Synthesis and Characterization of an Octanuclear Mixed-Ligand Copper(II) Complex of the Immunosuppressant Thiopurine Drug Azathioprine.
An octanuclear mixed-ligand copper(II) complex of the immunosuppressant drug azathioprine (AZA) and 2,2,6,6-tetramethylheptane-3,5-dione (THD), [{Cu(4)(AZA(-))(2)(THD(-))(5)(OH(-))}(2)].2CH(3)CN, has been synthesized and characterized by X-ray crystallography and by mass spectrometric and magnetic measurements. Eight copper(II) ions, four monodeprotonated azathioprine(-) ligands, ten monodeprotonated THD(-) ligands, and two hydroxide anions are assembled to form a centrosymmetric, octanuclear molecule, where two tetranuclear moieties of the molecule are connected by four coordination bonds between copper atoms and the N(3) and N(9) atoms of two different AZA ligands. In each half of the molecule, all four copper atoms are five-coordinated with a square pyramidal geometry. Three copper atoms are bridged through a &mgr;(3)-OH(-) group to form a Cu(3)OH cluster with Cu-Cu distances of 3.213(2), 3.585(2), and 3.672(2) Å, respectively, while the fourth one is separated from the cluster by a purine base. Antiferromagnetic coupling is observed within the two OH(-)-bridged trinuclear copper clusters of the octanuclear molecule. The magnetic susceptibility data fit well with the theoretical model proposed (J = -75 cm(-)(1), g = 2.235). Three of the four purine nitrogen atoms (N(3), N(7), and N(9)) bind to copper atoms in both crystallographically independent AZA moieties. All of the 6-mercaptopurine (6-MP) fragments of AZA, a biologically active component of the drug, are buried inside the complex molecule. According to ESI-MS measurements, at least the main skeleton of the molecule is still present in solution despite partial decomposition of the complex via ligand exchange with the solvent. Crystal data: P2(1)/n, a = 21.754(4) Å, b = 16.441(3) Å, c = 25.209(5) Å, beta = 97.07(2) degrees, V = 8948(3) Å(3), Z = 2.
Zhu Fc
Fu-chun
Institute of Inorganic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Schmalle
Helmut W.
HW
Fischer
Berthold
B
Dubler
Erich
E