Inclusion complexes of serotonin and dopamine with a dioxa-pentaaza-cyclophane

Introduction

In attempt to find new type of artificial receptors towards neurotransmitters, NMR studies were carried out on the supramolecular complexation of serotonin and dopamine with a dioxa-pentaaza-cyclophane derived from diethylenetriaminepentaacetic acid (known as DTPA) in neutral aqueous media, in which the macrocycle composed of three phenylene groups is negatively charged with three anionic -CH₂ CO₂⁻ arms, whereas the aromatic neurotransmitters carry a cationic -NH₃⁺ group.

Objectives

The main objective of the present study is to find new types of artificial receptors towards neurotransmitters.

Methods

Aromatic protons in the cyclophane exhibit up-field shifts due to the ring current effect of the neurotransmitters in NMR titration; the through-space interaction is confirmed by NOESY (Nuclear Overhauser Enhancement and Exchange Spectroscopy). Geometry optimization shows that the macrocycle can encapsulate either neurotransmitter molecule to form a 1:1-inclusion complex in which electrostatic and hydrogen-bonding interaction operate between the functional groups of the component molecules.

Results

The through-space interaction is stronger for serotonin because of its better fitness to the macrocyclic cavity. The thermodynamic stabilities of the complexes are about 20 M⁻¹ in D₂O and are very slightly decreased in the coexistence of electrolytes.

Conclusion

The complexation is promoted by the electrostatic and hydrogen bonds. The resulting ion-pair is stabilized by the successive encapsulation, which protects the weak bonds against the electrostatic field of the electrolyte. The combination of multiple types of interacting sites may be crucial in the design of receptors that can function under isotonic conditions.