Toward synthetic adrenaline receptors: strong, selective, and biomimetic recognition of biologically active amino alcohols by bisphosphonate receptor molecules.

In: Journal of Organic Chemistry (J.Org.Chem.), Jg. 63 (1998) ; Nr. 2, S. 264-272
ISSN: 0022-3263
Zeitschriftenaufsatz / Fach: Chemie
Xylylene bisphosphonates represent a new class of artificial receptor mols. for alkylammonium ions. Mol. recognition takes place in a 1:1 chelate binding mode and an almost ideal array of short, linear hydrogen bonds is created, that guarantees max. electrostatic and hydrogen bond interactions. The host mol. which was designed to imitate the natural adrenergic receptor is selective for 1,2- and 1,3-amino alcs. due to formation of an addnl. cooperative hydrogen bond between the phosphonate anion and the hydroxyl groups. Biol. important amino alcs. such as glucosamine, 1-aminosorbitol, ephedrine and the b-blocker propranol are bound in DMSO with Ka-values between 60000 and 130000 M-1. Secondary amines are complexed at least as strongly as their primary counterparts. The phosphonate ester groups allow lateral recognition of the substrate. This could be demonstrated for adrenaline model compds. which were recognized by phosphonates carrying extended arom. ester groups for p,p-interactions.