Group 10: platinum anticancer agents

Group 10: platinum anticancer agents

Group 10 of the periodic table of elements consists of the nonradioactive members nickel (Ni), palladium (Pd) and platinum (Pt) as well as the radioactive element darmstadtium (Ds) (Figure 7.14).

The noble metals palladium and platinum are resistant to corrosion and can be attacked by O₂, F₂ and Cl₂ only at very high temperatures. Palladium dissolves in hot oxidising acids, whereas platinum dissolves in only ‘aqua regia’ (1 : 3 mixture of HNO₃ and HCl).

Palladium is used as a hydrogenation catalyst, for H₂/D₂/T₂ separation and purification as well as a catalyst in the Wacker process. The Wacker process, which facilitates the oxidation of ethylene to acetaldehyde, was the first organopalladium reaction that was applied on an industrial scale. Platinum is also intensively used as a catalyst, for example, in HNO₃ production, as oxidation catalysts, in petroleum reforming, in hydrogenations and in many more chemical processes, as well as for jewellery.

All three nonradioactive elements of group 10 show a high diversity in their electronic configuration (Figure 7.15).

Most stable oxidation states are +II for all three nonradioactive elements, whereas Pt(II) and Pt(IV) are not only stable but also kinetically inert. The bromide and iodide salts of Pt(II) and Pd(II) are insoluble. Pt(II) has an electron configuration of d⁸, and the square planar geometry is the dominant structure. The [PtCl₄]²⁻ anion is an example where this square planar geometry is adapted. It is a stable anion, and indeed most platinum(II) chemistry starts with K₂[PtCl₄].

[PtCl₄]²⁻ is also the starting material for the synthesis of cis-diamminedichloroplatinum(II) (cisplatin, CDDP), a widely used chemotherapeutic drug (see Figure 7.16). The first NH₃ ligand is added to any of the four positions around the central Pt atom, as all four positions are equivalent. The second NH₃ will be directed cis to the first NH₃ group and cisplatin is obtained. The reason is that the Cl⁻ ligands have a larger so-called trans effect than NH₃ (Figure 7.17).

The trans effect or trans labellising effect is mainly seen in square planar complexes and describes the ability of some ligands to direct newly added ligands into the trans position. The intensity of the trans effect increases in the following order: F⁻, H₂O, OH⁻ < NH₃ < py < Cl⁻ < Br⁻ < I⁻, SCN⁻, NO₂⁻ < SO₃²⁻ < CH₃⁻ < H⁻, NO, CO, CN⁻.

In comparison, if the synthesis is started from Pt(NH₃)₄²⁺, transplatin is obtained. Again, the addition of the first ligand, in this case Cl⁻, can occur at any of the four positions. The addition of the second Cl⁻ ligand will be directed into the trans position by the initial Cl⁻ ligand as it has a higher trans effect than the NH₃ ligand (Figure 7.18).