Highly luminescent nitrogen and sulfur co-doped carbon dots for Sn2+ and S2- sensing and dual-mode anti-counterfeiting.

The preparation of nitrogen and sulfur co-doped carbon dots (N, S-CDs) with highly bright orange-red fluorescence is reported through a facile solvothermal approach with naphthalenetetracarboxylic dianhydride as starting material. The N, S-CDs exhibited superior properties, including intense long-wavelength emission with a narrow full width at half maxima (FWHM) of 33 nm, high fluorescence quantum yield (QY) of 60.5% in aqueous solution, excitation-independent emission behavior, and excellent water dispersibility. In addition, sulfide ions (S2-) could selectively recover the fluorescence of N, S-CDs quenched by Sn2+. The selective experiment suggested that the N, S-CDs/Sn2+ complex could be used as a fluorescence-enhancement sensor for sulfide ions (S2-), with the linear range of 5-50 µM and the LOD of 0.35 µM. The practicality and feasibility of this sensor for the determination of sulfide ions in tap and lake water were verified with good recoveries. Furthermore, because of their highly bright fluorescence and strong water solubility, the N, S-CDs could be easily fabricated into fluorescent ink and transparent films, demonstrating the promising application in anti-counterfeiting. Therefore, the designed N, S-CDs exhibited the advantages of facile preparation, intense fluorescence, high stability, easy processing, and selective fluorescence change for specific analytes, which showed high potential in fluorescence detection and anti-counterfeiting.

Fabrication of highly fluorinated porphyrin-based covalent organic frameworks decorated Fe3O4 nanospheres for magnetic solid phase extraction of fluoroquinolones.

A highly fluorinated porphyrin-based covalent organic frameworks magnetic adsorbent (FPy-COF@PDA@Fe3O4) was fabricated by using polydopamine (PDA) grafting Fe3O4 nanospheres as magnetic core and FPy-COF as shell for magnetic solid phase extraction (MSPE) of fluoroquinolones (FQs). FPy-COF was constructed by using 5,15-bis(4-aminophenyl)-10,20-bis(perfluorophenyl)porphyrin and 4,4'-biphenyldicarboxaldehyde as two building blocks. PDA as a bridge grafting on the surface of Fe3O4 nanospheres facilitated the growth of FPy-COF. The morphology and structure of FPy-COF@PDA@Fe3O4 adsorbent were characterized in detail. The prepared magnetic adsorbent exhibited good extraction capability to amphiphilic FQs due to their superior chemical affinities such as fluorophilic interaction and hydrogen-bond interaction from nitrogen-rich skeleton. Under the optimized conditions, the MSPE method combined with high performance liquid chromatography with ultraviolet detection (HPLC-UV) was developed to sensitively quantify trace level of six FQs in milk samples. The developed MSPE-HPLC method showed good linearity with wide concentration range, precision, and low limits of detection (S/N = 3) for six FQs as low as 2.3 ngꞏmL-1 in milk. The extraction recoveries of different spiked concentrations were in the range 77.8-110.4% for milk samples with RSD less than 9.7%.

Iron porphyrin-based porous organic polymer with high peroxidase-like activity as colorimetric sensor for glutathione and ascorbic acid assay.

A new iron porphyrin-based organic polymer (Fe-POP) was synthesized through the William ether reaction. The as-prepared Fe-POP presented high chemical stability, wide pore distribution, high iron content, and strong affinity with 3,3',5,5'-tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2), which contributed to its excellent peroxidase-mimicking performance. In the presence of H2O2, Fe-POP could catalyze the transparent TMB into blue ox-TMB, which could be easily distinguished by the naked eyes. Moreover, glutathione (GSH) and ascorbic acid (AA) could convert blue ox-TMB into colorless TMB due to the inhibitory effect of GSH/AA to the catalytic oxidation of TMB. Based on this phenomenon, a rapid and sensitive colorimetric method for the assay of H2O2, GSH, and AA was developed using Fe-POP as sensor. The detection limits of H2O2, GSH, and AA  were 1.37, 0.44, and 0.33 µM, respectively. Finally, the colorimetric method based on Fe-POP was used to evaluate the GSH and AA content in real samples, which provided the guidance for GSH and AA supplements in our daily diet, suggesting the significant potential of Fe-POP in practical applications.

