Co-reporter:Jacob J. Day, Deshka L. Neill, Shi Xu, and Ming Xian
Organic Letters July 21, 2017 Volume 19(Issue 14) pp:3819-3819
Publication Date(Web):July 3, 2017
DOI:10.1021/acs.orglett.7b01693
Sulfinic acids are commonly encountered intermediates found in natural product synthesis and medicinal chemistry. However, because of high reactivity, instability, and harsh reaction conditions, they are difficult to synthesize. Herein we have developed an oxidation-free method to produce sulfinic acids and sulfinate salts using 2-sulfinyl benzothiazole (BTS). We have also demonstrated the synthetic usefulness by developing one-pot syntheses of sulfones and sulfonamides.
Co-reporter:Yu Zhao, Hua Wang, and Ming Xian
Journal of the American Chemical Society January 12, 2011 Volume 133(Issue 1) pp:15-17
Publication Date(Web):December 10, 2010
DOI:10.1021/ja1085723
H2S, the newly discovered gasotransmitter, plays important roles in biological systems. However, the research on H2S has been hindered by the lack of controllable H2S donors that could mimic the slow and continuous H2S generation process in vivo. Herein we report a series of cysteine-activated H2S donors. Structural modifications of these molecules can regulate the rates of H2S generation. These compounds can be useful tools in H2S research.
Co-reporter:Dr. Wei Chen;Shi Xu;Jacob J. Day;Dr. Difei Wang; Dr. Ming Xian
Angewandte Chemie 2017 Volume 129(Issue 52) pp:16838-16842
Publication Date(Web):2017/12/22
DOI:10.1002/ange.201710688
AbstractNear-infrared (NIR) fluorescent dyes with favorable photophysical properties are highly useful for bioimaging, but such dyes are still rare. The development of a unique class of NIR dyes via modifying the rhodol scaffold with fused tetrahydroquinoxaline rings is described. These new dyes showed large Stokes shifts (>110 nm). Among them, WR3, WR4, WR5, and WR6 displayed high fluorescence quantum yields and excellent photostability in aqueous solutions. Moreover, their fluorescence properties were tunable by easy modifications on the phenolic hydroxy group. Based on WR6, two NIR fluorescent turn-on probes, WSP-NIR and SeSP-NIR, were devised for the detection of H2S. The probe SeSP-NIR was applied in visualizing intracellular H2S. These dyes are expected to be useful fluorophore scaffolds in the development of new NIR probes for bioimaging.
Co-reporter:Dr. Wei Chen;Shi Xu;Jacob J. Day;Dr. Difei Wang; Dr. Ming Xian
Angewandte Chemie International Edition 2017 Volume 56(Issue 52) pp:16611-16615
Publication Date(Web):2017/12/22
DOI:10.1002/anie.201710688
AbstractNear-infrared (NIR) fluorescent dyes with favorable photophysical properties are highly useful for bioimaging, but such dyes are still rare. The development of a unique class of NIR dyes via modifying the rhodol scaffold with fused tetrahydroquinoxaline rings is described. These new dyes showed large Stokes shifts (>110 nm). Among them, WR3, WR4, WR5, and WR6 displayed high fluorescence quantum yields and excellent photostability in aqueous solutions. Moreover, their fluorescence properties were tunable by easy modifications on the phenolic hydroxy group. Based on WR6, two NIR fluorescent turn-on probes, WSP-NIR and SeSP-NIR, were devised for the detection of H2S. The probe SeSP-NIR was applied in visualizing intracellular H2S. These dyes are expected to be useful fluorophore scaffolds in the development of new NIR probes for bioimaging.
Co-reporter:Caihong Zhang;Tyler D. Biggs;Nelmi O. Devarie-Baez;Shaomin Shuang;Chuan Dong
Chemical Communications 2017 vol. 53(Issue 82) pp:11266-11277
Publication Date(Web):2017/10/12
DOI:10.1039/C7CC06574D
The formation of S-nitrosothiols (SNO) in protein cysteine residues is an important post-translational modification elicited by nitric oxide (NO). This process is involved in virtually every class of cell signaling and has attracted considerable attention in redox biology. On the other hand, their unique structural characters make SNO potentially useful synthons. In this review, we summarized the fundamental chemical/physical properties of SNO. We also highlighted the reported chemical reactions of SNO, including the reactions with phosphine reagents, sulfinic acids, various nucleophiles, SNO-mediated radical additions, and the reactions of acyl SNO species.
Co-reporter:Jianming Kang; Zhen Li; Chelsea L. Organ; Chung-Min Park; Chun-tao Yang; Armando Pacheco; Difei Wang; David J. Lefer
Journal of the American Chemical Society 2016 Volume 138(Issue 20) pp:6336-6339
Publication Date(Web):May 12, 2016
DOI:10.1021/jacs.6b01373
Hydrogen sulfide (H2S) is a critical signaling molecule that regulates many physiological and/or pathological processes. Modulation of H2S levels could have potential therapeutic value. In this work, we report the rational design, synthesis, and biological evaluation of a class of phosphonamidothioate-based H2S-releasing agents (i.e., H2S donors). A novel pH-dependent intramolecular cyclization was employed to promote H2S release from the donors. These water-soluble compounds showed slow, controllable, and pH-sensitive production of H2S in aqueous solutions. The donors also showed significant cytoprotective effects in cellular models of oxidative damage. Most importantly, the donors were found to exhibit potent cardioprotective effects in an in vivo murine model of myocardial ischemia-reperfusion (MI/R) injury through a H2S-related mechanism.
Co-reporter:Chung-Min Park, Brett A. Johnson, Jicheng Duan, Jeong-Jin Park, Jacob J. Day, David Gang, Wei-Jun Qian, and Ming Xian
Organic Letters 2016 Volume 18(Issue 5) pp:904-907
Publication Date(Web):February 12, 2016
DOI:10.1021/acs.orglett.5b03557
The development of a functional disulfide, FmSSPy-A (Fm = 9-fluorenylmethyl; Py = pyridinyl), is reported. It can effectively convert small molecule and protein thiols (−SH) to form −S-SFm adducts under mild conditions. This method allows for a H2S-free and biomimetic protocol to generate highly reactive persulfides (in their anionic forms). The high nucleophilicity of persulfides toward a number of thiol-blocking reagents is also demonstrated. The method holds promise for further understanding the chemical biology of persulfides and S-sulfhydration.
