Integrated and Passive 1,2,3-Triazolyl Groups in Fluorescent Indicators for Zinc(II) Ions: Thermodynamic and Kinetic Evaluations

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• 作者：J. Tyler Simmons ; John R. Allen ; Deborah R. Morris ; Ronald J. Clark ; Cathy W. Levenson ; Michael W. Davidson ; Lei Zhu
• 刊名：Inorganic Chemistry
• 出版年：2013
• 出版时间：May 20, 2013
• 年：2013
• 卷：52
• 期：10
• 页码：5838-5850
• 全文大小：780K
• 年卷期：v.52,no.10(May 20, 2013)
• ISSN：1520-510X

文摘

In addition to being a covalent linker in molecular conjugation chemistry, the function of a 1,2,3-triazolyl moiety resulting from the copper(I)-catalyzed azide鈥揳lkyne cycloaddition reaction as a ligand for metal ions is receiving considerable attention. In this work, we characterize the thermodynamic and kinetic effects of incorporating a 1,2,3-triazolyl group in a multidentate ligand scaffold on metal coordination in the context of fluorescent zinc(II) indicator development. Ligands L14, BrL14, and FL14 (1,4-isomers) contain the 1,4-disubstituted-1,2,3-triazolyl group that is capable of binding with zinc(II) in conjunction with a di(2-picolylamino) (DPA) moiety within a multidentate ligand scaffold. Therefore, the 1,2,3-triazolyl in the 1,4-isomers is 鈥渋ntegrated鈥?in chelation. The 1,5-isomers L15, BrL15, and FL15 contain 1,2,3-triazolyls that are excluded from participating in zinc(II) coordination. These 1,2,3-triazolyls are 鈥減assive linkers鈥? Zinc(II) complexes of 2:1 (ligand/metal) stoichiometry are identified in solution using ¹H NMR spectroscopy and isothermal titration calorimetry (ITC) and, in one case, characterized in the solid state. The 1:1 ligand/zinc(II) affinity ratio of L14 over L15, which is attributed to the affinity enhancement of a 1,2,3-triazolyl group to zinc(II) over that of the solvent acetonitrile, is quantified at 18 (鈭?.7 kcal/mol at 298 K) using an ITC experiment. Fluorescent ligands FL14 and FL15 are evaluated for their potential in zinc(II) sensing applications under pH neutral aqueous conditions. The 1,4-isomer FL14 binds zinc(II) both stronger and faster than the 1,5-isomer FL15. Visualization of free zinc(II) ion distribution in live HeLa cells is achieved using both FL14 and FL15. The superiority of FL14 in staining endogenous zinc(II) ions in live rat hippocampal slices is evident. In summation, this work is a fundamental study of 1,2,3-triazole coordination chemistry, with a demonstration of its utility in developing fluorescent indicators.