Self-Assembled BODIPY Derivative with A-D-A Structure as Organic Nanoparticles for Photodynamic/Photothermal Cancer Therapy.

Organic nanomaterials have attracted considerable attention in the area of photodynamic and photothermal therapy, owing to their outstanding biocompatibility, potential biodegradability, well-defined chemical structure, and easy functionalization. However, it is still a challenge to develop a single organic molecule that obtains both photothermal and photodynamic effects. In this contribution, we synthesized a new boron-dipyrromethene (BODIPY)-based derivative (DPBDP) with an acceptor-donor-acceptor (A-D-A) structure by coupling 3,6-di(2-thienyl)-2,5-dihydropyrrolo [3,4-c] pyrrole-1,4-dione (DPP) and BODIPY. To enhance the hydrophilicity of the BODIPY derivative, the polyethylene glycol (PEG) chains were introduced to the meso- position of BODIPY core. The amphiphilic DPBDP was then self-assembled into related nanoparticles (DPBDP NPs) with improved hydrophilicity and enhanced absorbance in the NIR region. DPBDP NPs could simultaneously generate the singlet oxygen (1O2) and heat under the irradiation of a single laser (690 nm). The 1O2 quantum yield and photothermal conversion efficiency (PCE) of DPBDP NPs were calculated to be 14.2% and 26.1%, respectively. The biocompatibility and phototherapeutic effect of DPBDP NPs were evaluated through cell counting kit-8 (CCK-8) assay. Under irradiation of 690 nm laser (1.0 W/cm2), the half maximal inhibitory concentration (IC50) of DPBDP NPs was calculated to be 16.47 µg/mL. Thus, the as-prepared DPBDP NPs could be acted as excellent candidates for synergistic photodynamic/photothermal therapy.

Red-Emissive Sulfur-Doped Carbon Dots for Selective and Sensitive Detection of Mercury (II) Ion and Glutathione.

Carbon dots (CDs) show great potential in bioimaging and biosensing because of their good biocompatibility and excellent optical properties. However, CDs with intense red emissions for sensitive and selective detection are rarely reported. Herein, we prepared the red-emissive carbon dots (RCDs) through a facile hydrothermal method using tetra (4-carboxyphenyl) porphyrin (TCPP) and thiourea as starting materials. The obtained RCDs were characterized by TEM, XRD, and XPS. RCDs exhibited high water solubility and strong red emission (λem = 650 nm), with the fluorescence quantum yield as high as 26.7%, which was greatly higher than that of TCPP. Moreover, the as-prepared RCDs could be acted as a highly selective and sensitive probe for the detection of Hg2+ and glutathione (GSH) through the fluorometric titration method. The detection limits of Hg2+ and GSH were calculated to be 1.73 and 1.6 nM, respectively. The cellular experiments demonstrated the good biocompatibility of RCDs and their feasibility in bioimaging. Thus, this work provided a simple strategy to design and synthesize the highly red-emissive carbon dots, which showed promising application in biological and environmental assays.

Exploration of N-Arylsulfonyl-indole-2-carboxamide Derivatives as Novel Fructose-1,6-bisphosphatase Inhibitors by Molecular Simulation.

