Zhi-Lin Wang - Cochemist

Water-Soluble Conjugated Polymer as a Fluorescent Probe for Monitoring Adenosine Triphosphate Level Fluctuation in Cell Membranes during Cell Apoptosis and in Vivo

Co-reporter:Binghuan Huang, Zhirong Geng, Shihai Yan, Zan Li, Jun Cai, and Zhilin Wang

Analytical Chemistry September 5, 2017 Volume 89(Issue 17) pp:8816-8816

Publication Date(Web):July 28, 2017

DOI:10.1021/acs.analchem.7b01212

Adenosine triphosphate (ATP) is used as the energy source in cells and plays crucial roles in various cellular events. The cellular membrane is the protective barrier for the cytoplasm of living cells and involved in many essential biological processes. Many fluorescent probes for ATP have been successfully developed, but few of these probes were appropriate for visualizing ATP level fluctuation in cell membranes during the apoptotic cell death process. Herein, we report the synthesis of a new water-soluble cationic polythiophene derivative that can be utilized as a fluorescent sensor for detecting ATP in cell membranes. Poly((3-((4-methylthiophen-3-yl)oxy)propyl)triphenylphosphonium chloride) (PMTPP) exhibits high sensitivity and good selectivity to ATP, and the detection limit is 27 nM. The polymer shows low toxicity to live cells and excellent photostability in cell membranes. PMTPP was practically utilized for real-time monitoring of ATP levels in the cell membrane through fluorescence microscopy. We have demonstrated that the ATP levels in cell membranes increased during the apoptotic cell death process. The probe was also capable of imaging ATP levels in living mice.

Dual-target cancer theranostic for glutathione S-transferase and hypoxia-inducible factor-1α inhibition

Co-reporter:Zan Li;Jie Ding;Chunxia Chen;Jiayin Chang;Binghuan Huang;Zhirong Geng;Zhilin Wang

Chemical Communications 2017 vol. 53(Issue 92) pp:12406-12409

Publication Date(Web):2017/11/16

DOI:10.1039/C7CC08162F

We developed a dual-target theranostic F671, which could exhibit synergetic anticancer effects for inhibiting the activities of glutathione S-transferase and the accumulation of hypoxia inducible factor-1α. F671 undergoes self-immolative cleavage when exposed to GSTP1-1 in live cancer cells, facilitating the visualization of molecule release and distribution, as well as confirming the autophagy-induced apoptosis.

Molecular visualizing and quantifying immune-associated peroxynitrite fluxes in phagocytes and mouse inflammation model

Co-reporter:Zan Li, Shi-Hai Yan, Chen Chen, Zhi-Rong Geng, Jia-Yin Chang, Chun-Xia Chen, Bing-Huan Huang, Zhi-Lin. Wang

Biosensors and Bioelectronics 2017 Volume 90(Volume 90) pp:

Publication Date(Web):15 April 2017

DOI:10.1016/j.bios.2016.11.036

•F482 was applied in ratiometrically detecting ONOO-.•Carboxylic BODIPY formation by ONOO--induced diene oxidation was confirmed.•F482 enables us to quantify ONOO- in phagosomes by high-throughput flow cytometry.•Visualizing and quantifying ONOO- fluxes in mouse inflammation model was realized.Reactions of peroxynitrite (ONOO−) with biomolecules can lead to cytotoxic and cytoprotective events. Due to the difficulty of directly and unambiguously measuring its levels, most of the beneficial effects associated with ONOO− in vivo remain controversial or poorly characterized. Recently, optical imaging has served as a powerful noninvasive approach to studying ONOO− in living systems. However, ratiometric probes for ONOO− are currently lacking. Herein, we report the design, synthesis, and biological evaluation of F482, a novel fluorescence indicator that relies on ONOO−-induced diene oxidation. The remarkable sensitivity, selectivity, and photostability of F482 enabled us to visualize basal ONOO− in immune-stimulated phagocyte cells and quantify its generation in phagosomes by high-throughput flow cytometry analysis. With the aid of in vivo ONOO− imaging in a mouse inflammation model assisted by F482, we envision that F482 will find widespread applications in the study of the ONOO− biology associated with physiological and pathological processes in vitro and in vivo.

Lysosomal ATP imaging in living cells by a water-soluble cationic polythiophene derivative

Co-reporter:Bing-Huan Huang, Zhi-Rong Geng, Xiao-Yan Ma, Cui Zhang, Zhi-Yang Zhang, Zhi-Lin Wang

Biosensors and Bioelectronics 2016 Volume 83() pp:213-220

Publication Date(Web):15 September 2016

DOI:10.1016/j.bios.2016.04.064

•PEMTEI is the first fluorescent probe for the detection of ATP in lysosome.•PEMTEI exhibits high selectivity and sensitivity to ATP in physiological conditions.•PEMTEI has low cytotoxicity, good permeability and high photostability in cells.•Lysosomes in HeLa cells can release ATP through Ca2+-dependent exocytosis.Lysosomes in astrocytes and microglia can release ATP as the signaling molecule for the cells through ca2+-dependent exocytosis in response to various stimuli. At present, fluorescent probes that can detect ATP in lysosomes have not been reported. In this work, we have developed a new water-soluble cationic polythiophene derivative that can be specifically localized in lysosomes and can be utilized as a fluorescent probe to sense ATP in cells. PEMTEI exhibits high selectivity and sensitivity to ATP at physiological pH values and the detection limit of ATP is as low as 10−11 M. The probe has low cytotoxicity, good permeability and high photostability in living cells and has been applied successfully to real-time monitoring of the change in concentrations of ATP in lysosomes though fluorescence microscopy. We also demonstrated that lysosomes in Hela cells can release ATP through Ca2+-dependent exocytosis in response to drug stimuli.

Dose-dependent effects of selenite (Se4) on arsenite (As3)-induced apoptosis and differentiation in acute promyelocytic leukemia cells

Co-reporter:S Wang, Z Geng, N Shi, X Li and Z Wang

Cell Death & Disease 2015 6(1) pp:e1596

Publication Date(Web):2015-01-01

DOI:10.1038/cddis.2014.563

To enhance the therapeutic effects and decrease the adverse effects of arsenic on the treatment of acute promyelocytic leukemia, we investigated the co-effects of selenite (Se4+) and arsenite (As3+) on the apoptosis and differentiation of NB4 cells and primary APL cells. A 1.0-μM concentration of Se4+ prevented the cells from undergoing As3+-induced apoptosis by inhibiting As3+ uptake, eliminating As3+-generated reactive oxygen species, and repressing the mitochondria-mediated intrinsic apoptosis pathway. However, 4.0 μM Se4+ exerted synergistic effects with As3+ on cell apoptosis by promoting As3+ uptake, downregulating nuclear factor-кB, and activating caspase-3. In addition to apoptosis, 1.0 and 3.2 μM Se4+ showed contrasting effects on As3+-induced differentiation in NB4 cells and primary APL cells. The 3.2 μM Se4+ enhanced As3+-induced differentiation by promoting the degradation of promyelocytic leukemia protein–retinoic acid receptor-α (PML–RARα) oncoprotein, but 1.0 μM Se4+ did not have this effect. Based on mechanistic studies, Se4+, which is similar to As3+, might bind directly to Zn2+-binding sites of the PML RING domain, thus controlling the fate of PML–RARα oncoprotein.

One-step synthesis of carboxyl-functionalized rare-earth fluoride nanoparticles for cell imaging and drug delivery

Co-reporter:Zhiyang Zhang, Xiaoyan Ma, Zhirong Geng, Kuaibing Wang and Zhilin Wang

RSC Advances 2015 vol. 5(Issue 43) pp:33999-34007

Publication Date(Web):08 Apr 2015

DOI:10.1039/C5RA02217G

Rare-earth doped UCNPs with a carboxyl coating on the surface have been widely used in many fields of biology, however, the modification of nanoparticles with a carboxyl polymer group is relatively complicated, and thus, fabricating carboxyl polymer-coated UCNPs using a simple method is significant. Herein, we synthesized carboxyl polymer-coated NaYF4:Yb3+/Tm3+ nanoparticles through a hydrothermal route during which methacrylic acid polymerized and bound to the surface of the nanoparticles. Dependence of structure and morphology on the dosage of NaOH was investigated. The polymerization degree of poly(methacrylic acid) and the amount of capping carboxyl group influenced by the dosage of NaOH were also studied. Other carboxyl-functionalized rare-earth fluorides could be obtained by using this method, the mechanism for which was also investigated. Thus, this method was universal for the carboxyl capping of rare-earth doped fluoride nano-materials, and also provided a new approach for carboxylic functionalization of nanoparticles. cis-Dichlorodiammineplatinum(II) (cisplatin, CDDP)-loaded NaYF4:Yb3+/Tm3+ nanoparticles (NaYF4–CDDP) were characterized by transmission electron microscopy, energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy, and CDDP was loaded in the form of Pt–O bonds. Upconversion luminescence images revealed the time course of intracellular CDDP delivery by NaYF4–CDDP. Compared with CDDP alone, the NaYF4–CDDP composite exerted cytotoxic effects on HeLa and MCF-7 cancer cell lines depending more on time and more slowly due to time-dependent cellular uptake and drug release. Non-loaded NaYF4:Yb3+/Tm3+ nanoparticles were also eligible for upconversion luminescence cell imaging. Therefore, the as-prepared NaYF4:Yb3+/Tm3+ nanoparticles allow simultaneous cell imaging and drug delivery as promising anti-cancer theranostic agents.

