Selective recognition of neurotransmitters in aqueous solution by hydroxyphenyl aza-scorpiand ligands

The synthesis, acid-base behaviour and anion recognition of neurotransmitters (dopamine, tyramine and serotonin) in aqueous solution of different aza-scorpiand ligands functionalized with hydroxyphenyl and phenyl moieties (L1-L3 and L4, respectively) have been studied by potentiometry, NMR, UV-Vis and fluorescence spectroscopy and isothermal titration calorimetry (ITC). The analysis of the potentiometric results shows the selective recognition of serotonin at physiological pH (K-eff = 8.64 x 10(4)) by L1. This selectivity has an entropic origin probably coming from a fine pre-organization of the interacting partners. Thus, the complementarity of the receptor and the substrate allows the reciprocal formation of hydrogen bonds, p-p and cation-p interactions, stabilizing the receptors and slowing the rate of oxidative degradation, and satisfactory results are obtained at acidic and neutral pH values. NMR and molecular dynamics studies reveal the rotation blockage in the neurotransmitter side chain once complexed with L1.

Automated summary

This study investigated the synthesis, acid-base behavior, and anion recognition of neurotransmitters (dopamine, tyramine, and serotonin) using aza-scorpiand ligands functionalized with hydroxyphenyl and phenyl moieties (L1-L3 and L4, respectively). The results showed that L1 selectively recognized serotonin at physiological pH due to complementary hydrogen bonding, p-p, and cation-p interactions, leading to stabilization of the receptors. NMR and molecular dynamics studies revealed rotation blockage in the neurotransmitter side chain upon complexation with L1.