Molecular structures of thimerosal (merthiolate) and other arylthiolate mercury alkyl compounds

Article abstract of DOI:10.1021/ic8005426

The molecular structure of sodium ethylmercury thiosalicylate (also known as thimerosal and Merthiolate) and related arylthiolate mercury alkyl compounds, namely PhSHgMe and PhSHgEt, have been determined by single crystal X-ray diffraction. ¹H

Full text of DOI:10.1021/ic8005426

Inorg. Chem. 2008, 47, 6421-6426
Molecular Structures of Thimerosal (Merthiolate) and Other Arylthiolate
Mercury Alkyl Compounds
Jonathan G. Melnick, Kevin Yurkerwich, Daniela Buccella, Wesley Sattler, and Gerard Parkin*
Department of Chemistry, Columbia UniVersity, New York, New York 10027
Received March 26, 2008
The molecular structure of sodium ethylmercury thiosalicylate (also known as thimerosal and Merthiolate) and
related arylthiolate mercury alkyl compounds, namely PhSHgMe and PhSHgEt, have been determined by single
crystal X-ray diffraction. 1H NMR spectroscopic studies indicate that the appearance of the 199Hg mercury satellites
of the ethyl group of thimerosal is highly dependent on the magnetic field and the viscosity of the solvent as a
consequence of relaxation due to chemical shift anisotropy.
Introduction
Sodium ethylmercury thiosalicylate, [(ArCO )SHgEt]Na,
2
commonly known as thimerosal (Figure 1),1,2 is a contro-
versial vaccine preservative with proposed links to autism
in children, although the connection is being intensely
debated.3,4 Thimerosal was first introduced as a pharmaceuti-
cal ingredient in the early 1930s under the trade name
Merthiolate5 and found popular use for the topical treatment
of cuts and wounds.6 In addition to its use as a vaccine
preservative and as an antiseptic, other applications of
thimerosal that result from its antimicrobial properties
include: contact lens cleaners; soap-free cleansers; cosmetics;
Figure 1. Thimerosal.
eye, nose and ear drops; and skin test antigens.1,7 Considering
the widespread applications of thimerosal, and the fact that
many mercury compounds constitute a health risk,8 it is
* To whom correspondence should be addressed. E-mail: parkin@
columbia.edu.
surprising that the chemistry of this molecule is virtually
unknown9 and that its 3-dimensional structure has not been
(1) Geier, D. A.; Sykes, L. K.; Geier, M. R. J. Toxicol. EnViron. Health,
determined. Therefore, we report herein the molecular
structures of thimerosal and related arylthiolate mercury alkyl
compounds, namely PhSHgMe and PhSHgEt, as determined
by X-ray diffraction.
Part B 2007, 10, 575–596.
(2) In addition to the trade name Merthiolate, there are many other
synonyms for thimerosal, some of which include: thiomersal, elicide,
estivin, mercurothiolate, merfamin, merphol, merseptyl, mertorgan,
merzonin, and nosemack.
(3) (a) Blaxill, M. F.; Redwood, L.; Bernard, S. Med. Hypotheses 2004,
62, 788–794. (b) Geier, D. A.; Geier, M. R. J. Toxicol. EnViron. Health,
Part A 2007, 70, 837–851. (c) Baker, J. P. Am. J. Public Health 2008,
98, 2–11.
Results and Discussion
Structural and Spectroscopic Characterization of
Thimerosal. Although thimerosal was first reported in
192810–12 and subsequently found many applications, there
(4) (a) Bernard, S. New Eng. J. Med. 2008, 358, 93. (b) Rooney, J. P. K.
New Eng. J. Med. 2008, 358, 93–94. (c) Thompson, W. W.; Price,
C.; DeStafano, F. New Eng. J. Med. 2008, 358, 94.
(5) Powell, H. M.; Jamieson, W. A. Am. J. Hygiene 1931, 13, 296–310.
