical monomer or supramolecular dimer of viologen cation radicals, respectively. With the existence of CB[8], absorption bands ranging from the UV to the NIR regionpeaking at 366, 542, and 872 nm were observed, which were attributed to the characteristic absorption of the supramolecular dimer of viologen cation radicals. In contrast, the characteristic absorption peaks of viologen cation radical monomer at 396 and 601 nm were observed in the absence of CB[8]. These results suggest the formation of viologen cation radicals. Figure 1 | (a) UV–vis spectra and images of the solution of VDV with or without CB[8] after incubating with E. coli at 37 °C for 20 h. (b) EPR spectra of VDV with or without CB[8] after incubating with E. coli at 37 °C for 40 h. (c and d) UV–vis spectra and images of the solution of VDV and CB[8] after incubating with E. coli, E. faecalis, B. subtilis, P. aeruginosa, or S. aureus at 37 °C for 20 h (VDV: 0.20 mM, CB[8]: 0.20 mM, medium: LB medium). Download figure Download PowerPoint The generation of viologen cation radicals by E. coli reduction was further confirmed by EPR. As shown in Figure 1b, an EPR signal with g factor of 2.0034 was observed after incubating E. coli with VDV. When incubating E. coli with equimolar amounts of VDV and CB[8], an EPR signal with the same g factor but significantly lower intensity was observed. Given that no EPR signal was observed when incubating E. coli without any additives, the observed signals were ascribed to viologen cation radical monomer; the lower signal intensity observed in the presence of CB[8] indicated that most of the generated viologen cation radicals self-assembled with CB[8] to form the supramolecular dimer of viologen cation radicals.48,72 In contrast, no EPR signal was observed when incubating VDV or VDV-CB[8] with aerobic bacteria B. subtilis, indicating the negligible reducing ability of B. subtilis to viologen ( Supporting Information Figure S10). To understand whether E. coli was the only bacteria possessing the reducing ability, five types of bacteria including E. coli, E. faecalis, B. subtilis, S. aureus, and P. aeruginosa were incubated with VDV-CB[8], and UV–vis spectra were recorded after 20 h incubation. As shown in Figure 1c, only E. coli presented remarkable reducing ability to generate viologen cation radicals. E. faecalis showed a much weaker reducing capacity than E. coli. For the other three types of bacteria, no absorption of viologen cation radicals was observed (Figure 1d), indicating their low reducing ability. To study the reducing ability of different types of bacteria quantitatively, the redox potential of the medium of different types of bacteria after incubation was measured. As shown in Table 1, the redox potential of E. coli culture medium reached as low as −551 mV. As for E. faecalis, the redox potential of the medium was −429 mV. The other bacteria media exhibited higher redox potential (Table 1). Compared with the first one-electron reduction potential of VDV (−558 mV) and VDV-CB[8] (−481 mV) measured by differential pulse voltammetry ( Supporting Information Figure S12), we judged that E. coli could reduce VDV to generate viologen cation radicals with or without CB[8]. E. faecalis could only reduce a small proportion of VDV with the existence of CB[8], whereas the other three types of bacteria could not reduce VDV. All the above results reveal that only E. coli possesses the remarkable reducing ability to generate viologen cation radicals, and the viologen cation radicals self-assemble into supramolecular dimer of viologen cation radicals in the presence of CB[8]. Table 1 | The Redox Potential of the Medium of Different Types of Bacteria after Incubationa Bacteria Redox Potential (mV) E. coli −551 E. faecalis −429 B. subtilis −171 P. aeruginosa −289 S. aureus −300 aAll redox potential values were measured related to saturated Ag/AgCl electrode. The formation of supramolecular polymers in solution driven by the host–guest complexation between viologen cation radicals and CB[8] was investigated by diffusion-ordered NMR spectroscopy (DOSY). Equimolar amounts of VDV and CB[8] were dissolved in D2O and then VDV was reduced via a photoinduced electron transfer process under 254 nm UV irradiation. After the complete reduction of viologen moieties, the diffusion coefficient of the species in solution measured by DOSY decreased significantly from 1.80 × 10−10 to 6.35 × 10−11 m2·s−1, indicating the formation of supramolecular polymers. According to the Stokes–Einstein