Nanoporous Vesicular Membranes of Amphiphilic Polymers Containing <i>Trans</i> / <i>Cis</i> Isomers

Open AccessCCS ChemistryRESEARCH ARTICLE5 Aug 2022Nanoporous Vesicular Membranes of Amphiphilic Polymers Containing Trans/Cis Isomers Hui Chen, Xia Yu, Yujiao Fan, Xiangjun Xing, Sylvain Trépout and Min-Hui Li Chen Beijing Advanced Innovation Center for Soft Matter Science Engineering, University Chemical Technology, Chaoyang District, 100029 Chimie ParisTech, PSL Paris, CNRS, Institut de Recherche UMR8247, 75231 Paris Cedex 05 Google Scholar More articles by this author , Yu Fan Xing *Corresponding authors: E-mail Address: [email protected] Wilczek Quantum Center, School Physics Astronomy, Shanghai Jiao Tong University, 200240 Curie, Université Paris-Saclay, CNRS UMS2016, Inserm US43, Multimodal Imaging 91400 Orsay https://doi.org/10.31635/ccschem.022.202201916 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Nanoporous membranes vesicles are interesting systems with potential in applications offering channels material exchange. Herein, nanoporous polymersomes developed self-assembly trans- cis-stereoisomers amphiphilic polymers. Two polymers, PEG550-TPE-Chol PEG550-SS-TPE-SS-Chol, containing a central tetraphenylethene (TPE), cholesterol (Chol), poly(ethylene glycol) (PEG550) studied. Their difference resides the spacers connecting TPE Chol PEG, where PEG550-SS-TPE-SS-Chol contains disulfide bonds (–SS–) two longer more flexible compared PEG550-TPE-Chol. For PEG550-TPE-Chol, progressive transformation from standard porous vesicles, networks, cylindrical micelles is shown as trans/cis ratio increases. A local, hexagonal structure nanopores observed membrane (trans/cis = 50/50), while two-dimensional crystalline long-range order obtained that 50/50). This likely driven microphase separation between vesicle-forming trans-isomers micelle-forming cis-isomers, both kinetic effects free energy minimization play important roles. The pore organization facilitated higher molecular mobility due softer or temperature. All nanostructures exhibit cyan aggregation-induced emission fluorescence. Moreover, can be destroyed using reducing agents, which may useful controlled release. Download figure PowerPoint Introduction (also called perforated stomatosomes) were first clearly identified mixtures small amphiphiles,1–4 one amphiphile favors micelle formation, other vesicle formation. These evidenced intermediate structures transition bilayer amphiphiles varies.2 typical example mixture cetyltrimethylammonium chloride/egg phosphatidylcholine (C16TAC/EPC) NaCl aqueous solution molar C16TAC/EPC 50/50. Other examples include catanionic surfactant an excess anionic cationic species, such sodium dodecyl sulfate (SDS) trimethyl ammonium bromide (C12TAB, 35.6% mole) NaBr solution,5,6 myristic acid (MA) hydroxide (C16TAOH, 43% water.7 SDS, C12TAB, MA, C16TAOH alone form solution, SDS/C12TAB pair (1/1 ratio) MA/C16TAOH surfactants. system 35.6 mol % C12TAB yields SDS/catanionic-pair 45/55 ratio, formed vesicles. Interestingly, 43 results MA/catanionic-pair 25/75 ratio; forms icosahedra 12 pores their vertices. Here, instead spherical because catanionic-pair (2D) gel phase). Structuring into stable capsule extremely transportation However, made suffer low stability weight building blocks. Later, supramolecular capsules reported dumbbell-shaped rod-core8 dendritic fluorinated-core.9 In capsule, it was possible change size opening/closing varying temperature5 but mechanism formation these one-component has not been elucidated yet.8,9 Recently, our group self-assembled rod-coil polymer (Figure 1a).10 cis-isomers show distinct behaviors water, trans-PEG550-TPE-Chol classical cis-PEG550-TPE-Chol self-assembles micelles, 60/40), either naturally synthesized without isomeric during synthesis intentionally mixed yield nanopores. also light-gated, could opened upon UV illumination. Figure 1 | (a) (b) (50/50). To gain further insight nanopores, herein, we have studied complete series 95/5, 75/25, 60/40, 50/50, 40/60, 25/75, 5/95). interwoven ribbon observed. interestingly, equivalent (50/50), some local