TY - JOUR
T1 - Methyl transfer from a hydrophobic vitamin B12 derivative to arsenic trioxide
AU - Nakamura, Koichiro
AU - Hisaeda, Yoshio
AU - Pan, Ling
AU - Yamauchi, Hiroshi
N1 - Funding Information:
This study was partially supported by “Collaborative Development of Innovative Seeds” from Japan Science and Technology Agency (JST) and a Grant-in-Aid for Scientific Research on Priority Areas (460) and the Global COE Program “Science for Future Molecular Systems” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan.
PY - 2009/3/15
Y1 - 2009/3/15
N2 - The methylation reaction of arsenic trioxide conducted at 37 °C and pH 7.0 for 24 h using hydrophobic methylated vitamin B12, (methyl) (aquo) heptamethylcobyrinate perchlorate, CH3B12 ester, as a methyl donor in the presence of reduced glutathione (GSH) yielded monomethylarsonous acid (MMA), dimethylarsinic acid (DMA), and trimethylarsine oxide (TMAO) as products with a methylation rate over 95%. In contrast, when methylcobalamin (CH3B12) was used as the methyl donor, only MMA and DMA were produced and the methylation rate dropped to around 20%. Reductive demethylation of a methyl-corrinoid coordination complex mediated by GSH is suggested as a mechanism of methyl transfer to arsenic trioxide. The differences observed for different corrinoid coordination complexes with respect to the reactivity of methyl transfer to arsenic is ascribable to differences inherent in the base-on (CH3B12) and base-off (CH3B12 ester) natures of the compounds.
AB - The methylation reaction of arsenic trioxide conducted at 37 °C and pH 7.0 for 24 h using hydrophobic methylated vitamin B12, (methyl) (aquo) heptamethylcobyrinate perchlorate, CH3B12 ester, as a methyl donor in the presence of reduced glutathione (GSH) yielded monomethylarsonous acid (MMA), dimethylarsinic acid (DMA), and trimethylarsine oxide (TMAO) as products with a methylation rate over 95%. In contrast, when methylcobalamin (CH3B12) was used as the methyl donor, only MMA and DMA were produced and the methylation rate dropped to around 20%. Reductive demethylation of a methyl-corrinoid coordination complex mediated by GSH is suggested as a mechanism of methyl transfer to arsenic trioxide. The differences observed for different corrinoid coordination complexes with respect to the reactivity of methyl transfer to arsenic is ascribable to differences inherent in the base-on (CH3B12) and base-off (CH3B12 ester) natures of the compounds.
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U2 - 10.1016/j.jorganchem.2008.12.002
DO - 10.1016/j.jorganchem.2008.12.002
M3 - Article
AN - SCOPUS:60749111184
SN - 0022-328X
VL - 694
SP - 916
EP - 921
JO - Journal of Organometallic Chemistry
JF - Journal of Organometallic Chemistry
IS - 6
ER -