title: Fluorinated o-aminophenol derivatives for measurement of intracellular pH.
abstract: The simple 2-aminophenol group which serves as a building block for many cationic indicators has been modified to yield a series of pH sensitive probes. This approach is based on the replacement of one of the N-acetate groups of the chelator APTRA (o-aminophenol N,N,O-triacetate) by an N-ethyl group. The resulting series of (N-ethylamino)phenol (NEAP) compounds exhibit pK values in the physiological range and negligible affinity for physiological levels of other ions. Three fluorinated analogs have been prepared: N-ethyl-5-fluoro-2-aminophenol N,O-diacetate (5F NEAP), N-ethyl-2-((2-fluoro-4-carboxybenzyl)oxy)-4-fluoroaniline-N- acetic acid (5F NEAP-2), and 1-(2-(N-ethylamino)-5-fluorophenoxy)-2-(2-fluoro-4- aminophenoxy)ethane-N,N',N'-triacetic acid (5F NEAP-3). These derivatives exhibit total titration shifts of approximately 11 ppm. NEAP-2 and NEAP-3 contain an additional fluorine to serve as an internal chemical shift reference, and NEAP-3, the most highly charged analog prepared, was designed in order to minimize leakage.
authors.affiliation: Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Rhee
authors.forename: L A
authors.initials: LA
authors.lastname: Levy
authors.forename: R E
authors.initials: RE
authors.lastname: London
mesh_terms: D000627:Aminophenols / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: C093046:1-(2-(N-ethylamino)-5-fluorophenoxy)-2-(2-fluoro-4-aminophenoxy)ethane-N,N',N'-triacetic acid; D000627:Aminophenols; C093045:N-ethyl-2-((2-fluoro-4-carboxybenzyl)oxy)-4-fluoroaniline-N-acetic acid; C093044:N-ethyl-2-hydroxy-4-fluoroaniline-N,O-diacetic acid; C027667:2-aminophenol