Blue Emission of Tetrafluorobenzocarbazole Under the Interactions of Nitrogen-oxygen Saturated hydrogen Bonds with Aggregated Proton Acid.

Two novel tetrafluorobenzocarbazole and containing the amino branch introduced at the end of the molecule are synthesized by a simple method. The tetrafluorobenzocarbazole as the electron donor with electron-rich fluoride ions connected by π-benzyl ring conjugation structure, which affects the overall electron cloud density. Moreover, the amino branch introduced at the end of the molecule, which makes it easy to form intermolecular hydrogen bonds and affected photophysical properties. Meanwhile, the photophysical property of both compounds are discussed under different acidic conditions. The UV-absorption show that around ~286 nm is mainly attributed to the strong structural absorption band peak of the π-π ∗ transition of the carbazole moiety, and the irregular absorption band around ~314 nm and ~326 nm are mainly attributed to the n-π ∗ transition of the carbazole group conjugate with the adjacent molecule. The emission spectrum of both compounds showed that the intensity of fluorescence decreased in different degrees after the addition of the acidic solution. Furthermore, the electrochemical properties were evidenced by cyclic voltammetry (CV) and density functional theory (DFT) calculations, and the orbital conformation (HOMOs-LUMOs) was simulated by Gaussian 09 software and its crystal structure was observed by X-ray diffraction (XRD). The results exhibited that both compounds are electrochemically stable blue small-molecule fluorescent substances, and expected that both compounds can be novel and stable acid-sensitive organic blue-light materials.

Strategy of eudragit coated curcumin nanoparticles delivery system: Release and cell imaging studies in simulated gastrointestinal microenvironments.

Curcumin has a broad-spectrum anti-tumor effect and has no toxic side effects. However, the unique diketone structure of curcumin will undergo diketo-enol tautomerism under different acid-base conditions, resulting in its instability under physiological conditions. In addition, the low biocompatibility and absorption rate of curcumin also limit the use of curcumin drugs. In this paper, curcumin was modified by substitution of acryloyl and acrylsulfonyl groups, and four kinds of nanoparticles with regular morphology were prepared using non-toxic and non-irritating acrylic resin as coating material to improve the stability and bioavailability of the compounds. Zeta potential testing shows that the composites surface carries positive charges and have good stability. In the release experiment, four complexes have the potential for slow and controlled release. Imaging of Hela cells with different channels was performed, and the imaging results showed that the complexes could enter the cells and be absorbed by them, demonstrating good imaging performance. MTT experiments have shown that the complexes have certain anti-tumor activity and low cytotoxicity. In general, the complexes synthesized in this paper have potential in the field of drug fluorescence imaging detection. At the same time, this experiment provides a new idea for the design of slow and controlled release of drugs.

A novel strategy to bind pyrimidine sulfonamide derivatives with odd even chains: exploration of their design, synthesis and biological activity evaluation.

Based on the hybridization strategy of dominant fragments, a series of pyrimidine sulfonamide (PS) derivatives were obtained by combining the pharmacophore fragments (sulfonamide group and pyrimidine group) with different biological activities, and evaluated as a new type of anticancer drug. The compounds were evaluated for in vitro cytotoxicity against four human cancer cell lines (HeLa, HCT-116, A-549 and HepG2) and the normal human cell line L02. Compared with the anti-cancer drug 5-fluorouracil (5-FU), the antiproliferative activity of compound PS14 was close to 5-FU and it has good antitumor activity. The IC50 values were 15.13 ± 2.20, 19.87 ± 2.01, 12.64 ± 3.22, 22.20 ± 1.34 and 102.46 ± 2.27 µM, respectively. The structure activity relationship was analyzed. The antitumor activity of the compound tended to increase. When the substituents of the branch chain of sulfonamides were odd. In addition, the oil-water partition coefficient was also investigated. The logP value of PS14 was between 0 and 3, indicating that PS14 was a compound with good lipophilic property, poor water solubility and easy to be absorbed and transported through cell membrane. The anti-cancer mechanism was further studied by flow cytometry. After PS14 treated HeLa, HCT-116, A-549 and HepG2, the percentage of apoptotic cells was 45.30%, 28.2%, 31.00% and 35.20%, respectively, which was higher than that of the control 5-FU. The results of cell cycle showed that PRD2 mainly blocked the cell cycle in the S phase, thereby inhibiting cell proliferation. Furthermore, molecular docking analyzed possible interactions between the compound and the PI3Kα active site, this compound has good binding with PI3Kα. Overall, this study laid the groundwork for the development and structural modification of new pyrimidine sulfonamide drugs, and PS14 could be further developed into a cancer treatment drug.