(6) Ohno, H.; Doi, R.; Kashima, Y.; Murae, S.; Kizaki, T.; Hitomi, Y.;
Nakano, N.; Harada, M. Bull. EnViron. Contam. Toxicol. 2004, 73,
777–780.
(8) Clarkson, T. W.; Magos, L. Crit. ReV. Toxicol. 2006, 36, 609–662.
(9) For two brief reports pertaining to the chemistry of thimerosal, see:
(a) Trikojus, V. M. Nature 1946, 158, 472–473. (b) Tan, M.; Parkin,
J. E. Int. J. Pharm. 2000, 208, 23–34.
(7) (a) Gil, S.; Lavilla, I.; Bendicho, C. J. Anal. At. Spectrom. 2007, 22,
569–572. (b) Fagundes, A.; Marzochi, M. C. A.; Perez, M.; Schubach,
A.; Ferreira, A.; Silva, J. P.; Schubach, T.; Marzochi, K. B. F. Acta
Trop. 2007, 101, 25–30. (c) Meyer, B. K.; Ni, A.; Hu, B.; Shi, L.
J. Pharm. Sci. 2007, 96, 3155–3167.
(10) Kharasch, M. S. U.S. Patent 1,672,615, 1928.
(11) For a later synthesis, see:(a) Swirska, A.; Kotler-Brajtburg, J.; Dahlig,
W.; Pasynkiewicz, S. Przem. Chem. 1960, 39, 371–372.
10.1021/ic8005426 CCC: $40.75  2008 American Chemical Society
Inorganic Chemistry, Vol. 47, No. 14, 2008 6421
Published on Web 06/06/2008

Melnick et al.
Table 1. Comparison of Bond Length (Å) and Bond Angle (deg) Data
for the Six Independent Molecules of [(ArCO )SHgEt]Na in the
2
Asymmetric Unit
d(Hg-C)/Å
d(Hg-S)/Å
C-Hg-S/deg
molecule #1
molecule #2
molecule #3
molecule #4
molecule #5
molecule #6
2.075(13)
2.081(13)
2.129(12)
2.094(11)
2.100(12)
2.075(16)
2.383(3)
2.364(3)
2.391(3)
2.376(3)
2.371(3)
2.363(3)
178.0(4)
176.9(4)
173.3(4)
176.5(4)
175.0(5)
176.8(7)
Table 2. Comparison of Average Bond Length (Å) and Bond Angle
(deg) Data for ArSHgEt
d(Hg-C)/Å
d(Hg-S)/Å
C-Hg-S/deg
[(ArCO )SHgEt]Na
2.07(1)
2.07(1)
2.383(3)
2.369(2)
178.0(4)
178.1(3)
2
PhSHgEt
for alkyl and thiolate compounds.13–16 Selected bond lengths
-
and angles for the [(ArCO )SHgEt] moieties are summarized
Figure 2. Asymmetric unit of thimerosal.
2
in Table 1, with the average values listed in Table 2.
In view of the unusual hexameric composition of the
asymmetric unit, it was important to establish whether the
derived structure of the crystal studied is representative of
the bulk material. Evidence that the crystal is indeed representa-
tive of the bulk was provided by the favorable comparison of
the experimental X-ray powder diffraction pattern (Mo radia-
tion) with that predicted on the basis of the atomic coordinates
and unit cell parameters; furthermore, the powder pattern
predicted for Cu radiation (Figure 4) corresponds closely to the
experimental data reported elsewhere.17
199Hg NMR spectroscopic studies are in accord with
thimerosal also possessing a linear two-coordinate geometry
in solution. Specifically, the 199Hg NMR chemical shift of
thimerosal is -784 ppm, which is within the range observed
for two-coordinate mercury thiolate compounds.18,19 The
signal is a well-resolved triplet of quartets, corresponding
to 2JHg-H and 3JHg-H coupling to the hydrogen atoms of the
Figure 3. Molecular structure of one of the anions of thimerosal in the
asymmetric unit.