Real-time fluorescence assays of alkaline phosphatase and ATP sulfurylase activities based on a novel PPi fluorescent probe

Co-reporter:Xiaobo Wang, Zhiyang Zhang, Xiaoyan Ma, Jinghan Wen, Zhirong Geng, Zhilin Wang

Talanta 2015 Volume 137() pp:156-160

Publication Date(Web):15 May 2015

DOI:10.1016/j.talanta.2015.01.028

•A fluorescence assay of ATPS activity based on PPi probe was established firstly.•A fluorescence assay of ALP activity based on PPi probe was established.•[(ZnL)2–PPi] can be used to screen potentially ALP and ATPS inhibitors.An anthracene-armed tetraaza macrocyclic fluorescent probe 3-(9-anthrylmethyl)-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene(l) for detecting Zn2+ in aqueous medium was synthesized. L–Zn2+ complex, showed selectivity toward pyrophosphate ion (PPi) by quenching the fluorescence in aqueous HEPES buffer (pH 7.4). Furthermore, L–Zn2+ was also used to set up a real-time fluorescence assay for monitoring enzyme activities of alkaline phosphatase (ALP) and adenosine triphosphate sulfurylase (ATPS). In the presence of ALP inhibitor Na3VO4 and ATPS inhibitor chlorate, two enzymes activities decreased obviously, respectively.We established a real-time fluorescence assay of ATP sulfurylase activity by employing PPi as substrate. Furthermore, our fluorescence system can be used to screen potentially eligible ATP sulfurylase inhibitors.

Template-free synthesis and magnetic properties of hollow Cu/Fe3O4 heterodimer sub-microcactus

Co-reporter:Zhiming Chen, Wenhui Xu, Zhiyang Zhang, Zhirong Geng, Tingxian Tao, Renchun Yang, Rongmei Liu, Wenlin Xie and Zhilin Wang

CrystEngComm 2014 vol. 16(Issue 15) pp:3228-3233

Publication Date(Web):22 Jan 2014

DOI:10.1039/C3CE42331J

Hollow Cu/Fe3O4 heterodimer sub-microcactus has been successfully fabricated by a facile one-pot solvothermal method without any templates, which was confirmed by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectra (XPS) and a magnetic property measurement system. Batch experiments showed that the morphology is strongly influenced by the content of Cu in the Cu/Fe3O4 samples. A mechanism for the formation of the hollow heterodimer sub-microcactus by a cooperation of oriented attachment and localized Ostwald ripening processes has been proposed based on the observations of time-dependent experiments. Magnetic measurements illustrated that the prepared hollow heterodimer sub-microcactus are superparamagnetic magnets with a saturation magnetization of 65.2 emu g−1. The synthesized hollow Cu/Fe3O4 heterodimer sub-microcactus may have important applications in catalysis, energy storage and biomedical applications.

Controllable synthesis of NH4Eu3F10 nanospheres and application in bioimaging

Co-reporter:Zhiyang Zhang, Xiaoyan Ma, Zhiming Chen, Kuaibing Wang, Yidan Wang, Zhirong Geng and Zhilin Wang

CrystEngComm 2014 vol. 16(Issue 7) pp:1296-1303

Publication Date(Web):30 Oct 2013

DOI:10.1039/C3CE42193G

Cubic phase NH4Eu3F10 nanospheres with controllable sizes were synthesized via a modified hydrothermal route by varying the dosage of ammonium hydroxide solution. Dependence of structure and morphology on the dosage of ammonia water and reaction time were investigated by X-ray powder diffraction (XRD) and transmission electron microscopy (TEM). Being unstable, NH4Eu3F10 decomposed into EuF3 and NH4F during the long-time hydrothermal treatment. EDTA, as the chelation agent of Eu3+ and the capping ligand on the surface of as-obtained nanospheres, showed different chelating abilities depending on the dosage of ammonium hydroxide solution. Increasing the amount of ammonia not only decreased the effective concentration of Eu3+, but also decelerated the growth of NH4Eu3F10 nanospheres and stabilized them by reducing the surface energy. Given the satisfactory hydrophilicity, biocompatibility, and luminescence, the as-obtained nanospheres were applied as promising agents for cell imaging by presenting high contrast.

The first example of a model compound of RNase U2 and its intermediate with CPP directly monitored by ESI-MS

Co-reporter:Xiaoyan Ma, Yuxin Yin, Zhirong Geng, Zhen Yang, Jinghan Wen and Zhilin Wang

RSC Advances 2014 vol. 4(Issue 91) pp:50070-50073

Publication Date(Web):02 Oct 2014

DOI:10.1039/C4RA07950G

A Tb(III) complex of THP [1,4,7,10-tetrakis(2-hydroxypropyl)-cyclen] (THPTb) cleaved RNA phosphate ester bonds at A-specific sites to mimic RNase U2. The intermediates of the adducts of THPTb2+ and CPP− (cyclic propylene phosphate) or HPNP− (2-hydroxy propyl-p-nitrophenylphosphate) in the hydrolysis of HPNP were directly monitored by electrospray ionization mass spectrometry (ESI-MS).

An NBD-armed tetraaza macrocyclic lysosomal-targeted fluorescent probe for imaging copper(II) ions

Co-reporter:Xiaobo Wang, Xiaoyan Ma, Zhen Yang, Zhong Zhang, Jinghan Wen, Zhirong Geng and Zhilin Wang

Chemical Communications 2013 vol. 49(Issue 96) pp:11263-11265

Publication Date(Web):08 Oct 2013

DOI:10.1039/C3CC46585C

An NBD-armed tetraaza macrocyclic lysosomal-targeted fluorescent probe for detecting Cu2+ was synthesized and used for fluorescence imaging in HeLa cells. The probe was specifically localized in lysosomes and successfully applied to visualize Cu2+ as well as to monitor Cu2+ level changes in the lysosomes of living cells.

Luminescent Rhodamine B doped core–shell silica nanoparticle labels for protein microarray detection

Co-reporter:Haiping Liu, Ying Wang, Hui Li, Zhilin Wang, Danke Xu

Dyes and Pigments 2013 Volume 98(Issue 1) pp:119-124

Publication Date(Web):July 2013

DOI:10.1016/j.dyepig.2013.01.027

A class of hydrophilic, photostable, biocompatiable, and highly fluorescent streptavidin-functionalized silica nanoparticles were developed, in which Rhodamine B isothiocyanate molecules were covalently embedded by using Stöber method. The silica nanoparticles were ∼60 nm in size and had average fluorescence intensity 4000 times higher than dye molecules. To reduce the severe aggregation, silica nanoparticles were modified with amino groups on the surface by adding (3-aminopropyl)triethoxysilane together with methylphosphonate groups using 3-trihydroxysilylpropylmethylphosphonate, followed by functionalization with streptavidin. The resulting streptavidin-functionalized silica nanoparticles were used for the detection of by reverse-phase protein microarrays based on classical linkage system constituted by biotin-streptavidin conjugation. The calibration curve was linear over the range from 40 amol to 640 amol and the limit of detection was 10 amol, which was 8 times lower than that of streptavidin-labeled cyanine fluorescent dyes. This promising technology may be potential applied for multiplexed signaling and bioassays.Highlights► Highly fluorescent Rhodamine B doped core–shell silica nanoparticles were developed. ► The nanoparticles were used for the detection of human IgE by protein microarrays. ► This probe has higher sensitivity than a traditional fluorescent cyanine dye.