A series of N-arylsulfonyl-indole-2-carboxamide derivatives have been identified as potent fructose-1,6-bisphosphatase (FBPase) inhibitors (FBPIs) with excellent selectivity for the potential therapy of type II diabetes mellitus. To explore the structure-activity relationships (SARs) and the mechanisms of action of these FBPIs, a systematic computational study was performed in the present study, including three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling, pharmacophore modeling, molecular dynamics (MD), and virtual screening. The constructed 3D-QSAR models exhibited good predictive ability with reasonable parameters using comparative molecular field analysis (q2 = 0.709, R2 = 0.979, rpre2 = 0.932) and comparative molecular similarity indices analysis (q2 = 0.716, R2 = 0.978, rpre2 = 0.890). Twelve hit compounds were obtained by virtual screening using the best pharmacophore model in combination with molecular dockings. Three compounds with relatively higher docking scores and better ADME properties were then selected for further studies by docking and MD analyses. The docking results revealed that the amino acid residues Met18, Gly21, Gly26, Leu30, and Thr31 at the binding site were of great importance for the effective bindings of these FBPIs. The MD results indicated that the screened compounds VS01 and VS02 could bind with FBPase stably as its cognate ligand in dynamic conditions. This work identified several potential FBPIs by modeling studies and might provide important insights into developing novel FBPIs.

Exploration of Novel Xanthine Oxidase Inhibitors Based on 1,6-Dihydropyrimidine-5-Carboxylic Acids by an Integrated in Silico Study.

Xanthine oxidase (XO) is an important target for the effective treatment of hyperuricemia-associated diseases. A series of novel 2-substituted 6-oxo-1,6-dihydropyrimidine-5-carboxylic acids (ODCs) as XO inhibitors (XOIs) with remarkable activities have been reported recently. To better understand the key pharmacological characteristics of these XOIs and explore more hit compounds, in the present study, the three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, pharmacophore modeling, and molecular dynamics (MD) studies were performed on 46 ODCs. The constructed 3D-QSAR models exhibited reliable predictability with satisfactory validation parameters, including q2 = 0.897, R2 = 0.983, rpred2 = 0.948 in a CoMFA model, and q2 = 0.922, R2 = 0.990, rpred2 = 0.840 in a CoMSIA model. Docking and MD simulations further gave insights into the binding modes of these ODCs with the XO protein. The results indicated that key residues Glu802, Arg880, Asn768, Thr1010, Phe914, and Phe1009 could interact with ODCs by hydrogen bonds, π-π stackings, or hydrophobic interactions, which might be significant for the activity of these XOIs. Four potential hits were virtually screened out using the constructed pharmacophore model in combination with molecular dockings and ADME predictions. The four hits were also found to be relatively stable in the binding pocket by MD simulations. The results in this study might provide effective information for the design and development of novel XOIs.

Self-Assembled Naphthalimide Conjugated Porphyrin Nanomaterials with D-A Structure for PDT/PTT Synergistic Therapy.

Light-activated phototherapy, including photothermal and photodynamic therapy, has become a new way for spatiotemporal control and noninvasive treatment of cancer. In this study, two new organic porphyrin molecules (NI-Por and NI-ZnPor) with donor (D)-acceptor (A) structure were designed and synthesized. The donor-acceptor pairs facilitated the intermolecular electron transfer, resulting in the enhancement of near-infrared (NIR) absorbance and nonradiative heat generation. After self-assembling, the nanoparticles were formed with the size around 60 nm. Relative to that of organic molecules, the absorption of NI-Por NPs and NI-ZnPor NPs broadened and red-shifted to the near-infrared region. Moreover, the porphyrin-containing nanoparticles can generate heat and reactive oxygen species (ROS) simultaneously induced by a single laser (635 nm). The intracellular reactive oxygen species production of NI-Por NPs and NI-ZnPor NPs was confirmed using DCFH-DA as an indicator. Furthermore, the localization of NI-Por NP and NI-ZnPor NP in HeLa cells was verified by fluorescence confocal laser microscopy. The photocytoxicity of two nanoparticles against HeLa cells was evaluated through the CCK-8 method. The IC50 of NI-Por NPs and NI-ZnPor NPs upon 635 nm laser irradiation was calculated to be 6.92 µg/mL and 5.86 µg/mL, respectively. Furthermore, the PDT/PTT synergistic effect of NPs under a 635 nm laser was verified through different treatment groups in vitro. All these results demonstrated that the as-prepared porphyrin-based nanoparticles are promising nanoagents for PDT/PTT in clinic.

