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

Abstract

A new rationally designed receptor molecule binds adrenaline derivatives in water. Its binding pattern (see picture) imitates the interplay of noncovalent interactions operating in the natural receptor. High shape selectivity is achieved for the slim dopamine skeleton, and leads to rejection of substrates with an α‐substituent, such as amino acid derivatives.

Interactions with Aromatic Rings in Chemical and Biological Recognition

“…Recent investigations have employed cation–π interactions in the recognition of a plethora of biologically important cations in aqueous solution. Phosphonate‐based amino acid receptors of Schrader and co‐workers combine ion‐pairing interactions with cation–π contacts to efficiently bind amino acids (for example, Lys, His, and Arg),255 adrenaline,256 and small peptides (for example, the RGD sequence) 257. Likewise, the molecular clips of Klärner, Schrader, and co‐workers are efficient binders of N ‐alkylpyridinium salts (−Δ G =4.9–5.5 kcal mol −1 ), including the sizeable NAD + ion, in aqueous solution 258.…”

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.…”

“…Introduction of additional phosphonate units into macrocyclic ring of (13) resulted in efficient receptor (14) for catecholamines and related structures, such as -blockers with extended aromatic -faces (applied as hydrochlorides) [18]. The designed host is highly rigid and possesses two mobile bisphosphonate binding units placed in para-position to each other.…”

“…Binding abilities of receptor (14) embedded into monolayered Langmuir film of stearic acid were also studied. Complexation efficiency and selectivity towards catecholamines and -blockers were enhanced, leading to drastically different effects at concentrations approaching the micromolar regime.…”

Enantioselective binding of amino acids and amino alcohols by self-assembled chiral basket-shaped receptors

“…The binding of adrenaline (10) as a guest was also studied giving a binding constant of (12.8^0.5)£10 3 M 21 , one order of magnitude larger than those obtained for the former guests, and considerably higher than the values found in literature in aqueous solution. 10,16 In this case, the presence of the methyl group increases the hydrophobicity of the guest resulting in a strong binding spite of the presence of OH groups in the molecule. In order to prove the role played by the carboxylate groups in the binding of this kind of guests both enantiomers of the amino acids phenylalanine (L-11, D-11) and tryptophan (L-12, D-12) as well as the D-tyrosine (D-9) were also studied.…”