TOWARD SYNTHETIC ADRENALINE RECEPTORS - STRONG, SELECTIVE, AND BIOMIMETIC RECOGNITION OF BIOLOGICALLY-ACTIVE AMINO-ALCOHOLS BY BISPHOSPHONATE RECEPTOR MOLECULES

Xylylene bisphosphonates represent a new class of artificial receptor molecules for alkylammonium ions (Schrader, T. Angew. Chem., Int. Ed. Engl. 1996, 35, 2649-2651). Molecular recognition takes place in a 1:1 chelate-binding mode, and an almost ideal array of short, linear hydr ogen bonds is created that guarantees maximum electrostatic and hydrog en-bond interactions. The host molecule, which was designed to imitate the natural adrenergic receptor, is selective for 1,2- and 1,3-amino alcohols due to formation of an additional cooperative hydrogen bond b etween the phosphonate anion and the hydroxyl groups. Biologically imp ortant amino alcohols such as glucosamine, 1-aminosorbitol, ephedrine, and the beta-blocker propranolol are bound in DMSO with K-a values be tween 60 000 and 130 000 M-1. Secondary amines are complexed at least as strongly as their primary counterparts. The phosphonate ester group s allow lateral recognition of the substate. This could be demonstrate d for adrenaline model compounds that were recognized by phosphonates carrying extended aromatic ester groups for pi,pi-interactions.