Adrenaline recognition in water.
Host molecule 1 displays a high affinity in water towards catecholamines and especially related structures such as beta-blockers with extended aromatic pi-faces (up to 7x10(3) M(-1) for each single complexation step or 5x10(7) M(-2) for both steps). The amphiphilic structural design leads to an extensive self-association of host molecules through their aromatic flanks. Above a cmc (critical micelle concentration) of 3x10(-4) M, host 1 forms micelles that produce a favorable microenvironment for hydrophobic interactions with the included guest molecules. Electrostatic attraction of the ammonium alcohol by the phosphonate anions is thus combined with hydrophobic contributions between the aromatic moieties. Ionic hydrogen bonds with polar OH or NH groups of the guest enforce the non-covalent interactions, and finally lead to increased specificity. Both its affinity and its selectivity towards adrenergic receptor substrates are greatly enhanced if the receptor molecule 1 is transferred from water into a lipid monolayer. Catecholamines and beta-blockers lead to drastically different effects at concentrations approaching the micromolar regime. Especially beta-blockers with minute structural changes can be easily distinguished from each other. In both cases, extensive hydrophobic interactions with a self-associated and/or self-organized microenvironment are largely responsible for the observed high efficiency and specificity.
Molt
Oliver
O
Department of Chemistry, Philipps-Universität Marburg, Hans-Meerwein-Str., 35032 Marburg, Germany.
Rübeling
Daniel
D
Schäfer
Gerhard
G
Schrader
Thomas
T
D000319:Adrenergic beta-Antagonists / Q000737:chemistry; D002395:Catecholamines; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004837:Epinephrine / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D011487:Protein Conformation; D011941:Receptors, Adrenergic / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D008823:Micelles; D011941:Receptors, Adrenergic; D014867:Water; D004837:Epinephrine