Synthetic Model of the Phosphate Binding Protein: Solid-State Structure and Solution-Phase Anion Binding Properties of a Large Oligopyrrolic Macrocycle

The macrocyclic receptors 4−6 were synthesized via the anion-templated condensation of appropriately
chosen dialdehyde and diamine building blocks. Whereas all three products could be obtained directly
via the appropriate choice of reaction conditions, the larger [3+3] product, 6, which incorporates three
of each precursor subunit, could also be obtained conveniently via an indirect procedure involving ring
expansion of the smaller [2+2] macrocycle 4. As detailed earlier (Sessler, J. L.; Katayev, E. A.; Pantos,
G. D.; Reshetova, M. D.; Khrustalev, V. N.; Lynch, V. M.; Ustynyuk, Y. A. Angew. Chem. 2005, 117,
7552−7556; Angew. Chem., Int. Ed. 2005, 44, 7386−7390), this ring expansion occurs under
thermodynamic control in the presence of HSO4- and H2PO4- anions in acetonitrile solution and serves
to effect the conversion of 4 to 6. An analysis of the X-ray crystal structure of complex 6H22+·HPO42-
revealed a strong resemblance to the active site of the phosphate binding protein (PBP) with similar
structural analogies being drawn between the active site of the sulfate binding protein (SBP) and the
corresponding hydrogensulfate anion complex. In both cases, the anions are bound in a 1:1 fashion in
the solid state through a complementary hydrogen bond network involving both the receptor 6 and the
anions. UV−vis spectroscopic titrations provide support for the conclusion that macrocycle 6 binds the
hydrogensulfate and dihydrogenphosphate anion (studied as the corresponding tetrabutylammonium salts)
with high selectivity and affinity in acetonitrile (log Ka for the first binding interaction approaching 7),
albeit with different receptor-to-anion binding stoichiometries (1:1 vs 1:3 for HSO4- and H2PO4-,
respectively).