One-pot template-free synthesis of water-dispersive Fe3O4@C nanoparticles for adsorption of bovine serum albumin

Co-reporter:Zhiming Chen, Zhenglian Xue, Lin Chen, Zhirong Geng, Renchun Yang, Luyao Chen and Zhilin Wang

New Journal of Chemistry 2013 vol. 37(Issue 11) pp:3731-3736

Publication Date(Web):30 Aug 2013

DOI:10.1039/C3NJ00490B

Water-dispersive Fe3O4@C nanoparticles have been successfully synthesized on a large scale via a one-pot template-free solvothermal process. The core–shell structure of the product was confirmed by transmission electron microscopy (TEM) observations. Fourier transform infrared (FT-IR) and X-ray photoelectron spectra (XPS) of the sample indicated that abundant amide carbonyl groups are formed on the surface of the Fe3O4@C nanoparticles. Based on the thermogravimetric analysis (TGA) results, the contents of Fe3O4 and carbon are calculated to be 77.5% and 6.1%, respectively. Magnetic measurements illustrated that the prepared composites are superparamagnetic magnets with a saturation magnetization of 69.2 emu g−1. Because of their hydrophilic core–shell structure, the prepared Fe3O4@C nanoparticles show a high bovine serum albumin (BSA) protein adsorption capacity (82.78 mg g−1) and a fast adsorption rate (60 min) in aqueous solutions. This work demonstrates that the prepared magnetic nanoparticles have promising applications in enzyme and protein immobilization.

Azole derivatives as novel non-iron-chelating inhibitors of prolyl hydroxylase 3 for HIF-1 activation

Co-reporter:Jing Cao, Xiaoyan Ma, Xiaoxin Wang, Xiaobo Wang, Zhong Zhang, Zhirong Geng and Zhilin Wang

MedChemComm 2013 vol. 4(Issue 9) pp:1222-1230

Publication Date(Web):01 Jul 2013

DOI:10.1039/C3MD00117B

Prolyl hydroxylase 3 (PHD3) controls hypoxia-inducible factor-1 (HIF-1) degradation by oxygen dependent hydroxylation. PHD3 inhibitors are potential targets for HIF-1α activation, thereby treating a number of HIF-related diseases. We herein rationally designed a novel scaffold for PHD3 inactivation under the guidance of enzyme–ligand docking simulation studies. The potent inhibitors were able to non-covalently bind to the active site of PHD3, and to stabilize the core domain resisting to trypsin proteolysis. The conformational changes of the protein occurred concomitant with inhibitor binding, which thus deactivated the enzyme. The up-regulated levels of HIF-1α protein and downstream genes (glucose transporter-1 (GLUT-1) and vascular endothelial growth factor (VEGF)) suggest that the PHD inhibitors manage to mimic the cellular signalling effects of hypoxia. Interestingly, unlike available PHD inhibitors, the iron-chelating motif is not found in all azole compounds, among which we identified a unique compound 1-(2-(1H-benzo[d]imidazol-2-yl)ethyl)-1H-benzo[d][1,2,3]triazole (BEBT) as the most effective inhibitor. BEBT binds to the enzyme with the lowest predicted binding energy, and activates HIF activity most significantly in cellular systems. This novel non-iron-chelating inhibitor offers a new target for the drug design towards hypoxia-related diseases therapy with possibly minimized iron-relating side effects.

Indirect Transformation of Coordination-Polymer Particles into Magnetic Carbon-Coated Mn3O4 (Mn3O4@C) Nanowires for Supercapacitor Electrodes with Good Cycling Performance

Co-reporter:Dr. Kuaibing Wang;Xiaoyan Ma;Zhiyang Zhang;Dr. Mingbo Zheng;Zhirong Geng;Dr. Zhilin Wang

Chemistry - A European Journal 2013 Volume 19( Issue 22) pp:7084-7089

Publication Date(Web):

DOI:10.1002/chem.201300188

Abstract

Carbon-coated Mn₃O₄ nanowires (Mn₃O₄@C NWs) have been synthesized by the reduction of well-shaped carbon-coated bixbyite networks and characterized by TEM, X-ray diffraction, X-ray photoelectron spectroscopy, and electrochemical experiments. To assess the properties of 1D carbon-coated nanowires for their use in supercapacitors, cyclic voltammetry and galvanostatic charging–discharging measurements were performed. Mn₃O₄@C NWs could be charged and discharged faster and had higher capacitance than bare Mn₃O₄ nanostructures and other commercial materials. The capacitance of the Mn₃O₄@C NWs was 92 % retained after 3000 cycles at a charging rate of 5 A g⁻¹. This improvement can be attributed to the carbon shells, which promote fast Faradaic charging and discharging of the interior Mn₃O₄ core and also act as barriers to protect the inner core. These Mn₃O₄@C NWs could be a promising candidate material for high-capacity, low-cost, and environmentally friendly electrodes for supercapacitors. In addition, the magnetic properties of the as-synthesized samples are also reported to investigate the influence of the carbon coating.

Coordination-Induced Assembly of Coordination Polymer Submicrospheres: Promising Antibacterial and in Vitro Anticancer Activities

Co-reporter:Kuaibing Wang, Xiaoyan Ma, Dalin Shao, Zhirong Geng, Zhiyang Zhang, and Zhilin Wang

Crystal Growth & Design 2012 Volume 12(Issue 7) pp:3786-3791

Publication Date(Web):June 7, 2012

DOI:10.1021/cg3006162

Spheres-like coordination polymer architectures in submicro regimes have been synthesized from the hydrothermal reaction of transition metal ions and 3,5-bis(pyridin-3-ylmethylamino)benzoic acid (L1). The size of the final coordination polymer was dependent on the concentrations of reactants. Scanning electron microscopy studies monitored at numerous stages of growth reveal that coordination-induced morphology changes from uncoordinated flowerlike ligands to sphere-like coordination polymer particles. Moreover, variations of luminescent and antibacterial profiles are associated with coordination environments or the size of as-obtained coordination polymer samples. In addition, the newly synthesized Cu-based polymer particles may act as novel metal-based anticancer drugs in the future because of their potent in vitro anticancer activities against three chosen cancer lines MCF-7, HeLa, and NCI-H446.

Controllable Fabrication of Coordination Polymer Particles (CPPs): A Bridge between Versatile Organic Building Blocks and Porous Copper-Based Inorganic Materials

Co-reporter:Kuaibing Wang, Zhirong Geng, Mingbo Zheng, Luyao Ma, Xiaoyan Ma, and Zhilin Wang

Crystal Growth & Design 2012 Volume 12(Issue 11) pp:5606-5614

Publication Date(Web):September 14, 2012

DOI:10.1021/cg3011234

Hierarchically micro-/nanostructured coordination polymer [Cu(2,5-PDC)H2O]n architectures with tunable morphologies have been successfully prepared by rationally adjusting the preparation parameters, such as the reactant concentration, solvent, surfactant, and reaction temperature. Using simple calcinations of chosen shaped [Cu(2,5-PDC)H2O]n architectures, we can obtain several porous copper-based inorganic motifs, which show potential applications for the antibacterial field and lithium ion batteries. Therein, CuO-1 can kill the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus better than other materials. The value for initial discharge capacity of CuO-3 (1160 mAh g–1) is higher than the theoretical capacity (674 mAh g–1) and most copper oxide materials. Besides, Cu/C composites also show intense application in the antibacterial and Li-ions uptake-release field, which will provide a widely used method to prepare the nanosystem of carbon-coating or carbon-compositing materials by simple calcinations of shaped precursor coordination polymer particles used under the proper temperature.

Self-assembled hollow rare earth fluoride alloyed architectures with controlled crystal phase and morphology

Co-reporter:Zhiming Chen, Qun Zhao, Guojin Feng, Zhirong Geng and Zhilin Wang

CrystEngComm 2012 vol. 14(Issue 22) pp:7764-7770

Publication Date(Web):04 May 2012

DOI:10.1039/C2CE25165E

A general synthetic protocol has been developed to assemble EuF3:Ln3+ and EuF3:Ln3+/NH4+ (Ln = Y, Gd, Tb, Dy, Ho, Er, and Tm) alloyed nanocrystallites into hexagon-shaped sub-microcages and hollow sub-microspheres. The structure, morphology and growth kinetics of the alloyed crystallites are investigated. Based on the results obtained by X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and X-ray photoelectron spectra (XPS), it is proposed that the possible formation mechanisms for EuF3:Ln3+ and EuF3:Ln3+/NH4+ (Ln = Y, Gd, Tb, Dy, Ho, Er, and Tm) alloyed architectures involves a crystal-phase-mediated self-assembly process. The crystal structure and morphology are strongly influenced by the Eu/Ln feed molar ratio in the starting solution. A higher feed ratio of Eu to Ln facilitates the growth of hexagonal EuF3:Ln3+ (Ln = Y, Gd, Tb, Dy, Ho, Er, and Tm) alloyed crystallites and results in the formation of hexagon-shaped sub-microcages, while a lower feed ratio of Eu to Ln accelerates the growth of cubic NH4Ln3F10:Eu3+ (Ln = Y, Gd, Tb, Dy, Ho, Er, and Tm) alloyed crystallites and leads to the assembly of the alloyed nanocrystals into hollow sub-microspheres. Additionally, the as-synthesized alloyed architectures show good performance in highly efficient fluorescent host materials.

