Synthesis and Characterization of an Octanuclear Mixed-Ligand Copper(II) Complex of the Immunosuppressant Thiopurine Drug Azathioprine

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• 作者：Fu-chun Zhu ; Helmut W. Schmalle ; Berthold Fischer ; and Erich Dubler
• 刊名：Inorganic Chemistry
• 出版年：1998
• 出版时间：March 23, 1998
• 年：1998
• 卷：37
• 期：6
• 页码：1161 - 1168
• 全文大小：114K
• 年卷期：v.37,no.6(March 23, 1998)
• ISSN：1520-510X

文摘

An octanuclear mixed-ligand copper(II) complex ofthe immunosuppressant drug azathioprine (AZA) and 2,2,6,6-tetramethylheptane-3,5-dione (THD),[{Cu₄(AZA^-)₂(THD^-)₅(OH^-)}₂]·2CH₃CN,has been synthesized andcharacterized by X-ray crystallography and by mass spectrometric andmagnetic measurements. Eight copper(II)ions, four monodeprotonated azathioprine^- ligands, tenmonodeprotonated THD^- ligands, and twohydroxideanions are assembled to form a centrosymmetric, octanuclear molecule,where two tetranuclear moieties of themolecule are connected by four coordination bonds between copper atomsand the N(3) and N(9) atoms of twodifferent AZA ligands. In each half of the molecule, all fourcopper atoms are five-coordinated with a squarepyramidal geometry. Three copper atoms are bridged through a₃-OH^- group to form aCu₃OH cluster withCu-Cu distances of 3.213(2), 3.585(2), and 3.672(2)Å, respectively, while the fourth one is separated fromthecluster by a purine base. Antiferromagnetic coupling is observedwithin the two OH^--bridged trinuclear copperclusters of the octanuclear molecule. The magnetic susceptibilitydata 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 copperatoms in both crystallographically independent AZA moieties. Allof the 6-mercaptopurine (6-MP) fragments ofAZA, a biologically active component of the drug, are buried inside thecomplex molecule. According to ESI-MS measurements, at least the main skeleton of the molecule is stillpresent in solution despite partial decompositionof the complex via ligand exchange with the solvent. Crystaldata: P2₁/n, a =21.754(4) Å, b = 16.441(3) Å,c = 25.209(5) Å, = 97.07(2),V = 8948(3) ų, Z =2.