Methylcobalamin methylation of chloroplatinate: Bound chloride, valence state, and relative mutagenicity

Abstract

A methyl‐Pt compound formed by incubating K₂PtCl₆ with methylcobalamin (MeB‐12) is further characterized with respect to its chloride content, its Pt oxidation state, and its electro‐phoretic mobility. The complexed chloride has been determined from nuclear magnetic resonance (NMR) spectra of the Cl displaced by competing thiocyanate (SCN ) anions. Release of 3 chlorides per Pt combined with a Me/Pt ratio of 1.0 indicates a metal coordination number of 4. This is in agreement with X‐ray photoelectron spectra (ESCA) which show that the majority of the Me‐Pt product contains Pt in the +2 valence state. Based on this data and the anionic nature of the product at pHs from 2.5–7.5 it 2‐is presently represented as MePtCl₃.

In comparison to the closely related complexes K₂PtCl₄ and K₂PtCl₆, MePtCl₃ ^‐2 is slightly less cytotoxic to an auxotrdphic Chinese hamster ovary cell line (CHO AUXB1). All three of these chloro‐Pt compounds at concentrations of 15–70 μ? induce a 6–10 fold increase in the frequency of CHO AUXB1 revertants. Revertants arising either spontaneously (frequency ca. 5 × 10^‐7) or induced with chloroplatinates or 4‐nitroquinoline‐N‐oxide (4‐NQO) regain a permanent capacity to grow in medium lacking glycine + adenosine + thymidine. In contrast to the corresponding chloroplatinates, K₂PdCl₄ and K₂PdCl₆ are not mutagenic in CHO AUXB1 as inducers of reversion to prototrophy. They are also 5–10 times less cytotoxic than the chloroplatinates in this CHO AUXB1 system.

Key words:

• MethylB‐12
• chloroplatinate
• methylation
• ³⁵C1^‐ NMR
• ESCA
• CHO AUXB1 reversion