Template-free synthesis of mesoporous NaTbF4 and NaTbF4:Eu nano-rice and their luminescence properties

Co-reporter:Zhiming Chen, Zhirong Geng, Dalin Shao, Zhiping Zhou and Zhilin Wang

CrystEngComm 2012 vol. 14(Issue 6) pp:2251-2257

Publication Date(Web):25 Jan 2012

DOI:10.1039/C2CE05909F

Single-crystalline mesoporous NaTbF4 nano-rice have been successfully synthesized in large scale by reaction of aqueous Tb3+ with sodium fluoride in the presence of ethylenediaminetetraacetic acid (EDTA) at 110 °C for 12 h, which were confirmed by X-ray powder diffraction, energy dispersive X-ray analysis, transmission electron microscopy, scanning electron microscopy, and nitrogen adsorption–desorption isotherms. A mechanism for the formation of the mesoporous nano-rice by an EDTA-directed assembly process accompanied by the localized Ostwald ripening has been proposed based on the observations of time-dependent experiments. In addition, this novel nano-rice can be used as an excellent host lattice for Eu3+ ions, in which the luminescence properties of Eu3+ would be improved significantly. Our study indicates that the maximum quantum efficiency of NaTbF4:Eu nano-rice reaches up to 69.9%. This work demonstrates that morphology-controlled synthesis can offer a simple solution to fabricate mesoporous NaTbF4:Eu nano-rice for technological and biomedical applications.

Evidence for inhibition of HIF-1α prolyl hydroxylase 3 activity by four biologically active tetraazamacrocycles

Co-reporter:Jing Cao, Zhirong Geng, Xiaoyan Ma, Jinghan Wen, Yuxin Yin and Zhilin Wang

Organic & Biomolecular Chemistry 2012 vol. 10(Issue 19) pp:3913-3923

Publication Date(Web):12 Mar 2012

DOI:10.1039/C2OB07076F

Hypoxia inducible factor 1 (HIF-1) is central to the hypoxic response in mammals. HIF-1α prolyl hydroxylase 3 (PHD3) degrades HIF through the hydroxylation of HIF-1α. Inhibition of PHD3 activity is crucial for up-regulating HIF-1α levels, thereby acting as HIF-dependent diseases therapy. Macrocyclic polyamines which display high stability on iron-chelating may well inhibit the enzyme activity. Thus inhibition and interaction on catalytic PHD3 by four biologically active tetraazamacrocycles (1–4), which have two types of parent rings to chelate iron(II) dissimilarly, were studied. The apparent IC50 values of 2.56, 1.91, 5.29 and 2.44 μM, respectively, showed good inhibition potency of the four compounds. KI values were 7.86, 3.69, 1.59 and 2.92 μM for 1–4, respectively. Different inhibition actions of the two groups of compounds were identified. Circular dichroism (CD) and fluorescence spectrometries proved that one type of compound has significant effects on protein conformation while another type does not. Computational methodology was constructed to employ the equilibrium geometry of enzyme active site with the presence of substrate competitive inhibitor. Iron(II) coordination in the active site by inhibitors of this kind induces conformational change of the enzyme and blocks substrate binding.

Two heptadentate Co(III) and Mn(III) complexes with partially deprotonated cyclen derivative bearing four hydroxypropyl pendants: structure, DNA binding and DNA cleavage

Co-reporter:Yu-Xin Yin;Jing-Han Wen;Zhi-Rong Geng;Yi-Zhi Li

Applied Organometallic Chemistry 2012 Volume 26( Issue 12) pp:671-680

Publication Date(Web):

DOI:10.1002/aoc.2905

Two new complexes, (Co^III)₂(H₃L⁻)₂(0.5H₂O)₂(ClO₄)₄ (I) and (Mn^III)₂(H₃L⁻)₂(0.5H₂O)₂ (ClO₄)₄ (II), were synthesized and crystallographically characterized [H₄L = 1,4,7,10-tetra-(2-hydroxypropyl)-l,4,7,10-tetraazacyclododecane] using electrospray ionization mass spectrometry and X-ray photoelectron spectrometery. The characterizations confirmed that the valences of the metal ions increased from divalent to trivalent due to deprotonation of one OH group (H₄L was in the form of H₃L⁻). Owing to the instability of Co(III) and Mn(III) in both air and in solution, they preferred to exist in divalent form. The two heptadentate complexes are extraordinary in that the chiral pendants of the complexes are different in configuration. Spectroscopic studies, viscosity measurements, thermal denaturation experiments and circular dichroism spectra demonstrated that the complexes were prone to interact with DNA by groove binding. At micromolar concentrations and under physiological conditions, the two complexes were able to oxidatively cleave the supercoiled pUC19 plasmid DNA into its nicked and linear forms. Mechanistic studies using various additives suggest the complexes had structures different from those of other inorganic complexes. These are the first reported inorganic complexes not containing planar aromatic ligands and yet binding at the major groove. Copyright © 2012 John Wiley & Sons, Ltd.

A mononuclear Mn2+ complex based on a novel tris-(ethyl acetate) pendant-armed tetraazamacrocycle: Effect of pyridine on self-assembly and weak interactions

Co-reporter:Jinghan Wen, Zhirong Geng, Yuxin Yin, Zhilin Wang

Inorganic Chemistry Communications 2012 Volume 21() pp:16-20

Publication Date(Web):July 2012

DOI:10.1016/j.inoche.2012.03.042

A novel pyridine containing tetraazamacrocycle 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid ethyl ester (1) and its mononuclear Mn2+ complex (2) have been prepared. Pyridine induced the π–π stacking of [Mn1]2+ and provided donors for nonclassical CH…O hydrogen bonding as well. In the solid state of 2, the combination of π–π interactions and hydrogen bonding constructed a 3D crystal structure and thus formed pairs of interacting mononuclear complexes that mediated weak magnetic exchanges between the Mn2+ ions. Meanwhile, self-assembly of 2 dissociated in the aqueous solution, and the effect of pyridine on the nature of DNA binding with 2 have also been investigated.A novel tetraazamcrocycle ligand (1) and its mononuclear Mn2+ complex (2) were prepared. Pyridine induced the π-π stacking of [Mn1]2+ and provided donors for nonclassical C-H…O hydrogen bonding, which synergetically constructed a 3D structure and mediated weak magnetic exchanges. Effect of pyridine on the binding of 2-DNA was also investigated.Highlights► Pyridine containing tetraazamacrocycles are still in need of further investigations. ► Pyridine led to π–π stacking of [Mn1]2+ and nonclassical CH…O hydrogen bonding. ► The resulting interacting mononuclear complexes mediated weak magnetic exchanges. ► Pyridine affected the nature of DNA binding with 2.

A potent antitumor Zn2+ tetraazamacrocycle complex targeting DNA: the fluorescent recognition, interaction and apoptosis studies

Co-reporter:Jing-Han Wen, Cheng-Ying Li, Zhi-Rong Geng, Xiao-Yan Ma and Zhi-Lin Wang

Chemical Communications 2011 vol. 47(Issue 40) pp:11330-11332

Publication Date(Web):13 Sep 2011

DOI:10.1039/C1CC14107D

A Zn2+ tetraazamacrocycle complex (2) bearing three naphthalene moieties has been prepared. Complex 2 recognizes, binds and causes damage to DNA, and shows considerable cytotoxicity against human cervical (HeLa), breast (MCF-7) and lung (NCI-H157) cancer cell lines with a different apoptotic pathway from that of cisplatin.

