SYNTHESIS, CHARACTERIZATION, AND ALKALI-METAL STABILITY-CONSTANTS OF A NEW BIS(PHOSPHOTRIESTER) MACROBICYCLIC POLYETHER CRYPTAND

The synthesis of a new bis(phosphotriester) macrobicyclic polyether cr yptand, O=P[O(CH2)(2)O(CH2)(2)O(CH2)(2)O]P-3=O (9), called phosphocryp t, and its acyclic tripodal precursor O=P[O(CH2)(2)O(CH2)(2)O(CH2)(2)O H](3) (8) are described. The new cryptand 9 was synthesized by condens ation of 8 and phosphoryl chloride which were simultaneously added und er high dilution conditions in the presence of pyridine. The highest y ield of 9 (30%) was obtained with a final concentration of 3 mM in vig orously stirred methylene chloride. Both 8 and 9 form stable complexes with K+ and Rb+ in water. Log K-s values measured with a cation selec tive electrode for 8 are 3.6 and 3.0 and 3.7 and 3.6 for 9, respective ly. The K-s values for phosphocrypt are 1000-fold greater than those o f comparably sized nitrogen bridgehead cryptands. H-1 and C-13 NMR ind icate 9 is flexible at 20 degrees C. Molecular dynamics and mechanics calculations indicate that phosphocrypt has more cation-dipole interac tions and more favorable conformational changes associated with comple xation than comparably sized nitrogen bridgehead cryptands.