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Electrospray mass spectrometric studies of noncovalent complexes of buspirone hydrochloride and other serotonin 5‐HT 1A receptor ligands containing arylpiperazine moieties
Author(s) -
Kowalski Piotr,
Suder Piotr,
Kowalska Teresa,
Silberring Jerzy,
Duszyńska Beata,
Bojarski Andrzej J.
Publication year - 2003
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.1166
Subject(s) - chemistry , non covalent interactions , protonation , ligand (biochemistry) , electrospray ionization , amide , methylene , ionic bonding , stereochemistry , steric effects , phosphonate , mass spectrometry , electrospray , combinatorial chemistry , medicinal chemistry , hydrogen bond , receptor , organic chemistry , chromatography , molecule , ion , biochemistry
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. Copyright © 2003 John Wiley & Sons, Ltd.