A Zn2+-specific turn-on fluorescent probe for ratiometric sensing of pyrophosphate in both water and blood serum

Co-reporter:Jinghan Wen, Zhirong Geng, Yuxin Yin, Zhong Zhang and Zhilin Wang

Dalton Transactions 2011 vol. 40(Issue 9) pp:1984-1989

Publication Date(Web):17 Dec 2010

DOI:10.1039/C0DT01262A

A novel fluorescent sensor composed of a naphthalene functionalized tetraazamacrocycle ligand 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3-methyl naphthalene (1) and Zn2+ has been designed and prepared, which can be utilized for selective and ratiometric sensing of pyrophosphate (PPi) over other phosphate-containing anions in aqueous solution at physiological pH. Notably, the water soluble 1 itself also exhibits a selective enhanced fluorescent response to Zn2+, and the complex 1-Zn2+ thus formed eventually fulfils the synergic Zn2+ coordination-altered strategy with PPi. Furthermore, the ratiometric sensing of 1-Zn2+ towards PPi performed well even in blood serum milieu. Finally, the sensor 1-Zn2+ was successfully employed to monitor a real-time assay of inorganic pyrophosphatase (PPase) by means of ratiometric fluorescent measurements for the first time.

A versatile water soluble fluorescent probe for ratiometric sensing of Hg2+ and bovine serum albumin

Co-reporter:Jinghan Wen, Zhirong Geng, Yuxin Yin and Zhilin Wang

Dalton Transactions 2011 vol. 40(Issue 38) pp:9737-9745

Publication Date(Web):22 Aug 2011

DOI:10.1039/C1DT10362H

A novel tetraazamacrocycle fluorescent sensor (6-(1-(dimethylamino)-5-naphthalene sulfonyl)-3,6,9,15-tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene, 1) has been designed and prepared, which can be utilized for selective and ratiometric sensing of Hg2+ and bovine serum albumin (BSA) with two different responsive modes in aqueous solution at physiological pH (50 mM Tris-HCl, pH 7.6). Above 0.5 ppb Hg2+ can be discerned by coordination with 1 and the emission color changes enable 1 to be applied to a fast Hg2+ test paper assay. Sensor 1 has also been demonstrated to be easily cell-penetrable and applicable for Hg2+ imaging in living cells. Imaging of BSA in the gel using SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) stained in the medium containing 1 verified that the binding of 1 and BSA was successful in the presence of nonprotein substances. The linear range of 1 towards BSA utilizing ratiometric fluorescent calibration via noncovalent interaction in solution is 0–100 μg mL−1 with a detection limit of 1 μg mL−1, and has been successfully employed to determine the albumin concentration in blood serum by means of ratiometric fluorescent measurements for the first time. Finally, sensor 1 behaves as a fluorescent molecular switch composed of triple logic gates upon chemical inputs of Hg2+ and BSA, which potentially provides intelligent diagnostics for Hg2+ contaminated serum on the nanoscale.

Facile synthesis of zinc(II)-carboxylate coordination polymer particles and their luminescent, biocompatible and antibacterial properties

Co-reporter:Kuaibing Wang, Yuxin Yin, Chengying Li, Zhirong Geng and Zhilin Wang

CrystEngComm 2011 vol. 13(Issue 20) pp:6231-6236

Publication Date(Web):19 Aug 2011

DOI:10.1039/C1CE05705G

Four different morphologies, including 1D nanobelts (1), 3D nanorod-flowers (2), fan-like (3) and rhombus-like (4) architectures have been synthesized from the mild reaction of Zn(Ac)2·2H2O and 2,2′-bipyridine-4,4′-dicarboxylic acid (H2L). The shape of the resulting coordination polymer particles (CPPs) was dependent on the amount of solvent and the molar ratio of reactants used in the reaction. In the experimental process, some additives such as triethylamine and acetic acid played a vital role in the formation of CPPs as means of adjusting the deprotonation rate of the organic linker (H2L), and thus affected the morphology of the resulting CPPs. We also investigated the effect of the different morphologies on the luminescent properties and bioactivities.

Morphology effect on the luminescent property and antibacterial activity of coordination polymer particles with identical crystal structures

Co-reporter:Kuaibing Wang, Zhirong Geng, Yuxin Yin, Xiaoyan Ma and Zhilin Wang

CrystEngComm 2011 vol. 13(Issue 16) pp:5100-5104

Publication Date(Web):15 Jun 2011

DOI:10.1039/C1CE05202K

Four different morphologies of coordination polymer particles (CPPs) with identical structures, which have effects on their luminescent properties and antibacterial activities, have been synthesized. We accounted for the possible formation mechanisms of the different morphologies from the molecular level. The additives such as Et3N and acetic acid play an important role in the particle formation rate by means of manipulating the deprotonation rate of the organic linker and thus the particle size and shape. Meanwhile, in our future research work, we need to take the morphology effect into consideration.

Effects of polynitrogen compounds on the activity of recombinant human HIF-1α prolyl hydroxylase 3 in E. coli

Co-reporter:Zhirong Geng, Jingshu Zhu, Jing Cao, Jinlong Geng, Xiaoli Song, Zhong Zhang, Ningsheng Bian, Zhilin Wang

Journal of Inorganic Biochemistry 2011 Volume 105(Issue 3) pp:391-399

Publication Date(Web):March 2011

DOI:10.1016/j.jinorgbio.2010.12.001

Hypoxia inducible factor 1α (HIF-1α) becomes an important regulation factor within the histiocyte when it is under the hypoxia condition. Recently, prolyl hydroxylases (PHDs) have been identified to inactivation HIF-lα by hydroxylation. In this study, polynitrogen compounds were screened as HIF-1α PHD3 inhibitors. The coding region of human PHD3 DNA was optimized by using synonymous codons according to the code bias of Escherichia coli. Soluble and active human PHD3 was expressed in the E. coli with a Trx fusion tag under a lower induction temperature of 25 °C. Mass spectrometry analysis of the resultant peptide product indicated a mass increase of 16 daltons, consistent with hydroxylation of the proline residue in the HIF-1α (556–574) peptide substrate. Polynitrogen compounds (1–4) inhibited the enzymatic hydroxylation of HIF-1α peptide in a concentration-dependent manner, and the apparent IC50 values were 29.5, 16.0, 12.8 and 60.4 μM respectively. Double reciprocal (1/V versus 1/[HIF-1α peptide]) plots showed that these compounds are noncompetitive inhibitors of the hydroxylation by recombinant human PHD3 with Ki values of 67.0, 25.3, 67.3, and 82.1 μM respectively. On the other hand, the metal complexes of these polynitrogen compounds (1–4) cannot inhibit the catalytical activity of PHD3. We hypothesized that the inhibitory mechanism of PHD3 activity by polynitrogen compounds is due to their binding to iron to form stable coordination complexes. Our results in this study indicated that polynitrogen compounds (1–4) could be potential inhibitors of PHD3 to regulate the transcriptional activity of HIF-1α.Polynitrogen compounds (1–4) modulate the activity of PHD3 (Fe2+-dependent redox enzyme) due to their binding to iron to form stable coordination complexes. PHD3 hydroxylates human HIF-1α at Pro-564, and the hydroxylated protein is subject to ubiquitination and proteasomal degradation. On the contrary, inhibitors of PHD3 can effectively stabilize HIF-1α and activate HIF mediated gene expression.

Template-free synthesis of single-crystalline SmF3 rattle-structured sub-micropumpkins

Co-reporter:Zhiming Chen, Zhirong Geng, Zhiyang Zhang, Zhihui Liu and Zhilin Wang

CrystEngComm 2010 vol. 12(Issue 10) pp:2841-2846

Publication Date(Web):06 May 2010

DOI:10.1039/B926254G

Single-crystalline SmF3 sub-micropumpkins with a rattle-type structure have been successfully synthesized on a large scale by reaction of aqueous Sm3+ with ammonium fluoride in the presence of ethylenediaminetetraacetic acid (EDTA) at 110 °C for 16 h, which were confirmed by X-ray powder diffraction, energy dispersive X-ray analysis, transmission electron microscopy, and scanning electron microscopy. The reaction time and EDTA have been shown to play important roles in the formation of SmF3 rattle-structured sub-microcrystals. A mechanism for the formation of the SmF3 rattle-structured sub-micropumpkins via cooperation of an oriented aggregation process and Ostwald ripening has been proposed based on observations of time-dependent experiments. In addition, this crystal growth mode could be expanded to the synthesized Eu-doped SmF3 rattle-structured sub-microcrystals. It is believed that the results of the present investigation may provide a versatile approach for designing and fabricating a wide range of nano/microcrystals.

