Control of Kinetic Pathways toward Supramolecular Chiral Polymorphs for Tunable Circularly Polarized Luminescence.

An amphiphilic aza-BODIPY dye (S)-1 bearing two chiral hydrophilic side chains with S-stereogenic centers was synthesized. This dye exhibited kinetic-controlled self-assembly pathways and supramolecular chiral polymorphism properties in MeOH/H2O (9/1, v/v) mixed solvent. The (S)-1 monomers first aggregated into a kinetic controlled, off-pathway species Agg. A, which was spontaneously transformed into an on-pathway metastable aggregate (Agg. B) and subsequently into the thermodynamic Agg. C. The three aggregate polymorphs of dye (S)-1 displayed distinct optical properties and nanomorphologies. In particular, chiral J-aggregation characteristics were observed for both Agg. B and Agg. C, such as Davydov-split absorption bands (Agg. B), extremely sharp and intense J-band with large bathochromic shift (Agg. C), non-diminished fluorescence upon aggregation, as well as strong bisignated Cotton effects. Moreover, the AFM and TEM studies revealed that Agg. A had the morphology of nanoparticle while fibril or rod-like helical nanostructures with left-handedness were observed respectively for Agg. B and Agg. C. By controlling the kinetic transformation process from Agg. B to Agg. C, thin films consisting of Agg. B and Agg. C with different ratios were prepared, which displayed tunable CPL with emission maxima at 788-805 nm and g-factors between -4.2×10-2 and -5.1×10-2.

Supramolecular Structure and Photo-Thermo-Electric Property of Hydrogen-Bonded Liquid Crystalline Polymer Containing Poly(4-vinylpridine) and Cyanostilbene Side Chains.

A series of side-chain liquid crystalline polymers P4VP(CN-DBE)x , where x is the molar ratio of cyanostilbene (CN-DBE) to poly(4-vinylpyridine) (P4VP) repeating unit, was synthesized based on the intermolecular hydrogen bonding between P4VP and CN-DBE. Their luminescent property, liquid crystalline structure and photo-thermo-electric property were elucidated using photoluminescence spectra, X-ray diffraction, thermal imaging and thermoelectric experiments. With the increase of x, the supramolecular system can be changed from lamellar structure to hexagonal columnar structure. Moreover, the P4VP(CN-DBE)x polymer with columnar structure exhibits more efficient photothermal effect. The temperature of P4VP(CN-DBE)0.6 can rise to 130 °C within 10 s under the irradiation of ultraviolet lamp. In addition, the supramolecular system possesses unique photo-thermo-electric conversion ability, and 25 mA current can be detected in the circuit coupled with the thermoelectric module. This work broadens the potential applications of hydrogen-bonded polymer, and provides a simple and facile strategy to prepare liquid crystalline polymers with photo-thermo-electric property.

An amphiphilic B,O-chelated aza-BODIPY dye: synthesis, pH-sensitivity, and aggregation behaviour in a H2O/DMSO mixed solvent.

A novel amphiphilic B,O-chelated azadipyrromethene (aza-BODIPY) dye, containing hydrophobic dodecyloxy groups and hydrophilic tetraethylene glycol (TEG) chains, was synthesized and characterized by NMR, HRMS, Vis/NIR absorption and fluorescence spectroscopy. The B,O-chelated dye 1 exhibited largely bathochromically shifted NIR absorption and fluorescence spectra in comparison with common BF2-chelated aza-BODIPY dyes. Upon gradual addition of trifluoroacetic acid (TFA) to the dye 1 solution, obvious spectral changes were observed in Vis/NIR absorption and fluorescence spectroscopy measurements. Meanwhile, the colour change of the dye 1 solution from pink to blue was noticeable by the naked eye, indicating the pH-sensitivity of dye 1. The pH-sensitivity of dye 1 under acidic conditions could be ascribed to the formation of dye species 2·H+. Furthermore, owing to the amphiphilic feature of dye 1, it self-assembled into J-type aggregates in a mixed solvent of water/DMSO (2/8, v/v). Temperature-dependent Vis/NIR spectroscopic studies revealed a cooperative aggregation process of dye 1 and a nanowire-like morphology of the nanoaggregates was observed by AFM.

