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

Satish Jakkampudi, (1, 2) , Manabu Abe (1, 2) , Naomitsu Komori (2) , Ryukichi Tagaki (2) , Ko Furukawa (3) , Claudine Katan (4) , Wakako Sawada (5) , Noriko Takahashi (5) , Haruo Kasai (6, 1)

1 JST-CREST
2 HIRODAI - Department of Chemistry, Graduate School of Science, Hiroshima University
3 Niigata University
4 ISCR - Institut des Sciences Chimiques de Rennes
5 CDBIM - Laboratory of Structural Physiology, Graduate School of Medicine
6 CDBIM - Laboratory of Structural Physiology

Among biologically active compounds, calcium ions (Ca2+) 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 δu = 20.7 GM at 740 nm for 2-(4-nitrophenyl)benzofuran (NPBF)-substituted EGTA (NPBF-EGTA, Kd = 272 nM) and δu = 7.8 GM at 800 nm for 4-amino-4′-nitro-1,1′-biphenyl (BP)-substituted EGTA (BP-EGTA, Kd = 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 Ca2+-uncaging reaction triggered by TP photolysis in vivo.

Domains: Chemical Sciences; Theoretical and/or physical chemistry; Chemical Sciences; Chemical Sciences; Inorganic chemistry; Chemical Sciences; Medicinal Chemistry; Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]

Satish Jakkampudi,, Manabu Abe, Naomitsu Komori, Ryukichi Tagaki, Ko Furukawa, et al.. 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. ACS Omega, 2016, 1 (2), pp.193-201. ⟨10.1021/acsomega.6b00119⟩. ⟨hal-01395864⟩