equation, the degree of polymerization (DP) was approximately 23 (see Supporting Information). This result indicates that VR-SP is formed in aqueous solution successfully. To investigate whether VR-SP could be fabricated and adsorbed on the surface of E. coli, AFM imaging was employed. E. coli was incubated with equimolar amounts of VDV and CB[8] for 20 h to prepare VR-SP on the surface. After the color of the medium changed from light yellow to dark violet, E. coli was transferred into the petri dish, and fixed onto a poly-d-lysine coated mica disc. After that, E. coli was imaged directly by AFM. Compared with the untreated E. coli shown in Figure 2a, the edge of the E. coli incubated with VDV-CB[8] was uneven, as shown in Figures 2b, 2c, and 2e, suggesting the formation and adsorption of supramolecular polymers on the surface of E. coli. To further support that the adsorbed supramolecular polymers were responsible for the observed uneven edge of E. coli, the buffer in culture dish with the imaged bacteria in Figure 2c was carefully replaced by phosphate-buffered saline (PBS) without disturbing the bacteria. As shown in Figures 2d and 2f, the E. coli again exhibited the smooth edge, which could be explained as the oxidation of VR-SP by air; therefore, the adsorbed supramolecular polymers were degraded. Considering that VDV alone could not lead to the uneven edges of bacteria ( Supporting Information Figure S17), AFM observations suggest that VR-SP is formed and adsorbed on the surface of bacteria. Figure 2 | AFM images of (a) untreated E. coli and (b and c) E. coli incubated with 0.20 mM VDV and 0.20 mM CB[8]. (d) AFM image of the E. coli in image (c) after replacing the solution in the petri dish with PBS buffer. (e) Magnified image of the labeled area in (c). (f) Magnified image of the labeled area in (d). Download figure Download PowerPoint The DP of VR-SP generated on the surface of E. coli was further estimated by end-group analysis measured by EPR. Viologen cation radical monomer, which is the end group of VR-SP, can be characterized by EPR, whereas the supramolecular dimer of viologen cation radicals exhibits no EPR signal. Combining the EPR measurements of E. coli with VR-SP adsorption and viologen cation radical monomer, the DP of VR-SP was estimated to be approximately 17 (see Supporting Information). In comparison, the DP of the supramolecular polymer formed in aqueous solution at the same concentration was also measured by the end-group analysis using EPR, which was estimated to be approximately 21. This result indicated that VR-SP could be formed on the surface of E. coli though the bacteria surface might disturb the host–guest complexation between viologen cation radical and CB[8] a little. Therefore, by combining the AFM imaging and end-group analysis, we conclude that supramolecular polymers can be fabricated on the surface of bacteria through in situ supramolecular polymerization powered by E. coli. Based on the E. coli-powered supramolecular polymerization in situ, and the NIR absorption of the supramolecular dimer of viologen cation radicals, we further explored the bacterial inhibition activity of VR-SP by photothermal therapy. The photothermal conversion property of VR-SP prepared by chemical reduction was first studied. As shown in Supporting Information Figure S19, a significant temperature increase of VR-SP solutionwas observed under 1064 nm irradiation at the second NIR (NIR-II) window, indicating the effective photothermal conversion of VR-SP. The photothermal conversion efficiency was 22.0% (see Supporting Information). Next, the photothermal antibacterial experiments were conducted. As shown in Figures 3a and 3b, under NIR irradiation at 1064 nm, the temperature of the medium with VR-SP adsorbed E. coli increased significantly. It rose from to °C after 12.5 min irradiation, indicating that VR-SP energy into When E. coli was incubated with VDV the increase of temperature was lower than the VR-SP group after irradiation for the same When E. coli was treated with viologen VMA (Figure and CB[8], which could be reduced to generate supramolecular dimer of viologen cation radicals but not supramolecular the temperature increase was to that of the control group without any agent under the same irradiation The significantly higher temperature increase of the VR-SP group could be ascribed to the local enrichment and enhanced adsorption of VR-SP onto the surface of E. coli. As shown in Supporting Information Table the potential