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

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. Copyright © 2003 John Wiley & Sons, Ltd.