Palladium porphyrin complexes for photodynamic cancer therapy: effect of porphyrin units and metal.

Photodynamic therapy (PDT) has been extensively explored for malignant tissue treatment. In this work, we successfully synthesized and characterized a series of porphyrin compounds by connecting porphyrin units with alkyl chains, which were then coordinated with palladium to yield related metal complexes, named Pd-Monopor, Pd-Dipor, and Pd-Tripor, respectively. The generation of reactive oxygen species (ROS) of six porphyrin compounds was investigated by the dichlorofluorescein (DCFH) method. As expected, the palladium porphyrin complexes showed the higher efficiency of ROS generation relative to free base porphyrins, probably due to the heavy atom effect. Remarkably, the efficiency of ROS generation increased with the number of porphyrin units in the photosensitizers. The order of ROS generation efficiency of the synthesized porphyrins was Pd-Tripor > Tripor > Dipor > Pd-Monopor > Pd-Dipor > Monopor. MTT assay suggested the good biocompatibility of the synthesized photosensitizers in the dark. Upon light irradiation, the palladium porphyrin complex exhibited higher therapeutic activity than free base porphyrin. The half-maximal inhibitory concentration (IC50) of Tripor and Pd-Tripor under light irradiation was calculated to be 18.2 and 9.6 µM, respectively. The cellular uptake and subcellular localization experiments indicated that Tripor was mainly localized in the lysosomes of cancer cells.

Correction: A folate-conjugated platinum porphyrin complex as a new cancer-targeting photosensitizer for photodynamic therapy.

Correction for 'A folate-conjugated platinum porphyrin complex as a new cancer-targeting photosensitizer for photodynamic therapy' by Mengqian Yang et al., Org. Biomol. Chem., 2019, 17, 5367-5374.

Multifunctional theranostic agents based on prussian blue nanoparticles for tumor targeted and MRI-guided photodynamic/photothermal combined treatment.

The independence of photodynamic or photothermal modality create difficulties in the success of tumor therapy. In this current study, a multifunctional nanotheranostic agent of PDE-Ce6-HA was developed for tumor targeted and MRI-guided photodynamic/photothermal combined therapy (PDT/PTT). For this purpose, the near-infrared-absorbing nanoparticles of prussian blue were coated with polydopamine and successively conjugated with chlorin e6 (Ce6) for reactive oxygen species (ROS) generation. The resultant nanoparticles, denoted as PDE-Ce6, were then modified with hyaluronic acid (HA) through electrostatic interaction to yield the final therapeutic agent of PDE-Ce6-HA NPs. PDE-Ce6-HA NPs not only exhibited high colloid stability, good biocompatibility and suitable transverse relaxation rate (0.54 mM-1 s-1), but also high photothermal conversion efficiency (40.4%) and excellent ROS generation efficiency under NIR light irradiation. The confocal microscopy images demonstrated a selective uptake of PDE-Ce6-HA by CD44 overexpressed HeLa cells via HA-mediated endocytosis. Meanwhile, in vitro anti-cancer evaluation verified the significant photodynamic and photothermal combined effects of PDE-Ce6-HA on cancer cells. Moreover, PDE-Ce6-HA led to an increase of T1-MRI contrast in tumor site. Furthermore, in vivo anti-tumor evaluation proved that the PDE-Ce6-HA under both 808 and 670 nm laser showed significantly high tumor growth inhibition effects compared with individual PTT or PDT. Hence, PDE-Ce6-HA is applicable in tumor targeted and MRI-guided photodynamic/photothermal combined treatment.

Photodynamic and photothermal synergistic behavior of triphenylamine-porphyrin nanoparticles for DNA interaction, cellular cytotoxicity and localization.