1
ethyl group (Figure 5). Correspondingly, the H and 13C
NMR spectra exhibit 199Hg satellites (16.9% abundance), as
illustrated in Figures 6 and 7. JHg-C and JHg-H coupling
constant data are listed in Table 3. Of particular note, while
are almost no reported details pertaining to its structure,
spectroscopic properties and reactivity. For this reason, we
deemed it appropriate to determine the molecular structure
of thimerosal by X-ray diffraction.
The crystal structure of thimerosal (obtained from metha-
nol), as illustrated in Figures 2 and 3, is composed of a
(13) (a) Casa, J. S.; Garc´ıa-Tasende, M. S.; Sordo, J. Coord. Chem. ReV.
1999, 193-195, 283–359. (b) Holloway, C. E.; Meln´ık, M. J.
Organomet. Chem. 1995, 495, 1–31. (c) Rabenstein, D. L. Acc. Chem.
Res. 1978, 11, 100–107.
-
complex network consisting of [(ArCO )SHgEt] anions
2
connected to Na+ cations via both the oxygen and sulfur
atoms of the thiosalicylate ligand. The asymmetric unit
consists of six formula units of {[(ArCO )SHgEt]Na} that
(14) Wright, J. G.; Natan, M. J.; MacDonnell, F. M.; Ralston, D. M.;
O’Halloran, T. V. Prog. Inorg. Chem. 1990, 38, 323–412.
(15) The propensity of mercury to adopt linear coordination is often
attributed to relativistic effects which stabilize the 6s orbital, thereby
resulting in a large 6s-6p energy gap which limits the use of the 6p
2
differ in subtle ways. For example, some of the sodium ions
coordinate only to the carboxylate oxygen atoms, while other
2
orbitals, and to a small 5d-6s energy gap that favors linear sdz
hybridization. Other factors have also, nevertheless, been considered.
See, for example: (a) Pyykko¨, P.; Desclaux, J.-P. Acc. Chem. Res.
1979, 12, 276–281. (b) Pyykko¨, P. Chem. ReV. 1988, 88, 563–594.
(c) Kaupp, M.; von Schnering, H. G. Inorg. Chem. 1994, 33, 2555–
2564. (d) Tossell, J. A.; Vaughan, D. J. Inorg. Chem. 1981, 20, 3333–
3340.
sodium ions also coordinate to the sulfur atom. With respect
-
to the [(ArCO )SHgEt] moieties, the principal differences
2
are associated with the torsion angles involving the (ArCO
)
2
group, such that the Hg · · ·O distances within each unit range
(16) As observed for many linear mercury complexes, in addition to the
primary interactions, the mercury centers exhibit longer range second-
ary interactions to the thiolate sulfur atoms of adjacent molecules.
(17) Koundourellis, J. E.; Malliou, E. T.; Sullivan, R. A. L.; Chapman, B.
J. Chem. Eng. Data 2000, 45, 1001–1006.
from 2.71 Å to 4.91 Å. Other than the torsion angles, the
-
structures of [(ArCO )SHgEt] are similar, with each mercury
2
having the linear two-coordinate geometry that is common
(18) Wright, J. G.; Natan, M. J.; MacDonnell, F. M.; Ralston, D. M.;
O’Halloran, T. V. Prog. Inorg. Chem. 1990, 38, 323–412.
(19) (a) Almagro, X.; Clegg, W.; Cucurull-Sa´nchez, L.; Gonza´lez-Duarte,
P.; Traveria, M. J. Organomet. Chem. 2001, 623, 137–148. (b) Carlton,
L.; White, D. Polyhedron 1990, 9, 2717–2720.
(12) The name “thimerosal” for sodium ethylmercury thiosalicylate ap-
peared in the literature much later. For an early use of the name
“thimerosal”, see: Hughes, E. J. Drug Stand. 1952, 20, 121–124.