Redox stimulus disulfide conjugated polyethyleneimine as a shuttle for gene transfer.

Redox-responsive cationic polymers have gained considerable attention in gene delivery due to low cytotoxicity and spatio-temporal release of DNA into the cells. Here, we reported the synthesis of reducible disulfide conjugated polyethyleneimine (1.8 kDa) (denoted as SS-PEI) and its application to transfer pEGFP-ZNF580 plasmid (pZNF580) into EA.hy926 cell. This reducible SS-PEI polymer was prepared by one-step polycondensation reaction of low molecular weight PEI with bis-(p-nitrophenyl)-3,3'-dithiodipropionate. The SS-PEI successfully condensed pZNF580 into nano-sized complexes (170 ± 1.5 nm to 255 ± 1.6 nm) with zeta potentials of 3 ± 0.4 mV to 17 ± 0.9 mV. The complexes could be triggered to release pZNF580 when exposed to the reducing environment of 5 mM dithiothreitol. Besides, the SS-PEI exhibited low cytotoxicity. In vitro transfection results showed that SS-PEI exhibited good transfection efficiency comparable to PEI25kDa. Thus, the SS-PEI could act as an reducible gene carrier with good transfection efficiency and low cytotoxicity.

Multifunctional Gene Carriers Labeled by Perylene Diimide Derivative as Fluorescent Probe for Tracking Gene Delivery.

Multifunctional carriers with both gene transfection property and fluorescent tracking function have attracted significant attention in recent years. Herein, a kind of perylene diimide derivative (PDI-C10C8) is conjugated onto the polyethylenimine-g-poly(lactide-co-glycolide)-g-polyethylenimine (PLGA-PEI) polymer to obtain fluorescent multifunctional polymer and micelles (abbreviated as MP). Then, the REDV-G-TAT-G-NLS (TP-G) peptide sequence is grafted onto this MP to obtain multifunctional micelles labeled by perylene diimide derivative (MP-TP-G). These micelles exhibit enhanced photobleaching stability compared with the reference Cy5-labeled micelles, and the fluorescent images of cellular uptake show bright red emission without any background noise. Confocal laser scanning microscope (CLSM) experiments show that gene complexes can deliver gene into nucleus. MP-TP-G carriers do not enter into the cell nucleus, which proves that the nuclear localization signal sequence may not exert its nucleus accumulation ability via conjugating to the amphiphilic polymers. The high transfection efficiency and the enhanced photobleaching stability, combined with the ability to monitor the detailed process of cellular uptake and gene delivery, make these multifunctional micelles have great potential application for endothelialization of artificial blood vessels and gene delivery process study.

Synthesis, Self-Assembly and Characterization of Tandem Triblock BPOSS-PDI-X Shape Amphiphiles.

In this article, we report the facile synthesis, self-assembly, and characterization of shape amphiphiles (BPOSS-PDI-X) based on isobutyl-functionalized polyhedral oligomeric silsesquioxane (BPOSS), perylene tetracarboxylic diimide (PDI), and (60)fullerene (C60) moieties. Firstly, an asymmetrically functionalized diblock shape amphiphile precursor (BPOSS-PDI-OH) was obtained through the one-pot reaction between perylene-3,4,9,10-tetracarboxylic dianhydride and two different amines, namely BPOSS-NH2 and 3-amino-1-propanol. It was further conjugated with C60-COOH to give a tri-block shape amphiphile (BPOSS-PDI-C60). Their chemical structures were thoroughly characterized by NMR, IR and MALDI-TOF MS spectrometry. In order to gain insights on the structure-property relationship, their self-assembly in gas phase, in solution, and in solid state were characterized using traveling wave ion mobility mass spectrometry (TWIM-MS), UV/Vis absorption, fluorescence emission spectrophotometer, and transmission electron microscopy, respectively. It was found that BPOSS-PDI-OH formed more complicated dimers than BPOSS-PDI-C60. Both samples showed unique aggregation behaviors in solution with increasing concentration, which could be attributed neither to H- nor to J-type and might be related to the discrete dimers. While BPOSS-PDI-C60 could hardly crystalize into ordered structures, BPOSS-PDI-OH could form nanobelt-shaped single crystals, which may hold potential applications in microelectronics.

