Abrégé

Novel fluorophores for fluorescent ion indicators incorporate water-solubilizing functional groups. These fluorophores enable visible-wavelength analysis of ion concentrations with chelators that are insoluble or poorly soluble in water. A green version of the fluorophore comprises a putative fluorescein with carboxylate appendages. An orange version of the fluorophore comprises a putative rhodamine, also with carboxylate appendages. Attaching the fluorophore to a 12-crown-4, a 15-crown-5, a 18-crown-6, a 21-crown-7, or a 24-crown-8 produces lithium, sodium, potassium, rubidium, and cesium indicator families, respectively. Attaching the fluorophore to diaza [1,1,1], [1,1,2], [1,2,2], [2,2,2], [2,2,3], [2,3,3], or [3,3,3] cryptands produces more selective lithium, sodium, potassium, rubidium, and cesium indicator families, respectively. Attaching the fluorophore to BAPTA, APTRA, or half- BAPTA or their analogs produces new calcium, magnesium, and other metal ions indicator families that strongly resist leakage from the cell.

Classes IPC  ?

• C07D 413/14 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle contenant au moins trois hétérocycles

Abrégé

A new generation of fluorescent ion indicators for measuring cytosolic concentrations of calcium. These new indicators emit in the red portion of the visible spectrum and are ratiometric. The ratiometry consists of shifting in the emission upon binding calcium when exciting with an argon laser at 488 nm. These indicators also show marked increases in red fluorescence when excited with visible light at longer wavelengths. Like all calcium indicators, they comprise the usual chelating portion based on BAPTA (Bis Amino Phenyl Tetraacetic Acid) and a fluorophore portion, either a seminaphthofluorescein/seminaphthorhodamine or dinaphthofluorescein, which enable ratiometry. Unlike other naphthofluoresceins, the pKa has been adjusted on the naphtho moiety to make it suitable for biological calcium measurements. The invention relates to the structures of the indicators and to the method of synthesizing these indicators.

Classes IPC  ?

• C07D 279/00 - Composés hétérocycliques contenant des cycles à six chaînons comportant un atome d'azote et un atome de soufre comme uniques hétéro-atomes du cycle