structuring overall random organization. We similar polymer, PEG-TPE TPE-Chol moieties 1b). Remarkably, well-ordered 2D revealed superstructure believed Finally, (AIE) reduction-responsive properties disulfide-containing investigated. Experimental Methods Materials 4-Methoxybenzophenone (≥98%), titanium tetrachloride (TiCl4, >98%), boron tribromide (BBr3, 4-dimethylaminopyridine (DMAP, >99%), Zn powder (2.5 cm, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, lithium (LiOH, ≥98%), (Chol, >95%), methyl ether (MeO-PEGn-OH, n 12, Mn 550 Da, Mw/Mn 1.01), 3,3ʹ-dithiodipropionic purchased Alfa Aesar (Bejing, China), purification. Instruments measurements 1H NMR 13C spectra recorded on Bruker AV 400 spectrometers (Bruker, Billerica, United States). shifts δ given ppm referenced tetramethylsilane CDCl3 (0 ppm). measured Milton Ray Spectronic 3000 Array spectrophotometer (Milton Roy Company, Davidson, NC, Photoluminescence (PL) Horiba FluoroMax spectrofluorometers (Horiba, Kyoto, Japan). Hydrodynamic diameters self-assemblies distributions pure water at 25 °C dynamic light scattering (DLS, Malvern zetasizer 3000HS; Panalytical, Malvern, Kingdom) 633 nm laser. 90° angle used all measurements. Self-assembled morphologies cryo-electron microscopy (cryo-EM). Cryo-EM images acquired JEOL 2200FS (JEOL Ltd., Tokyo, Japan) energy-filtered (20 eV slit) field gun electron microscope operating 200 kV Gatan US1000 camera. sample preparation, total 5 μL samples deposited onto 200-mesh holey copper grid (Ted Pella Inc., Redding, CA, States) flash-frozen liquid ethane cooled nitrogen temperature Leica EM-CPC (Leica, Wetzlar, Germany). Giant epifluorescence DMR Germany) upright equipped Retiga Exi charge-coupled device (CCD) camera (Teledyne Technologies, Thousand Oaks, light-emitting diode (LED) Lamp (λ 365 nm). Samples (10 μL) glass slide cover slip spacers. Then, observations performed 100x objective lens (N.A. 1.3). Images Image-Pro Plus (Media Cybernetics, Rockville, MD, processed/analyzed ImageJ. Synthesis TPE-SS-Chol-OH TPE-2OH (2.75 mmol, 1.0 g), SS-Chol (2.60 1.5 (3-dimethylaminopropyl)ethyl-carbodiimide monohydrochloride 3.30 0.63 DMAP (3.30 0.40 g) dissolved 50 mL dichloromethane, trimethylamine (5.50 0.56 then added. described Supporting Information. resultant stirred room overnight. Then reaction washed saturated three times. After solvent evaporation, crude product purified flash chromatography (petroleum (PE)/ethyl acetate (EA) 5:1). Yield: 53%. (400 MHz, CDCl3): 7.10–6.98 (m, 12H, ArH), 6.91–6.81 4H, 6.57 (t, 2H, J (H,H) 8.00 Hz, 5.38 (s, 1H, C CH), 4.66 COOCH), 3.04–2.91 6H, CH2CH2SSCH2), 2.71 2.00 CH2COO), 2.34 (d, CH2), 2.02–0.68 45H, alkane). HOOC-SS-TPE-SS-Chol (1.08 1.00 0.23 EDCI (1.30 0.20 0.16 (2.16 0.22 overnight thrice solution. (PE:EA 1:1). 40%. 7.14–7.00 14H, 6.88–6.83 C=CH), 3.02–2.93 COOCH2CH2SSCH2), 2.82 CH2COOH), 2.74–2.70 CCH2C), 2.05–0.68 TPE-SS-Chol (0.36 (MeO-PEG12-OH, 1.01) (0.32 0.18 (0.43 67 mg), 53 mg) dichloromethane. organic phase mol/L HCl dried Na2SO4 filtered. (Dichloromethane: MeOH 30:1). 70%. 7.14–6.97 6.88–6.81 5.37 4.67–4.59 3.70–3.53 H PEG), 3.37 3H, OCH3) 3.01–2.92 2.79–2.69 2.33 CHCH2C, Hz), 2.07–0.67 Self-assembly film hydration Typically, mg stereoisomer chloroform (CDCl3). 30 min achieve dissolution. about uniformly surface roughened Teflon plate (2 cm × 2 cm). vacuum least h remove obtain film. placed bottle, deionized gently sealing thin hydrated 65 48 h. DLS cryo-EM nanoprecipitation 2.5 dimethylformamide (DMF; concentration: mg/mL). slowly injected rate μL/h slight shaking. whole process carried out turbid dialyzed against over days DMF Spectra/Por regenerated cellulose cutoff 3500 Da (water frequently freshened). Results Discussion Syntheses Both hydrophobic part composed rigid cores, (TPE) group, moiety, hydrophilic (PEG550, Da) (see 1). 