Co-reporter:Jiang Wu, Yi Li, Chaochao He, Jianming Kang, Jingjing Ye, Zecong Xiao, Jingjing Zhu, Anqi Chen, Sheng Feng, Xiaokun Li, Jian Xiao, Ming Xian, and Qian Wang
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 41) pp:27474
Publication Date(Web):August 9, 2016
DOI:10.1021/acsami.6b06466
Hydrogen sulfide (H2S), together with nitric oxide and carbon monoxide, has been recognized as an important gasotransmitter. It plays an essential physiological role in regulating cyto-protective signal process, and H2S-based therapy is considered as the next generation of promising therapeutic strategies for many biomedical applications, such as the treatment of cardiovascular disease. Through electrospinning of polycaprolactone (PCL) containing JK1, a novel pH-controllable H2S donor, nanofibers with H2S releasing function, PCL-JK1, are fabricated. This fibrous scaffold showed a pH-dependent H2S releasing behavior, i.e., lower pH induced greater and faster H2S release. In addition, the H2S release of JK1 was prolonged by the fibrous matrix as shown by decreased releasing rates compared to JK1 in solutions. In addition, in vitro studies indicated that PCL-JK1 exhibited excellent cyto-compatibility, similar to PCL fibers. Finally, we investigated PCL-JK1 as a wound dressing toward a cutaneous wound model in vivo and found that PCL-JK1 could significantly enhance the wound repair and regeneration compared with the control PCL scaffold, likely due to the release of H2S, which results in a broad range of physiologically protective functions toward the wound.Keywords: controlled release; electrospinning; fibrous materials; hydrogen sulfide; polycaprolactone; wound healing
Co-reporter:Jacob J. Day, Zhenhua Yang, Wei Chen, Armando Pacheco, and Ming Xian
ACS Chemical Biology 2016 Volume 11(Issue 6) pp:1647
Publication Date(Web):March 31, 2016
DOI:10.1021/acschembio.6b00106
Sulfur dioxide (SO2) has long been considered a toxic environmental pollutant and byproduct of industrial processing. Recently it has become evident that SO2 may also have regulatory functions in mammalian pulmonary systems. However, the study of these effects has proven to be challenging due to the difficulty in administering SO2 in a reliable manner. In this work, we report the discovery of a new pH-dependent and water-soluble SO2 donor, benzothiazole sulfinate (BTS). We have found BTS to have slow and sustained SO2 release at physiological pH. Additionally, we have explored its vasorelaxation properties as compared to the authentic SO2 gas solutions. The slow release of BTS should make it a useful tool for the study of endogenously generated SO2.
Co-reporter:Shi Xu, Chun-Tao Yang, Fu-Hui Meng, Armando Pacheco, Li Chen, Ming Xian
Bioorganic & Medicinal Chemistry Letters 2016 Volume 26(Issue 6) pp:1585-1588
Publication Date(Web):15 March 2016
DOI:10.1016/j.bmcl.2016.02.005
Ammonium tetrathiomolybdate (TTM) was found to be a slow hydrogen sulfide (H2S) releasing agent. Its H2S generation capability in aqueous solutions was confirmed by UV–vis and fluorescence assays. TTM also showed H2S-like cytoprotective effects in hydrogen peroxide (H2O2)-induced oxidative damage in HaCaT cells.
Co-reporter:Chung-Min Park, Tyler D Biggs and Ming Xian
The Journal of Antibiotics 2016 69(4) pp:313-318
Publication Date(Web):January 13, 2016
DOI:10.1038/ja.2015.144
S-Nitrosothiols (RSNOs) have many biological implications but are rarely used in organic synthesis. In this work we report the development of proline-based phosphoramidite substrates that can effectively convert RSNOs to proline-based sulfenamides through a reductive ligation process. A unique property of this method is that the phosphine oxide moiety on the ligation products can be readily removed under acidic conditions. In conjugation with the facile preparation of RSNOs from the corresponding thiols (RSHs), this method provides a new way to prepare proline-based sulfenamides from simple thiol starting materials.
Co-reporter:Dr. Wei Chen;Armo Pacheco;Yoko Takano;Jacob J. Day;Dr. Kenjiro Hanaoka;Dr. Ming Xian
Angewandte Chemie International Edition 2016 Volume 55( Issue 34) pp:9993-9996
Publication Date(Web):
DOI:10.1002/anie.201604892
Abstract
Hydrogen sulfide (H2S) and hydrogen polysulfides (H2Sn, n>1) are endogenous regulators of many physiological processes. In order to better understand the symbiotic relationship and cellular cross-talk between H2S and H2Sn, it is highly desirable to develop single fluorescent probes which enable dual-channel discrimination between H2S and H2Sn. Herein, we report the rational design, synthesis, and evaluation of the first dual-detection fluorescent probe DDP-1 that can visualize H2S and H2Sn with different fluorescence signals. The probe showed high selectivity and sensitivity to H2S and H2Sn in aqueous media and in cells.
Co-reporter:Dr. Wei Chen;Armo Pacheco;Yoko Takano;Jacob J. Day;Dr. Kenjiro Hanaoka;Dr. Ming Xian
Angewandte Chemie 2016 Volume 128( Issue 34) pp:10147-10150
Publication Date(Web):
DOI:10.1002/ange.201604892
Abstract
Hydrogen sulfide (H2S) and hydrogen polysulfides (H2Sn, n>1) are endogenous regulators of many physiological processes. In order to better understand the symbiotic relationship and cellular cross-talk between H2S and H2Sn, it is highly desirable to develop single fluorescent probes which enable dual-channel discrimination between H2S and H2Sn. Herein, we report the rational design, synthesis, and evaluation of the first dual-detection fluorescent probe DDP-1 that can visualize H2S and H2Sn with different fluorescence signals. The probe showed high selectivity and sensitivity to H2S and H2Sn in aqueous media and in cells.
