Complexes of azathioprine, a biologically active mercaptopurine derivative, with Pt(II), Pd(II), Rh(III), Ru(III) and Ag(I).

In order to possibly elucidate the prevailing factors determining the binding sites in the interactions of azathioprine (AZAH), a biologically active 6-mercaptopurine derivative, with the platinum group and other heavy metals, we probed the binding sites of AZAH with Pt(II), Pd(II), Rh(III), Ru(III), and Ag(I) by using 1H and 195Pt NMR, ESR, and IR spectroscopic techniques as well as magnetic susceptibility measurements and mass spectrometry. The altered coordination behavior of AZAH with respect to the parent 6-mercaptopurine, with sulfur no longer being the primary binding site, was ascertained. In the Pt(II), Rh(III), and Ru(III) complexes, 1H NMR data imply coordination of the metal through the N(3) and N(9) positions of the purine ring, while in the case of the Pt(II) compound, 195Pt NMR data further ascertain AZAH binding in a bridging mode through ring nitrogens. As opposed to the aforementioned metals, in the Pd(II) and Ag(I) compounds, 1H NMR data suggest binding via the N(9) position of deprotonated AZAH. Conductivity measurements for all compounds, except for that of Pt(II), showed a nonelectrolyte behavior in solution; the presence of ionic nitrate in the Pt(II) compound was further ascertained by IR spectroscopy. The coordination sphere of the metal in the cases of the Pt(II) and Pd(II) compounds is completed by ammonia and water molecules, respectively, while in those of the Rh(III) and Ru(III) compounds is completed by chloride bridge. For the Ru(III) compound, the latter is confirmed by magnetic susceptibility measurements.

Synthesis, spectroscopic and magnetic resonance studies of mercury (II) and methylmercury (II) complexes of azathioprine, a biologically active mercaptopurine derivative.

Synthetic and spectroscopic studies of the Hg(II) and MeHg(II) complexes of azathioprine (AZA), a biologically active 6-mercaptopurine derivative, were undertaken. The altered coordination behavior of AZA with respect to the parent mercaptopurine, with sulfur no longer being the primary donor atom, was confirmed. As concluded by the 1H NMR, 13C NMR, and IR spectroscopic data, Hg(II) binds to the N(9) position of deprotonated AZA, while in the MeHg(II) compound, coordination occurs through the N(3) and N(9) positions of the purine ring. The values of the coupling constants 2J (199Hg-1H), 1J(199Hg-13C) for the MeHg(II) compound further support complexation via nitrogen atoms of the purine. Elemental analyses confirmed the compounds to be Hg(AZA)2 (1) and [(MeHg)2(AZA)](NO3) (2); conductivity measurement values show that 1 is a nonelectrolyte and 2 is a 1:1 electrolyte. Furthermore, the FAB-MS of the compounds confirms direct binding of the metal to the ligand, and in the case of the MeHg(II) compound, the successive loss of one and two MeHg(II) moieties can be clearly observed.