Self-Healing Hydrogen-Bonded Organic Frameworks for Low-Concentration Ammonia Capture.

The self-healing behavior has been extensively used in intelligent sensing systems capable of molecular recognition. However, most rigid crystalline frameworks, once collapsed under external stimuli like pressure, heat, or vacuum, could hardly recover to their crystalline phases under ambient conditions. Here, we report the self-healing of a new microporous hydrogen-bonded organic framework, FDU-HOF-3 (FDU = Fudan University), for ammonia (NH3) capture and compared it with the established mesoporous HOF-101. With the introduction of low-concentration NH3 into the pores, the HOFs became disordered but were then simply heated under a vacuum to return to their original crystalline states after NH3 removal. Close characterizations revealed that the repeatable self-healing behavior of these HOFs was achieved due to the COOH-NH3 acid-base interactions accompanied by the breaking and regeneration of complementary COOH-COOH hydrogen bonds. FDU-HOF-3 showed a record-capturing capability for low-concentration NH3 (8.13 mmol/g at 25 mbar) among all HOFs and displayed a quick photocurrent decrease after exposure to 250 ppm NH3 for less than 10 s. These self-healing HOFs were used to capture and release NH3 for over 10 cycles without any decrease in the adsorption capacities.

Tadpole-Like Carbon Nanotube with Fe Nanoparticle Encapsulated at the Head and Zn Single-Atom Anchored on the Body: One-Pot Carbonization for Tetramodal Synergistic Cancer Therapy.

Precise integration of diverse therapeutic approaches into nanomaterials is the key to the development of multimodal synergistic cancer therapy. In this work, tadpole-like carbon nanotubes with Fe nanoparticle encapsulated at the head and Zn single-atom anchored on the body (Fe@CNT-Zn) is precisely designed and facilely prepared via one-pot carbonization. In vitro studies revealed the integration of chemotherapy (CT), chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT) in Fe@CNT-Zn as well as the near-infrared light (NIR)-responsive cascade therapeutic efficacy. Furthermore, in vivo studies demonstrated the NIR-triggered cascade-amplifying synergistic cancer therapy in a B16 tumor-bearing mouse model. The results not only showcased the Fe@CNT-Zn as a potential tetramodal therapeutic platform, but also demonstrated a proof-of-concept on metal-organic framework-based "one stone for multiple birds" strategy for in situ functionalization of carbon materials.

A General Strategy for the Synthesis of Hierarchically Ordered Metal-Organic Frameworks with Tunable Macro-, Meso-, and Micro-Pores.

Hierarchically ordered porous materials with tailored and inter-connected macro-, meso-, and micro-pores would facilitate the heterogeneous adsorption and catalysis processes for a wide range of applications but remain a challenge for synthetic chemists. Here, a general and efficient strategy for the synthesis of inverse opal metal-organic frameworks (IO MOFs) with a tunable size of macro-, meso-, and micro-pores is reported. The strategy is based on the step-wise template formation, precursor infiltration, solvo-thermal reaction, and chemical etching. As a proof of the general applicability of this strategy, a series of inverse opal zirconium-based MOFs with intrinsic micro- and/or meso-pores, including UiO-66, MOF-808, NU-1200, NU-1000 and PCN-777, and tunable macropores (1 µm, 2 µm, 3 µm, 5 µm, and 10 µm), have been prepared with outstanding yields. These IO MOFs demonstrate significantly enhanced absorption rates and faster initial hydrolysis rates for organophosphorus (OPs) aggregates compared to those of the pristine MOFs. This work paves the way for the further development of hierarchically ordered MOFs for advanced applications.

Reticular Chemistry of the Fcu-Type Gd(III)-Doped Metal-Organic Framework for T1 -Weighted Magnetic Resonance Imaging.

Nanoscale metal-organic frameworks (nanoMOFs) are emerging as an important class of nanomaterials for the systematical investigation of biomedically relevant structure-property relationship (SPR) due to their highly tailorable features. In this work, the reticular chemistry approach is shown to explore the SPR of a fcu-type Zr(IV)-nanoMOF for T1 -weighted magnetic resonance imaging (MRI). Isoreticular replacement of the eight-coordinated square-antiprismatic Zr(IV) by nine-coordinated Gd(III) brings a stoichiometric water capped on the square-antiprismatic site, enabling the relaxation transfer in the inner-sphere, giving the r1 value of 4.55 mM-1 ·s-1 at the doping ratio of Gd : Zr = 1 : 1. Then, these isoreticular engineering studies provide feasible ways to facilitate the relaxation transfer in the second- and outer-sphere of the Gd(III)-doped Zr-oxo cluster for the relaxation respectively. Finally, these in vitro and in vivo MRI studies revealed that the Gd(III)-doped Zr-oxo cluster aggregated underlying the fcu-type framework surpasses its discrete molecular cluster for MRI. These results demonstrated that there is plenty of room inside MOFs for T1 -weighted MRI by reticular chemistry.