Co-reporter:Vivian S. Lin, Wei Chen, Ming Xian and Christopher J. Chang
Chemical Society Reviews 2015 vol. 44(Issue 14) pp:4596-4618
Publication Date(Web):04 Dec 2014
DOI:10.1039/C4CS00298A
Hydrogen sulfide (H2S), a gaseous species produced by both bacteria and higher eukaryotic organisms, including mammalian vertebrates, has attracted attention in recent years for its contributions to human health and disease. H2S has been proposed as a cytoprotectant and gasotransmitter in many tissue types, including mediating vascular tone in blood vessels as well as neuromodulation in the brain. The molecular mechanisms dictating how H2S affects cellular signaling and other physiological events remain insufficiently understood. Furthermore, the involvement of H2S in metal-binding interactions and formation of related RSS such as sulfane sulfur may contribute to other distinct signaling pathways. Owing to its widespread biological roles and unique chemical properties, H2S is an appealing target for chemical biology approaches to elucidate its production, trafficking, and downstream function. In this context, reaction-based fluorescent probes offer a versatile set of screening tools to visualize H2S pools in living systems. Three main strategies used in molecular probe development for H2S detection include azide and nitro group reduction, nucleophilic attack, and CuS precipitation. Each of these approaches exploits the strong nucleophilicity and reducing potency of H2S to achieve selectivity over other biothiols. In addition, a variety of methods have been developed for the detection of other reactive sulfur species (RSS), including sulfite and bisulfite, as well as sulfane sulfur species and related modifications such as S-nitrosothiols. Access to this growing chemical toolbox of new molecular probes for H2S and related RSS sets the stage for applying these developing technologies to probe reactive sulfur biology in living systems.
Co-reporter:Wei Chen, Ethan W. Rosser, Di Zhang, Wen Shi, Yilin Li, Wen-Ji Dong, Huimin Ma, Dehong Hu, and Ming Xian
Organic Letters 2015 Volume 17(Issue 11) pp:2776-2779
Publication Date(Web):May 11, 2015
DOI:10.1021/acs.orglett.5b01194
A hydrogen polysulfide mediated aziridine ring-opening reaction was discovered. Based on this reaction, a novel H2Sn-specific chemosensor (AP) was developed. AP showed high sensitivity and selectivity for H2Sn. Notably, the fluorescent turn-on product (1) exhibited excellent two-photon photophysical properties, a large Stokes shift, and high solid state luminescent efficiency.
Co-reporter:Bo Peng, Caihong Zhang, Eizo Marutani, Armando Pacheco, Wei Chen, Fumito Ichinose, and Ming Xian
Organic Letters 2015 Volume 17(Issue 6) pp:1541-1544
Publication Date(Web):February 27, 2015
DOI:10.1021/acs.orglett.5b00431
Here we report a unique reaction between phenyl diselenide-ester substrates and H2S to form 1,2-benzothiaselenol-3-one. This reaction proceeded rapidly under mild conditions. Thiols could also react with the diselenide substrates. However, the resulted S–Se intermediate retained high reactivity toward H2S and eventually led to the same cyclized product 1,2-benzothiaselenol-3-one. Based on this reaction two fluorescent probes were developed and showed high selectivity and sensitivity for H2S. The presence of thiols was found not to interfere with the detection process.
Co-reporter:Yu Zhao; Chuntao Yang; Chelsea Organ; Zhen Li; Shashi Bhushan; Hiro Otsuka; Armando Pacheco; Jianming Kang; Hector C. Aguilar; David J. Lefer
Journal of Medicinal Chemistry 2015 Volume 58(Issue 18) pp:7501-7511
Publication Date(Web):August 28, 2015
DOI:10.1021/acs.jmedchem.5b01033
Hydrogen sulfide (H2S) is a signaling molecule which plays regulatory roles in many physiological and/or pathological processes. Therefore, regulation of H2S levels could have great potential therapeutic value. In this work, we report the design, synthesis, and evaluation of a class of N-mercapto (N-SH)-based H2S donors. Thirty-three donors were synthesized and tested. Our results indicated that controllable H2S release from these donors could be achieved upon structural modifications. Selected donors (NSHD-1, NSHD-2, and NSHD-6) were tested in cellular models of oxidative damage and showed significant cytoprotective effects. Moreover, NSHD-1 and NSHD-2 were also found to exhibit potent protective effects in a murine model of myocardial ischemia reperfusion (MI/R) injury.
Co-reporter:Sheng Feng, Yu Zhao, Ming Xian, Qian Wang
Acta Biomaterialia 2015 Volume 27() pp:205-213
Publication Date(Web):November 2015
DOI:10.1016/j.actbio.2015.09.010
Abstract
By electrospinning of polycaprolactone (PCL) solutions containing N-(benzoylthio)benzamide (NSHD1), a H2S donor, fibrous scaffolds with hydrogen sulfide (H2S) releasing capability (H2S-fibers) are fabricated. The resultant microfibers are capable of releasing H2S upon immersion in aqueous solution containing biological thiols under physiological conditions. The H2S release peaks of H2S-fibers appeared at 2–4 h, while the peak of donor alone showed at 45 min. H2S release half-lives of H2S-fibers were 10–20 times longer than that of donor alone. Furthermore, H2S-fibers can protect cells from H2O2 induced oxidative damage by significantly decreasing the production of intracellular reactive oxygen species (ROS). Finally, we investigated the H2S-fibers application as a wound dressing in vitro. Given that H2S has a broad range of physiological functions, H2S-fibers hold great potential for various biomedical applications.
Statement of significance
Hydrogen sulfide, as a gaseous messenger, plays a crucial role in many physiological and pathological conditions. Recent studies about functions of H2S suggests H2S-based therapy could be promising therapeutic strategy for many diseases, such as cardiovascular disease, arthritis, and inflammatory bowel disease. Although many H2S donors have been developed and applied for biomedical studies, most of H2S donors have the shortage that the H2S release is either too fast or uncontrollable, which poorly mimic the biological generation of H2S. By simply combining electrospinning technique with our designed biological thiols activated H2S donor, NSHD1, we fabricated H2S releasing microfibers (H2S-fibers). This H2S-fibers significantly prolonged the releasing time compared to H2S donor alone. By adjusting the electrospinning parameters, tunable releasing profiles can be achieved. Moreover, the H2S fibers can protect cardiac myoblasts H9c2 and fibroblast NIH 3T3 from oxidative damage and support their proliferation as cellular scaffolds. To our knowledge, this is the first report of electrospun fibers with H2S releasing capacity. We anticipate this H2S-releasing scaffold will have great potential for biomedical applications.
