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 hydrogen bonds is created that guarantees maximum electrostatic and hydrogen-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 between the phosphonate anion and the hydroxyl groups. Biologically important amino alcohols such as glucosamine, 1-aminosorbitol, ephedrine, and the beta-blocker propranolol are bound in DMSO with K-a values between 60 000 and 130 000 M-1. Secondary amines are complexed at least as strongly as their primary counterparts. The phosphonate ester groups allow lateral recognition of the substate. This could be demonstrated for adrenaline model compounds that were recognized by phosphonates carrying extended aromatic ester groups for pi,pi-interactions.