Gelothermal Synthesis of Monodisperse MIL-88A Nanoparticles with Tunable Sizes and Metal Centers for Potential Bioapplications.

Developing novel synthetic strategies to downsize metal-organic frameworks (MOFs) from polydisperse crystals to monodisperse nanoparticles is of great importance for their potential bioapplications. In this work, a novel synthetic strategy termed gelothermal synthesis is proposed, in which coordination polymer gel is first prepared and followed by a thermal reaction to give the monodisperse MOF nanoparticles. This novel synthetic strategy successfully leads to the isolation of Materials of Institute Lavoisier (MIL-88), Cu(II)-fumarate MOFs (CufumDMF), and Zeolitic Imidazolate Frameworks (ZIF-8) nanoparticles. Focused on MIL-88A, the studies reveal that the size can be well-tuned from nanoscale to microscale without significant changes in polydispersity index (PDI) even in the case of in situ metal substitution. A possible mechanism is consequently proposed based on extensive studies on the gelothermal condition including sol-gel chemistry, thermal condition, kinds of solvents, and so on. The unique advantages of monodisperse MIL-88A nanoparticles over polydisperse ones are further demonstrated in terms of in vitro magnetic resonance imaging (MRI), cellular uptake, and drug-carrying properties.

Discovery of a photosensitizing PI3K inhibitor for tumor therapy: Design, synthesis and in vitro biological evaluation.

In drug development, optical triggering of cancer therapy is increasingly used. Herein, we report a novel photosensitive PI3K inhibitor FD2157, which bears a photoprotecting moiety and can be efficiently cleaved with enhanced anticancer activity upon short-term light irradiation. In biological assessment, FD2157 exhibited remarkably enhanced anticancer activity in inhibition of PI3K pathway against melanoma cell lines upon light irradiation (4 min). Hence, this photosensitive PI3K inhibitor FD2157 may represent a valuable tool compound for studying the PI3K pathway and further optimization toward light-triggered cancer treatment.

Design, synthesis and in vitro biological evaluation of 2-aminopyridine derivatives as novel PI3Kδ inhibitors for hematological cancer.

Phosphoinositide-3-kinase (PI3K) involves in regulation of proliferation, cell cycle, and apoptosis, and is overexpressed in most of human malignant tumors. Therefore, the development of PI3K inhibitors has attracted great interest in tumor treatment. In this study, we designed and synthesized a series of 2-aminopyridine derivatives via a bioisosterism strategy. Among them, compound MR3278 showed superior PI3Kδ inhibitory activity (IC50 = 30 nM), as well as higher inhibitory activity to most of AML cells (e.g., MOLM-16 and Mv-4-11 cells with IC50 values of 2.6 µM and 3.7 µM, respectively) than Idelalisib. Further cell studies indicated that MR3278 could induce G2/M phase arrests and cell apoptosis of Mv-4-11 cells via PI3K dependent pathway in a dose dependent manner. In addition, in silico physicochemical and ADMET evaluation revealed its drug-like properties with satisfactory toxicity profiles. These results indicate that MR3278 can be identified as a promising new lead compound to the current PI3Kδ inhibitor and is worthy of further profiling.

Discovery and identification of a novel PI3K inhibitor with enhanced CDK2 inhibition for the treatment of triple negative breast cancer.

Blocking the PI3K pathway has been recognized as a promising strategy for cancer therapy. Herein, we report the discovery of novel PI3K inhibitors utilizing 7-azaindole-based fragment-oriented growth. Among them, compound FD2056 stands out as the most promising candidate, maintaining potent inhibitory activity against PI3K and enhanced CDK2 inhibition, and showing moderate selectivity among 108 kinases. In cellular assays, the inhibitor FD2056 demonstrated superior anti-proliferative profiles over reference compounds against TNBC cells and significantly increased apoptosis of MDA-MB-231 cells in a dose-dependent manner. Moreover, FD2056 showed more efficacious anti-TNBC activity than the corresponding drugs BKM120 and CYC202 at an oral dose of 15 mg/kg in the MDA-MB-231 xenograft model, inhibiting tumor growth by 43% with no observable toxic effects. All these results suggest that FD2056 has potential for further development as a promising anticancr compound, and co-targeting PI3K and CDK2 pathways may provide an alternative therapeutic strategy for the treatment of TNBC.