Co-reporter:Chung-Min Park, Laksiri Weerasinghe, Jacob J. Day, Jon M. Fukuto and Ming Xian
Molecular BioSystems 2015 vol. 11(Issue 7) pp:1775-1785
Publication Date(Web):07 May 2015
DOI:10.1039/C5MB00216H
Recent studies conducted in hydrogen sulfide (H2S) signaling have revealed potential importance of persulfides (RSSH) in redox biology. The inherent instability of RSSH makes these species difficult to study and sometimes controversial results are reported. In this review article we summarize known knowledge about both small molecule persulfides and protein persulfides. Their fundamental physical and chemical properties such as preparation/formation and reactivity are discussed. The biological implications of persulfides and their detection methods are also discussed.
Co-reporter:Tyler D. Biggs, Laksiri Weerasinghe, Chung-Min Park, Ming Xian
Tetrahedron Letters 2015 Volume 56(Issue 21) pp:2741-2743
Publication Date(Web):20 May 2015
DOI:10.1016/j.tetlet.2015.04.017
S-Nitrosothiols (SNO) and their biological implications as an important post-translational modification are under active investigation. In our work on bioorthogonal reactions of protein SNO we have uncovered the chemistry of this functionality that shows synthetic promise. Herein we report a phosphine-mediated reaction between SNO and aldehydes to form thioimines. A simple synthesis of benzoisothiazole based on this reaction is presented.
Co-reporter:Dr. Wei Chen;Ethan W. Rosser;Dr. Tetsuro Matsunaga;Armo Pacheco;Dr. Takaaki Akaike;Dr. Ming Xian
Angewandte Chemie International Edition 2015 Volume 54( Issue 47) pp:13961-13965
Publication Date(Web):
DOI:10.1002/anie.201506887
Abstract
Endogenous hydrogen polysulfides (H2Sn; n>1) have been recognized as important regulators in sulfur-related redox biology. H2Sn can activate tumor suppressors, ion channels, and transcription factors with higher potency than H2S. Although H2Sn are drawing increasing attention, their exact mechanisms of action are still poorly understood. A major hurdle in this field is the lack of reliable and convenient methods for H2Sn detection. Herein we report a H2Sn-mediated benzodithiolone formation under mild conditions. This method takes advantage of the unique dual reactivity of H2Sn as both a nucleophile and an electrophile. Based on this reaction, three fluorescent probes (PSP-1, PSP-2, and PSP-3) were synthesized and evaluated. Among the probes prepared, PSP-3 showed a desirable off/on fluorescence response to H2Sn and high specificity. The probe was successfully applied in visualizing intracellular H2Sn.
Co-reporter:Dr. Wei Chen;Ethan W. Rosser;Dr. Tetsuro Matsunaga;Armo Pacheco;Dr. Takaaki Akaike;Dr. Ming Xian
Angewandte Chemie 2015 Volume 127( Issue 47) pp:14167-14171
Publication Date(Web):
DOI:10.1002/ange.201506887
Abstract
Endogenous hydrogen polysulfides (H2Sn; n>1) have been recognized as important regulators in sulfur-related redox biology. H2Sn can activate tumor suppressors, ion channels, and transcription factors with higher potency than H2S. Although H2Sn are drawing increasing attention, their exact mechanisms of action are still poorly understood. A major hurdle in this field is the lack of reliable and convenient methods for H2Sn detection. Herein we report a H2Sn-mediated benzodithiolone formation under mild conditions. This method takes advantage of the unique dual reactivity of H2Sn as both a nucleophile and an electrophile. Based on this reaction, three fluorescent probes (PSP-1, PSP-2, and PSP-3) were synthesized and evaluated. Among the probes prepared, PSP-3 showed a desirable off/on fluorescence response to H2Sn and high specificity. The probe was successfully applied in visualizing intracellular H2Sn.
Co-reporter:Chunrong Liu ; Wei Chen ; Wen Shi ; Bo Peng ; Yu Zhao ; Huimin Ma
Journal of the American Chemical Society 2014 Volume 136(Issue 20) pp:7257-7260
Publication Date(Web):May 8, 2014
DOI:10.1021/ja502968x
Reactive sulfur species have received considerable attention due to their various biological functions. Among these molecules, hydrogen polysulfides (H2Sn, n > 1) are recently suggested to be the actual signaling molecules derived from hydrogen sulfide (H2S). Hydrogen polysulfides may also have their own biosynthetic pathways. The research on H2Sn is rapidly growing. However, the detection of H2Sn is still challenging. In this work we report a H2Sn-mediated benzodithiolone formation under mild conditions. Based on this reaction, specific fluorescent probes for H2Sn are prepared and evaluated. The probe DSP-3 shows good selectivity and sensitivity for H2Sn.
Co-reporter:Yu Zhao, Jianming Kang, Chung-Min Park, Powell E. Bagdon, Bo Peng, and Ming Xian
Organic Letters 2014 Volume 16(Issue 17) pp:4536-4539
Publication Date(Web):August 20, 2014
DOI:10.1021/ol502088m
A class of novel thiol-activated H2S donors has been developed on the basis of the gem-dithiol template. These donors release H2S in the presence of cysteine or GSH in aqueous solutions as well as in cellular environments.
Co-reporter:Di Zhang, Wei Chen, Zhengrui Miao, Yong Ye, Yufen Zhao, S. Bruce King and Ming Xian
Chemical Communications 2014 vol. 50(Issue 37) pp:4806-4809
Publication Date(Web):10 Mar 2014
DOI:10.1039/C4CC01288G
A reductive ligation based fluorescent probe (SNOP1) for the detection of S-nitrosothiols (SNO) was developed. The probe showed good selectivity and sensitivity for SNO.
Co-reporter:Yu Zhao, Tyler D. Biggs and Ming Xian
Chemical Communications 2014 vol. 50(Issue 80) pp:11788-11805
Publication Date(Web):04 Jul 2014
DOI:10.1039/C4CC00968A
Hydrogen sulfide (H2S) is a newly recognized signaling molecule with very potent cytoprotective actions. The fields of H2S physiology and pharmacology have been rapidly growing in recent years, but a number of fundamental issues must be addressed to advance our understanding of the biology and clinical potential of H2S in the future. Hydrogen sulfide releasing agents (also known as H2S donors) have been widely used in these fields. These compounds are not only useful research tools, but also potential therapeutic agents. It is therefore important to study the chemistry and pharmacology of exogenous H2S and to be aware of the limitations associated with the choice of donors used to generate H2S in vitro and in vivo. In this review we summarized the developments and limitations of currently available donors including H2S gas, sulfide salts, garlic-derived sulfur compounds, Lawesson's reagent/analogs, 1,2-dithiole-3-thiones, thiol-activated donors, photo-caged donors, and thioamino acids. Some biological applications of these donors were also discussed.