1510 1650 Da. only molecules spacers: bond –S–S– inserted PEG Chol, respectively, 1a) core stilbene-type moiety structurally thermally cis-stereoisomers.10 according published procedure,10 them, different isomer prepared. special trans cis synthetic section Information Scheme S1 Figures S1–S3 detail), final products contained Self-assemblies thin-film method high (T °C) accelerate self-organization, section. trans-PEG550-TPE-Chol, cis-PEG550-TPE-Chol, ratios 75/25) carefully sizes characterized cryo-transmission (cryo-TEM), 2. As discussed previous paper,10 5% cis-isomer 95/5), trans-isomer Nevertheless, trace opposite isomers did influence cis-PEG550-TPE-Chol.10 2a 2b, normal whereas assembled micelles. expected, since already giant liposomes immersed lysolipids incorporate lipid bilayers, up 10 %.11 Qualitatively following theory Israelachvili et al.,12,13 packing parameter p v/al should around value decreases approaches 1/2 (where v volume, optimal interfacial area, l length block interface). schematic representation 2b. 95/5 (a), 75/25 (c), 60/40 (d), 50/50 (e), 40/60 (f), (g), 5/95 (b). behave like respectively main text). models (b), respectively. red ellipsoid represents green trefoil group. line aliphatic spacer, blue PEG550 chain. model, empty ellipsoids represent highlight along cylinder long axis. cis-PEG-TPE-Chol, axis turn Scale bars 100 nm. thickness diameter (all parts) evaluated full width half maximum density profile perpendicular through statistical analysis images. 7.5 ± 0.5 nm, 6.5 plausible parts cis-PEG-TPE-Chol interdigitated (1) (e nm) extended lengths ltrans (4.54 2ltrans (9.08 nm), (2) (dc lcis (4.05 2lcis (8.10 Note versatile support membranes14 fibril structures15,16 its rigidity, self-assembling nature, asymmetric carbons, so on. most representative five prepared 25/75) displayed 2c–2g, supplemental present S4–S8. 2c, 25% content sufficient introduce homogeneous size. 20% <7.0 55% 7.0–15 >15 S4). cis-isomers: cis-rich domains hemicylindrical edges ribbons. coexistence very suggests effect dominant separation. When contents balanced, (including ones) (Figures 2d–2f S5–S7). At ratios, become 12–13 diameter. note round, convex polygon. Therefore, exist. case tend organize locally inside frames 2e, S6). many few ribbons (meshes) 2g S8). 2b). Table summarizes values (dc), (dh), minimal wall (ew) 3c definition) mixtures. thicknesses ∼ 7.2–7.4 remain nearly same (ew 6.8–7.0 close (slightly than) hemicylinder radius). there little space adjacent pores. Size Characterization Different Morphologies Mixtures Cryo-EM. Self-Assembly Method Is Film Hydration Sample Membrane Thickness e (nm) Cylindrical Micelle Diameter dc Pore dh Wall ew – Mixture I 7.4 0.6 5.2–100a II 60/40) 7.2 13.0 1.7 6.9 0.7 III 50/50) 7.3 11.5 1.2 7.0 IV 40/60) 11.9 V 11.3 3.0b 6.8 0.6b aThe heterogeneous. 5.2 lowest measurable visible holes. Big holes, located loose mesh parts. bThe meshes. 3 network Schematic illustration appearance when added trans-isomer. morphological increasing fraction cis-isomer. (c) indicate (ew), (e). transitions heuristically understood follows 3a 3b). impose positive spontaneous curvature constituent monolayers (leaflets). Due separate tendency isomers, flat critical concentration (cc) here cc > ratio. Above concentration, takes place, assemble negative (the pores), perforation 3a). shapes sizes, determined jointly kinetics cis-isomers. With increases grow areas shrink. Consequently, sequence bilayers numbers pores, network, finally scenario previously proposed diglycerol monodecanoate (DGMD)/monoglycerol (GMD)/water system.2 especially interested mixture. understand relationship nanopore properties, polymers chemical TPE-Chol. Among specific process, showed extraordinary properties. Perforated observed, self-organized surfaces 4a–4e S9). directly seen sharp Bragg peaks Fourier transforms (FT) FT insets 4c). locations, darker 4c left) bright turned lattices rotated 15° (in plane rotation) relative another, showing those dark new rather superposition membranes. 4 magnifications 30000x (a–c) 60000x (d–e). perform self-assembly. image (c–e) Observation characterization lattice (f) (g) high-resolution after recover information lattice. (h) hexagonally organized membrane. single (blue region) superimposition (red region). together Measurements 8.4 7.9 than expected (–S–S–) middle. counter 5.26 4.77 \PEG-SS-TPE-SS-Chol, (ltrans 4.54 4.05 Comparing 7.