Transition metal ions and selenite modulate the methylation of arsenite by the recombinant human arsenic (+3 oxidation state) methyltransferase (hAS3MT)

Co-reporter:Xiaoli Song, Zhirong Geng, Chengying Li, Xin Hu, Zhilin Wang

Journal of Inorganic Biochemistry 2010 Volume 104(Issue 5) pp:541-550

Publication Date(Web):May 2010

DOI:10.1016/j.jinorgbio.2010.01.005

This report demonstrates that transition metal ions and selenite affect the arsenite methylation by the recombinant human arsenic (+3 oxidation state) methyltransferase (hAS3MT) in vitro. Co2+, Mn2+, and Zn2+ inhibited the arsenite methylation by hAS3MT in a concentration-dependent manner and the kinetics indicated Co2+ and Mn2+ to be mixed (competitive and non-competitive) inhibitors while Zn2+ to be a competitive inhibitor. However, only a high concentration of Fe2+ could restrain the methylation. UV–visible, CD and fluorescence spectroscopy were used to study the interactions between the metal ions above and hAS3MT. Further studies showed that neither superoxide anion nor hydrogen peroxide was involved in the transition metal ion or selenite inhibition of hAS3MT activity. The inhibition of arsenite methylating activity of hAS3MT by selenite was reversed by 2 mM DTT (dithiothreitol) but neither by cysteine nor by β-mercaptoethanol. Whereas, besides DTT, cysteine can also prevent the inhibition of hAS3MT activity by Co2+, Mn2+, and Zn2+. Free Cys residues were involved in the interactions of transition metal ions or selenite with hAS3MT. It is proposed that the inhibitory effect of the ions (Co2+, Mn2+, and Zn2+) or selenite on hAS3MT activity might be via the interactions of them with free Cys residues in hAS3MT to form inactive protein adducts.Transition metal ions (Co2+, Mn2+ and Zn2+) and selenite modulate the structure and activity of hAS3MT through their interactions with the enzyme. Co2+ and Mn2+ are mixed (competitive and non-competitive) inhibitors of iAs3+ methylation by hAS3MT while Zn2+ is a competitive inhibitor. However, SeO32- might bind to the non-active sites of the enzyme as a non-competitive inhibitor of iAs3+ methylation by hAS3MT.

Preparation and Recognition Properties of Bovine Hemoglobin Magnetic Molecularly Imprinted Polymers

Co-reporter:Xianwen Kan, Qun Zhao, Dalin Shao, Zhirong Geng, Zhilin Wang and Jun-Jie Zhu

The Journal of Physical Chemistry B 2010 Volume 114(Issue 11) pp:3999-4004

Publication Date(Web):February 25, 2010

DOI:10.1021/jp910060c

A simple method for the preparation of core−shell micro/nanostructured magnetic molecularly imprinted polymers (MIPs) for protein recognition is described. Magnetic MIPs were synthesized by copolymering γ-aminopropyltrimethoxysilane and tetraethyl orthosilicate at the surface of Fe3O4 nanospheres, which were directly covalently bound with template molecule, bovine hemoglobin (BHb), through imine bond. Transmission electron microscopy and scanning electron microscopy images showed that the Fe3O4 nanospheres with diameter about 50−150 nm were coated with the MIPs layer with average thickness about 10 nm, which enabled the magnetic MIPs to have a sensitive and fast magnetic response. The proximity between the thickness of MIPs layer and the spatial size of BHb indicated that the imprinted sites almost situated at the surface of magnetic MIPs, leading a rapid adsorption saturation within 1 h. And the adsorption amounts of magnetic MIPs toward BHb were estimated to be 10.52 mg/g at pH 6.5, which was 4.6 times higher than that of magnetic nonmolecularly imprinted polymers. Meanwhile, the result of selective test showed that the magnetic MIPs had an excellent recognition capacity to BHb compared to the other nontemplate proteins. Except for the spatial size complementary between BHb and the binding sites in magnetic MIPs, the electrostatic interaction also was proven to be an important factor for recognizing the imprinting molecule.

Single-Crystalline EuF3 Hollow Hexagonal Microdisks: Synthesis and Application as a Background-Free Matrix for MALDI-TOF-MS Analysis of Small Molecules and Polyethylene Glycols

Co-reporter:Zhiming Chen, Zhirong Geng, Dalin Shao, Yuhua Mei and Zhilin Wang

Analytical Chemistry 2009 Volume 81(Issue 18) pp:7625

Publication Date(Web):August 14, 2009

DOI:10.1021/ac901010p

Single-crystalline EuF3 hexagonal microdisks with hollow interior were fabricated to serve as a background-free matrix for analysis of small molecules and polyethylene glycols (PEGs) by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The long-lived excited state of europium ions can transfer energy to high-energy vibrations of organic molecules, which provides the potential technological application in MALDI-TOF-MS analysis of small molecules and PEGs. The efficiency of the hollow microdisks as a novel matrix of low molecular weight compounds was verified by analysis of small peptide, amino acid, organic compounds, and hydroxypropyl β-cyclodextrin (HP-β-CD). The advantage of this matrix in comparison with α-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB) was demonstrated by MALDI-TOF-MS analysis of an amino acid mixture and a peptide mixture. This matrix is successfully used for analysis of PEGs (PEG 2000, PEG 4000, PEG 8000, PEG 15000, and PEG 30000), suggesting a potential for monitoring reactions and for synthetic polymer quality control. The upper limit of detectable mass range was ∼35 000 Da (PEG 30000). It is believed that this work will not only offer a new technique for high-speed analysis of small molecules and PEGs but also open a new field for applications of rare earth fluorides.

Construction of EuF3 hollow sub-microspheres and single-crystal hexagonal microdiscs viaOstwald ripening and oriented attachment

Co-reporter:Zhiming Chen, Zhirong Geng, Menglu Shi, Zhihui Liu and Zhilin Wang

CrystEngComm 2009 vol. 11(Issue 8) pp:1591-1596

Publication Date(Web):07 Apr 2009

DOI:10.1039/B902838B

Hexagonal phase EuF3 hollow sub-microspheres and single-crystal hexagonal microdiscs with controllable sizes were fabricated via a facile hydrothermal route at 110 °C for 8 and 14 h, respectively. Increasing the Eu(NO3)3 concentration (from 0.125 to 0.2 M) increased the size of the microdiscs, but decreased the diameter of the sub-microspheres. Detailed investigations on samples at different preparation stages revealed that the hollow sub-microspheres were formed via a self-transformation process within the same aggregated particles accompanied by the localized Ostwald ripening. Subsequently, hexagonal microdiscs were achieved at the consumption of the hollow sub-microspheres, which were attributed to oriented attachment mechanism. Moreover, the Ostwald ripening mechanism acted to form the secondary particles before the attachment. This kind of cooperation of two basic mechanisms may give us a new insight into the growth of EuF3 microcrystals and opens a new way for controllable synthesis of other well-defined crystals in morphology and dimensionality.

Effects of selenium on the structure and function of recombinant human S-adenosyl-l-methionine dependent arsenic (+3 oxidation state) methyltransferase in E. coli

Co-reporter:Zhirong Geng;Xiaoli Song;Zhi Xing

JBIC Journal of Biological Inorganic Chemistry 2009 Volume 14( Issue 4) pp:485-496

Publication Date(Web):2009 May

DOI:10.1007/s00775-008-0464-6

The effects of SeIV on the structure and function of recombinant human arsenic (+3 oxidation state) methyltransferase (AS3MT) purified from the cytoplasm of Escherichia coli were studied. The coding region of human AS3MT complementary DNA was amplified from total RNA extracted from HepG2 cell by reverse transcription PCR. Soluble and active human AS3MT was expressed in the E. coli with a Trx fusion tag under a lower induction temperature of 25 °C. Spectra (UV–vis, circular dichroism, and fluorescence) were first used to probe the interaction of SeIV and recombinant human AS3MT and the structure–function relationship of the enzyme. The recombinant human AS3MT had a secondary structure of 29.0% α-helix, 23.9% β-pleated sheet, 17.9% β-turn, and 29.2% random coil. When SeIV was added, the content of the α-helix did not change, but that of the β-pleated sheet increased remarkably in the conformation of recombinant human AS3MT. SeIV inhibited the enzymatic methylation of inorganic AsIII in a concentration-dependent manner. The IC50 value for SeIV was 2.38 μM. Double-reciprocal (1/V vs. 1/[inorganic AsIII]) plots showed SeIV to be a noncompetitive inhibitor of the methylation of inorganic AsIII by recombinant human AS3MT with a Ki value of 2.61 μM. We hypothesized that SeIV interacts with the sulfhydryl group of cysteine(s) in the structural residues rather than the cysteines of the active site (Cys156 and Cys206). When SeIV was combined with cysteine(s) in the structural residues, the conformation of recombinant human AS3MT changed and the enzymatic activity decreased. Considering the quenching of tryptophan fluorescence, Cys72 and/or Cys226 are deduced to be primary targets for SeIV.