Co-reporter:Di Zhang, Wei Chen, Jianming Kang, Yong Ye, Yufen Zhao and Ming Xian
Organic & Biomolecular Chemistry 2014 vol. 12(Issue 35) pp:6837-6841
Publication Date(Web):08 Jul 2014
DOI:10.1039/C4OB01031K
Three sulfonyl benzothiazole-based fluorescent probes (RSHP1, RSHP2, and RSHP3) for the detection of biothiols (cysteine, homocysteine, and glutathione) are developed based on thiol-mediated nucleophilic aromatic substitutions. The probes exhibited good selectivity and sensitivity toward biothiols over other analytes. The probes were successfully applied for visualizing endogenous thiols in living cells.
Co-reporter:Bo Peng ; Ming Xian
Asian Journal of Organic Chemistry 2014 Volume 3( Issue 9) pp:
Publication Date(Web):
DOI:10.1002/ajoc.201490019
Co-reporter:Bo Peng ; Ming Xian
Asian Journal of Organic Chemistry 2014 Volume 3( Issue 9) pp:914-924
Publication Date(Web):
DOI:10.1002/ajoc.201402064
Abstract
Hydrogen sulfide (H2S) is an important signaling molecule with potent cytoprotective actions. Current results strongly suggest that modulation of H2S levels could have potential therapeutic values for a number of disease states, but its exact mechanisms of action are still unclear. A number of fundamental issues must be addressed to advance our understanding of the biology and clinical potential of H2S in the future. It is important, therefore, to understand the chemistry and properties of H2S and to appreciate the limitation and errors that may be generated when measuring H2S in biological samples. In the past several years a number of fluorescent probes for H2S detection have been developed. These probes are based on H2S-mediated reactions and are useful research tools. Herein, we provide an overview of current progress in this field. The development and properties of representative probes are discussed.
Co-reporter:Bo Peng;Dr. Wei Chen;Dr. Chunrong Liu;Ethan W. Rosser;Armo Pacheco;Yu Zhao; Hector C. Aguilar; Ming Xian
Chemistry - A European Journal 2014 Volume 20( Issue 4) pp:1010-1016
Publication Date(Web):
DOI:10.1002/chem.201303757
Abstract
The design, synthesis, properties, and cell imaging applications of a series of 2-pyridyl disulfide based fluorescent probes (WSP1, WSP2, WSP3, WSP4 and WSP5) for hydrogen sulfide detection are reported. The strategy is based on the dual-nucleophilicity of hydrogen sulfide. A hydrogen sulfide mediated tandem nucleophilic substitution-cyclization reaction is used to release the fluorophores and turn on the fluorescence. The probes showed high sensitivity and selectivity for hydrogen sulfide over other reactive sulfur species, including cysteine and glutathione.
Co-reporter:Dr. Dehui Zhang;Igor Macinkovic;Dr. Nelmi O. Devarie-Baez;Dr. Jia Pan;Dr. Chung-Min Park; Kate S. Carroll;Dr. Milos R. Filipovic; Ming Xian
Angewandte Chemie International Edition 2014 Volume 53( Issue 2) pp:575-581
Publication Date(Web):
DOI:10.1002/anie.201305876
Abstract
Protein S-sulfhydration (forming -S-SH adducts from cysteine residues) is a newly defined oxidative posttranslational modification and plays an important role in H2S-mediated signaling pathways. In this study we report the first selective, “tag-switch” method which can directly label protein S-sulfhydrated residues by forming stable thioether conjugates. Furthermore we demonstrate that H2S alone cannot lead to S-sulfhydration and that the two possible physiological mechanisms include reaction with protein sulfenic acids (P-SOH) or the involvement of metal centers which would facilitate the oxidation of H2S to HS..
Co-reporter:Wei Chen, Chunrong Liu, Bo Peng, Yu Zhao, Armando Pacheco and Ming Xian
Chemical Science 2013 vol. 4(Issue 7) pp:2892-2896
Publication Date(Web):09 May 2013
DOI:10.1039/C3SC50754H
A sulfane sulfur mediated benzodithiolone formation was developed. Based on this reaction, two fluorescent probes (SSP1 and SSP2) for the detection of sulfane sulfur species (persulfide, polysulfide, and elemental sulfur) were prepared and evaluated. The probes showed high selectivity and sensitivity to sulfane sulfurs. Moreover, SSP2 was successfully applied for bioimaging sulfane sulfurs in living cells.
Co-reporter:Nelmi O. Devarie-Baez, Powell E. Bagdon, Bo Peng, Yu Zhao, Chung-Min Park, and Ming Xian
Organic Letters 2013 Volume 15(Issue 11) pp:2786-2789
Publication Date(Web):May 22, 2013
DOI:10.1021/ol401118k
“Caged” gem-dithiol derivatives that release H2S upon light stimulation have been developed. This new class of H2S donors was proven, by various spectroscopic methods, to generate H2S in an aqueous/organic medium as well as in cell culture.
Co-reporter:Yu Zhao, Shashi Bhushan, Chuntao Yang, Hiroyuki Otsuka, Jason D. Stein, Armando Pacheco, Bo Peng, Nelmi O. Devarie-Baez, Hector C. Aguilar, David J. Lefer, and Ming Xian
ACS Chemical Biology 2013 Volume 8(Issue 6) pp:1283
Publication Date(Web):April 2, 2013
DOI:10.1021/cb400090d
Hydrogen sulfide (H2S), known as an important cellular signaling molecule, plays critical roles in many physiological and/or pathological processes. Modulation of H2S levels could have tremendous therapeutic value. However, the study on H2S has been hindered due to the lack of controllable H2S releasing agents that could mimic the slow and moderate H2S release in vivo. In this work we report the design, synthesis, and biological evaluation of a new class of controllable H2S donors. Twenty-five donors were prepared and tested. Their structures were based on a perthiol template, which was suggested to be involved in H2S biosynthesis. H2S release mechanism from these donors was studied and proved to be thiol-dependent. We also developed a series of cell-based assays to access their H2S-related activities. H9c2 cardiac myocytes were used in these experiments. We tested lead donors’ cytotoxicity and confirmed their H2S production in cells. Finally we demonstrated that selected donors showed potent protective effects in an in vivo murine model of myocardial ischemia-reperfusion injury, through a H2S-related mechanism.