In this paper, amphiphilic conjugated triphenylamine-porphyrins TPA-Por-TPA and TPA-Por were designed and synthesized. The water-soluble nanostructures TPA-Por-TPA NPs and TPA-Por NPs spontaneously assembled after π-π stacking, which can be changed by improving the internal transfer ability of electrons. The intercalation and external binding modes of these free porphyrins and nanoporphyrins interacting with ct-DNA were confirmed by UV-vis and fluorescence spectroscopy. Reactive oxygen species (ROS) production was studied by 2',7'-dichlorofluorescein diacetate, demonstrating that the rate of production of ROS is TPA-Por-TPA NPs > TPA-Por-TPA > TPA-Por NPs > TPA-Por. In addition, the structure of the NP enhanced the acceptor-donor conjugated structure, resulting in fluorescence quenching and promoting non-radiative heat generation. The photothermal conversion efficiencies of the TPA-Por-TPA NPs and TPA-Por NPs were measured and calculated to be 34.89% and 37.99%, respectively. At the same time, the three nanomaterials showed good photocytotoxicity, and the IC50 of the TPA-Por-TPA NPs and TPA-Por NPs was 32.18 and 36.62 µg ml-1, respectively, at 10 min after laser irradiation. The cellular uptake and subcellular localization of these NPs were further evaluated through a confocal laser scanning microscope. The results showed that the conjugated NPs have good biocompatibility properties in the cancer cells. These properties make it possible for triphenylamine porphyrin NPs to become photosensitizers for the photodynamic and photothermal synergistic treatment of tumors, and have potential prospects for applications in cancer diagnosis and treatment.

Metalloporphyrin-indomethacin conjugates as new photosensitizers for photodynamic therapy.

Photodynamic therapy (PDT) is a promising cancer treatment approach with the advantages of low toxicity and noninvasive characteristics. In this study, a series of metalloporphyrin-indomethacin conjugates tethered with poly(ethylene glycol) (PEG) chains were prepared and characterized. The singlet oxygen production of the conjugates was evaluated through 2', 7'-dichlorofluorescin (DCFH) method. Because of the heavy atom effect, the metal porphyrin complexes exhibited the higher singlet oxygen (1O2) quantum yield than that of free base porphyrin. The order of 1O2 yield of the synthesized porphyrins was PtPor > PdPor > ZnPor > Por. The MTT assay using HeLa cells verified the low cytotoxicity of porphyrin-indomethacin conjugates in the dark. Upon irradiation, the platinated porphyrin (PtPor) showed the highest therapeutic activity among these conjugates, probably due to its high efficiency of 1O2 generation. The cellular uptake and subcellular localization of the conjugates were further evaluated through a confocal laser scanning microscope. The results showed that the conjugates were primarily localized in the lysosomes of HeLa cells.

A folate-conjugated platinum porphyrin complex as a new cancer-targeting photosensitizer for photodynamic therapy.

A new folate-conjugated platinum porphyrin complex (Por 4) was synthesized and characterized. The singlet oxygen production of the conjugates was evaluated through a 1,3-diphenylisobenzofuran method. The targeting ability and subcellular localization of Por 4 were confirmed by confocal laser scanning microscopy in HeLa cells (overexpression of FR) as well as in A549 cells (low expression of FR). The results suggested that the modification of the carboxyl group with a porphyrin compound did not decrease the binding affinity of folic acid to FR positive cancer cells. Moreover, the MTT assay using HeLa cells and A549 cells verified the low cytotoxicity of Por 4 in the dark. Upon irradiation, Por 4 showed noticeable improvement in toxicity against cancer cells with the overexpression of FR. Upon the treatment of Por 4 at the concentration of 20 µM, the cell viability was determined as 22% and 75% for HeLa and A549 cells, respectively, indicating that the folate-conjugated platinum porphyrin complex could be a promising PDT agent for cancer with overexpression of the folate receptor.

