An activatable small-molecule fluorogenic probe for detection and quantification of beta-amyloid aggregates.

Extracellular accumulation of ß amyloid (Aß) peptides in the brain is thought to be a pathological hallmark and initial event before the symptom starts of Alzheimer's patients. Herein, we developed two series of benzo[d]thiazole-based small-molecule compounds (BM1-BM4, BPM1-BPM4) with a donor-acceptor (D-A) or donor-π-acceptor (D-π-A) architecture, respectively, based on structure-activity relationship. Among them, the optimized BPM1 not only displayed the highest binding affinity to Aß aggregates over other proteins or Aß monomers, but was readily activated its fluorescence with 10-fold fluorescence enhancement, allowing for specifically and sensitively detecting Aß aggregates. BPM1 also exhibits several other advantages including low molecular weight, low cytotoxicity and excellent biological stability. Besides, cell staining results confirmed that SK-N-BE(2) cells can be fluorescently lighted up as well as cell permeability and damage when treated with BPM1-bound Aß1-42 aggregates.

Rheological Behavior of DNP/HMX Melt-Cast Explosives with Bimodal and Trimodal Particle-Size Distributions.

As a matrix for melt-cast explosives, 3,4-dinitropyrazole (DNP) is a promising alternative to 2,4,6-trinitrotoluene (TNT). However, the viscosity of molten DNP is considerably greater compared with that of TNT, thus, requiring the viscosity of DNP-based melt-cast explosive suspensions to be minimized. In this paper, the apparent viscosity of a DNP/HMX (cyclotetramethylenetetranitramine) melt-cast explosive suspension is measured using a Haake Mars III rheometer. Both bimodal and trimodal particle-size distributions are used to minimize the viscosity of this explosive suspension. First, the optimal diameter ratio and mass ratio (two crucial process parameters) between coarse and fine particles are obtained from the bimodal particle-size distribution. Second, based on the optimal diameter ratio and mass ratio, trimodal particle-size distributions are used to further minimize the apparent viscosity of the DNP/HMX melt-cast explosive suspension. Finally, for either the bimodal or trimodal particle-size distribution, if the original data between the apparent viscosity and solid content are normalized, the resultant plot of the relative viscosity versus reduced solid content collapses to a single curve, and the effect of the shear rate on this curve is further investigated.

Multifunctional behavior of a carbazole derivative: Red phosphorescent emission, aggregation-induced long-life exciton and light-emitting diode application.

A D-π-A typed cyanyl-carboxylic derivative (named as CECZA) merely produced prompt fluorescence with lifetime at nanosceond scale in dilute solutions, whose solid-state luminescence exhibited 3.36 µs lifetime with 13.80 % quantum yield (QY, captured at 522 nm for powder at nanometer scale) at 298 K and 43.36 ms lifetime with 30.46 % QY (650 nm, 80 K, tiny crystals). Femtosecond transient absorption, Raman spectroscopy and quantum chemical calculation provided valid clues to reveal its excitonic transition mechanism. The results indicated that the restricted vibration of benzene ring on carbazole group and alkyl chain weakened the vibrational modes of CECZA molecule and strengthened inter-molecular interactions between adjacent molecules at low temperatures, which promoted the persistent phosphorescent emission. Due to strong UV-vis absorption, high quantum efficiency and excellent thermal stability, CECZA can be used as a potential candidate in light-emitting diode (LED) application. Combined with a commercial InGaN blue-emitting chip, CECZA-InGaN emitted daylight white light.

Tuning Intermolecular Interactions to Enhance the Cyclability of Non-Aqueous, Organic Redox Flow Batteries.

