New method for bis (methylmercuric) selenide synthesis from methylmercuric chloride, sodium selenite and reduced glutathione

Chemosphere,Vol.10, No.4, pp 441 - 443, 1981 Printed in Great Britain

0045-6535/81/040441-03~02.00/0 ©1981 Pergamon Press Ltd.

NEW METHOD FOR BIS(METHYLMERCURIC) CHLORIDE,

SELENIDE

SYNTHESIS

SODIUM SELENITE AND REDUCED GLUTATHIONE

Akira Naganuma and Nobumasa Department

of Public Health,

Kitasato

FROM METHYLMERCURIC

University,

Imura*

School of Pharmaceutical

9-1 Shirokane

Sciences

5 chome, Minato-ku

Tokyo 108, Japan

ABSTRACT Bis(methylmercuric)

selenide

reaction of methylmercuric reduced glutathione and useful

[BMS,

chloride

or cysteine

(CH3Hg) 2Se] was obtained by the

and sodium selenite

in a reasonable

yield.

in the presence The reaction

of

is simple

for BMS synthesis.

INTRODUCTION Formation of bis(methylmercuric) mercury

and selenite

selenide

[BMS,

(CH3Hg) 2Se]

in animal tissues has been observed

(1,2).

from methylThe BMS

formation may take a role in modifying effect of selenium on methylmercury toxicity

(3,4,5).

from reaction

Breitinger

and Morel1

(6) reported that BMS was obtained

of H2Se with CH3HgBr in methanol

here a new simple method

for BMS synthesis

under nitrogen.

We describe

using reduced glutathione

(GSH)

and

Na2SeO 3 instead of H2Se.

MATERIALS Eight millimoles

AND METHODS

of GSH was dissolved

in i00 ml of distilled water and

pH of the solution was adjusted to 7.4 with NaOH. to the GSH solution

and dissolved

completely.

441

CH3HgCl

(i nm~ole) was added

To the solution was added

442

0.4 m m o l e of N a 2 S e O 3 and the m i x t u r e was shaken v i g o r o u s l y for a few minutes. The m i x t u r e was e x t r a c t e d w i t h 100 ml of b e n z e n e w a s h e d once w i t h 100 ml of 0.5% GSH s o l u t i o n w i t h 100 ml of d i s t i l l e d water. reduced pressure

Then,

to a b o u t 10 ml.

appeared.

The r e s i d u a l

(pH 7.4),

layer was

and further w a s h e d twice

the b e n z e n e was e v a p o r a t e d at 50°C under

To the r e s i d u a l b e n z e n e was added 15 ml of

ethanol and e v a p o r a t i o n was c o n t i n u e d

were r e c r y s t a l l i z e d

and the b e n z e n e

until

a trace of s i l v e r c r y s t a l s

s o l u t i o n was c o o l e d and silvery f l a k e - l i k e c r y s t a l s

from e t h a n o l

(under 60°C),

M a s s s p e c t r a were taken w i t h a J M S - D I 0 0

collected,

and d r i e d in vacuo.

s p e c t r o m e t e r using a d i r e c t inlet

system at 20 eV.

RESULTS A N D D I S C U S S I O N The r e a c t i o n of m e t h y l m e r c u r i c (0.4 mmole)

in the p r e s e n c e of GSH

chloride (8 mmoles)

p r o d u c t was i d e n t i f i e d as BMS by mp. (Calcd.

for C2H6Hg2Se:

C, 4.72%;

H, 1.29%;

G a n t h e r et al.,

Hg,

C, 4.70%; 79.46%;

(i mmole)

gave 134 mg of crystals.

(130°C, d e c o m p o s e d ) ,

H, 1.18%; Hg, Se,

15.60%)

78.64%;

On this m e t h o d for BMS

and Morell

(i), it s h o u l d be stored at -20°C.

(A)

.o

5~

109

o

.'_c 10(

4) cc

Since BMS is

(6) r e p o r t e d that the y i e l d of BMS by tile r e a c t i o n

10(

®

the

s e l e n i u m does not react w i t h

O p t i m u m pH of this r e a c t i o n was about 7.4.

at room t e m p e r a t u r e

Breitinger

Found: (Fig. i).

c h l o r i d e have to be added to GSH s o l u t i o n b e f o r e

a d d i t i o n of N a 2 S e O 3, b e c a u s e i n s o l u b l e e l e m e n t a l

unstable

Se, 15.48%.

The

analysis

(7) r e p o r t e d that N a 2 S e O 3 r e a c t e d w i t h GSH and the r e a c t i o n

methylmercuric

methylmercury.

elemental

and mass s p e c t r o m e t r y

gave i n s o l u b l e e l e m e n t a l s e l e n i u m as a final product. synthesis,

and s o d i u m selenite

(S)

201

,I

295

4iS

l,, I,

510

295

-"

,I

~

~

II.

~

I,

~

T

.~"

m/e

Fig. i. Mass spectra of BMS (A) and the product by the reaction of methylmercury and sodium selenite in the presence of GSH (B). BMS was synthesized by the method of Breitinger and Morell (6).

443

of CH3HgBr and H2Se was about 30%.

The present method using GSH and Na2SeO 3

instead of H2Se gave BMS in a higher yeild (about 66% from Na2SeO 3 used, after recrystallization)

than that of Breitinger and Morell

(6).

Cysteine was proved to be able to substitute for GSH in this reaction, giving BMS in a yeild of 62% and appeared to be preferable starting material because of its low price.

Together with the relatively high yield the sim-

plicity of the procedure seems to make this new synthetic method quite useful.

REFERENCES i.

Naganuma, A. and Imura, N.,

2.

Naganuma, A., Kojima, Y. and Imura, N., Res. Commun. Chem. Pathol. Pharma-

3.

Ganther, H. E., Gondie, C., Sunde, M. L., Kopecky, M. J., Wanger, P. A.,

163,

Res. Commun. Chem. Pathol. Pharmacol.,

(1980).

col.,

30, 301,

(1980).

Oh, S. E. and Hoekstra, W. G., Science, 4.

Iwata, H., Okamoto, H. and Ohsawa, Y., col.,

5.

5, 673,

175, 1122,

Res. Commun. Chem. Patho. Pharma-

Ohi, G., Nishigaki, S., Seki, H., Tamura, Y., Maki, T., Konno, H., Ochiai, 12, 49,

I. and Yague, H.,

Environ.

Inorg. Nucl. Chem. Letters,

10, 409,

(1976).

Breitinger,

D. and Morell, W.,

(1974). 7.

(1972).

(1973).

S., Yamada, H., Shimamura, Y., Mizoguchi, 6.

27,

Ganther, H. E.,

(Received in

Biochemistry,

Japan 24March 1901)

~, 2898,

(1968).

Res.,