Manganese-doped carbon quantum dots for fluorometric and magnetic resonance (dual mode) bioimaging and biosensing.

Manganese-doped carbon quantum dots (MnCQDs) were prepared through one-step hydrothermal method using citric acid and manganese tetraphenyl porphyrin as carbon sources in aqueous media. The structure of MnCQDs was confirmed by TEM, XRD, and XPS. The MnCQDs display a typical excitation-dependent emission behavior and exhibit bright green luminescence (with a peak at 482 nm) under UV irradiation (365 nm) and a fluorescence quantum yield of 13%. The MnCQDs can be used as a fluorescent probe for ferric ion in aqueous solution with a 220 nM detection limit. The MTT assay demonstrated the low cytotoxicity of MnCQDs towards HeLa cells. Due to the excitation-dependent emission properties, MnCQDs can be used as a multi-color (blue, green, and red) bioimaging agent in cancer cells and in living zebrafish. The application of MnCQDs as selective biosensing probe for Fe3+ was also realized in cells and zebrafish mode. Because of the existence of paramagnetic ions, MnCQDs demonstrate an enhanced magnetic resonance (MR) signal. Thus, the MnCQDs can serve as a positive contrast agent for MR imaging. Graphical abstract Schematic presentation of the preparation of luminescent manganese-doped carbon quantum dots (MnCQDs). MnCQDs showed good magnetic resonance effect and can be used as a fluorescence probe for the detection of Fe3+ in HeLa cells and zebrafish.

Platinated porphyrin as a new organelle and nucleus dual-targeted photosensitizer for photodynamic therapy.

Organelle and nucleus dual-targeted anticancer drugs are being increasingly used for efficient cancer therapy as they can attack the double vital sites of tumor cells. In this work, we synthesized and characterized two new porphyrin compounds Pt-Por-RB and Me-Por-RB. The spectral titration results suggest that both Pt-Por-RB and Me-Por-RB bind to DNA efficiently in an intercalation binding mode. Upon irradiation, Pt-Por-RB with low dark-cytotoxicity can rapidly generate singlet oxygen to damage the tumor cells through the process of photodynamic therapy. Compared with Me-Por-RB, Pt-Por-RB was not only internalized in the organelles, but also in the nuclei of HeLa cells, probably due to the presence of platinum complexes, as analyzed using the confocal laser scanning microscope. Thus, with the combination of organelle and nucleus dual-targeting property and high efficiency of singlet oxygen generation, Pt-Por-RB showed a significant therapeutic activity against tumor cells.

Photocytotoxicity, cellular uptake and subcellular localization of amidinophenylporphyrins as potential photodynamic therapeutic agents: An in vitro cell study.

The cell-based studies of 5, 10, 15, 20-Tetrakis (4-amidinophenyl) porphyrin (Por1), its Zn complex (Por2) and amidinophenyl bisporphyrin (Por3) were carried out to examine their photocytotoxicity, cellular uptake and sub-cellular localization with human nasopharyngeal carcinoma cell (HK-1), using 5, 10, 15, 20-Tetrakis (N-methyl-4-pyridyl) porphyrin (H2TMPyP) as a reference. These porphyrins showed low dark-cytotoxicity and high photo-cytotoxicity against HK-1. The amphiphilic amidinophenyl bisporphyrin (Por3) displayed better cellular uptake than the single hydrophilic Por1, Por2 and H2TMPyP. As seen from the extent of overlapping of the fluorescence profiles, lysosomal localization of amidinophenylporphyrin Por1-Por3 and mito/lyso localization of the H2TMPyP occurred in the cells. The results suggest these porphyrins with amidine group could be used as potential agents in photodynamic therapy.

B, N co-doped carbon dots as efficient nanozymes for colorimetric and fluorometric dual-mode detection of cholesterol.

