Novel polynuclear platinum adducts detected during the reactions of [Pt(Met-S,N)Cl2] with gamma-glutathione and L-cysteine.
The reactions of platinum(II) complexes with thiol containing molecules are highly relevant to the mechanism of action of platinum-based drugs. This work presents the electrospray mass spectrometry (ESMS) and NMR results on the reactions of [Pt(l-MetH-S,N)Cl(2)] (l-MetH: l-methionine) with gamma-glutathione (GSH) and l-cysteine (l-Cys) at different pH and different molar ratios. Polymeric species such as [Pt(2)(micro-SG-S)(2)(Met-S,N)(2)], [Pt(3)(micro-SG-S)(4)(Met-S,N)(2)], [Pt(4)(micro-SG-S)(6)(Met-S,N)(2)] and [Pt(5)(micro-SG-S)(8)(Met-S,N)(2)] (l-Met: deprotonated l-methionine) were detected and were stable for long hours. For both reactions, the polymerization extent decreased with the increase of pH. For the reaction of l-Cys, only mononuclear complex [Pt(l-Met-S,N)(l-Cys-S,N)] was observed when pH>9. The observation and identification of polymeric (higher than binuclear) adducts of Pt(II)/GSH and Pt(II)/l-Cys appears to be unprecedented.
Liu
Qin
Q
State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, Nanjing University, 210093 Nanjing, PR China.
Wei
Haiying
H
Lin
Jun
J
Zhu
Longgen
L
Guo
Zijian
Z
D002945:Cisplatin / Q000737:chemistry / Q000633:toxicity; D003545:Cysteine / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D017671:Platinum Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D017671:Platinum Compounds; D005978:Glutathione; D003545:Cysteine; D002945:Cisplatin