of E. coli significantly increased from of untreated E. coli to when incubated with equimolar amounts of VDV and CB[8]. As a comparison, when incubated with only VDV, the potential increased to mV. These results that the adsorption of VR-SP onto the surface of E. coli is higher than that of VDV of the of of supramolecular polymers. As for bacteria with low reducing ability, B. subtilis for since no viologen cation radicals were generated and no supramolecular polymers could be the increase of temperature was after irradiation in the presence or absence of VDV-CB[8] °C or °C with or without VDV-CB[8], The results of these groups that the of VR-SP is to a higher temperature in photothermal therapy. Figure | (a) of the medium with E. coli or B. subtilis, or with E. coli or B. subtilis treated with different agents under irradiation. (b) images of the medium with E. coli or B. subtilis, or with E. coli or B. subtilis treated with different agents after 12.5 min irradiation. (c) The chemical of VMA (VDV: 0.20 mM, CB[8]: 0.20 mM, 0.40 mM, medium: LB medium). Download figure Download PowerPoint The antibacterial activity was by of As shown in Figure the inhibition efficiency of VR-SP to E. coli was after 12.5 min of 1064 nm irradiation, which was significantly higher than that of VDV and In contrast, equimolar amounts of VDV and CB[8] exhibited no inhibition of B. subtilis after irradiation under the same since no supramolecular polymers were It is that after 12.5 min irradiation under air, the absorption peaks of supramolecular dimer of viologen cation radicals in the UV–vis ( Supporting Information Figure and the EPR signal of viologen cation radicals ( Supporting Information Figure both of which the of VR-SP after the inhibition of E. coli. This is since E. coli reduce viologen to prevent the Therefore, these results that VR-SP is an NIR photothermal antibacterial agent with outstanding bacterial inhibition efficiency, high specificity E. coli, and Figure 4 | ratio of E. coli or B. subtilis incubated with or without different agents after 12.5 min irradiation figure of the ratio of VR-SP adsorbed E. coli group shown are ± from = = by the with the E. coli or B. subtilis group without any or Download figure Download PowerPoint To the of VR-SP as biological materials, the of equimolar amounts of VDV and CB[8] on cells was To this end, cell BEAS-2B and cell NCM460 were as As shown in Figures and when treated with equimolar amounts of VDV and CB[8] ranging from 0.10 to 0.40 mM, the cell viability of both BEAS-2B cell and NCM460 cell measured by CCK-8 was A was also observed on the cells treated with VDV alone ( Supporting Information Figure Therefore, VDV-CB[8] VDV alone exhibited at a high concentration (0.40 mM), which was the concentration used in antibacterial Therefore, VR-SP may be a potential agent for photothermal therapy. Figure 5 | of equimolar amounts of VDV and CB[8] to (a) BEAS-2B cell and (b) NCM460 Download figure Download PowerPoint We fabricated an NIR photothermal antibacterial agent through E. coli

Three different pi-conjugated oligomers (a blue-emitting oligofluorene, a green-emitting oligo(phenylene vinylene), and a red-emitting perylene bisimide) have been functionalized with self-complementary quadruple hydrogen bonding ureidopyrimidinone (UPy) units at both ends. The molecules self-assemble in solution and in the bulk, forming supramolecular polymers. When mixed together in solution, random noncovalent copolymers are formed that contain all three types of chromophores, resulting in energy transfer upon excitation of the oligofluorene energy donor. At a certain mixing ratio, a white emissive supramolecular polymer can be created in solution. In contrast to their unfunctionalized counterparts, bis-UPy-chromophores can easily be deposited as smooth thin films on surfaces by spin coating. No phase separation is observed in these films, and energy transfer is much more efficient than in solution, giving rise to white fluorescence at much lower ratios of energy acceptor to donor. Light emitting diodes based on these supramolecular polymers have been prepared from all three types of pure materials, yielding blue, green, and red devices, respectively. At appropriate mixing ratios of these three compounds, white electroluminescence is observed. This approach yields a toolbox of molecules that can be easily used to construct pi-conjugated supramolecular polymers with a variety of compositions, high solution viscosities, and tuneable emission colors.