Co-reporter:Chung-Min Park, Yu Zhao, Zhaohui Zhu, Armando Pacheco, Bo Peng, Nelmi O. Devarie-Baez, Powell Bagdon, Hui Zhang and Ming Xian
Molecular BioSystems 2013 vol. 9(Issue 10) pp:2430-2434
Publication Date(Web):05 Jul 2013
DOI:10.1039/C3MB70145J
A series of O-aryl- and alkyl-substituted phosphorodithioates were designed and synthesized as hydrogen sulfide (H2S) donors. H2S releasing capability of these compounds was evaluated using fluorescence methods. O-aryl substituted donors showed slow and sustained H2S release while O-alkylated compounds showed very weak H2S releasing capability. We also evaluated donors' protective effects against hydrogen peroxide (H2O2)-induced oxidative damage in myocytes and donors' toxicity toward B16BL6 mouse melanoma cells.
Co-reporter:Dehui Zhang, Nelmi O. Devarie-Baez, Qian Li, Jack R. Lancaster Jr., and Ming Xian
Organic Letters 2012 Volume 14(Issue 13) pp:3396-3399
Publication Date(Web):June 8, 2012
DOI:10.1021/ol301370s
A new thiol blocking reagent, methylsulfonyl benzothiazole, was discovered. This reagent showed good selectivity and high reactivity for protein thiols.
Co-reporter:Chunrong Liu, Bo Peng, Sheng Li, Chung-Min Park, A. Richard Whorton, and Ming Xian
Organic Letters 2012 Volume 14(Issue 8) pp:2184-2187
Publication Date(Web):April 9, 2012
DOI:10.1021/ol3008183
A reaction based fluorescence turn-on strategy for hydrogen sulfide (H2S) was developed. This strategy was based on a H2S-specific Michael addition–cyclization sequence. Other biological thiols such as cysteine and glutathione did not pursue the reaction and therefore did not turn on the fluorescence/consume the substrates. The probes showed good selectivity and sensitivity for hydrogen sulfide.
Co-reporter:Chung-Min Park, Wei Niu, Chunrong Liu, Tyler D. Biggs, Jiantao Guo, and Ming Xian
Organic Letters 2012 Volume 14(Issue 17) pp:4694-4697
Publication Date(Web):August 27, 2012
DOI:10.1021/ol3022484
A proline-based phosphine template enabling a rapid Staudinger ligation of azide-containing substrates under mild conditions is reported. This reaction has a second-order rate constant of 1.12 M–1 s–1. It is expected that the proline-based Staudinger ligation strategy will be a useful method for bioconjugation and proline based peptide coupling.
Co-reporter:Jia Pan and Ming Xian
Chemical Communications 2011 vol. 47(Issue 1) pp:352-354
Publication Date(Web):23 Aug 2010
DOI:10.1039/C0CC02076A
A phosphine-mediated one-step disulfide formation from S-nitrosothiols has been developed. This reaction can convert unstable S-nitrosothiols to stable disulfidesviasulfenamide intermediates under very mild conditions. It has the potential to be used for the detection ofS-nitrosothiols.
Co-reporter:Dr. Chunrong Liu;Jia Pan;Dr. Sheng Li;Yu Zhao;Lisa Y. Wu; Clifford E. Berkman; A. Richard Whorton; Ming Xian
Angewandte Chemie 2011 Volume 123( Issue 44) pp:10511-10513
Publication Date(Web):
DOI:10.1002/ange.201104305
Co-reporter:Dr. Chunrong Liu;Jia Pan;Dr. Sheng Li;Yu Zhao;Lisa Y. Wu; Clifford E. Berkman; A. Richard Whorton; Ming Xian
Angewandte Chemie International Edition 2011 Volume 50( Issue 44) pp:10327-10329
Publication Date(Web):
DOI:10.1002/anie.201104305
Co-reporter:Dehui Zhang, Nelmi O. Devarie-Baez, Jia Pan, Hua Wang, and Ming Xian
Organic Letters 2010 Volume 12(Issue 24) pp:5674-5676
Publication Date(Web):November 16, 2010
DOI:10.1021/ol102491n
Protein S-nitrosation is an important post-translational modification. However, the detection of S-nitrosation is still problematic because S-nitrosation products, that is, S-nitrosothiols, are unstable species. Here a new reaction which can selectively convert unstable S-nitrosothiols to stable thioethers in one-pot under very mild conditions is reported. This reaction has the potential to be applied in the detection of protein S-nitrosation.
Co-reporter:Jiming Zhang, Sheng Li, Dehui Zhang, Hua Wang, A. Richard Whorton, and Ming Xian
Organic Letters 2010 Volume 12(Issue 18) pp:4208-4211
Publication Date(Web):August 23, 2010
DOI:10.1021/ol101863s
A one-step reductive ligation mediated disulfide formation of S-nitrosothiols was developed. This reaction involves the reaction of the S-nitroso group with phosphine-thioesters to form sulfenamide and thiolate intermediates, which then undergo a fast intermolecular disulfide formation to form stable conjugates. This reaction can be used to design new biosensors of S-nitrosated proteins.
Co-reporter:Nelmi O. Devarie-Baez and Ming Xian
Organic Letters 2010 Volume 12(Issue 4) pp:752-754
Publication Date(Web):January 15, 2010
DOI:10.1021/ol9028447
A synthesis of 3-substituted benzisothiazoles starting from readily available o-mercaptoacylphenones is presented. The key cyclization step features a mild S-nitrosation and its succeeding intramolecular aza-Wittig reaction leading to the construction of the title compounds.
Co-reporter:Hua Wang ; Jiming Zhang
Journal of the American Chemical Society 2009 Volume 131(Issue 37) pp:13238-13239
Publication Date(Web):August 28, 2009
DOI:10.1021/ja905558w
A reductive elimination of S-nitrosocysteines using phosphine substrates has been developed. This reaction converts unstable S-nitrosocysteines to dehydroalanine derivatives under very mild conditions. It can potentially be applied for the detection of protein S-nitrosation.