In this work, the B, N co-doped carbon dots (B, N-CDs) were synthesized via facile hydrothermal approach with 6-aminopyridine boronic acid as precursor. In addition to emitting intense blue luminescence when exposed to ultraviolet light, the prepared B, N-CDs displayed remarkable peroxidase-like activity, which could efficiently catalyze the oxidation of 3, 3', 5, 5' -tetramethylbenzidine (TMB) to blue ox-TMB in the presence of hydrogen peroxide (H2O2). Furthermore, the fluorescence intensity of B, N-CDs increased gradually upon the addition of H2O2. Since cholesterol oxidase (ChOx) can catalyze the oxidation of cholesterol to form H2O2, the as-prepared B, N-CDs was then used as both colorimetric and fluorometric sensors for the detection of cholesterol with detection limit of 0.87 and 2.31 µM, respectively. Finally, the dual-mode approach based on B, N-CDs was effectively utilized for detecting cholesterol levels in serum samples, proving the potential application of B, N-CDs in the field of biological assay.

Design, synthesis, and biological evaluation of 5-(1H-indol-5-yl)isoxazole-3-carboxylic acids as novel xanthine oxidase inhibitors.

Xanthine oxidase (XO) is a key enzyme for the production of uric acid in the human body. XO inhibitors (XOIs) are clinically used for the treatment of hyperuricemia and gout, as they can effectively inhibit the production of uric acid. Previous studies indicated that both indole and isoxazole derivatives have good inhibitory effects against XO. Here, we designed and synthesized a novel series of N-5-(1H-indol-5-yl)isoxazole-3-carboxylic acids according to bioisosteric replacement and hybridization strategies. Among the obtained target compounds, compound 6c showed the best inhibitory activity against XO with an IC50 value of 0.13 µM, which was 22-fold higher than that of the classical antigout drug allopurinol (IC50 = 2.93 µM). Structure-activity relationship analysis indicated that the hydrophobic group on the nitrogen atom of the indole ring is essential for the inhibitory potencies of target compounds against XO. Enzyme kinetic studies proved that compound 6c acted as a mixed-type XOI. Molecular docking studies showed that the target compound 6c could not only retain the key interactions similar to febuxostat at the XO binding site but also generate some new interactions, such as two hydrogen bonds between the oxygen atom of the isoxazole ring and the amino acid residues Ser876 and Thr1010. These results indicated that 5-(1H-indol-5-yl)isoxazole-3-carboxylic acid might be an efficacious scaffold for designing novel XOIs and compound 6c has the potential to be used as a lead for further the development of novel anti-gout candidates.

In situ growth of porous organic framework on iron wire for microextraction of polycyclic aromatic hydrocarbons.

In this work, a novel spherical metal organic framework (MOF) was first in situ grown on the surface of iron wire (IW), in which IW served as the substrate and metal source for MOF (type NH2-MIL88) growth without adding additional metal salts in the process, while spherical NH2-MIL88 provided more active sites for further construction of multifunctional composites. Subsequently, a covalent organic framework (COF) was covalently bonded to the surface of the NH2-MIL88 to obtain the IW@NH2-MIL88@COF fibers, which were used for headspace solid-phase microextraction (HS-SPME) of polycyclic aromatic hydrocarbons (PAHs) in milk samples prior to determination by gas chromatography-flame ionization detection (GC-FID). Compared with the fiber prepared by physical coating, the IW@NH2-MIL88@COF fiber prepared by in situ growth and covalent bonding exhibits better stability and possesses more uniform layer. The extraction mechanism of the IW@NH2-MIL88@COF fiber for PAHs was discussed, which mainly owed to π-π interactions and hydrophobic interactions. After optimization of the primary extraction conditions, the SPME-GC-FID method was established for five PAHs with a wide linear range (1-200 ng mL-1), good linearity coefficient (0.9935-0.9987) and low detection limits (0.017-0.028 ng mL-1). The relative recoveries for PAHs detection in milk samples ranged from 64.69 to 113.97%. This work not only provides new ideas for the in situ growth of other types of MOF, but also provides new methods for the construction of multifunctional composites.