Multivariate Hydrogen-Bonded Organic Frameworks with Tunable Permanent Porosities for Capture of a Mustard Gas Simulant.

Precise synthesis of topologically predictable and discrete molecular crystals with permanent porosities remains a long-term challenge. Here, we report the first successful synthesis of a series of 11 isoreticular multivariate hydrogen-bonded organic frameworks (MTV-HOFs) from pyrene-based derivatives bearing -H, -CH3 , -NH2 and -F groups achieved by a shape-fitted, π-π stacking self-assembly strategy. These MTV-HOFs are single-crystalline materials composed of tecton, as verified by single-crystal diffraction, nuclear magnetic resonance (NMR) spectra, Raman spectra, water sorption isotherms and density functional theory (DFT) calculations. These MTV-HOFs exhibit tunable hydrophobicity with water uptake starting from 50 to 80 % relative humidity, by adjusting the combinations and ratios of functional groups. As a proof of application, the resulting MTV-HOFs were shown to be capable of capturing a mustard gas simulant, 2-chloroethyl ethyl sulfide (CEES) from moisture. The location of different functional groups within the pores of the MTV-HOFs leads to a synergistic effect, which resulted in a superior CEES/H2 O selectivity (up to 94 %) compared to that of the HOFs with only pure component and enhanced breakthrough performance (up to 4000 min/g) when compared to benchmark MOF materials. This work is an important advance in the synthesis of MTV-HOFs, and provides a platform for the development of porous molecular materials for numerous applications.

A Solution-Processable Porphyrin-Based Hydrogen-Bonded Organic Framework for Photoelectrochemical Sensing of Carbon Dioxide.

Detecting CO2 in complex gas mixtures is challenging due to the presence of competitive gases in the ambient atmosphere. Photoelectrochemical (PEC) techniques offer a solution, but material selection and specificity remain limiting. Here, we constructed a hydrogen-bonded organic framework material based on a porphyrin tecton decorated with diaminotriazine (DAT) moieties. The DAT moieties on the porphyrin molecules not only facilitate the formation of complementary hydrogen bonds between the tectons but also function as recognition sites in the resulting porous HOF materials for the selective adsorption of CO2 . In addition, the in-plane growth of FDU-HOF-2 into anisotropic molecular sheets with large areas of up to 23000 µm2 and controllable thickness between 0.298 and 2.407 µm were realized in yields of over 89 % by a simple solution-processing method. The FDU-HOF-2 can be directly grown and deposited onto different substrates including silica, carbon, and metal oxides by self-assembly in situ in formic acid. As a proof of concept, a screen-printing electrode deposited with FDU-HOF-2 was fabricate as a label-free photoelectrochemical (PEC) sensor for CO2 detection. Such a signal-off PEC sensor exhibits low detection limit for CO2 (2.3 ppm), reusability (at least 30 cycles), and long-term working stability (at least 30 days).

Physical and Chemical Cues at the Nano-Bio Interface for Immunomodulation.

Immunomodulation has made remarkable progress in fighting infectious disease and cancer. Conventionally, immunomodulation largely relies on chemical/biochemical agents, which, unfortunately, suffer from sever off-target adverse effects. Recent insights into nano-bio interactions suggest that nanomaterials can directly participate in immunomodulation. A range of physical and chemical cues at the nano-bio interface have been harnessed to regulate diverse immuno-signaling for disease control and treatment. In this Minireview, we summarize recent studies on the physical and chemical cues enabled by intrinsic nanomaterials to trigger immunological signaling. First, we discuss physical cues mediated by surface topography, hydrophobicity, charge, and heat at the nano-bio interface for immunomodulation. Then, various nanomaterials enabled chemical cues, such as metal species and oxidative species are outlined. Finally, our perspectives on challenges and possible future directions are provided.

Discovery of cinnoline derivatives as potent PI3K inhibitors with antiproliferative activity.

Cinnoline is a potential pharmacophore which has rarely been reported for uses as PI3K inhibitors. In this study, a series of cinnoline derivatives were developed as PI3K inhibitors and evaluated for enzymatic and cellular activities. Most compounds displayed nanomolar inhibitory activities against PI3Ks, among which 25 displayed high LLE and micromolar inhibitory potency against three human tumor cell lines (IC50 = 0.264 µM, 2.04 µM, 1.14 µM).

