Premium
Synthesis and Characterization of Two Improved NMR Indicators for Cytosolic Ca 2+ : 3FBAPTA and 35FBAPTA
Author(s) -
Levy Louis A.,
Gabel Scott A.,
London Robert E.
Publication year - 1996
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/(sici)1097-458x(199606)34:6<440::aid-omr901>3.0.co;2-m
Subject(s) - chemistry , calcium , bapta , dissociation constant , dissociation (chemistry) , fluorine , chelation , medicinal chemistry , ion , reaction rate constant , kinetics , stereochemistry , inorganic chemistry , organic chemistry , biochemistry , physics , receptor , quantum mechanics
Fluorinated derivatives of the calcium‐selective chelator BAPTA [1,2‐bis(2‐aminophenoxy)ethane‐ N , N , N′ , N′ ‐tetraacetic acid] are popular NMR probes for cytosolic calcium ion concentration. Two such derivatives were synthesized and evaluated, 3FBAPTA [1,2‐bis(2‐amino‐3‐fluorophenoxy)ethane‐ N , N , N′ , N′ ‐tetraacetic acid] and 35FBAPTA [1,2‐bis(2‐amino‐3,5‐difluorophenoxy)ethane‐ N , N , N′ , N′ ‐tetraacetic acid]. The dissociation constant ratios obtained at 37°C were K D 3F / K D 5F = 0.60 and K D 35F / K D 5F = 0.88; similar values were obtained at 25°C. Hence 3FBAPTA binds calcium ions more tightly than 5FBAPTA [1,2‐bis(2‐amino‐5‐fluorophenoxy)ethane‐ N , N , N′ , N′ ‐tetraacetic acid, the currently most frequently utilized indicator], while the doubly substituted derivative exhibits intermediate affinity. The dissociation rate constants for the calcium complexes measured at 37°C exhibit a similar trend, with k ‐1 5 > k ‐1 35 > k ‐1 3 . Both of the additional derivatives exhibit slow exchange kinetics, and should be superior fluorine NMR probes owing to the decreased T 1 values and, in the case of 35FBAPTA, the presence of two calcium‐sensitive fluorine nuclei which are measured simultaneously.