6422 Inorganic Chemistry, Vol. 47, No. 14, 2008

Thimerosal (Merthiolate)
shift anisotropy,21 a mechanism that not only applies to
199Hg,22 but other nuclei such as 31P,23 77Se,23b,24 57Fe,25
103Rh,26 195Pt,27 207Pb,28 and 205Tl.29,30 Specifically, for
situations in which the condition ω0τc , 1 is satisfied, the
relaxation component due to chemical shift anisotropy is
21
2
directly proportional to B0 . Thus, as the strength of the
magnetic field increases, w1/2 of the satellites increases such
3
that it is not possible to resolve the JH-H coupling.
Since relaxation via chemical shift anisotropy is influenced
by the rotational correlation time (τc), the line width of the
satellites is a function of the viscosity of the solvent.
Specifically, for ω0τc , 1, relaxation due to chemical shift
anisotropy is proportional to the rotational correlation time
(τc) which is dependent on the viscosity.21 For this reason,
the multiplet structure of the mercury satellites of the ethyl
group of thimerosal are much better resolved in methanol
(Figure 8) and acetone that have a lower viscosity than that
of water.31
Figure 4. Calculated powder pattern for thimerosal on the basis of the
experimental unit cell data (Cu radiation).
Structural Characterization of PhSHgMe and
PhSHgEt. Interestingly, while arylthiolate mercury com-
plexes of the type ArSHgR are known,19,32 structurally
characterized examples listed in the Cambridge Structural
Database33 are restricted to methyl and phenyl derivatives.
As such, we considered it worthwhile to determine the
(21) (a) Farrar, T. C.; Becker, E. D. Pulse and FT NMR; Academic Press:
New York, 1971. (b) Farrar, T. C. Introduction to Pulse NMR
Spectroscopy; The Farragut Press: Chicago, Madison, 1989. (c)
Thouvenot, R. L’Actualite Chimique 1996, 7, 102–111. (d) Kow-
alewski, J.; Ma¨ler, L. Nuclear Spin Relaxation in Liquids: Theory,
Experiments, and Applications; Taylor and Francis: New York, 2006.
(22) (a) Benn, R.; Gu¨nther, H.; Maercker, A.; Menger, V.; Schmitt, P.
Angew. Chem., Int. Ed. Engl. 1982, 21, 295–296. (b) Gillies, D. G.;
Blaauw, L. P.; Hays, G. R.; Huis, R.; Clague, A. D. H. J. Magn. Reson.
1981, 42, 420–428. (c) Cecconi, F.; Ghilardi, C. A.; Innocenti, P.;
Midollini, S.; Orlandini, A.; Ienco, A.; Vacca, A. J. Chem. Soc., Dalton
Trans. 1996, 2821–2826.
Figure 5. 199Hg NMR spectrum (53.75 MHz) of thimerosal in D2O.
1JHg-C (1316 Hz) is considerably larger than 2JHg-C (74 Hz),
2JHg-H (176 Hz) is significantly smaller than 3JHg-H (250 Hz).
(23) (a) Randall, L. H.; Carty, A. J. Inorg. Chem. 1989, 28, 1194–1196.
(b) Penner, G. H. Can. J. Chem. 1991, 69, 1054–1056.
2
3
A similar trend in JHg-H and JHg-H coupling constants is
(24) Wong, T. C.; Ang, T. T.; Guziec, F. S., Jr.; Moustakis, C. A. J. Magn.
Reson. 1984, 57, 463–470.
also observed for other EtHgX derivatives.20
Other interesting aspects of the H NMR spectrum of
(25) Baltzer, L.; Becker, E. D.; Averill, B. A.; Hutchinson, J. M.; Gansow,
O. A. J. Am. Chem. Soc. 1984, 106, 2444–2446.
1
thimerosal pertain to the chemical shifts of the CH2 and CH3
groups and the nature of the 199Hg satellites. With respect to
the chemical shifts, it is noteworthy that the 1H NMR
chemical shift of the CH2 group is downfield of the CH3
group (Figure 7), an order that is opposite to that for other
EtHgX derivatives (X ) CN, Br, Cl, NO3, I, ClO4), with
the exception of Et2Hg.20
(26) (a) Socol, S. M.; Meek, D. W. Inorg. Chim. Acta 1985, 101, L45-L46.