Enhancing the electrochemical stability and reversibility of redox-active organic molecules is crucial to improve the performance of non-aqueous redox flow batteries (RFBs). Compared with the widely adopted strategy of molecular engineering, we show in this study that tuning the intermolecular interaction between the active material with the supporting electrolyte is another feasible way to address the performance of non-aqueous organic RFBs. Combined with theoretical and experimental investigations, the influence of Lewis acidity of the supporting electrolyte cations and anions on the electrochemical stability and reversibility of bipyridine-based anode material is revealed. As a demonstration, a redox flow cell based on 4,4'-bipyridine anolyte and ferrocene catholyte shows greatly enhanced performance by using supporting electrolyte composed of soft Lewis acid and soft Lewis base. This study provides an alternative, yet highly effective way to addressing the cyclability of an organic compound for non-aqueous RFBs.

Separate Calibration of Johnson-Cook Model for Static and Dynamic Compression of a DNAN-Based Melt-Cast Explosive.

When describing the relation between the flow stress and plastic strain of a material under a wide range of strain rates and temperatures, the original Johnson-Cook model generally requires a complicated modification, resulting in a loss of simplicity and clear physical interpretation. In this paper, without modification, the original Johnson-Cook model was calibrated separately for the static and dynamic compression of a DNAN-based melt-cast explosive. The stress-strain curves for static and dynamic compression of this explosive were experimentally measured with a universal testing machine and a split-Hopkinson pressure bar, respectively. Based on the stress-strain curves, the flow stress vs. plastic strain data were extracted and used to calibrate the Johnson-Cook model. The calibration process is described. The parameters for the strain term, strain rate term, and temperature term were fitted sequentially. One set of model parameters was not able to fully describe the relationship between flow stress and plastic strain for both the static and dynamic compression of the DNAN-based melt-cast explosive. Two sets of model parameters were separately calibrated and compared for the static and dynamic compression of this explosive. The effects of the adiabatic temperature rise and the definition of the yield point on this calibration were also investigated.

Functional Platinum(II) Complexes with Four-Photon Absorption Activity, Lysosome Specificity, and Precise Cancer Therapy.

Multiphoton materials are in special demand in the field of photodynamic therapy and multiphoton fluorescence imaging. However, rational design methodology for these brands of materials is still nascent. This is despite transition-metal complexes favoring optimized nonlinear-optical (NLO) activity and heavy-atom-effected phosphorescent emission. Here, three four-photon absorption (4PA) platinum(II) complexes (Pt1-Pt3) are achieved by the incorporation of varied functionalized C^N^C ligands with high yields. Pt1-Pt3 exhibit triplet metal-to-ligand charge-transfer transitions at ∼460 nm, which are verified multiple times by transient absorption spectra, time-dependent density functional theory calculations, and low-temperature emission spectra. Further, Pt1-Pt3 undergo 4PA. Notably, one of the complexes, Pt2, has maximum 4PA cross-sectional values of up to 15.2 × 10-82 cm8 s3 photon-3 under excitation of a 1600 nm femtosecond laser (near-IR II window). The 4PA cross sections vary when Pt2 is binding to lecithin and when it displays its lysosome-specific targeting behavior. On the basis of the excellent 4PA property of Pt2, we believe that those 4PA platinum(II) complexes have great potential applications in cancer theranostics.

NF-κB hijacking theranostic Pt(ll) complex in cancer therapy.

Platinum complexes have been used for anti-cancer propose for decades, however, their high side effects resulting from damage to healthy cells cannot be neglected and prevent further clinical utilisation. Here, we designed a cyclometalated platinum (II) complex that can bind the endogenous nuclear factor-κB (NF-κB) protein. Employing detailed colocalization studies in co-culture cell line models, we show that by binding to NF-κB, the platinum (II) complex is capable of upregulated nuclear translocation specifically in cancer but not normal cells, thereby impairing cancer proliferation without disturbing healthy cells. In a murine tumour model, the platinum (II) complex prevents tumour growth to a greater extent than cisplatin and with considerably lower side-effects and kidney damage. Considering its weak damage to normal cells combined with high toxicity to cancer cells, this NF-κB-binding platinum complex is a potential anti-cancer candidate and acts to verify the strategy of hijacking endogenous trans-nuclear proteins to achieve cancer-cell specificity and enhance therapeutic indices.

