Design and Synthesis of a 4‑Nitrobromobenzene Derivative Bearing an Ethylene Glycol Tetraacetic Acid Unit for a New Generation of Caged Calcium Compounds with Two-Photon Absorption Properties in the Near-IR Region and Their Application in Vivo
2016-08-09T15:20:51Z (GMT) by
Among biologically active compounds, calcium ions (Ca<sup>2+</sup>) are one of the most important species in cell physiological functions. Development of new calcium chelators with two-photon absorption (TPA) properties is a state-of-the-art challenge for chemists. In this study, we report the first and efficient synthesis of 5-bromo-2-nitrobenzyl-substituted ethylene glycol tetraacetic acid (EGTA) as a platform for a new generation of calcium chelators with TPA properties in the near-infrared region. New calcium chelators with high TPA properties, that is, a two-photon (TP) fragmentation efficiency of δ<sub>u</sub> = 20.7 GM at 740 nm for 2-(4-nitrophenyl)benzofuran (NPBF)-substituted EGTA (NPBF-EGTA, <i>K</i><sub>d</sub> = 272 nM) and δ<sub>u</sub> = 7.8 GM at 800 nm for 4-amino-4′-nitro-1,1′-biphenyl (BP)-substituted EGTA (BP-EGTA, <i>K</i><sub>d</sub> = 440 nM) derivatives, were synthesized using Suzuki–Miyaura coupling reactions of the bromide with benzofuran-2-boronic acid and 4-(dimethylamino)phenyl boronic acid, respectively. The corresponding acetoxymethyl (AM) esters were prepared and successfully applied to the Ca<sup>2+</sup>-uncaging reaction triggered by TP photolysis in vivo.
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