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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 王宗興 | zh_TW |
| dc.contributor.advisor | Tsung-Shing Wang | en |
| dc.contributor.author | 林子鉦 | zh_TW |
| dc.contributor.author | Zih-Jheng Lin | en |
| dc.date.accessioned | 2025-09-17T16:07:54Z | - |
| dc.date.available | 2025-09-18 | - |
| dc.date.copyright | 2025-09-17 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-08-11 | - |
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Forsleff, L.; Schauss, A. G.; Bier, I. D.; Stuart, S. Evidence of functional zinc deficiency in Parkinson's disease. J. Altern. Complement. Med. 1999, 5, 57-64. 7. Peters, K.; Staehlke, S.; Rebl, H.; Jonitz-Heincke, A.; Hahn, O. Impact of Metal Ions on Cellular Functions: A Focus on Mesenchymal Stem/Stromal Cell Differentiation. Int. J. Mol. Sci. 2024, 25(18), 10127. 8. Zhang, Y. Y.; Li, X. S.; Ren, K. D.; Peng, J.; Luo, X. J. (2023). Restoration of metal homeostasis: a potential strategy against neurodegenerative diseases. Ageing Res. Rev. 2023, 87, 101931. 9. Ciesienski, K. L.; Franz, K. J. Keys for unlocking photolabile metal-containing cages. Angew. Chem. Int. Ed. 2011, 50, 814-824. 10. Ellis-Davies, G. C. R. Useful Caged Compounds for Cell Physiology. Acc. Chem. Res. 2020, 53, 1593-1604. 11. Brieke, C.; Rohrbach, F.; Gottschalk, A.; Mayer, G.; Heckel, A. Light-controlled tools. Angew. Chem. Int. Ed. 2012, 51, 8446-8476. 12. Miyazaki, I.; Tsao, K. 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Photochemical reactivity of the iron(III) complex of a mixed-donor, α-hydroxy acid-containing chelate and its biological relevance to photoactive marine siderophores. Inorg. Chem. 2014, 53, 5781-5787. 32. Ciesienski, K. L.; Haas, K. L.; Franz, K. J. Development of next-generation photolabile copper cages with improved copper binding properties. Dalton Trans. 2010, 39, 9538-9546. 33. Kumbhar, A. A.; Franks, A. T.; Butcher, R. J.; Franz, K. J. Light uncages a copper complex to induce nonapoptotic cell death. Chem. Commun. (Camb) 2013, 49, 2460-2462. 34. Ciesienski, K. L.; Haas, K. L.; Dickens, M. G.; Tesema, Y. T.; Franz, K. J. A photolabile ligand for light-activated release of caged copper. J. Am. Chem. Soc. 2008, 130, 12246-12247. 35. Ciesienski, K. L.; Hyman, L. M.; Derisavifard, S.; Franz, K. J. Toward the detection of cellular copper(II) by a light-activated fluorescence increase. Inorg. Chem. 2010, 49, 6808-6810. 36. Ciesienski, K. L.; Hyman, L. M.; Yang, D. T.; Haas, K. 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Abraham Patchornik: The Contemporary Relevance of His Work for Chemistry and Biology. JACS Au 2025, 5, 3-16. 42. Dose, K. Catalytic Decarboxylation of α-Amino-Acids. Nature 1957, 179, 734-735. 43. Claes, L.; Janssen, M.; De Vos, D. E. Organocatalytic Decarboxylation of Amino Acids as a Route to Bio‐based Amines and Amides. ChemCatChem 2019, 11, 4297-4306. 44. Walkup, G. K.; Burdette, S. C.; Lippard, S. J.; Tsien, R. Y. A New Cell-Permeable Fluorescent Probe for Zn2+. J. Am. Chem. Soc. 2000, 122, 5644-5645. 45. Kobayashi, T.; Komatsu, T.; Kamiya, M.; Campos, C.; González-Gaitán, M.; Terai, T.; Hanaoka, K.; Nagano, T.; Urano, Y. Highly activatable and environment-insensitive optical highlighters for selective spatiotemporal imaging of target proteins. J. Am. Chem. Soc. 2012, 134, 11153-11160. 