Chelators whose affinity for calcium is decreased by illuminatio

Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof

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546 23, 546171, 549220, 549336, 549439, 558 44, 560 21, 424DIG6, C07C10126, C07D21538

Patent

active

046894322

ABSTRACT:
The present invention discloses a group of calcium chelating compounds which have a descreased affinity for calcium following illumination. These new compounds contain a photolabile nitrobenzyl derivative coupled to a tetracarboxylate Ca.sup.2+ chelating parent compound having the octacoordinate chelating groups characteristic of EGTA or BAPTA. In a first form, the new compounds are comprised of a BAPTA-like chelator coupled to a single 2-nitrobenzyl derivative, which in turn is a photochemical precursor of a 2-nitrosobenzophenone. In a second form, the new compounds are comprised of a BAPTA-like chelator coupled to two 2-nitrobenzyl derivatives, themselves photochemical prcursors of the related 2-nitrosobenzophenones.
The present invention also discloses a novel method for preparing 1-hydroxy- or 1-alkoxy-1-(2-nitroaryl)-1-aryl methanes. Methanes of this type are critical to the preparation of, or actually constitute, the photolabile Ca.sup.2+ chelating compounds disclosed and claimed herein.

REFERENCES:
Henry A. Lester and Jeanne M. Nerbonne "Physiological and Pharmacological Manipulations with Light Flashes", Div. of Biology 156-29, California Institute of Technology, Pasadena, Calif. 91125, Ann. Rev. Biophys. Bioeng. 1982:11-151-75.
A. Patchornik, "Photosensitive Protecting Groups", Journ. of the American Chemical Society, 92:21, Oct. 21, 1970.
Roger Y. Tsien, "New Calcium Indicators and Buffers with High Selectivity against Magnesium and Protons: Design, Synthesis, and Properties of Prototype Structures", Am. Chem, Soc. 1980.
Roger Y. Tsien, "Intracellular Measurements of Ion Activities", Ann. Rev. Biophys. Bioeng., 12:91-116, 1983.

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