Series of C

It is currently challenged that nonlinear optical (NLO) properties in the near-infrared region (NIR) of metal complexes can be tunable with an assistant ligand. Herein, the linear and nonlinear photophysical properties of the novel C^N^C cyclometalated Pt(II) complexes with different substituents as auxiliary ligands are presented. The complexes displayed intense triplet metal/ligand-to-ligand charge-transfer (3MLCT/3LLCT) and intraligand 3π, π* emission at low-temperature. The excited-state characteristics are further confirmed over the TD-DFT calculations, transient absorption, and emission lifetimes. The Pt-3 possesses a relatively high quantum yield (9.1%), a moderate triplet excited-state lifetime (5.32 µs), and a broad excited-state absorption from the visible to the near-IR region. Interestingly, it was found that Pt-3 exhibited high 2PA cross section values (σ2 up to 367 GM at 820 nm), as well as good optical limiting properties over a tunable femtosecond laser. The relationships between the structures and properties were systematically investigated on the basis of crystal structural information. Hence, cyclometalated Pt(II) complexes would become candidates for the application of the NIR NLO materials.

Double labelling of intracellular mitochondria and nucleolus using thiophene pyridium salt with high quantum yield as biosensor and its application in stimulated emission depletion nanoscopy.

Probe for dual-site target distinct subcellular compartments from cytosol and nucleus is an attractive approach, however, which was scarcely reported. Herein, a series of small-molecular thiophene pyridium salt derivatives (MitoNuc1-4) possessing water-soluble, high quantum yield and two-photon activity were rationally designed, and their structures were crystallographic confirmed. Systematic photophysical and biological imaging property investigations were carried out for them. It was found that MitoNuc1-4 exhibit two-photon absorption properties in the near infrared region, and MitoNuc1 has membrane permeability and cationic nature, rendering it to be double labelling of mitochondria and nucleolus in living cells with superb photo-stability and non-invasiveness. It also demonstrated that MitoNuc1 in living cells can monitor mitochondrial division in real time and revealed nucleolar ultrastructure under stimulated emission depletion nanoscopy.

Pyridyl group design in viologens for anolyte materials in organic redox flow batteries.

Organic redox compounds represent an emerging class of active materials for organic redox-flow batteries (RFBs), which are highly desirable for sustainable electrical energy storage. The structural diversity of organic redox compounds helps in tuning the electrochemical properties as compared to the case of their inorganic counterparts. However, the structural diversity makes the design and identification of redox-active organic materials difficult because it is challenging to achieve appropriate redox potential, solubility and stability together, which are the major concerns regarding the practical applicability of these materials to RFBs. Herein, we report the design, synthesis, and application of viologen molecules as anolyte materials for organic RFBs that are compatible with Li-ion electrolytes. Structural screening assisted by density functional theory (DFT) calculations suggests that the (CH2)5CH3-substituted viologen molecule exhibits reduction potential as low as 2.74 V vs. Li/Li+, good structural stability due to effective charge delocalization within the two pyridinium rings, and a solubility of up to 1.3 M in carbonate-based electrolytes. When paired with a 2,2':6',2''-terpyridine-iron complex catholyte, the cell shows a high discharge voltage of 1.3-1.5 V with coulombic efficiency > 98% and energy efficiency > 84%. Both the anolyte and catholyte materials are built from earth-abundant elements and can be produced with high yields; thus, they may represent a promising choice for sustainable electrical energy storage.

Intracellular "activated" two-photon photodynamic therapy by fluorescent conveyor and photosensitizer co-encapsulating pH-responsive micelles against breast cancer.