Bioactivity and Cell Imaging of Antitumor Fluorescent Agents (Curcumin Derivatives) Coated by Two-Way Embedded Cyclodextrin Strategy.

Curcumin has a wide range of pharmacological activities, which can be used to treat tumors, inflammation and other diseases. However, curcumin's poor solubility and low bioavailability limit its application. In this article, the structure of curcumin was modified with boron trifluoride ether to change fluorescent labeling. The compounds were then embedded into the hydrophobic cavity of α-cyclodextrin and hydroxypropyl ß-cyclodextrin to form inclusion complexes. The two inclusion complexes have excellent photophysical properties, and the maximum emission wavelength is in the range of 550-565 nm. In addition, the two compounds were applied to the fluorescence imaging of HCT-116 cells and HeLa cells, and the proliferation toxicity of the compounds was detected. Both compounds showed certain inhibitory effects on the proliferation of cancer cells. In short, the fluorescent drug molecule synthesized in this article has great reference value for the development of new dosage forms of curcumin.

Recent advances in the discovery and development of glyoxalase I inhibitors.

Glyoxalase I (GLO1) is a homodimeric Zn2+-metalloenzyme that catalyses the transformation of methylglyoxal (MG) to d-lacate through the intermediate S-d-lactoylglutathione. Growing evidence indicates that GLO1 has been identified as a potential target for the treatment cancer and other diseases. Various inhibitors of GLO1 have been discovered or developed over the past several decades including natural or natural product-based inhibitors, GSH-based inhibitors, non-GSH-based inhibitors, etc. The aim of this review is to summarize recent achievements of concerning discovery, design strategies, as well as pharmacological aspects of GLO1 inhibitors with the target of promoting their development toward clinical application.

Hydroxyl-PEG-Phosphonic Acid-Stabilized Superparamagnetic Manganese Oxide-Doped Iron Oxide Nanoparticles with Synergistic Effects for Dual-Mode MR Imaging.

The T1-T2 dual-mode contrast agents for magnetic resonance imaging (MRI) can generate self-complementary confirmed T2 and T1 images, hence greatly improving the reliability. Facilely synthesizing nanoparticles with the ultrasensitive contrast property remains extremely challenging in nanoscience. Moreover, uncovering the mechanism correlating the signal enhancements and chemical constituents is vital for designing novel efficient synergistically enhanced T1-T2 dual-mode MRI nanoprobes. Herein, we report a one-pot facile method to synthesize the superparamagnetic manganese oxide-doped iron oxide (Fe3O4/MnO) nanoparticles for T1-T2 dual-mode MR imaging. Under external magnetic field, the local magnetic field intensities of MnO and Fe3O4 could be simultaneously enhanced through embedding MnO into Fe3O4 nanoparticles and hence can cause synergistic T1 and T2 contrast enhancements. Moreover, a novel and facile cost-effective method for large-scale synthesis of hydroxyl-polyethylene glycol-phosphonic acid-stabilizing ligands is designed. The facile synthetic method and surface coating strategy of superparamagnetic Fe3O4/MnO nanoparticles offer an idea for the chemical design and preparation of superparamagnetic nanoparticles with ultrasensitive MRI contrast abilities for disease evaluation and treatment.

Direct large-scale synthesis of water-soluble and biocompatible upconversion nanoparticles for in vivo imaging.

Deep tissues can be optically imaged using near-infrared windows without radiation hazard. This work proposes a straightforward one-pot method for directly synthesizing water-soluble and biocompatible upconversion nanoparticles on a large scale for in vivo imaging. Safety assessment, coupled with luminescence imaging in mice, demonstrates the excellent stability and promising biological applications of the upconversion nanoparticles.

Large-scale in situ self-assembly and doping engineering of zinc ferrite nanoclusters for high performance bioimaging.

Iron oxide nanomaterials has good biocompatibility and safety, and has been used as contrast agents for magnetic resonance imaging (MRI). However, its clinical usefulness is hampered by its difficult preparation on large scale, its rapid clearance in vivo and low target tissue enrichment efficiency. Here, we report the synthesis of water-soluble, biocompatible, superparamagnetic non-stoichiometric zinc ferrite nanoclusters (nZFNCs) of approximately 50 g in a single batch using a one-pot synthesis technique. nZFNCs is a secondary cluster structure with a size of about 40 nm composed of zinc-doped iron oxide nanoparticles with a size of about 6 nm. The surface of nZFNCS is endowed with a large number of carboxyl groups as active sites. By simply controlling the synthesis process and adjusting the proportion of metal precursors, the amount of zinc doping can be controlled, while maintaining the same size to ensure similar pharmacokinetics. Compared with undoped, the magnetic responsiveness and relaxation efficiency of nZFNCs are significantly improved, and the transverse relaxation efficiency (r2) can reach 425.5 mM-1 s-1 (doping amount x = 0.25), which is 7 times higher than that of commercial Resovist and 10 times higher than that of Feridex. In vivo imaging results also further confirmed the excellent contrast enhancement performance of the nanoclusters, which can achieve high contrast for more than 2 h in the liver. The advantage of this platform over comparable systems is that the contrast enhancement features are derived from simple techniques that do not require complex physical and chemical methods.