Development of anti-breast cancer PI3K inhibitors based on 7-azaindole derivatives through scaffold hopping: Design, synthesis and in vitro biological evaluation.

Breast cancer is the cancer with the highest incidence all over the world. Phosphatidylinositol 3-kinase is an important regulator of intracellular signaling pathways, which is frequently mutated and overexpressed in majority of human breast cancers, and the inhibition of PI3K has been considered as a promising approach for the treatment of the cancer. Here, we report our design and synthesis of new 7-azaindole derivatives as PI3K inhibitors through the scaffold hopping strategy. By varying the groups at the 3-position of 7-azaindole, we identified a series of potent PI3K inhibitors, whose antiproliferative activities against two human breast cancer MCF-7 and MDA-MB-231 cell lines were evaluated. Representative derivatives FD2054 and FD2078 showed better activity than BKM120 in antiproliferation, reduced the levels of phospho-AKT and induced cell apoptosis. All these results suggested that FD2054 and FD2078 are potent PI3K inhibitors that could be considered as potential candidates for the development of anticancer agents.

Enhanced upconversion luminescence intensity of core-shell NaYF4 nanocrystals guided by morphological control.

How to further increase the upconversion luminescence (UCL) efficiency of core-shell upconversion nanoparticles (UCNPs) is highly desirable for their photoelectric and bio-logical applications. Herein, a novel but facile strategy is proposed to substantially enhance the UCL intensity of NaYF4 based core-shell UCNPs by morphological control. The morphologies of core-shell UCNPs can be optimized from rod-like to spherical like by changing the ratio of oleic acid (OA) to 1-octadecene (ODE) during the shell growth process with other reaction conditions constant. The mechanism of shape control is further investigated based on the competitive absorption between OA molecules and lanthanide ions (Y3+, Yb3+, Er3+ or Tm3+) onto the different crystal axes (a, b and c) to guide their shell growth speed. The absolute quantum yields were up to 2.7% and 1.8% for spherical and rod like core-shell UCNPs under excitation of 980 nm laser (power density of 1.6 W cm-2), respectively. Moreover, the UCL intensity and effective lifetime (τ eff ) of Er3+ emission at 541 nm of spherical like core-shell UCNPs increased by 11.7 and 1.82 folds than rod like core-shell UCNPs. Therefore, our designed novel strategy can greatly improve the UCL efficiency of core-shell UCNPs and promote their development in diverse applications.

Facile synthesis of upconversion nanoparticles with high purity using lanthanide oleate compounds.

A novel strategy for preparing highly pure NaYF4-based upconversion nanoparticles (UCNPs) was developed using lanthanide oleate compounds [Ln(OA)3] as the precursor, denoted as the Ln-OA preparation method. Compared to the conventional solvothermal method for synthesizing UCNPs using lanthanide chloride compounds (LnCl3) as the precursor (denoted as the Ln-Cl method), the Ln-OA strategy exhibited the merits of high purity, reduced purification process and a uniform size in preparing core and core-shell UCNPs excited by a 980 or 808 nm near infrared (NIR) laser. This work sheds new insight on the preparation of UCNPs and promotes their application in biomedical fields.

Integrating Zeolite-Type Chalcogenide with Titanium Dioxide Nanowires for Enhanced Photoelectrochemical Activity.

Developing photoanodes with efficient visible-light harvesting and excellent charge separation still remains a key challenge in photoelectrochemical water splitting. Here zeolite-type chalcogenide CPM-121 is integrated with TiO2 nanowires to form a heterostructured photoanode, in which crystalline CPM-121 particles serve as a visible light absorber and TiO2 nanowires serve as an electron conductor. Owing to the small band gap of chalcogenides, the hybrid electrode demonstrates obvious absorption in visible-light range. Electrochemical impedance spectroscopy (EIS) shows that electron transport in the hybrid electrode has been significantly facilitated due to the heterojunction formation. A >3-fold increase in photocurrent is observed on the hybrid electrode under visible-light illumination when it is used as a photoanode in a neutral electrolyte without sacrificial agents. This study opens up a new avenue to explore the potential applications of crystalline porous chalcogenide materials for solar-energy conversion in photoelectrochemistry.

Cation-Exchange Approach to Tuning the Flexibility of a Metal-Organic Framework for Gated Adsorption.