Molecularly imprinted polymers microsphere prepared by precipitation polymerization for hydroquinone recognition

Co-reporter:Xianwen Kan, Qun Zhao, Zhong Zhang, Zhilin Wang, Jun-Jie Zhu

Talanta 2008 Volume 75(Issue 1) pp:22-26

Publication Date(Web):15 March 2008

DOI:10.1016/j.talanta.2007.08.038

A one-step precipitation polymerization synthesis was adopted for the preparation of molecularly imprinted polymers (MIPs) by using hydroquinone as a template molecule. The transmission electron microscopy (TEM) exhibited that the polymers were uniform spheres with the diameter of about 700 nm. The results of adsorption experiments showed that the microspherical imprinted polymers possessed fast adsorption dynamics. Compared to the structurally similar compounds, catechol and resorcinol, the MIPs exhibited a high recognizable capacity to hydroquinone. And the electrochemical sensor fabricated by modifying the prepared MIPs microsphere on the glassy carbon electrode surface was used to detect the hydroquinone concentration. The current response was proportional to the concentration of hydroquinone in the range of 2.0 × 10−6 to 1.0 × 10−4 mol/L with the detection limit of 1.0 × 10−6 mol/L.

Selective oxidation of sulfide catalysed by Cu complex of a triazamacrocyclic ligand with carbamoyl pendant arms

Co-reporter:Rui Liu, Li-zhen Wu, Xi-mei Feng, Zhong Zhang, Yi-zhi Li, Zhi-lin Wang

Inorganica Chimica Acta 2007 Volume 360(Issue 2) pp:656-662

Publication Date(Web):1 February 2007

DOI:10.1016/j.ica.2006.08.008

Copper(II) complex with a new ligand 1,4,7-tris(carbamoylethyl)-1,4,7-triazacyclononane (L) has been synthesized and characterized by elemental analysis, FT-IR, ES-MS, UV–Vis and cyclic voltammetry. Determined by X-ray analysis, the crystal structure shows the metal center is six-coordinated. The compound can catalyze the oxygenation of ethyl phenyl sulfide (EPS) utilizing H2O2 under ambient conditions. EPS was converted to the corresponding sulfoxide and sulfone step by step which was confirmed by 1H NMR spectra. The existence of sulfoxide and sulfone was identified by GC–MS. The gradually disappearance of EPS’s ultraviolet absorption at 290 nm was significantly correlated with the rates of sulfide consumption. The initial reaction rate during the first 3 h is consistent with the first-order law in substrate concentration. The averaged pseudo-first-order rate constant is calculated to be (2.25 ± 0.42) × 10−3 min−1 at 25 °C and (4.44 ± 0.17) × 10−3 min−1 at 30 °C. The oxidation product is almost sulfoxide by choosing the molar concentrations of Cu complex (2% of substrate) and H2O2 (seven times as much as substrate).Copper(II) complex with a new ligand 1,4,7-tris(carbamoylethyl)-1,4,7-triazacyclononane (L) crystallizes in the space group P21/c. This six-coordinated complex can catalyze the oxygenation of ethyl phenyl sulfide (EPS) utilizing H2O2 under ambient conditions. Dislike the reaction product (almost sulfone) using Mn–Me3TACN catalyst as once reported, the oxidation product is almost sulfoxide by choosing appropriate concentration of Cu complex and hydroperoxide.

Complexes of N,N′,N′′-tris(2-hydroxypropyl)-1,4,7-triazacyclononane (L): Structures of [CuL](ClO4)(NO3), [CoL](ClO4)2, [ZnL](ClO4)2 and the catalytic activity of [MnL](ClO4)2 towards olefin epoxidation with hydrogen peroxide

Co-reporter:Xi-Mei Feng;Zhong Zhang;Yi-Zhi Li;Ning-Sheng Bian

Transition Metal Chemistry 2007 Volume 32( Issue 1) pp:95-101

Publication Date(Web):2007/02/01

DOI:10.1007/s11243-006-0137-7

Complexes of N,N′,N′′-tris(2-hydroxypropyl)-1,4,7-triazacyclononane (L), [CuL](ClO4)(NO3) (1), [CoL](ClO4)2(2), [ZnL](ClO4)2(3) and [MnL](ClO4)2(4), have been synthesized and characterized on the basis of elemental analysis, electrospray ionization mass spectrometry, UV–Vis measurements and cyclic voltammetry. Crystal structures of the former three complexes, characterized by X-ray crystallography, show that these complexes are monoclinic with space group P21/n and P21/c. Each metal central in the complexes is six-coordinate with three N atoms of the macrocycle and three O atoms from the pendant hydroxypropyl arms, forming a distorted octahedral configuration. [MnL](ClO4)2(4) is employed as catalyst in olefin epoxidation with H2O2. The final results indicate that complex (4) has good catalytic activity towards olefin epoxidation. Under mild conditions, the olefin conversion is moderate and epoxidation selectivity is 95–100%.

A novel 1D coordination polymer based on rhombus [Cu4O4] building block: Synthesis, crystal structure and magnetic properties

Co-reporter:Jun Chen, Tian-Wei Wang, Zhong Zhang, You Song, Qun Zhao, Jun Ni, Zhi-Lin Wang

Journal of Molecular Structure 2006 Volume 794(1–3) pp:154-159

Publication Date(Web):7 August 2006

DOI:10.1016/j.molstruc.2006.01.047

A novel 1D polymer [Cu3(μ3-OH)2(μ2–H2O)2(H2O)2(Agly)2]·(ClO4)2 was synthesized through the self-assembly of Cu2+ and acetylglycine (Agly) in aqueous solution and characterized by X-ray structure analysis. The compound crystallizes in the monoclinic P2(1)/c space group (a=5.4762(1) Å, b=15.6136(1) Å, c=13.9036(5) Å, β=98.584(1)°, Z=2) and represents the first 1D coordination polymer with tetranuclear rhombus-like [Cu4O4] unit as building block. It should be noted that the rhombus are sharing two vertices and the structure can also be viewed as a zigzag chain based on [Cu3] building blocks. Agly ligand adopts η2-coordinated mode and is used to connect two copper ions. With the help of hydrogen bonds, the 1D chains are further linked into ‘∞’ like channels in which counter-anions ClO4− are located. The magnetic susceptibility measurements (1.8–300 K) agree with a moderately strong antiferromagnetic interaction between the Cu centers with a J value of −40(2) cm−1.

Crystallographic report: Bis(acetato-O,O′){4-[N,N-bis(2-cyanoethyl)amino] pyridine}bis(methanol)cadmium(II), [Cd(C11H12N4) (CH3CO2)2(CH3OH)2]

Co-reporter:Jun Ni;Yi-Zhi Li;Zhong Zhang;Hui-Lan Chen

Applied Organometallic Chemistry 2005 Volume 19(Issue 1) pp:

Publication Date(Web):6 JAN 2005

DOI:10.1002/aoc.673

The cadmium atom is coordinated in distorted pentagonal bipyramidal geometry by the pyridine-nitrogen atom of the 4-[N,N-bis(2-cyanoethyl)amino]pyridine ligand, two oxygen atoms of two methanol molecules and four oxygen atoms of two acetate groups. Copyright © 2005 John Wiley & Sons, Ltd.

Crystallographic report: Bis{4-[N,N-bis(2-cyanoethyl)amino]pyridine} dichlorozinc(II)

Co-reporter:Jun Ni;Wei Xu;Zheng Xue;Yi-Zhi Li;Hui-Lan Chen

Applied Organometallic Chemistry 2004 Volume 18(Issue 9) pp:

Publication Date(Web):19 AUG 2004

DOI:10.1002/aoc.644

In (C₁₁H₁₂N₄)₂ZnCl₂, the zinc(II) center is coordinated by the pyridine nitrogen atoms of two 4-[N,N-bis(2-cyanoethyl)amino]pyridine ligands and two chlorine atoms in a tetrahedral geometry. Copyright © 2004 John Wiley & Sons, Ltd.