The application of photodynamic therapy (PDT) for the diagnosis and treatment of cancer is hindered by the intrinsic defects of the currently available photosensitizers (PSs), such as poor water solubility and limited light-penetration depth. In this study, pH-responsive polymeric micelles that co-encapsulate therapeutic PSs and organooxotin two-photon compounds were applied for two-photon PDT (TP-PDT) against breast cancer. The TP-PDT effect of the drug-loaded micelles was "activated" when the micelles turned into aggregates at a triggering pH level. The in vitro therapeutic effect was evaluated on 4T1 murine breast cancer cells by viability assays, real-time morphology collapsing, and reactive oxygen species determination. Time-dependent ex vivo organ distribution and in vivo anticancer efficacy results suggested that the drug carriers could accumulate in tumors and suppress tumor growth by TP-PDT. The delivery system could enhance the solubility and distribution of PSs and, if administered along with a tissue-penetrating prolonged light source, could thus have good potential for cancer therapy.

Highly Hydrophilic, Two-photon Fluorescent Terpyridine Derivatives Containing Quaternary Ammonium for Specific Recognizing Ribosome RNA in Living Cells.

A two-photon fluorescent probe (J1) that selectively stains intracellular nucleolar RNA was screened from three water-soluble terpyridine derivatives (J1-J3) with quaternary ammonium groups. The photophysical properties of J1-J3 were systemically investigated both experimentally and theoretically, revealing that J1-J3 possess large Stokes shifts and the two-photon absorption action cross sections range from 38 to 97 GM in the near-infrared region. This indicates that J1 could specifically stain nucleoli by targeting the nucleolar rRNA from the recognition experiments in vitro, the two-photon imaging experiments, and the stimulated emission depletion in vivo. The mechanism of action in which J1 binds to the nucleolar rRNA was researched via both experiments and molecular modeling. The high binding selectivity of J1 to nucleolar RNA over cytosolic RNA made this probe a potential candidate to visualize rRNA probe in the living cells.

Halides tuning the subcellular-targeting in two-photon emissive complexes via different uptake mechanisms.

We reported a simple and universal strategy by tuning halides (Cl, Br and I) in terpyridine-Zn(ii) complexes to achieve different subcellular organelle targeting (nucleolus, nucleus and intracellular membrane systems, respectively) via different cellular uptake mechanisms, resulting from halide triggering different polymorphs of these complexes.

Localization matters: a nuclear targeting two-photon absorption iridium complex in photodynamic therapy.

We present a two-photon (2P, 800 nm) PDT cyclometalated Iridium(iii) complex (Ir-Es) that targets the intracellular nucleus. The complex is capable of migrating sequentially from the nucleus to mitochondria and inducing dual-damage under light exposure. This study suggests that with minor modification of the terminal moieties of complexes, their final intracellular destinations and PDT efficiency can be significantly impacted.

A series of water-soluble A-π-A' typological indolium derivatives with two-photon properties for rapidly detecting HSO3 -/SO3 2- in living cells.

It is believed that HSO3 - and SO3 2- play important roles in several physiological processes. However, probes with two-photon absorption to detect HSO3 - or SO3 2- in living cells are still limited. Herein, a series of novel indolium derivatives (L1-L4) with an A-π-A' structure was designed and synthesized as ratiometric probes to detect HSO3 -/SO3 2-in vitro. L3 and L4 display a colorimetric and ratiometric fluorescence dual response to HSO3 -/SO3 2- with a very fast (∼15 s) and high specificity, as well as low detection limits (∼22 nM). Furthermore, their detection is also carried out by using a two-photon excited fluorescence method. A nucleophilic addition reaction is proposed for the sensing mechanism, which is supported by MS, 1H NMR, and density functional theory (DFT) investigations. Importantly, L3 was successfully used for detecting intrinsically generated intracellular HSO3 -/SO3 2- in cancerous cells under one- and two-photon excited fluorescence imaging.

A water-soluble two-photon fluorescence chemosensor for ratiometric imaging of mitochondrial viscosity in living cells.

