A H-1 NMR study of the interaction of antitumor metallocenes with glutathione

The interaction of the antitumor active metallocene dihalides Cp2MCl2 (M=Ti , Nb, Mo) and 1 equiv. of glutathione was studied by H-1 NMR spectroscopy a t pD 2-7 in 4 mM NaCl solutions. No interaction between glutathione and tit anocene dichloride was detected at pD 2, while at pD 5-7 competitive hydrol ysis of the cyclopentadienyl ligands occurred. With niobocene dichloride fo rmation of similar to 20% of an adduct was observed at pD 2 and 5, but hydr olysis of the Cp ligands in the adduct occurred over 24 h. Molybdocene dich loride formed two stable adducts at pD 6 which were tentatively assigned as a Cp2Mo-glutathione chelate involving coordination of the cysteine thiol a nd glycine carboxylate to the metal centre, and a thiol centred 1:2 Cp2Mo-g lutathione complex. The implications for the mechanism of antitumor action of the metallocene dihalides is discussed. (C) 2001 Elsevier Science B.V. A ll rights reserved.