Inhibitory mechanism of dimercaptopropanesulfonic acid (DMPS) in the cellular biomethylation of arsenic

Co-reporter:Shuping Wang, Nan Shi, Zhirong Geng, Xiangli Li, Xin Hu, Zhilin Wang

Biochimie (November 2014) Volume 106() pp:167-174

Publication Date(Web):November 2014

DOI:10.1016/j.biochi.2014.08.017

Mutational analysis of residues in human arsenic (III) methyltransferase (hAS3MT) belonging to 5 Å around S-adenosylmethionine (SAM)

Co-reporter:Xiangli Li, Zhirong Geng, Jiayin Chang, Xiaoli Song, Zhilin Wang

Biochimie (December 2014) Volume 107(Part B) pp:396-405

Publication Date(Web):December 2014

DOI:10.1016/j.biochi.2014.10.014

Functional evaluation of Asp76, 84, 102 and 150 in human arsenic(III) methyltransferase (hAS3MT) interacting with S-adenosylmethionine

Co-reporter:Xiangli Li, Zhirong Geng, Shuping Wang, Xiaoli Song, ... Zhilin Wang

FEBS Letters (11 July 2013) Volume 587(Issue 14) pp:2232-2240

Publication Date(Web):11 July 2013

DOI:10.1016/j.febslet.2013.05.052

•hAS3MT mutants D76P, D76N, D84P, D84N, D102P, D102N, D150P and D150N were designed.•All mutants except for D150N were inactive.•Asp76, 84, 102 and 150 of hAS3MT greatly affected hAS3MT catalytic activity.•Asp102 plays a dominant role in SAM-binding via forming hydrogen bonds with SAM.We prepared eight mutants (D76P, D76N, D84P, D84N, D102P, D102N, D150P and D150N) to investigate the functions of residues Asp76, 84, 102 and 150 in human arsenic(III) methyltransferase (hAS3MT) interacting with the S-adenosylmethionine (SAM)-binding. The affinity of all the mutants for SAM were weakened. All the mutants except for D150N completely lost their methylation activities. Residues Asp76, 84, 102 and 150 greatly influenced hAS3MT catalytic activity via affecting SAM-binding or methyl transfer. Asp76 and 84 were located in the SAM-binding pocket, and Asp102 significantly affected SAM-binding via forming hydrogen bonds with SAM.

An NBD-armed tetraaza macrocyclic lysosomal-targeted fluorescent probe for imaging copper(II) ions

Co-reporter:Xiaobo Wang, Xiaoyan Ma, Zhen Yang, Zhong Zhang, Jinghan Wen, Zhirong Geng and Zhilin Wang

Chemical Communications 2013 - vol. 49(Issue 96) pp:NaN11265-11265

Publication Date(Web):2013/10/08

DOI:10.1039/C3CC46585C

An NBD-armed tetraaza macrocyclic lysosomal-targeted fluorescent probe for detecting Cu2+ was synthesized and used for fluorescence imaging in HeLa cells. The probe was specifically localized in lysosomes and successfully applied to visualize Cu2+ as well as to monitor Cu2+ level changes in the lysosomes of living cells.

A Zn2+-specific turn-on fluorescent probe for ratiometric sensing of pyrophosphate in both water and blood serum

Co-reporter:Jinghan Wen, Zhirong Geng, Yuxin Yin, Zhong Zhang and Zhilin Wang

Dalton Transactions 2011 - vol. 40(Issue 9) pp:NaN1989-1989

Publication Date(Web):2010/12/17

DOI:10.1039/C0DT01262A

A novel fluorescent sensor composed of a naphthalene functionalized tetraazamacrocycle ligand 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3-methyl naphthalene (1) and Zn2+ has been designed and prepared, which can be utilized for selective and ratiometric sensing of pyrophosphate (PPi) over other phosphate-containing anions in aqueous solution at physiological pH. Notably, the water soluble 1 itself also exhibits a selective enhanced fluorescent response to Zn2+, and the complex 1-Zn2+ thus formed eventually fulfils the synergic Zn2+ coordination-altered strategy with PPi. Furthermore, the ratiometric sensing of 1-Zn2+ towards PPi performed well even in blood serum milieu. Finally, the sensor 1-Zn2+ was successfully employed to monitor a real-time assay of inorganic pyrophosphatase (PPase) by means of ratiometric fluorescent measurements for the first time.

Evidence for inhibition of HIF-1α prolyl hydroxylase 3 activity by four biologically active tetraazamacrocycles

Co-reporter:Jing Cao, Zhirong Geng, Xiaoyan Ma, Jinghan Wen, Yuxin Yin and Zhilin Wang

Organic & Biomolecular Chemistry 2012 - vol. 10(Issue 19) pp:NaN3923-3923

Publication Date(Web):2012/03/12

DOI:10.1039/C2OB07076F

Hypoxia inducible factor 1 (HIF-1) is central to the hypoxic response in mammals. HIF-1α prolyl hydroxylase 3 (PHD3) degrades HIF through the hydroxylation of HIF-1α. Inhibition of PHD3 activity is crucial for up-regulating HIF-1α levels, thereby acting as HIF-dependent diseases therapy. Macrocyclic polyamines which display high stability on iron-chelating may well inhibit the enzyme activity. Thus inhibition and interaction on catalytic PHD3 by four biologically active tetraazamacrocycles (1–4), which have two types of parent rings to chelate iron(II) dissimilarly, were studied. The apparent IC50 values of 2.56, 1.91, 5.29 and 2.44 μM, respectively, showed good inhibition potency of the four compounds. KI values were 7.86, 3.69, 1.59 and 2.92 μM for 1–4, respectively. Different inhibition actions of the two groups of compounds were identified. Circular dichroism (CD) and fluorescence spectrometries proved that one type of compound has significant effects on protein conformation while another type does not. Computational methodology was constructed to employ the equilibrium geometry of enzyme active site with the presence of substrate competitive inhibitor. Iron(II) coordination in the active site by inhibitors of this kind induces conformational change of the enzyme and blocks substrate binding.

A versatile water soluble fluorescent probe for ratiometric sensing of Hg2+ and bovine serum albumin

Co-reporter:Jinghan Wen, Zhirong Geng, Yuxin Yin and Zhilin Wang

Dalton Transactions 2011 - vol. 40(Issue 38) pp:NaN9745-9745

Publication Date(Web):2011/08/22

DOI:10.1039/C1DT10362H

A novel tetraazamacrocycle fluorescent sensor (6-(1-(dimethylamino)-5-naphthalene sulfonyl)-3,6,9,15-tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene, 1) has been designed and prepared, which can be utilized for selective and ratiometric sensing of Hg2+ and bovine serum albumin (BSA) with two different responsive modes in aqueous solution at physiological pH (50 mM Tris-HCl, pH 7.6). Above 0.5 ppb Hg2+ can be discerned by coordination with 1 and the emission color changes enable 1 to be applied to a fast Hg2+ test paper assay. Sensor 1 has also been demonstrated to be easily cell-penetrable and applicable for Hg2+ imaging in living cells. Imaging of BSA in the gel using SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) stained in the medium containing 1 verified that the binding of 1 and BSA was successful in the presence of nonprotein substances. The linear range of 1 towards BSA utilizing ratiometric fluorescent calibration via noncovalent interaction in solution is 0–100 μg mL−1 with a detection limit of 1 μg mL−1, and has been successfully employed to determine the albumin concentration in blood serum by means of ratiometric fluorescent measurements for the first time. Finally, sensor 1 behaves as a fluorescent molecular switch composed of triple logic gates upon chemical inputs of Hg2+ and BSA, which potentially provides intelligent diagnostics for Hg2+ contaminated serum on the nanoscale.

A potent antitumor Zn2+ tetraazamacrocycle complex targeting DNA: the fluorescent recognition, interaction and apoptosis studies

Co-reporter:Jing-Han Wen, Cheng-Ying Li, Zhi-Rong Geng, Xiao-Yan Ma and Zhi-Lin Wang

Chemical Communications 2011 - vol. 47(Issue 40) pp:NaN11332-11332

Publication Date(Web):2011/09/13

DOI:10.1039/C1CC14107D

A Zn2+ tetraazamacrocycle complex (2) bearing three naphthalene moieties has been prepared. Complex 2 recognizes, binds and causes damage to DNA, and shows considerable cytotoxicity against human cervical (HeLa), breast (MCF-7) and lung (NCI-H157) cancer cell lines with a different apoptotic pathway from that of cisplatin.