From S,N-Heteroacene to Large Discotic Polycyclic Aromatic Hydrocarbons (PAHs): Liquid Crystal versus Plastic Crystalline Materials with Tunable Mechanochromic Fluorescence.

A novel type of discotic polycyclic aromatic hydrocarbon (PAH) based on an enlarged dibenzo[a,c]phenazine core has been developed. The large conjugated mesogenic core with increased dipole moment derived from S,N heteroatoms facilitates the formation of highly ordered columnar superstructures both in solution and bulk. Columnar mesophases, including liquid crystal (LC) and plastic crystal (PC) assemblies could form unprecedentedly based on the same PAH core. The cores are delicately modulated by the peripherical alkoxy chains. Both mesogens have mechanochromic fluorescent (MCF) character, which is also structure dependent and correlated with the different mesophase formation. For the first time, MCF properties can be realized in such a large conjugated mesogenic system.

Ionic Self-Assembled Derivative of Tetraphenylethylene: Synthesis, Enhanced Solid-State Emission, Liquid-Crystalline Structure, and Cu2+ Detection Ability.

A novel tetraphenylethylene complex composed of 4',4'',4''',4''''-(ethene-1,1,2,2-tetrayl)tetrabiphenyl-4-carboxylic acid (H4 ETTC) and dimethyldioctadecylammonium bromide (DOAB) with enhanced solid-state emission is designed and synthesized through an ionic self-assembly (ISA) strategy. The aggregation-induced emission property, phase behavior, and supramolecular structure of the complex are characterized by a combination of experimental measurements. The experimental results reveal that the ISA complex can self-assemble into an ordered helical supramolecular structure with enhanced luminescent properties, although the ETTC cores possess extensive conjugation and high rigidity. Due to the prolonged conjugation length, the fluorescence quantum yield of ETTC-DOAB is boosted to 66 %. Moreover, it is demonstrated that assemblies of the ISA complex are an effective sensor for Cu2+ . Owing to the disassembly modulation of ETTC-DOAB aggregations, the fluorescence emission of the assemblies can be selectively and sensitively quenched by Cu2+ , with a detection limit as low as 12.6 nm. The enhanced emission efficiency, in combination with the liquid crystallinity and superior sensing performance to Cu2+ , make the ETTC-DOAB complex a potential candidate for the fabrication of a luminescent device and chemosensor for Cu2+ detection.

A portable fluorescence detection device based on a smartphone employing carbon nanodots for Mn2+ sensing.

The measurement of fluorescence emission for quantitative analysis is typically based on a traditional spectrofluorometer, which limits an onsite detection approach. Thus, an alternative device should be developed for fulfilling this analysis outside of the laboratory. Therefore, a low-cost, portable, and low-energy consumption fluorescence reader-based smartphone device was developed. An ultraviolet light-emitting diodes (UV-LED) was used to construct the fluorescence device-based smartphone as a low-power excitation light source. The smartphone camera was used as a detector for detecting photons from the fluorescence emission process of the fluorescence probe and was connected to a digital image platform. Transparent acrylic with orange and yellow colors was employed as a filter for reducing the interference from light source intensity. The obtained digital image was converted to red, green and blue (RGB) intensity using a custom-designed smartphone application. N,S-doped carbon nanodots (N,S-CDs) were demonstrated to be a good fluorescence indicator for determining trace quantities of Mn2+ in cosmetics. The approach exhibited high selectivity and sensitivity, detecting and quantifying analytes at 1-5 µM concentrations. Furthermore, the method's detection limit of 0.5 µM reflects its capacity to detect trace amounts of a target analyte. Mn2+ in cosmetic products was successfully analyzed using this device with high accuracy comparable with the results from inductively coupled plasma-optical emission spectroscopy (ICP-OES).

