A (1)H NMR study of the interaction of antitumor metallocenes with glutathione.
The interaction of the antitumor active metallocene dihalides Cp(2)MCl(2) (M=Ti, Nb, Mo) and 1 equiv. of glutathione was studied by (1)H NMR spectroscopy at pD 2-7 in 4 mM NaCl solutions. No interaction between glutathione and titanocene dichloride was detected at pD 2, while at pD 5-7 competitive hydrolysis of the cyclopentadienyl ligands occurred. With niobocene dichloride formation of approximately 20% of an adduct was observed at pD 2 and 5, but hydrolysis of the Cp ligands in the adduct occurred over 24 h. Molybdocene dichloride formed two stable adducts at pD 6 which were tentatively assigned as a Cp(2)Mo-glutathione chelate involving coordination of the cysteine thiol and glycine carboxylate to the metal centre, and a thiol centred 1:2 Cp(2)Mo-glutathione complex. The implications for the mechanism of antitumor action of the metallocene dihalides is discussed.
Mokdsi
G
G
School of Chemistry, University of Sydney, Sydney N.S.W. 2006, Australia.
Harding
M M
MM
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D003517:Cyclopentanes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D003517:Cyclopentanes; D008024:Ligands; D009942:Organometallic Compounds; C013108:metallocene; C024389:molybdocene dichloride; C103086:niobocene dichloride; D005978:Glutathione; C020528:titanocene dichloride