Towards Synthetic Adrenaline Receptors—Shape-Selective Adrenaline Recognition in Water

Abstract

In spite of their key role in signal transduction, the mechanism of action of adrenergic receptors is still poorly understood. We have imitated the postulated binding pattern of the large membrane protein with a small, rationally designed synthetic host molecule. Experimental evidence is presented for the simultaneous operation of electrostatic attraction, hydrogen bonds, π stacking, and hydrophobic interactions. By virtue of this combination of weak attractive forces, adrenaline derivatives in water are bound with high shape selectivity for the slim dopamine skeleton. We think that these findings support the postulated cooperative interplay of noncovalent interactions in the natural receptors. In addition, they provide access to a new type of adrenaline sensor. This may be the first step towards an artificial signal‐transduction system.

Organophosphorus Supramolecular Chemistry. Part 2. Organophosphorus Receptors

“…The next group of the cleft receptors (8,9) was also designed as a model of adrenergic -receptor [13,14,15]. On the contrary to compound (7), the macrocyclic host (8) [14,15] revealed the shape selectivity towards adrenaline derivatives, such as e.g.…”

“…On the contrary to compound (7), the macrocyclic host (8) [14,15] revealed the shape selectivity towards adrenaline derivatives, such as e.g. Substitution of bridging unit by pyridine-2,6-dicarboxamide (host compound (9)) resulted in diminished binding constants when comparing to (8) (K a for adrenaline hydrochloride equal 153 M -1 and 21 M -1 , for noradrenaline hydrochloride 215 M -1 and 136 M -1 and, for dopamine hydrochloride 246 M -1 and 142 M -1 for receptors (8) and (9), respectively in MeOD/D 2 O (1:1) solution) [15]. The multiple non-covalent interactions such as electrostatic attraction, hydrogen bonding, -stacking and hydrophobic forces were found to be responsible for the recognition process.…”

“…dopamine, which were complexed with the highest affinities among other biogenic amines. However, compound (9) is even more selective than (8) against -substituted alkylammonium ions such as amino acid esters and related compounds [15]. Moreover, experiments performed by NMR (in MeOD/D 2 O (1:1) and d 6 -DMSO solutions) reinforced by molecular dynamic calculations confirmed mutual binding pattern and revealed the stacking interactions between the catecholamine ring and the sidewalls of receptor with forma-tion of net of hydrogen bonds between the isophthalamide head group of host molecule and hydroxyl groups of catecholamine fragment of guest molecules.…”

A Water‐Soluble Perylene Bisimide Cyclophane as a Molecular Probe for the Recognition of Aromatic Alkaloids

“…[4] In this regard, cyclodextrins and cucurbiturils as well as hydrophilic pillararenes and calixarenes evolved as universal hosts for the complexation of drugs,v itamins,f ragrances,a nd other desirable guest molecules. By additionally employing p-p-a nd CÀH-p-interactions for guest encapsulation, cyclophanes are suitable hosts not only for biologically important aromatic molecules such as certain amino acids, [8] nucleotides, [7b, 9] and the neurotransmitters epinephrine or dopamine [10] but also for carbohydrates [11] in water.However,the design of cyclophanes,which possess larger cavities and are composed of dyes,r emains challenging. [6] This holds in particular true for so-called molecular probes which, in addition to ah igh selectivity for the recognition of specific guest molecules,a re required to show as pecific response to the respective analyte such as ac hange in absorbance or fluorescence.…”

“…[6] This holds in particular true for so-called molecular probes which, in addition to ah igh selectivity for the recognition of specific guest molecules,a re required to show as pecific response to the respective analyte such as ac hange in absorbance or fluorescence. By additionally employing p-p-a nd CÀH-p-interactions for guest encapsulation, cyclophanes are suitable hosts not only for biologically important aromatic molecules such as certain amino acids, [8] nucleotides, [7b, 9] and the neurotransmitters epinephrine or dopamine [10] but also for carbohydrates [11] in water. By additionally employing p-p-a nd CÀH-p-interactions for guest encapsulation, cyclophanes are suitable hosts not only for biologically important aromatic molecules such as certain amino acids, [8] nucleotides, [7b, 9] and the neurotransmitters epinephrine or dopamine [10] but also for carbohydrates [11] in water.…”