Field Effect Transistor Gas Sensors Based on Mechanically Exfoliated Van der Waals Materials.

The high surface-to-volume ratio and flatness of mechanically exfoliated van der Waals (vdW) layered materials make them an ideal platform to investigate the Langmuir absorption model. In this work, we fabricated field effect transistor gas sensors, based on a variety of mechanically exfoliated vdW materials, and investigated their electrical field-dependent gas sensing properties. The good agreement between the experimentally extracted intrinsic parameters, such as equilibrium constant and adsorption energy, and theoretically predicted values suggests validity of the Langmuir absorption model for vdW materials. Moreover, we show that the device sensing behavior depends crucially on the availability of carriers, and giant sensitivities and strong selectivity can be achieved at the sensitivity singularity. Finally, we demonstrate that such features provide a fingerprint for different gases to quickly detect and differentiate between low concentrations of mixed hazardous gases using sensor arrays.

Living supramolecular polymerization of an amphiphilic aza-BODIPY dye realized by water-assisted kinetic trapping.

The kinetic assembly pathways of a newly synthesized amphiphilic aza-BODIPY dye 1 were tuned by using H2O as a co-solvent in MeOH. Accordingly, the biphasic aggregation pathways resulting in kinetically-trapped and thermodynamically stable aggregates of 1 were established and the multiple cyclic seeded living supramolecular polymerization of this dye was realized.

Superlow Dosage of Intrinsically Bioactive Zinc Metal-Organic Frameworks to Modulate Endothelial Cell Morphogenesis and Significantly Rescue Ischemic Disease.

Despite long-term efforts for ischemia therapy, proangiogenic drugs hardly satisfy therapy/safety/cost/mass production multiple evaluations and meanwhile with a desire to minimize dosages, thereby clinical applications have been severely hampered. Recently, metal ion-based therapy has emerged as an effective strategy. Herein, intrinsically bioactive Zn metal-organic frameworks (MOFs) were explored by bridging the dual superiorities of proangiogenic Zn2+ and facile/cost-effective/scalable MOFs. Zn-MOFs could enhance the morphogenesis of vascular endothelial cells (ECs) via the PI3K/Akt/eNOS pathway. However, high dosage is inevitable and Zn-MOFs suffer from insolubility and low stability, which lead to the bioaccumulation of Zn-MOFs and seriously potential toxicity risks. To alleviate this, it is required to decrease the dosage, but this can be entrapped into the dosage/therapy/safety contradiction and disappointing therapy effect. To address these challenges, the bioavailability of Zn-MOFs is urgent to improve for the minimization of dosage and significant therapy/safety. The mitochondrial respiratory chain is Zn2+ active, which inspired us to codecorate EC-targeted and mitochondria-localizing-sequence peptides onto Zn-MOF surfaces. Interestingly, after codecoration, a 100-fold reduced dosage acquired equally powerful vascularization, and the superlow dosage significantly rescued ischemia (4.4 µg kg-1, about one order of magnitude lower than the published minimal value). Additionally, no obvious muscle injury was found after treatment. Potential toxicity risks were alleviated, benefiting from the superlow dosage. This advanced drug simultaneously satisfied comprehensive evaluations and dosage minimization. This work utilizes engineering thought to rationally design "all-around" bioactive MOFs and is expected to be applied for ischemia treatment.

Tetraphenylethylene sulfonate derivative as turn-on fluorescent sensor for berberine chloride detection in aqueous solution.