(b) Cocivera, M.; Ferguson, G.; Lenkinski, R. E.; Szczecinski, P.;
Lalor, F. J.; O’Sullivan, D. J. J. Magn. Reson. 1982, 46, 168–171.
(27) (a) Lallemand, J.-Y.; Soulie´, J.; Chottard, J.-C. J. Chem. Soc., Chem.
Commun. 1980, 436–438. (b) Anklin, C. G.; Pregosin, P. S. Magn.
Reson. Chem. 1985, 23, 671–675. (c) Benn, R.; Bu¨ch, H. M.;
Reinhardt, R.-D. Magn. Reson. Chem. 1985, 23, 559–564. (d) Dechter,
J. J.; Kowaleski, J. J. Magn. Reson. 1984, 59, 146–149. (e) Pregosin,
P. S. Coord. Chem. ReV. 1982, 44, 247–291. (f) Ismail, I. M.; Kerrison,
S. J. S.; Sadler, P. J. Polyhedron 1982, 1, 57–59. (g) Skvortsov, A. N.
Russ. J. Gen. Chem. 2000, 70, 1023–1027. (h) Hughes, R. P.; Sweetser,
J. T.; Tawa, M. D.; Williamson, A.; Incarvito, C. D.; Rhatigan, B.;
Rheingold, A. L.; Rossi, G. Organometallics 2001, 20, 3800–3810.
(i) Reinartz, S.; Baik, M.-H.; White, P. S.; Brookhart, M.; Templeton,
J. L. Inorg. Chem. 2001, 40, 4726–4732. (j) Reinartz, S.; White, P. S.;
Brookhart, M.; Templeton, J. L. Organometallics 2000, 19, 3854–
3866.
The feature of interest pertaining to the 199Hg satellites of
1
the H NMR spectrum is concerned with the fact that,
whereas the main signals associated with the ethyl group
consist of a well defined triplet and quartet, the satellites
are broad such that 3JH-H is not well resolved. Furthermore,
the appearance of the 199Hg satellites are dependent on the
magnetic field, with the ability to resolve 3JH-H coupling in
the satellites decreasing with increasing magnetic field
strength (Figure 7). The origin of the magnetic field
dependence of the satellites is due to relaxation by chemical
(28) (a) Hawk, R. M.; Sharp, P. R. J. Chem. Phys. 1974, 60, 1522–1527.
(b) Hays, G. R.; Gillies, D. G.; Blaauw, L. P.; Clague, A. D. H. J.
Magn. Reson. 1981, 45, 102–107.
(29) (a) Brady, F.; Matthews, R. W.; Forster, M. J.; Gillies, D. G. Inorg.
Nucl. Chem. Lett. 1981, 17, 155–159. (b) Hinton, J. F.; Ladner, K. H.
J. Magn. Reson. 1978, 32, 303–306. (c) Brady, F.; Matthews, R. W.;
Forster, M. J.; Gillies, D. G. J. Chem. Soc., Chem. Commun. 1981,
911–912. (d) Ghosh, P.; Desrosiers, P. J.; Parkin, G. J. Am. Chem.
Soc. 1998, 120, 10416–10422.
(20) Petrosya, V. S.; Reutov, O. A. J. Organomet. Chem. 1974, 76, 123–
(30) Benn, R.; Rufinska, A. Angew. Chem., Int. Ed. Engl. 1986, 25, 861–
881.
169.
Inorganic Chemistry, Vol. 47, No. 14, 2008 6423

Melnick et al.
Figure 6. 13C{1H} NMR spectrum (75.4677 MHz) of thimerosal in D2O.
