Binding properties and stoichiometries of a palladium(II) complex to metallothioneins in vivo and in vitro

This paper will be the first to discuss the in vivo and in vitro properties of a Pd(II) complex, K2PdCl4, interacting with metallothioneins (MTs). In vivo experiments revealed that intraperitoneal injections of K2PdCl4 into r abbits led to the simultaneous synthesis of Pd-MT in the kidney and Zn7MT i n the liver. The renal Pd-MT complex contains 3.6 +/- 0.3 Pd, 2.1 +/- 0.2 Z n, and 1.0 +/- 0.1 Cu per mole protein. It was found that pre-treatment wit h Zn(NO3)(2) before K2PdCl4 injections significantly enhanced renal Pd-MT l evel. The same pre-treatment also increases hepatic Zn-MT levels. These res ults strongly suggest that Pd(II) ions can be bound in vivo by MT existing in the rabbit kidneys to form Pd-MT. Gel-filtration chromatographic studies after the incubation of either native Cd(5)Zn(2)MT2 or Zn(7)MT2 with K2PdC l4 in vitro demonstrate that Pd(II) ions promote the non-oxidative oligomer ization of native MTs. Increasing the level of Pd(II) relative to MT led to a concomitant increase in the apparent yield of MT oligomers. At relativel y low Pd-MT ratio, Pd(lI) is found predominantly in the oligomers while the monomeric products are chiefly composed of the reactants, Cd(5)Zn(2)MT2 or Zn(7)MT2. Based on our experimental data, the mechanisms of the reactions between Pd(II) and MTs in vivo and in vitro are discussed. (C) 1998 Elsevie r Science Inc. All rights reserved.