Achieving tailorable gated adsorption by tuning the dynamic behavior of a host porous material is of great interest because of its practical application in gas adsorption and separation. Here we devise a unique cation-exchange approach to tune the dynamic behavior of a flexible anionic framework, [Zn2(bptc)(datrz)]- (denoted as MAC-6, where H4bptc = [1,1'-biphenyl]-3,3',5,5'-tetracarboxylic acid and Hdatrz = 3,5-diamine-1H-1,2,4-triazole), so as to realize the tailorable gated adsorption. The CO2 adsorption amount at 273 K can be enhanced by exchanging the counterion of protonated dimethylamine (HDMA+) with tetraethylammonium (TEA+), tetrabutylammonium (TBA+), and tetramethylammonium (TMA+), where the adsorption behavior is transferred from nongated to gated adsorption. Interestingly, the Pgo for gate-opening adsorption can be further tuned from 442 to 331 mmHg by simply adjusting the ratio of HDMA+ and TMA+. The origin of this unique tunable property, as revealed by X-ray diffraction experiments and structure models, is rooted at the cation-responsive characteristic of this flexible framework.

[Retrieving Chromophoric Dissolved Organic Matter in Guanting Reservoir Based on in-situ Measured Reflectance Data].

In the present paper, Guanting Reservoir located in Zhangjiakou City, Hebei province and Yanqing District, Beijing, was selected as the study area, and Chromophoric dissolved organic matter (CDOM) content (represented by the CDOM absorption coefficient at 440 nm, aCDOM (440)) was inverted through semi-analytical method and empirical method. The data used in this paper include the spectral data (R (λ)) collected on October 26, 2013 over Guanting Reservoir and aCDOM (λ) measured in the laboratory. A semi-analytical method (QAA-CDOM) was validated and improved accordingly. The inversion result accuracy of QAA-CDOM was not bad, the root-mean-square error (RMSE) was 0.10 and the mean relative error (σ) was 10.8%. The QAA-CDOM method was improved by recalculating the value of Q (the ratio of upwelling irradiance to upwelling radiance just below the water surface) by the field spectral data to replace the fixed value. After this improvement, the inversion accuracy was slightly improved, with RMSE of 0.09 and σ of 10.2%. After that, four band ratios were used in linear regression with aCDOM (440) to build empirical inversion models. The results showed that the performance of the model based on Rrs (531)/Rrs (551) was the best, with R2 of 0.63. The RMSE and σ of the aCDOM(440) result inverted by the empirical method were 0.08 and 8.8% respectively. The empirical method was of higher precision than that of the semi-analytical method, but the bands and coeffi- cients used in the empirical method need to be calibrated by concurrently measured data in each study area. On the contrary, semi-analytical method does not need calibration, and is easier to be applied.

Quadruple switching of pleated foldamers of tetrathiafulvalene-bipyridinium alternating dynamic covalent polymers.

Two dynamic covalent polymers P1 and P2 were prepared by alternately linking electron-rich tetrathiafulvalene (TTF) and electron-deficient bipyridinium (BIPY(2+) ) through hydrazone bonds. In acetonitrile, the polymers were induced by intramolecular donor-acceptor interactions to form pleated foldamers, which unfolded upon oxidation of the TTF units to the radical cation TTF(.+) . Reduction of the BIPY(2+) units to BIPY(.+) led to the formation of another kind of pleated secondary structures, which are stabilized by intramolecular dimerization of the BIPY(.+) units. The diradical dicationic cyclophane cyclobis(paraquat-p-phenylene) (CBPQT(2(.+)) ) could further force the folded structures to unfold by including the BIPY(.+) units of the polymers. Upon oxidation of the BIPY(.+) units of the cyclophane and polymers to BIPY(2+) , the first folded state was regenerated. Switching or conversion between the four conformational states was confirmed by UV/Vis spectroscopic experiments.

Mesoporous carbon hemispheres integrated with Fe-Gd nanoparticles for potential MR/PA imaging-guided photothermal therapy.

Asymmetric carbon has emerged as an important material to enrich morphologies as well as enhance functions for bioapplications. Here, asymmetric mesoporous carbon hemispheres (CHS) integrated with γ-Fe2O3 and GdPO4 (Fe-Gd) nanoparticles are proposed and prepared for potential imaging-guided photothermal therapy (PTT). Interestingly, Fe-Gd/CHS contributes to an almost 1.5 times enhancement in light harvesting and photothermal conversion efficiency as compared with its corresponding spherical analogue. The possible underlying mechanism is discussed in view of the unique asymmetric structure-featured carbon. Further identification of the inherited photoacoustic (PA) and magnetic resonance (MR) imaging properties leads to the consequent in vivo evaluation of its imaging and PTT performances, which demonstrates its capability as a function-integrated system for potential theranostics.