Figure 7. 1H NMR spectra of Thimerosal in D2O as a function of the
magnetic field strength.
1
Table 3. H and 13C NMR Spectroscopic Data for the Ethyl Ligand of
Thimerosal in D2O
1H
13C
1
Figure 8. H NMR spectra of thimerosal in CD3OD as a function of the
δ(CH2) ) 1.65
δ(CH2) ) 28.3
magnetic field strength.
2
1
3JH-H ) 8; JHg-H ) 176
1JC-H ) 136; JHg-C ) 1316
δ(CH3) ) 1.26
δ(CH3) ) 15.9
exerts any influence on the coordination geometry of the
mercury center. The molecular structure of PhSHgEt, as
determined by X-ray diffraction, is illustrated in Figure 9,
while selected metrical data are summarized in Table 2.
3
2
3JH-H ) 8; JHg-H ) 250
1JC-H ) 126; JHg-C ) 74
molecular structure of the ethyl complex PhSHgEt34,35 to
evaluate whether the anionic subsituent on the phenyl group
6424 Inorganic Chemistry, Vol. 47, No. 14, 2008

Thimerosal (Merthiolate)
1
possesses a similar coordination geometry at mercury. H
NMR spectroscopic studies indicate that the appearance of
the 199Hg mercury satellites of the ethyl group of thimerosal
is highly dependent on the magnetic field and the viscosity
of the solvent, an observation that is attributed to relaxation
due to chemical shift anisotropy.
Experimental Section
General Considerations. All manipulations were performed
using a combination of glovebox, high-vacuum and Schlenk
techniques under a nitrogen or argon atmosphere, except where
otherwise stated. Solvents were purified and degassed by standard
procedures. NMR spectra were measured on Bruker 300 DRX,
Bruker 400 DRX and Bruker Avance 500 DMX spectrometers. For
solutions in organic solvents, 1H NMR spectra are reported in ppm
relative to SiMe4 (δ ) 0) and were referenced internally with respect
to the protio solvent impurity (δ 7.16 for C6D5H, 2.05 for (CD3)2CO,
Figure 9. Molecular structure of one of the crystallographically independent
molecules of PhHgEt in the asymmetric unit.
and 3.31 for CD3OD).36 For aqueous solutions, H and 13C NMR
1
chemical shift data are reported relative to the most upfield signal
of internal sodium 3-(trimethylsilyl)-1-propanesulfonate, also known
as sodium 2,2-dimethyl-2-silapentane-5-sulfonate, DSS (δDSS
)
0).37 199Hg NMR chemical shifts are reported relative to HgMe2
(δ ) 0) but in view of the toxicity of the latter compound, the
spectra were referenced externally with respect to HgI2 (1 M in
d6-DMSO, δ ) -3106).38 Coupling constants are given in hertz.
IR spectra were recorded as KBr pellets on a Nicolet Avatar DTGS
spectrometer, and the data are reported in reciprocal centimeters.
Thimerosal (Acros), MeHgCl (Aldrich), EtHgCl (Strem), and
PhSNa (Fluka) were obtained commercially. Crystals of Thimerosal
suitable for X-ray diffraction were obtained from methanol solution
at room temperature.
Figure 10. Molecular structure of PhHgMe.
Table 4. Comparison of Bond Length (Å) and Bond Angle (deg) Data
for ArSHgMe
Caution! All mercury compounds are toxic and appropriate
safety precautions must be taken in handling these compounds.