46. Chen, M. C.; Chen, D. G.; Chou, P. T. Fluorescent Chromophores Containing the Nitro Group: Relatively Unexplored Emissive Properties. ChemPlusChem 2021, 86, 11-27. 47. Wang, Y.; Hollingsworth, A. D.; Yang, S. K.; Patel, S.; Pine, D. J.; Weck, M. Patchy Particle Self-Assembly via Metal Coordination. J. Am. Chem. Soc. 2013, 135, 14064-14067. 48. Seven, I.; Weinrich, T.; Gränz, M.; Grünewald, C.; Brüß, S.; Krstić, I.; Prisner, T. F.; Heckel, A.; Göbel, M. W. Photolabile Protecting Groups for Nitroxide Spin Labels. Eur. J. Org. Chem. 2014, 4037-4043. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99609 | - |
| dc.description.abstract | 金屬離子在生物系統內扮演著很重要的角色。比如說鈣離子與肌肉收縮、血液凝固相關，也是很多酵素的輔因子。鐵離子負責攜帶氧氣，鋅離子則是扮演著訊號傳送、基因表達等角色。也有很多疾病像是阿茲海默症、癲癇都與金屬離子的不正常分布相關，由此可知研究金屬離子相關的生物現象是非常重要的。然而，金屬離子相關的生物現象往往發生的相當快，因此金屬的光解螯合試劑就被開發出來。光解螯合劑提供了一種具高度時空解析度的金屬釋放策略，協助幫助研究金屬在生物過程中的功能。在本研究中，我們設計了一種螢光活化型光可解螯合劑DEACM-oNB-EDTA，其結構由乙二胺四乙酸配位基、鄰硝基苯光保護基與7-二乙氨基-4-甲基香豆素螢光團所組成。照光後，其金屬結合親和力下降三個數量級，有效釋放鋅離子，並同時活化螢光訊號以進行細胞標記。我們已透過區域選擇性照光證明其優異的時空控制能力。我們預期此策略能促進對未知鋅離子相關生物過程的探究，並可望擴展至其他金屬離子，比如說銅、鐵、鉑，用於研究具動態性且依賴金屬的細胞機制。 | zh_TW |
| dc.description.abstract | Metal ions play crucial roles in biological systems. For example, calcium ions are involved in muscle contraction and blood coagulation, and they also serve as cofactors for various enzymes. Iron ions are responsible for oxygen transport, while zinc ions participate in signaling and gene regulation. Abnormal metal ion distribution is associated with numerous diseases, such as Alzheimer's disease and epilepsy, highlighting the importance of studying metal-related biological processes. However, these processes often occur on rapid timescales. Therefore, photolabile metal chelators were invented. These compounds enable precise spatiotemporal control over metal release, facilitating investigations into the functions of metal ions in biological contexts.
In this study, we designed a fluorescence-activatable photolabile chelator, DEACM-oNB-EDTA, which consists of an ethylenediaminetetraacetic acid (EDTA) metal-binding moiety, an ortho-nitrobenzyl (oNB) photoprotecting group, and a 7-diethylamino-4-methylcoumarin (DEACM) fluorophore. Upon light irradiation, its metal-binding affinity decreases by three orders of magnitude, leading to efficient zinc ion release and simultaneous activation of fluorescence for cellular labeling. We have demonstrated its excellent spatiotemporal resolution through regioselective irradiation experiments. We anticipate that this strategy will facilitate the exploration of previously uncharacterized zinc-related biological processes and can potentially be extended to other metal ions, such as copper, iron, and platinum, for studying dynamic and metal-dependent cellular mechanisms. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-09-17T16:07:54Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-09-17T16:07:54Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 I
