Structure and synthesis of nitrophenyl-EGTA, a caged calcium, in

Organic compounds -- part of the class 532-570 series – Organic compounds – Heavy metal containing

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556131, 556148, 562434, 562489, 562565, 562568, 564441, 564442, 564443, 568 44, 568 45, 568 46, 568 54, 568 55, 568 56, 568584, 568587, 568588, 568593, 568608, 568630, 568651, 568656, 568662, 568663, 2041574, C07F 1300, C07F 300, C07C22900

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054461863

ABSTRACT:
The synthesis and compound of a new caged calcium which is an ortho-nitrophenyl derivative of EGTA and various intermediates. It is synthesized in ten steps and 24% overall yield. The photosensitive chelator, nitrophenyl-EGTA, has a K.sub.d for Ca.sup.2+ of 80 nM and for Mg.sup.2+ of 8.8 mM. Upon exposure to ultra-violet light (in the region of 350 nm), the chelator is cleaved, yielding iminodiacetic acid photoproducts with known low Ca-affinity (K.sub.d =1 mM). The quantum yield of photolysis of nitrophenyl-EGTA in the presence of Ca.sup.a+ is 0.23 and in the absence of Ca.sup.2+ is 0.20. In experiments with chemically skinned skeletal muscle fibers, a fully relaxed fiber equilibrated with nitrophenyl-EGTA:Ca.sup.2+ complex, in the presence of physiological [Mg.sup.2+ ] (i.e. 1.0 mM), produced maximal contraction after a single flash from a frequency doubled ruby laser (347 nm). Half-maximal tension was achieved in 18 ms at 15.degree. C. Nitrophenyl-EGTA provides a new tool for the investigation of the mechanism of Ca.sup.2+ -dependent physiological processes, since under conditions of normal intracellular Ca.sup.2+ and Mg.sup.2+ ions, only Ca.sup.2+ ions are bound by the photolabile chelator and on illumination are released rapidly and in high photochemical yield.

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