A new 19F NMR indicator for intracellular sodium

Abstract

The effect of increased benzo substitution on the cation-binding strength of diaza-18-crown-6 has been investigated. The planarity constraint imposed by increased substitution reduces the effective cavity size thus giving rise to an increased selectivity for sodium over potassium, magnesium and calcium that is sufficient to provide a class of indicators suitable for measuring intracellular free sodium. The cation binding parameters and the associated spectral changes of a selection of compounds with varied aryl fluorination patterns have shown that there is very little electronic interaction between the aromatic rings and the bound cation through the heteroatoms of the crown ether. Only small adjustments to the cation affinity can therefore be achieved via alteration of the aryl substitution patterns. Aryl substitution adjacent to the hetero atoms gives a reduction in the cation affinity of the tribenzo-crown ether, similar to that found on fluorination of the calcium chelator BAPTA ortho to the oxyethylene bridge. These observations have led to the preparation of a new indicator for intracellular sodium that we have called FCrown-1. The new indicator has a dissociation constant for sodium of 11 mmol dm^–3 and a selectivity for sodium over potassium of 173-fold. The sodium concentration is reported by the chemical shift (fast exchange) of one of the two types of fluorine present with a maximum sodium-induced shift of 4.6 ppm downfield. The resonance arising from the other fluorine substituents is insensitive to sodium and acts as an internal chemical shift reference at 8.8 to 13.4 ppm upfield from the reporting signal.