Abstract II 中文摘要 IV Table of Contents V List of Figures VIII List of Schemes X Abbreviations XI Chapter 1 Introduction 1 1.1 Bio-related Metal in Cells 1 1.2 Bioactivity of Molecules Blocked by Ortho-nitrobenzyl (oNB) Group 1 1.3 Photolabile Chelators of Bio-related Metals 3 1.4 Fluorogenic Fluorophore Serving as a Photoactivation Reporter 4 Chapter 2 Result and Discussion 6 2.1 Molecular Design 6 2.2 Synthesis of oNB-EDTA (5) 8 2.3 In Vitro Characterization of oNB-EDTA (5) 9 2.3.1 Photolysis of oNB-EDTA (5) Monitored by HPLC and NMR 9 2.3.2 Determination of Binding Constant between Zn2+ and oNB-EDTA (5) 16 2.3.3 Photo-triggered Zn²⁺ Release and Post-irradiation Binding Constant of oNB-EDTA (5) 18 2.4 Synthesis of DEACM-oNB-EDTA (14) 21 2.5 in vitro Characterization of DEACM-oNB-EDTA (14) 24 2.5.1 Fluorogenic Property of DEACM-oNB-EDTA (14) 24 2.5.2 Cell Labeling via the Photoactivated Fluorophore of DEACM-oNB-EDTA (14) 27 2.5.3 Evaluation of Zn2+ Probe ZP by Using Different Exogenous Zinc Sources 30 2.5.4 Dual Photoactivation of Zn²⁺ Release and Fluorescence Labeling from Zn-DEACM-oNB-EDTA 32 2.5.5 Demonstration of Spatiotemporal Control of DEACM-oNB-EDTA (14) by Regioselective Irradiation 34 Chapter 3 Conclusion and Perspectives 36 Chapter 4 Methods 38 4.1 General Synthetic Materials and Instruments 38 4.2 Synthesis and Characterization of Compounds 39 4.3 HPLC Assay 52 4.3.1 Method of Photolysis of oNB-EDTA (5) and Zn-oNB-EDTA 52 4.3.2 Method of Photolysis of DEACM-NB (8) 53 4.4 NMR Assay 53 4.4.1 Method of Photolysis of oNB-EDTA (5) by NMR 53 4.5 UV-Vis Spectroscopy Assay 54 4.4.1 Determination of Extinction Coefficient of Zn(PAR)2 54 4.4.2 Determination of Zn2+ Binding Constant by Using PAR Competition Experiments 54 4.4.3 Tracking Zn²⁺ Release Dynamics of Zn-oNB-EDTA under Irradiation 55 4.4.4 Calculation for Binding Constant 55 4.5 Plate Reader Assay 56 4.5.1 Fluorogenic Property of DEACM-NB (8), DEACM-oNB-EDTA (14), and Zn- DEACM-oNB-EDTA 56 4.6 General Biological Materials and Methods 57 4.6.1 Cell Culture 57 4.6.2 Cell Labeling by DEACM-oNB-EDTA (14) under Irradiation 57 4.6.3 Fluorescence Imaging to Evaluate ZP Sensing 58 4.6.4 Fluorescence Imaging for Simultaneous Zn²⁺ Release and Cell Labeling by Zn-DEACM-oNB-EDTA under irradiation 58 4.6.5 Fluorescence Imaging with Regioselective Irradiation 59 Reference 60 Appendix 68 | - |
| dc.language.iso | en | - |
| dc.subject | 光敏感螯合劑 | zh_TW |
| dc.subject | 螢光產生性螢光分子 | zh_TW |
| dc.subject | 鋅 | zh_TW |
| dc.subject | 籠型化合物 | zh_TW |
| dc.subject | 時空選擇性控制 | zh_TW |
| dc.subject | spatiotemporal control | en |
| dc.subject | cage compounds | en |
| dc.subject | Zinc | en |
| dc.subject | photolabile chelator | en |
| dc.subject | fluorogenic fluorophore | en |
| dc.title | 具螢光特性光敏螯合劑之開發以實現生物相關金屬離子釋放的時空控制 | zh_TW |
| dc.title | Development of Fluorogenic Photolabile Chelators for Spatiotemporal Control of Bio-related Metal Release | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 謝俊結;黃人則 | zh_TW |
| dc.contributor.oralexamcommittee | Jiun-Jie Shie;Jen-Tse Huang | en |
| dc.subject.keyword | 螢光產生性螢光分子,光敏感螯合劑,時空選擇性控制,籠型化合物,鋅, | zh_TW |
| dc.subject.keyword | fluorogenic fluorophore,photolabile chelator,spatiotemporal control,cage compounds,Zinc, | en |
| dc.relation.page | 79 | - |
| dc.identifier.doi | 10.6342/NTU202503833 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2025-08-14 | - |
| dc.contributor.author-college | 理學院 | - |
| dc.contributor.author-dept | 化學系 | - |
| dc.date.embargo-lift | 2025-12-01 | - |
| Appears in Collections: | 化學系 | |
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| ntu-113-2.pdf | 2.86 MB | Adobe PDF | View/Open |
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