A convenient and rationally designed water-soluble two-photon excited fluorescence (TPEF) sensor for monitoring viscosity with specific targeting at the subcellular level remains a challenge. Herein, we reported a novel water-soluble ratiometric TPEF chemosensor EIN that is specifically responsive and singularly sensitive to mitochondria viscosity in living cells. Because its fluorescence emission bands at two different wavelengths show obvious enhancement with increased solvent viscosity, we found that the fluorescence intensity ratio (I569/I384) versus the logarithm of the viscosity (log η) enables monitoring and quantifying of abnormal changes of mitochondria viscosity. More importantly, EIN was successfully utilized to distinguish the normal and nystatin treated HepG2 cell viscosity difference of mitochondria. In a word, the merits of the NIR property, high selectivity and signal ratio provide a more convenient means for studying biological processes and mitochondria viscosity related diseases.

A Series of Imidazole Derivatives: Synthesis, Two-Photon Absorption, and Application for Bioimaging.

A new series of D-π-A type imidazole derivatives have been synthesized and characterized. Two corresponding imidazolium salts (iodine and hexafluorophosphate) were prepared from the imidazole compound. Their electron-withdrawing ability can be largely tunable by salt formation reaction or ion exchange. UV-vis absorption and single-photon fluorescence spectra have been systematically investigated in different solvents. The two-photon cross sections (δ 2PA) of the imidazole derivatives are measured by two-photon excited fluorescence (2PEF) method. Compared with those of T-1 (107 GM) and T-3 (96 GM), T-2 (imidazolium iodine salt) has a large two-photon absorption (2PA) cross section value of 276 GM. Furthermore, the cytotoxicity and applications in bioimaging for the imidazole derivatives were carried out. The results showed that T-1 can be used as a lysosomal tracker with high stability and water solubility within pHs of 4-6, while T-2 and T-3 can be used as probes for cell cytoplasm.

Two novel bipyrazole derivative ligands: Synthesis, crystal structure, theoretical studies, and sensitive response toward Fe(3.).

Two novel bipyrazole derivative ligands L1 (4-(di(1H-pyrazol-1-yl)methyl)-N,N-diphenylaniline) and L2 (4-(di(1H-pyrazol-1-yl)methyl)-N,N-bis(4-ethoxy phenyl)aniline), were synthesized, and fully characterized. The crystal structures of the two ligands were confirmed by single-crystal X-ray diffraction analysis. The structural analysis revealed that two pyrazole units are attached to the same carbon atom connected with triphenylamine moiety. The UV-vis absorption and fluorescence spectral properties of the ligands were investigated and explained relying on theoretical calculation. Significantly, it was found that the ligands display an exclusively selective and sensitive response toward Fe(3+) with aid of UV-vis absorption spectroscopic methods.

Synthesis, characterization, cytotoxicity and antibacterial activity of an anthracenyl-linked bis(pyrazolyl)methane ligand and its zinc(II) complexes.

Three novel Zn(II) complexes (1-3) with 1,1'-(anthracen-9-ylmethylene)bis(1H-pyrazole) (L(2)) have been prepared and structurally characterized by X-ray crystallography. Among them, 1 is a binuclear Zn(II) complex while 2 and 3 are mononuclear. The in vitro cytotoxic and antibacterial activities of these complexes were also evaluated. The three complexes exhibit cytotoxic specificity and significant antitumor activity. The MIC50 value of complex 1 against Pseudomonas putida reaching 0.011 µg/mL much lower than that the positive control chloromycin (0.182 µg/mL), indicates that complex 1 is a potent antibacterial agent.

N,N-Diethyl-4-[1-phenyl-3-(pyridin-2-yl)-4,5-di-hydro-1H-pyrazol-5-yl]aniline.

In the title mol-ecule, C24H26N4, the pyrazoline ring assumes an envelope conformation with the aniline-bearing C atom at the flap position. The benzene ring and the pyridine ring form with the pyrazoline ring dihedral angles of 4.53 (1) and 6.26 (1)°, respectively. In turn, the aniline group is nearly perpendicular to the pyrazoline ring [dihedral angle = 79.96 (1)°]. The ethyl groups of the di-ethyl-amine substituent are disordered over two sets of sites, with an occupancy ratio of 0.624 (8):0.376 (8).