A negatively-charged tetraphenylethylene derivative (TPE-SE) was designed and synthesized as turn-on fluorescent sensor for berberine chloride (BBC) detection in aqueous solution. The fluorescent property and detection mechanism were elucidated by UV-vis absorption spectra, photoluminescence spectra, dynamic light scattering experiments. The results reveal that the BBC can lead to aggregation-induced emission of TPE-SE due to the electrostatic interactions, endowing TPE-SE with excellent turn-on detecting ability, high selectivity and sensitivity to BBC. The detection limit is as low as 6.58 × 10-6M. These results should be applicable to fabricate special turn-on fluorescent sensors towards various antibiotics, and it is crucially important for achieving reasonable control and intake of small biomolecules.

Structural and Nanotribological Properties of a BODIPY Self-Assembly.

Boron-dipyrromethenes (BODIPY) are promising functional dyes, whose exceptional optical properties are closely related to their supramolecular assembly. Herein, the self-assembly of a BODIPY derivative functionalized with uracil groups is explicitly and thoroughly investigated by using scanning tunneling microscopy (STM). Based on the simulation and calculation by density functional theory (DFT) method, it can be concluded that the construction of ordered self-assembly structure is attributed to the formation of hydrogen bonds between uracil groups. Moreover, the nanotribological property of the self-assembly on HOPG surface is measured by using atomic force microscopy (AFM). The effort on self-assembly of the BODIPY derivative could enhance the understanding of surface assembly mechanism.

Activation of Pd-precatalysts by organic compounds for vinyl-addition polymerization of a norbornene derivative.

An approach to activating Pd-complexes without using additives such as Lewis acids has been developed for addition polymerization of norbornenes. Aryl iodides and aryl diazonium salts were efficiently applied as cocatalysts to Pd(0)- and Pd(2+)-complexes. The developed systems catalyzed polymerization of norbornenes containing bulky and polar functional groups both in an inert atmosphere and air resulting in soluble and high-molecular-weight saturated polymers.

A two-pronged approach to regulate the behaviors of ECs and SMCs by the dual targeting-nanoparticles.

Inhibiting vascular restenosis remains a tricky challenge for the postoperative development of cardiovascular interventional therapy. The ideal approaches should activate endothelial cells (ECs) and restrain smooth muscle cells (SMCs), however, they are commonly contradictory. Herein, a strategy was developed for synchronizing ECs promotion and SMCs inhibition by codelivery DNA and siRNA for combination therapy. Thus, an easy and efficient strategy integrated dual-superiorities of precise targeting and dual therapeutic genes to precisely regulate the behaviors of ECs and SMCs. The ECs-targeting REDV peptide and SMCs-targeting VAPG peptide grafted anionic polymers were used to surface-functionalize the delivery nanoplatforms for vascular endothelial growth factor (VEGF) plasmids and ERK2 siRNA delivery, respectively. The dual targeting-nanoparticles were prepared by physical mixing method, and their outstanding advantages were confirmed by the co-culture experiments. In comparison with single targeting-nanoparticles and dual non-targeting-nanoparticles, the dual targeting-nanoparticles simultaneously enhanced ECs proliferation/migration and restrained SMCs proliferation/migration. Moreover, the dual targeting-nanoparticles group manifested the highest VEGF expression in ECs and the lowest ERK2 expression in SMCs. In summary, the two-pronged strategy with dual targeting-nanoparticles provides a valuable cornerstone for synchronizing ECs promotion and SMCs inhibition.

Peripherally Modified Tetraphenylethene: Emerging as a Room-Temperature Luminescent Disc-Like Nematic Liquid Crystal.

A blue-light-emitting liquid crystalline (LC) material was designed and prepared. By employing a twisted luminescent core (i.e., tetraphenylethene), four peripheral LC units with long alkyl chains and the small polar benzyl-ether-typed linking groups, the resulting material displayed a hexagonal columnar phase near room temperature and a disc-like nematic phase between 32 and 70 °C. The columnar LC showed a high quantum yield of 0.49 at 20 °C, and the efficient luminescence property was retained even in the isotropic phase at high temperature. Additionally, the fluidity of the nematic phase rendered the LC a non-volatile solvent, and the proper addition of a red dye led to the achievement of polarized white-light emission, which revealed a promising application prospect in LC display fabrication.

