Electrospray mass spectrometric studies of noncovalent complexes of buspirone hydrochloride and other serotonin 5-HT(1A) receptor ligands containing arylpiperazine moieties.

Abstract

Noncovalent complexes consisting of two protonated amines and a chloride anion were observed under electrospray ionization mass spectrometry (ESI-MS) conditions. The observed phenomenon was investigated for the hydrochlorides of buspirone, a well-known anxiolytic drug, and 23 other arylpiperazine derivatives that had been developed as serotonin 5-HT(1A) receptor ligands. Due to the major role of ionic interactions in a vacuum, it was proposed that the detected complexes were formed by NH(+)---Cl(-)---NH(+) bridges. It was found that complexation depended on structural features of the analyzed compounds. For derivatives with a shorter linker (three methylene groups) containing a terminal cyclic amide fragment, complex ions were not observed. It was postulated that, in the latter case, steric hindrance due to a terminal group could disturb ionic bridge formation. Since both the observed complexation and ligand-binding processes are driven by noncovalent forces, and a qualitative relationship between them was found (compounds with a 4-carbon chain always display higher affinity for 5-HT(1A) receptors than do their 3-carbon analogues), such ESI-MS studies may yield valuable information on ligand-receptor interactions.