Structural and Dynamic Evidence for C−H···O Hydrogen Bonding in Lariat Ethers:  Implications for Protein Structure

Abstract

Seven diaza-18-crown-6 ethers having aromatic sidearms were studied: benzyl ( 1 ), 2-hydroxybenzyl ( 2 ), dansyl ( 3 ), 1-naphthylmethyl ( 4 ), 2-naphthylmethyl ( 5 ), 9-anthrylmethyl ( 6 ), and 1-pyrenylmethyl ( 7 ). Solution studies of these compounds included homogeneous binding constant determination, picrate extraction efficiency, and/or bulk chloroform membrane transport rate experiments. Compounds 2, 3, 4, 6, and 7 exhibited binding affinities for alkali metal cations that were surprisingly low. Fifteen crystal structures have been used to understand the conformations of 1 − 7 and their alkali metal complexes. Unusually weak cation binding in solution was found to correlate with intramolecular interactions observed between the crown's macroring and both sidearms. For one of the five weakly binding crowns ( 2 ) the low binding affinity is attributed to an intramolecular O−H···N hydrogen bond, confirmed by the solid-state structure and IR studies. The weak cation binding abilities of 3, 4, 6, and 7 are ascribed to intramolecular C−H···O contacts that appear to define both structure and binding affinity. A total of ten C−H···O hydrogen bonds are observed in seven of the solid-state structures. Unusual conformations, dominated by intramolecular aromatic−oxygen interactions, are observed in cases that involve C−H···O hydrogen bond formation. The observed C−H···O contacts are paralleled in proteins, where a crystal structure of myoglobin exhibits an analogous interaction.