Preparation and physical properties of chitosan benzoic acid derivatives using a phosphoryl mixed anhydride system.

Direct benzoylation of the two hydroxyl groups on chitosan was achieved using a phosphoryl mixed anhydride system, derived from trifluoroacetic anhydride (TFAA), benzoic acids (BAs), and phosphoric acid (PA). The reaction is operated as a one pot process under mild conditions that does not require neither an inert atmosphere nor dry solvents. The structures of the synthesized compounds were confirmed by NMR and IR spectroscopy. Solubility tests on the products revealed that they were soluble in organic solvents such as N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), and acetone. In the meantime, a morphological study by scanning electron microscopy (SEM) evidently indicated that the chitosan benzoates underwent significant structural changes after the benzoylation.

Facile synthesis of superparamagnetic nickel-doped iron oxide nanoparticles as high-performance T1 contrast agents for magnetic resonance imaging.

Small-sized iron oxide nanoparticles (IONPs) are an excellent alternative to clinical gadolinium-based contrast agents (GBCAs) in T1-weighted magnetic resonance imaging (MRI) due to their biosafety. However, their relaxation efficiency and contrast enhancement are not significant compared with those of GBCAs, and the nanomaterials face stability problems in vivo and difficulties in large-scale synthesis. Here, we designed and synthesized a series of 7 nm monodispersed biocompatible and superparamagnetic nickel-doped iron oxide nanoparticles (NiIO NPs) as safe contrast agents (CAs) for ultra-sensitive T1-weighted MR imaging. The nickel doping strategy transforms the iron oxide nanoparticles from traditional T2 CAs to T1 CAs. The Ni0.31Fe2.69O4 NPs exhibited a high longitudinal relaxivity (r1) of 9.1 mM-1 s-1, which is much higher than that of IONPs and 2.4 times that of clinical T1 CAs (Magnevist, 3.8 mM-1 s-1). NiIO NPs enable high-resolution T1-weighted and T2-weighted dual-mode MR imaging in vivo with long circulation time. These results, in hand with the excellent colloidal stability and superior biosafety, demonstrate the potential use of NiIO NPs for accurate diagnosis in deep-tissue T1-T2 dual-mode MR imaging.

Biocompatible Superparamagnetic Europium-Doped Iron Oxide Nanoparticle Clusters as Multifunctional Nanoprobes for Multimodal In Vivo Imaging.

Magnetic nanoparticle clusters composed of primary magnetic nanoparticles can not only significantly enhance the magnetic properties of the assembly but also retain the superparamagnetic properties of the individual primary nanoparticle, which is of great significance for promoting the development of multifunctional advanced materials. Herein, water-soluble biocompatible and superparamagnetic europium-doped iron oxide nanoparticle clusters (EuIO NCs) were directly synthesized by a simple one-pot method. The obtained EuIO NCs have excellent water solubility, colloidal stability, and biocompatibility. Europium doping significantly improved the contrast enhancement effect of EuIO NCs in T1-weighted MR imaging. In addition, EuIO NCs can be functionalized by active molecules, and the rhodamine123-functionalized EuIO NCs have long circulation time and excellent fluorescence imaging performance in vivo. This study provides a simple strategy for the design and construction of a novel multifunctional magnetic nanoplatform and provides solutions for the development of multimodal imaging probes and the diagnosis of disease.

Large-scale one-pot synthesis of water-soluble and biocompatible upconversion nanoparticles for dual-modal imaging.

Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted considerable attentions in the area of molecular imaging, targeted therapy and diagnosis. The UCNPs synthesized by conventional methods are usually hydrophobic and require additional surface modification to give them water solubility and biocompatibility. Herein, we designed a simple and convenient strategy for the direct synthesis of water-soluble and biocompatible lanthanum-doped UCNPs through a one-pot reaction without further purification and screening. The doping amount of lanthanide can be adjusted by simply changing the proportion of precursor in the reaction solution. The resulting water-soluble UCNPs possess excellent colloidal stability in physiological media. Under 980 nm excitation, NaGdF4:Yb3+/Er3+ and NaGdF4:Yb3+/Tm3+ nanoparticles exhibited a dominant green emission band (4S3/2→4I15/2) of Er3+ and a dominant blue emission band (1G4→3H6) of Tm3+, respectively. Toxic response was not observed with concentration up to 50 mg/L. The hemolysis to rabbit red blood cells was less than 2% in the concentration up to 20 mg/L. The NaGdF4:Yb3+/Er3+ nanoparticles exhibited a high r1 relaxivity of 4.7 mM-1s-1, demonstrating that the water-soluble and biocompatible UCNPs can be efficient T1 contrast agents. The in vivo results show that UCNPs exhibit excellent T1-weighted imaging and fluorescence imaging abilities simultaneously, and can be used as a versatile promising theranostic nanoplatform.

Controllable synthesis of exceptionally small-sized superparamagnetic magnetite nanoparticles for ultrasensitive MR imaging and angiography.

The superparamagnetic magnetite nanoparticles have broad application prospects in the diagnosis and treatment of cancer. Herein, a series of monodispersed exceptionally small-sized superparamagnetic magnetite nanoparticles (ESM NPs) with tunable size were synthesized through thermal decomposition of an iron precursor by simply changing the reaction temperature and stabilizing agents. The underlying mechanisms of regulating the size and properties of ESM NPs were studied. The surface of hydrophobic ESM NPs was modified with a carboxyl-polyethylene glycol-phosphoric acid ligand, and the obtained water-soluble ESM NPs showed extremely high long-term stability under various aqueous environments and physiological conditions. The hemolysis and cytotoxicity evaluations showed that the ESM NPs had good blood compatibility and no obvious cytotoxicity. The 2.3 nm ESM NPs exhibited an extremely high longitudinal relaxivity (r1) of 6.0 mM-1 s-1, which was higher than that of the clinical gadolinium complex contrast agent (r1 = 3.8 mM-1 s-1), and had an appropriate r2/r1 ratio of 4.0. The in vivo results showed that the nanoparticles exhibited superior contrast effects in both T1 and T2 MR imaging, as well as high-resolution contrast in MR angiography. This study provides a general strategy for the controlled synthesis of ESM NPs and reveals the size and property regulation mechanisms, which undoubtedly provides the possibility of designing highly sensitive MR imaging probes based on small-sized magnetic nanoparticles for clinical diagnostic applications.

One-pot synthesis of water-soluble and biocompatible superparamagnetic gadolinium-doped iron oxide nanoclusters.

The synthesis of superparamagnetic nanoclusters is critical for ultra-sensitive magnetic resonance imaging (MRI). Herein, we describe the synthesis of water-soluble, biocompatible and superparamagnetic gadolinium-doped iron oxide nanoclusters (GdIO NCs) via a one-pot reaction by thermal decomposition of ferric oleate and gadolinium oleate precursors with α,ω-dicarboxyl poly(ethylene glycol) as a surfactant. The resulting water-dispersible GdIO NCs possess good stability and monodispersity with narrow size distribution, and exhibit superparamagnetic behaviors. We also explored the effect of gadolinium doping amounts on the magnetic properties and longitudinal (r1) and transverse relaxivity (r2) of the nanoclusters. In addition, the GdIO NCs can be functionalized with fluorescein isothiocyanate (FITC) while maintaining their magnetic properties and biocompatibility. The GdIO NCs and FITC conjugated NCs were preliminarily evaluated as MRI and fluorescent probes. The results show that the GdIO NCs provide an important nano-platform for theranostics with non-invasive MRI and optical monitoring capabilities.

Photocatalytic Dehydrogenation of Primary Alcohols: Selectivity Goes against Adsorptivity.

Solid/liquid heterogeneous photocatalysis was often considered to occur on the active sites of a solid catalyst surface. Herein, we report that the selectivity of photocatalytic dehydrogenative oxidations of aliphatic primary alcohols in acetonitrile solution into corresponding aldehydes exhibits an anomalous relationship with adsorption behavior of the alcohols. By using Pt-loaded TiO2 photocatalyst in an inert atmosphere under UV light illumination, primary short-chain alcohols (SCAs) with strong adsorption were dehydrogenated into aldehydes in very poor selectivity, whereas weak-adsorbable long-chain alcohols (LCAs) were transformed into corresponding aldehydes with much higher selectivity. More than 20 examples of primary LCAs (C4-C10) were successfully transformed into their corresponding aldehydes with satisfactory selectivity and yield. Both solid-state magic-angle-spinning 13C NMR and attenuated total reflectance-Fourier transform infrared spectroscopy studies provided concrete differences in adsorption behaviors on the Pt-TiO2 photocatalyst surface between SCA ethanol and LCA n-octanol. To further uncover the mechanism for different selectivities of SCAs and LCAs in photodehydrogenation, in situ electron paramagnetic resonance (EPR) experiments (at 8 K temperature) were employed to observe the oxidation features of photogenerated hole in the valance band of Pt-TiO2 (hvb +). The EPR experimental studies exhibited that unlike ethanol, either n-octanol or solvent acetonitrile alone all could not scavenge photogenerated hvb + on Pt-P25 photocatalyst and only n-octanol dissolved in acetonitrile solvent could smoothly react with photoinduced hole. This indicated that selective oxidations of LCAs were achieved by solvent-delivered oxidation rather than directly destructive oxidation of photogenerated hvb +. Our results may open an alternative way in selective dehydrogenative oxidation of various substrates sensitive to both dioxygen and high-temperature treatments.

