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.
Kowalski
Piotr
P
Institute of Organic Chemistry and Technology, Cracow University of Technology, 24 Warszawska Street, 31-155 Cracow, Poland.
Suder
Piotr
P
Kowalska
Teresa
T
Silberring
Jerzy
J
Duszyńska
Beata
B
Bojarski
Andrzej J
AJ
D002065:Buspirone / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry*; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D008024:Ligands; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D002065:Buspirone