Co-reporter:Nelmi O. Devarie-Baez, Won-Suk Kim, Amos B. Smith III. and Ming Xian
Organic Letters 2009 Volume 11(Issue 8) pp:1861-1864
Publication Date(Web):March 20, 2009
DOI:10.1021/ol900434k
Effective, one-pot syntheses of 2,3-disubstituted furans and thiophenes, exploiting 2-tert-butyldimethylsilyl-3-formylfuran and -thiophene as the respective bifunctional linchpins, have been developed. The synthetic protocol involves multicomponent type II Anion Relay Chemistry (ARC) mediated by a solvent-controlled C(sp2)→O 1,4-Brook rearrangement. Simple organolithiums and α-disubstituted ester enolates prove effective as the initiating nucleophiles.
Co-reporter:Jia Pan, Jonathan A. Downing, Jeanne L. McHale and Ming Xian
Molecular BioSystems 2009 vol. 5(Issue 9) pp:918-920
Publication Date(Web):23 Mar 2009
DOI:10.1039/B822283E
Here we describe a coumarin-phosphine dye that undergoes activation of coumarin fluorescence upon reaction with S-nitrosothiols.
Co-reporter:Honghua Wang, Bo Liu, Xiaoqing Liu, Jinwen Zhang and Ming Xian
Green Chemistry 2008 vol. 10(Issue 11) pp:1190-1196
Publication Date(Web):19 Sep 2008
DOI:10.1039/B803295E
Rosin is an abundantly available natural product. Rosin is a mixture of acidic (ca. 90%) and neutral (ca. 10%) compounds. The characteristic fused ring structure of rosin acids is analogous to that of some aromatic compounds in rigidity, and makes rosin and its derivatives potential substitutes for those aromatic compounds in polymers. In this study, the synthesis of biobased epoxy and curing agent using rosin and the cure reaction were investigated. Abietyl glycidyl ether and methyl maleopimarate were synthesized from one of the rosin acids. Abietyl glycidyl ether was used as a model compound representing rosin-based epoxies, while methyl maleopimarate was used as a model compound representing rosin-based anhydride curing agents. The synthesis methods of the model compounds were examined and the chemical structures were confirmed by 1H NMR, 13C NMR, FT-IR and ESI-MS. Curing of abietyl glycidyl ether with aniline and curing of methyl maleopimarate with phenyl glycidyl ether were investigated separately. Nonisothermal curing of the model systems was studied by DSC, and the cured products were characterized by 1H NMR.
Co-reporter:Hua Wang Dr. Dr.
Angewandte Chemie International Edition 2008 Volume 47( Issue 35) pp:6598-6601
Publication Date(Web):
DOI:10.1002/anie.200801654
Co-reporter:Hua Wang Dr. Dr.
Angewandte Chemie 2008 Volume 120( Issue 35) pp:6700-6703
Publication Date(Web):
DOI:10.1002/ange.200801654
Co-reporter:Sheng Feng, Yu Zhao, Ming Xian, Qian Wang
Acta Biomaterialia (November 2015) Volume 27() pp:205-213
Publication Date(Web):1 November 2015
DOI:10.1016/j.actbio.2015.09.010
By electrospinning of polycaprolactone (PCL) solutions containing N-(benzoylthio)benzamide (NSHD1), a H2S donor, fibrous scaffolds with hydrogen sulfide (H2S) releasing capability (H2S-fibers) are fabricated. The resultant microfibers are capable of releasing H2S upon immersion in aqueous solution containing biological thiols under physiological conditions. The H2S release peaks of H2S-fibers appeared at 2–4 h, while the peak of donor alone showed at 45 min. H2S release half-lives of H2S-fibers were 10–20 times longer than that of donor alone. Furthermore, H2S-fibers can protect cells from H2O2 induced oxidative damage by significantly decreasing the production of intracellular reactive oxygen species (ROS). Finally, we investigated the H2S-fibers application as a wound dressing in vitro. Given that H2S has a broad range of physiological functions, H2S-fibers hold great potential for various biomedical applications.Statement of significanceHydrogen sulfide, as a gaseous messenger, plays a crucial role in many physiological and pathological conditions. Recent studies about functions of H2S suggests H2S-based therapy could be promising therapeutic strategy for many diseases, such as cardiovascular disease, arthritis, and inflammatory bowel disease. Although many H2S donors have been developed and applied for biomedical studies, most of H2S donors have the shortage that the H2S release is either too fast or uncontrollable, which poorly mimic the biological generation of H2S. By simply combining electrospinning technique with our designed biological thiols activated H2S donor, NSHD1, we fabricated H2S releasing microfibers (H2S-fibers). This H2S-fibers significantly prolonged the releasing time compared to H2S donor alone. By adjusting the electrospinning parameters, tunable releasing profiles can be achieved. Moreover, the H2S fibers can protect cardiac myoblasts H9c2 and fibroblast NIH 3T3 from oxidative damage and support their proliferation as cellular scaffolds. To our knowledge, this is the first report of electrospun fibers with H2S releasing capacity. We anticipate this H2S-releasing scaffold will have great potential for biomedical applications.Download high-res image (149KB)Download full-size image
Co-reporter:Bo Peng, Chunrong Liu, Zhen Li, Jacob J. Day, Yun Lu, David J. Lefer, Ming Xian
Bioorganic & Medicinal Chemistry Letters (1 February 2017) Volume 27(Issue 3) pp:
Publication Date(Web):1 February 2017
DOI:10.1016/j.bmcl.2016.12.023
Here we report the model studies of the reactions between NADH models (using HEH and BNAH) and sulfane sulfurs (using polysulfides). Such reactions could lead to the oxidation of NADH models and the production of hydrogen sulfide (H2S). Kinetics of the reaction between BNAH and elemental sulfur S8 were determined in ethanol and the second-order rate constant was found to be 0.074 M−1 min−1 (at 37 °C) suggesting this is a slow process.
Co-reporter:Nelmi O. Devarie-Baez, Dehui Zhang, Sheng Li, A. Richard Whorton, Ming Xian
Methods (1 August 2013) Volume 62(Issue 2) pp:171-176
Publication Date(Web):1 August 2013
DOI:10.1016/j.ymeth.2013.04.018
•Recent developments of direct methods for protein SNO labeling are reviewed.•Detailed procedures for the preparation of the biotin-phosphine substrate are reported.•Detailed procedures of using the phosphine substrate to label protein SNO in cells are described.S-nitrosylation of protein cysteine residues is known to be an important mechanism for nitric oxide signaling. However, the detection of protein S-nitrosylation is still challenging due to technical limitations of current methods. This chapter provides a brief review on recent developments of methods, which directly target S-nitroso moieties for detection. We also describe in detail the protocol of an organophosphine-based biotin labeling of protein S-nitroso moieties.