The preparation of organoboron-based stilbene nanoparticles for cell imaging.

In this work, a series of nanoparticles were prepared assembled by a highly emissive solid-state organoboron-based stilbene (OBS) and PS-PEG-COOH via regulating the ratio of these two compounds using a co-precipitation method. The resultant OBS nanoparticles (OBSNs) were homogeneously dispersed in water media with average sizes of 36-82 nm and exhibited large Stokes shift, high fluorescence quantum yield, excellent photostability and low cytotoxicity. These organic nanoparticles could be internalized by MCF-7 cells and could accumulate in the cytoplasm outside the organelles. In addition, it is found that the nanoparticles with least negative charge and moderate size are most easily internalized by cells. Furthermore, the internalized nanoparticles could be retained inside the live cells for a long time and could be uniformly separated into two cells after the cell division process, permitting long-term cellular imaging applications.

A mussel-inspired chitooligosaccharide based multidentate ligand for highly stabilized nanoparticles.

Inspired by the adhesion behaviors of mussels, we synthesized a chitooligosaccharide (COS) based multidentate ligand (ML) for preparing robust biocompatible magnetic iron oxide nanoparticles (IONPs). The COS was modified with mussel adhesive protein (MAP) mimetic multiple catechol groups and branched poly(ethylene glycol) moieties, which can not only strongly bind to IONPs through multiple catechol groups, but also afford IONPs with good colloidal stability and biocompatibility due to PEG integrated into the COS coating. The resultant ML-stabilized IONPs consist of single nanoparticles coated with ML shells and exhibited high dispersion stability in aqueous solution for a wide range of pH and concentrated salt solutions. The potential of ML-stabilized IONPs as contrast agents for T2-weighted magnetic resonance imaging was demonstrated by conducting in vivo imaging and relaxivity measurements. The ML-stabilized IONPs are therefore expected to be useful for magnetic resonance imaging under physiological conditions.

Synthesis of lipoic acid-peptide conjugates and their effect on collagen and melanogenesis.

We report new examples of lipoic acid (LA)-peptide conjugates, their potential as codrugs having anti-melanogenic and anti-aging properties was evaluated. These multifunctional molecules were prepared by linking lipophilic moiety (LA) to the pentapeptide KTTKS. The inhibitory effect of LA-peptide conjugates on melanin synthesis and tyrosinase activity is stronger than that of LA or the pentapeptide alone. Importantly, the conjugates display no cytotoxicity at a high concentration. LA-KTTKS and LA-PEG-KTTKS also inhibit UV-induced matrix metalloproteinase-1 expression up to 49.5% and 69.5% at 0.5 mM, respectively. LA-peptide conjugates stimulate collagen biosynthesis in fibroblasts more efficiently than their parent molecules do. These data suggest that LA-peptide conjugates may have cosmeceutical application as anti-melanogenic and anti-aging agents.

Design, synthesis and evaluation of PEGylated lipoic acid derivatives with functionality as potent anti-melanogenic agents.

The novel PEGylated lipoic acid (LA) derivatives with functionality were synthesized in satisfactory yield by simple procedures and evaluated about its anti-melanogenic activity on the B16F10 melanoma cells. Grafting a PEG moiety onto the carboxyl group of LA has reduced the cell cytotoxicity and provided the water solubility and functionality to incorporate the other bioactive moieties. We have found that derivatives showed inhibition of melanin formation by up to 36.5% at 0.1 mM, whereas LA decreased the melanin formation by 8.6%. In addition, it also inhibits at least 86.4% UV-induced MMP-1 expression at 0.1 mM which is higher than LA. These data suggest that the novel PEGylated LA derivatives with functionality may thus serve as a potentially effective anti-melanogenic and anti-aging agent.