Reaction of a platinum(IV) complex with native Cd,Zn-metallothionein in vitro.
The first observation of a redox process following a substitution reaction between a platinum(IV) complex K2PtCl6 with rabbit liver native Cd,Zn-MT is presented. The reaction features and products are studied by UV-visible and circular dichroism spectroscopy, chromatography, and X-ray photoelectron spectroscopic measurements. It is a significant complicated reaction comprising redox and substitution reactions. The reaction generates monomeric and dimeric products, and higher oligomers precipitate with intra- or intra- and intermolecular CyS-SCy linkages. Pt(IV) is reduced to Pt(II), which then binds to the monomeric and dimeric products, and may also bind to higher oligomers. The beta-cluster is more reactive than the alpha-cluster, and reacts first with K2PtCl6. Cd5Pt2 and Cd4Pt4 were found when native Cd,Zn-MT reacted with 2 and 4 molar equivalents of Pt(IV) for 2 h in which four Cd ions were located in the alpha-cluster. The amounts of Cd and Pt ions decreased in both monomeric and dimeric products when the reaction was prolonged and intramolecular CyS-SCy linkages increased. Besides the oligomers which precipitated, only dimeric products were formed when the reaction molar ratio of Pt(IV) to MT was more than 10:1. Cd3Pt6 and Cd1Pt8 were obtained when the reaction occurred for 2 and 72 h, respectively. The structure of the clusters may exist when native Cd, Zn-MT reacts with substoichiometric quantities of K2PtCl6 (< 0.5 K2PtCl6 per MT thiolate) for a short time (2 h), but may be partly disrupted with stoichiometric or excess quantities of K2PtCl6 (> or = 0.5 K2PtCl6 per MT thiolate) for a long time. The disruption of the cluster structures results in an increase of the nonbridge thiolate and an increase of the binding sites to Pt ions. The mechanism of the antitumor activity and developing drug resistance of Pt(IV) complex drugs is discussed.
Zhong
W
W
State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, Nanjing University, P.R. China.
Zhang
Q
Q
Yan
Y
Y
Yue
S
S
Zhang
B
B
Tang
W
W
D000818:Animals; D001665:Binding Sites; D002104:Cadmium / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D002942:Circular Dichroism; D008668:Metallothionein / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010984:Platinum / Q000737:chemistry / Q000378:metabolism*; D017671:Platinum Compounds; D011817:Rabbits; D013057:Spectrum Analysis / Q000379:methods; D014466:Ultraviolet Rays; D015032:Zinc / Q000378:metabolism*
D017671:Platinum Compounds; D002104:Cadmium; D010984:Platinum; D008668:Metallothionein; D015032:Zinc