The effect of increased benzo substitution on the cation-binding stren
gth of diaza-18-crown-6 has been investigated. The planarity constrain
t 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 indic
ators suitable for measuring intracellular free sodium. The cation bin
ding 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 smal
l adjustments to the cation affinity can therefore be achieved via alt
eration of the aryl substitution patterns. Aryl substitution adjacent
to the hetero atoms gives a reduction in the cation affinity of the tr
ibenzo-crown ether, similar to that found on fluorination of the calci
um chelator BAPTA ortho to the oxyethylene bridge. These observations
have led to the preparation of a new indicator for intracellular sodiu
m that we have called FCrown-1. The new indicator has a dissociation c
onstant for sodium of 11 mmol dm-3 and a selectivity for sodium over p
otassium of 1 73-fold. The sodium concentration is reported by the che
mical shift (fast exchange) of one of the two types of fluorine presen
t with a maximum sodium-induced shift of 4.6 ppm downfield. The resona
nce arising from the other fluorine substituents is insensitive to sod
ium and acts as an internal chemical shift reference at 8.8 to 13.4 pp
m upfield from the reporting signal.