Alignment of supramolecular J-aggregates based on uracil-functionalized BODIPY dye for polarized photoluminescence.

A BODIPY dye functionalized with uracil-ethynyl groups at the 2,6-positions supramolecularly polymerized into J-aggregates directed by intermolecular H-bonds and featured intense absorption and resonant fluorescence. The alignment of J-aggregated chromophores in a thin film was achieved by a rubbing method and polarized photoluminescence with a dichroic ratio up to 14.3 was obtained.

Unexpected Amplification of Synergistic Gene Expression to Boom Vascular Flow in Advantageous Dual-Gene Co-expression Plasmid Delivery Systems over Physically Mixed Strategy.

Gene therapy exerts powerful potential in the treatment of various diseases, such as overexpressing pro-angiogenic gene to accelerate angiogenesis and restore vascular flow of ischemic tissue. Tremendous efforts have been invested in developing gene carriers for high transfection efficiency, while little research has been devoted to synergistically expressing functional proteins via optimizing therapeutic genes. Actually, the amplified gene expression is the ultimate goal of gene delivery. Dual-gene co-delivery and coordinate expression become a "breach" of strengthened gene expression. Herein, we explored the synergistic effects on gene expression and pro-angiogenesis by two typical dual-gene delivery strategies to determine which one is more efficient. The physical mixing method used ZNF580 and VEGF165 plasmids with a 1/1 weight ratio (p1:1), and the other strategy involved chemically inserting ZNF580 and VEGF165 genes into one plasmid as a dual-gene co-expression plasmid (pZNF-VEGF). p1:1 and pZNF-VEGF were loaded by REDV-TAT-NLS-H12 carrier, a promising peptide carrier, to form corresponding dual-gene delivery systems. Both systems exhibited approximately similar size and zeta potential, guaranteeing almost the same cellular uptake. We comprehensively evaluated two delivery systems through gene expression at mRNA and protein levels and angiogenesis-related activities in vitro and in vivo. Interestingly, the pZNF-VEGF group showed a remarkably amplified synergistic effect in the expression of ZNF580 and VEGF165 genes in comparison with the p1:1 group. More importantly, the unexpected amplified synergistic effect of dual-gene co-expression plasmid was further verified for proliferation, migration, and angiogenesis in vitro and in vivo. Accordingly, we believed that the co-delivery of dual genes via constructing co-expression plasmids offers a better option for gene therapy, which can more effectively enhance the synergistic expression of target genes than the physical mixing method.

Cascaded bio-responsive delivery of eNOS gene and ZNF580 gene to collaboratively treat hindlimb ischemia via pro-angiogenesis and anti-inflammation.

Gene therapy is a promising strategy for treating ischemic disease by solving the dual dilemma of ischemia and inflammation. However, its development remains limited by inefficient gene transfection. Hence, we propose a "dual genes + all-adaptive carrier" idea. We have innovatively co-delivered eNOS gene and the ZNF580 gene encoding its transcription factor to enhance the efficiency of eNOS expression. The overexpressed ZNF580 protein significantly promotes angiogenesis via regulating the transcription of multiple genes. This implies a potential synergistic effect of eNOS and ZNF580 genes in anti-ischemic therapy. Additionally, we have designed an all-adaptive gene carrier with cascaded bio-responsive functions based on the characteristic bio-signals of the ischemic site (including extracellular excessive matrix metalloproteinase-2, the endo/lysosomal pH gradient and high cytoplasmic glutathione level). This carrier can sequentially overcome transfection bottlenecks and achieve high transfection. Excitingly, this cascaded bio-responsive delivery strategy remarkably enhanced blood perfusion, accelerated angiogenesis and alleviated inflammation in critical limb ischemia (CLI) mice, which was attributed to the combined effects of pro-angiogenic ZNF580 expression and synergistically produced eNOS expression. Thereby, we believe that the co-delivery of eNOS and ZNF580 genes assisted by a cascaded bio-responsive carrier is a powerful strategy to treat CLI.