Platinum tetrachloride: Mutagenicity and methylation with methylcobálamin

Abstract

It was reported earlier that methylcobalamin (MeB‐12) plus K₂PtCl₆ or Na₂PtCl₆ under acidic conditions yields a single square planar Pt²⁺ species, MePtCl^2‐ ₃. A reaction between MeB‐12 and PtCl₄ in H₂O has now been shown to occur. Complete demethylation requires two equivalents of PtCl₄ and MePtCl^2‐ ₃ is the principal product. In addition, a second Me‐Pt product has been detected and isolated. It has a Me/Pt ratio of 1.0, but it lacks the 260 nm absorption maximum of MePtCl^2‐ ₃ and it has a lower electrophoretic mobility at pH 4.5. The proton NMR spectrum of this product shows a typical triplet pattern, but the chemical shift of the center band and the spin coupling constant change with pH. Its NMR parameters suggest that this species is MePt(H₂O)Cl^1‐ ₂ (pKa ca. 4.5). A linear bridged intermediate is proposed to account for the methylation products obtained from MeB‐12 and K₂PtCl₆ (or PtCl₄) and the catalytic role of K₂PtCl₄.

As part of a systematic study of Pt‐complex mutagenesis, we also report quantitative data on the cytotoxicity and mutagenicity of PtCl₄ in two closely related Chinese hamster ovary lines, CHO‐S and CHO‐AUXB1. In CHO‐S cells PtCl₄ induces forward mutations to 8‐azaguanine resistance/hypoxanthine‐guanine phosphoribosyl transferase locus (8‐AG^R/HGPRT locus), but not to ouabain resistance (OUA^R). It also induces the reversion of CHO AUXB1, a triple auxotroph. The mutagenic effects of PtCl₄ in both CHO lines are dose dependent in the 5–30 μM concentration range.

Key words:

• MethylB‐12
• PtCl₄
• methylation
• ¹H NMR
• CHO cell mutagenicity