Co-reporter:Yu Zhao ; Hua Wang
Journal of the American Chemical Society () pp:
Publication Date(Web):December 10, 2010
DOI:10.1021/ja1085723
H2S, the newly discovered gasotransmitter, plays important roles in biological systems. However, the research on H2S has been hindered by the lack of controllable H2S donors that could mimic the slow and continuous H2S generation process in vivo. Herein we report a series of cysteine-activated H2S donors. Structural modifications of these molecules can regulate the rates of H2S generation. These compounds can be useful tools in H2S research.
Co-reporter:Di Zhang, Wei Chen, Jianming Kang, Yong Ye, Yufen Zhao and Ming Xian
Organic & Biomolecular Chemistry 2014 - vol. 12(Issue 35) pp:NaN6841-6841
Publication Date(Web):2014/07/08
DOI:10.1039/C4OB01031K
Three sulfonyl benzothiazole-based fluorescent probes (RSHP1, RSHP2, and RSHP3) for the detection of biothiols (cysteine, homocysteine, and glutathione) are developed based on thiol-mediated nucleophilic aromatic substitutions. The probes exhibited good selectivity and sensitivity toward biothiols over other analytes. The probes were successfully applied for visualizing endogenous thiols in living cells.
Co-reporter:Yu Zhao, Tyler D. Biggs and Ming Xian
Chemical Communications 2014 - vol. 50(Issue 80) pp:NaN11805-11805
Publication Date(Web):2014/07/04
DOI:10.1039/C4CC00968A
Hydrogen sulfide (H2S) is a newly recognized signaling molecule with very potent cytoprotective actions. The fields of H2S physiology and pharmacology have been rapidly growing in recent years, but a number of fundamental issues must be addressed to advance our understanding of the biology and clinical potential of H2S in the future. Hydrogen sulfide releasing agents (also known as H2S donors) have been widely used in these fields. These compounds are not only useful research tools, but also potential therapeutic agents. It is therefore important to study the chemistry and pharmacology of exogenous H2S and to be aware of the limitations associated with the choice of donors used to generate H2S in vitro and in vivo. In this review we summarized the developments and limitations of currently available donors including H2S gas, sulfide salts, garlic-derived sulfur compounds, Lawesson's reagent/analogs, 1,2-dithiole-3-thiones, thiol-activated donors, photo-caged donors, and thioamino acids. Some biological applications of these donors were also discussed.
Co-reporter:Di Zhang, Wei Chen, Zhengrui Miao, Yong Ye, Yufen Zhao, S. Bruce King and Ming Xian
Chemical Communications 2014 - vol. 50(Issue 37) pp:NaN4809-4809
Publication Date(Web):2014/03/10
DOI:10.1039/C4CC01288G
A reductive ligation based fluorescent probe (SNOP1) for the detection of S-nitrosothiols (SNO) was developed. The probe showed good selectivity and sensitivity for SNO.
Co-reporter:Vivian S. Lin, Wei Chen, Ming Xian and Christopher J. Chang
Chemical Society Reviews 2015 - vol. 44(Issue 14) pp:NaN4618-4618
Publication Date(Web):2014/12/04
DOI:10.1039/C4CS00298A
Hydrogen sulfide (H2S), a gaseous species produced by both bacteria and higher eukaryotic organisms, including mammalian vertebrates, has attracted attention in recent years for its contributions to human health and disease. H2S has been proposed as a cytoprotectant and gasotransmitter in many tissue types, including mediating vascular tone in blood vessels as well as neuromodulation in the brain. The molecular mechanisms dictating how H2S affects cellular signaling and other physiological events remain insufficiently understood. Furthermore, the involvement of H2S in metal-binding interactions and formation of related RSS such as sulfane sulfur may contribute to other distinct signaling pathways. Owing to its widespread biological roles and unique chemical properties, H2S is an appealing target for chemical biology approaches to elucidate its production, trafficking, and downstream function. In this context, reaction-based fluorescent probes offer a versatile set of screening tools to visualize H2S pools in living systems. Three main strategies used in molecular probe development for H2S detection include azide and nitro group reduction, nucleophilic attack, and CuS precipitation. Each of these approaches exploits the strong nucleophilicity and reducing potency of H2S to achieve selectivity over other biothiols. In addition, a variety of methods have been developed for the detection of other reactive sulfur species (RSS), including sulfite and bisulfite, as well as sulfane sulfur species and related modifications such as S-nitrosothiols. Access to this growing chemical toolbox of new molecular probes for H2S and related RSS sets the stage for applying these developing technologies to probe reactive sulfur biology in living systems.
Co-reporter:Jia Pan and Ming Xian
Chemical Communications 2011 - vol. 47(Issue 1) pp:NaN354-354
Publication Date(Web):2010/08/23
DOI:10.1039/C0CC02076A
A phosphine-mediated one-step disulfide formation from S-nitrosothiols has been developed. This reaction can convert unstable S-nitrosothiols to stable disulfidesviasulfenamide intermediates under very mild conditions. It has the potential to be used for the detection ofS-nitrosothiols.
Co-reporter:Wei Chen, Chunrong Liu, Bo Peng, Yu Zhao, Armando Pacheco and Ming Xian
Chemical Science (2010-Present) 2013 - vol. 4(Issue 7) pp:NaN2896-2896
Publication Date(Web):2013/05/09
DOI:10.1039/C3SC50754H
A sulfane sulfur mediated benzodithiolone formation was developed. Based on this reaction, two fluorescent probes (SSP1 and SSP2) for the detection of sulfane sulfur species (persulfide, polysulfide, and elemental sulfur) were prepared and evaluated. The probes showed high selectivity and sensitivity to sulfane sulfurs. Moreover, SSP2 was successfully applied for bioimaging sulfane sulfurs in living cells.
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![methyl N-[(benzyloxy)carbonyl]glycylserinate](http://img.cochemist.com/ccimg/10300/10239-27-7.png)
![methyl N-[(benzyloxy)carbonyl]glycylserinate](http://img.cochemist.com/ccimg/10300/10239-27-7_b.png)
![1,1',1''-[(nitrososulfanyl)methanetriyl]tribenzene](http://img.cochemist.com/ccimg/6400/6316-86-5.png)
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