Azacalixarene: synthesis, conformational analysis, and recognition behavior toward anions

The synthesis of an azacalix[4]arene (4) having four primary amino groups o n the upper rim has been achieved. The synthesis was accomplished by a one- step cyclization starting from two easily synthesized building blocks. H-1 NMR spectra indicate that this azacalixarene prefers a cone conformation, b ut that rapid interconversion among different conformations occurs at room temperature. It is shown that 4 is a useful receptor for sensing various an ionic guests, such as inositol triphosphate (IP3), in aqueous solution. In a competition binding assay, fluorescent probes bound within 4 were replace d by anionic guests in buffered aqueous solution, causing a modulation in t he fluorescence intensity. NMR spectra of 4 in the presence of fructose 1,6 -diphosphate suggest that this guest is bound inside the cavity which adopt s a cone conformation.