Phosphinegold(I) Complexes Containing the Purine-6-thiolate Anion, and Their Antiarthritic Activity

Abstract

A series of complexes of the general formulae R₃PAu(6-mp), R₃P = Et₃P, Ph₃P, Cy₃P, PhMe₂P, (o-tol)₃P, (m-tol)₃P or (p-tol)₃P, (AuCl)Ph₂P(CH₂)nPPh₂(Au(6-mp)), n = 2 or 3, and Ph₂P(CH₂)_nPPh₂(Au(6-mp))₂, n = 1, 2 or 3 and 6-mp is the anion derived from 6-mercaptopurine (purine-6-thiol), have been prepared and characterized by spectroscopic methods (i.r., ¹H, ¹³C, ³¹P n.m.r. and f.a.b. m.s.) and, in the case of the Ph₃PAu(6-mp) complex, by single-crystal X-ray diffraction methods. The spectroscopic data show that the 6-mp ligand coordinates as a thiolate ligand and that the gold atoms exist in linear P-Au-S (or P-Au-Cl) geometries. This has been confirmed by an X-ray study on Ph₃PAu(6-mp), isolated as an ethanol solvate; the study shows the gold atom to be linearly coordinated by the phosphorus and sulfur atoms: Au-P(1) 2.237(2), Au-S(6) 2.287(1) Ǻ and P-Au-S 173.71(6)°. Crystals of Ph₃PAu(6-mp).EtOH are triclinic, space group Pī, with unit cell dimensions a 11.066(3), b 13.552(3), c 8.705(2) Ǻ, α 91.51(2), β 113.06(2), γ 89.69(2)°, V 1200.8(5) Ǻ³, Z 2. The structure was refined by a full-matrix least-squares procedure to R 0.034 for 3978 reflections with I ≥ 3.0σ(I). Preliminary results of testing for antiarthritic activity among the new complexes in rats are also reported showing that some of them are more potent/less toxic than current gold(I) thiolates used clinically.