Owing to the mastery exhibited by Nature in integrating both covalent and noncovalent interactions in a highly efficient manner, the quest to construct polymeric systems that rival not only the precision and fidelity but also the structure of natural systems has remained a daunting challenge. Supramolecular chemists have long endeavored to control the interplay between covalent and noncovalent bond formation, so as to examine and fully comprehend how function is predicated on self-assembly. The ability to reliably control polymer self-assembly is essential to generate "smart" materials and has the potential to tailor polymer properties (i.e., viscosity, electronic properties) through fine-tuning the noncovalent interactions that comprise the polymer architecture. In this context, supramolecular polymers have a distinct advantage over fully covalent systems in that they are dynamically modular, since noncovalent recognition motifs can be engineered to either impart a desired functionality within the overall architecture or provide a designed bias for the self-assembly process. In this Account, we describe engineering principles being developed and pursued by our group that exploit the orthogonal nature of noncovalent interactions, such as hydrogen bonding, metal coordination, and Coulombic interactions, to direct the self-assembly of functionalized macromolecules, resulting in the formation of supramolecular polymers. To begin, we describe our efforts to fabricate a modular poly(norbornene)-based scaffold via ring-opening metathesis polymerization (ROMP), wherein pendant molecular recognition elements based upon nucleobase-mimicking elements (e.g., thymine, diaminotriazine) or SCS-Pd(II) pincer were integrated within covalent monofunctional or symmetrically functionalized polymers. The simple polymer backbones exhibited reliable self-assembly with complementary polymers or small molecules. Within these systems, we applied successful protecting group strategies and template polymerizations to enhance the control afforded by ROMP. Main-chain-functionalized alternating block polymers based upon SCS-Pd(II) pincer-pyridine motifs were achieved through the combined exploitation of bimetallic initiators and supramolecularly functionalized terminators. Our initial design principles led to the successful fabrication of both main-chain- and side-chain-functionalized poly(norbornenes) via ROMP. Utilizing all of these techniques in concert led to engineering orthogonality while achieving complexity through the installation of multiple supramolecular motifs within the side chain, main chain, or both in our polymer systems. The exploitation and modification of design principles based upon functional ROMP initiators and terminators has resulted in the first synthesis of main-chain heterotelechelic polymers that self-assemble into A/B/C supramolecular triblock polymers composed of orthogonal cyanuric acid-Hamilton wedge and SCS-Pd(II) pincer-pyridine motifs. Furthermore, supramolecular A/B/A triblock copolymers were realized through the amalgamation of functionalized monomers, ROMP initiators, and terminators. To date, this ROMP-fabricated system represents the only known method to afford polymer main chains and side chains studded with orthogonal motifs. We end by discussing the impetus to attain functional materials via orthogonal self-assembly. Collectively, our studies suggest that combining covalent and noncovalent bonds in a well-defined and precise manner is an essential design element to achieve complex architectures. The results discussed in this Account illustrate the finesse associated with engineering orthogonal interactions within supramolecular systems and are considered essential steps toward developing complex biomimetic materials with high precision and fidelity.

A biscalix[5]arene-C60 supramolecular structure was utilized for the development of supramolecular fullerene polymers. Di- and tritopic hosts were developed to generate the linear and network supramolecular polymers through the complexation of a dumbbell-shaped fullerene. The molecular association between the hosts and the fullerene were carefully studied by using (1) H NMR, UV/Vis absorption, and fluorescence spectroscopy. The formation of the supramolecular fullerene polymers and networks was confirmed by diffusion-ordered (1) H NMR spectroscopy (DOSY) and solution viscometry. Upon concentrating the mixtures of di- or tritopic hosts and dumbbell-shaped fullerene in the range of 1.0-10 mmol L(-1) , the diffusion coefficients of the complexes decreased, and the solution viscosities increased, suggesting that large polymeric assemblies were formed in solution. Scanning electron microscopy (SEM) was used to image the supramolecular fullerene polymers and networks. Atomic force microscopy (AFM) provided insight into the morphology of the supramolecular polymers. A mixture of the homoditopic host and the fullerene resulted in fibers with a height of (1.4±0.1) nm and a width of (5.0±0.8) nm. Interdigitation of the alkyl side chains provided secondary interchain interactions that facilitated supramolecular organization. The homotritopic host generated the supramolecular networks with the dumbbell-shaped fullerene. Honeycomb sheet-like structures with many voids were found. The growth of the supramolecular polymers is evidently governed by the shape, dimension, and directionality of the monomers.