Steric Gearing used to Preorganize Hydrogen Bonding Sites around half of a Benzene Scaffold. Applications in Cyclitol Molecular Recognition

Abstract

Three preorganized receptors incorporating a series of amides and ditopic phenanthroline-based hydrogen-bonding motifs were designed, synthesized, and studied for binding cyclitols in low dielectric media. The preorganization was achieved with a steric gearing strategy. The designs were developed in an attempt to overcome the inhibition of binding which results from the intramolecular hydrogen bonds present in cyclitols and saccharides. However, the design motif was only moderately successful, in that the binding constants were only slightly improved relative to those obtained for other earlier systems. Yet, the steric gearing design motif represents a novel approach to aligning hydrogen-bonding groups in a convergent manner, thereby forming a small compact cleft. A crystal structure confirms the gearing, and this general design motif is discussed as a means to preorganize binding groups on only one portion of a benzene ring.