Synthesis and evaluation of fluorinated calcium chelators with enhanced relaxation characteristics

✍ Scribed by Louis A. Levy; Elizabeth Murphy; Bore Raju; Robert E. London

• Book ID: 102950322
• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 772 KB
• Volume: 30
• Category: Article
• ISSN: 0749-1581
• DOI: 10.1002/mrc.1260300807

✦ Synopsis

Abstract

The fluorinated calcium ion chelator 5F BAPTA [1,2‐bis(2‐amino‐5‐fluorophenoxy)ethane‐N, N, N′, N′‐tetra‐acctic acid] was used for the determination of cytosolic Ca^2+^ ion levels in cells and tissues by ^19^F NMR. The possibility of enhancing the sensitivity of these measurements by modifying the relaxation behavior of the chelator was evaluated. These strategies involved the design of a chelator with reduced __T__1 value viz. 5F RBAPTA {1,2‐bis [2‐amino‐4‐(1‐carboxy‐2‐methyl‐2‐propyl)‐5‐fluorophenoxy]ethane‐N, T, N′, N‐tetraacetic acid}, and the evaluation of chelator with slower exchange characteristics, viz 5F BenzEGTA [1‐(2‐amino‐5‐fluorophenoxy)‐2‐(2‐aminoethoxy)ethane‐N, N, N′, N′‐tetraacetic acid]. Both analogs exhibit chemical shift differences on calcium complexation which are similar to those of the parent compound, 5F BAPTA. In the case of BenzEGTA, a considerably greater p^H^ dependence of the apparent calcium, dissociation constant, K^D^, also results from the presence of a tertiary amine with a p^K^ value above the physioligical range. Additionally, the synthetic approach used for RBAPTA can lead to wide variety of derivatives with variable chemical, biochemical and NMR properties.