Ar
d(Hg-C)/Å d(Hg-S)/Å C-Hg-S/deg ref
1
C6H5
o-C6H4NO2
2.068(6)
2.08(2)
2.04(2)
2.074(14)
2.092(16)
2.383(2)
2.379(4)
2.366(4)
2.373(4)
2.379(4)
2.383(3)
2.379(3)
2.369(7)
2.384(8)
176.6(2)
176.4(5)
177.0(5)
175.5(5)
174.8(5)
178.7(4)
178.3(5)
176.5(11)
176.2(10)
Spectroscopic Data for Thimerosal. H NMR (D2O): 1.26 [t,
32f
19a
19a
19a
3JH-H ) 8, 3JH-Hg ) 249, 3 H of NaO2CC6H4SHgCH2CH3], 1.65 [q,
3JH-H )8, 3JH-Hg ) 173, 2 H of NaO2CC6H4SHgCH2CH3], 7.13-7.23
[m, 3H of NaO2CC6H4SHgCH2CH3], 7.49 [m, 1 H of NaO2CC6-
m-C6H4NH2
1
3
3
m-C6H4NdCHC6H4OH 2.071(12)
H4SHgCH2CH3]. H NMR (CD3OD): 1.35 [t, JH-H ) 8, JH-Hg
)
)
2.092(12)
2.05(4)
2.11(3)
232, 3 H of NaO2CC6H4SHgCH2CH3], 1.65 [q, 3JH-H ) 8, 3JH-Hg
p-C6H4NdCHC6H4OH
173, 2 H of NaO2CC6H4SHgCH2CH3], 7.00-7.07 [m, 2 H of
NaO2CC6H4SHgCH2CH3], 7.24 [m, 1H of NaO2CC6H4SHgCH2-
CH3], 7.41 [m, 1 H of NaO2CC6H4SHgCH2CH3]. 1H NMR ((CD3)2-
Evaluation of the data listed in Table 2 indicate that the
coordination geometries about mercury in neutral PhSHgEt
(31) Viscosity of water ) 0.890 cP; viscosity of methanol ) 0.544 cP;
viscosity of acetone ) 0.306. See: CRC Handbook of Chemistry and
Physics, 88th ed. (Internet Version 2008); Lide, D. R., Ed.; CRC Press/
Taylor and Francis: Boca Raton, FL; pp 175-179.
(32) (a) Bach, R. D.; Weibel, A. T. J. Am. Chem. Soc. 1976, 98, 6241–
6249. (b) Block, E.; Brito, M.; Gernon, M.; McGowty, D.; Kang, H.;
Zubieta, J. Inorg. Chem. 1990, 29, 3172–3181. (c) Systma, L. F.; Kline,
R. J. J. Organomet. Chem. 1973, 54, 15–21. (d) Sachs, G. Ann. Chem.
1923, 433, 154–163. (e) Scheffold, R. HelV. Chim. Acta 1967, 50,
1419–1422. (f) Aupers, J. H.; Howie, R. A.; Wardell, J. L. Polyhedron
1997, 16, 2283–2289.
-
and anionic [(ArCO )SHgEt] are similar, such that the ortho
2
carboxylate group does not significantly influence the Hg-Et
bond length.
In contrast to mercury ethyl compounds of the type
ArSHgEt, several mercury methyl counterparts have been
structurally characterized, with the exception of the parent,
PhSHgMe. Therefore, we have also determined the molecular
structure of PhSHgMe (Figure 10). Consideration of the data
in Table 4 indicates that the substituents, whether located in
the ortho, meta, or para positions, has little impact on the
mercury coordination geometry.
(33) Cambridge Structural Database (Version 5.28). 3D Search and
Research Using the Cambridge Structural Database; Allen, F. H.;
Kennard, O. Chemical Design Automation News 1993, 8 (1), 31–37.
(34) PhSHgMe and PhSHgEt were obtained by the reaction of RHgCl (R
) Me, Et) with NaSPh (see Experimental Section), which is a slight
modification of the general synthesis for R′SHgR involving the reaction
of RHgCl with NaOH and R′SH. See reference 32a.
Summary
(35) For an early report of PhSHgEt, see reference 32d.
(36) Gottlieb, H. E.; Kotlyar, V.; Nudelman, A. J. Org. Chem. 1997, 62,
7512–7515.
In conclusion, single crystal X-ray diffraction studies
demonstrate that, in the solid state, thimerosal consists of a
complex network that features six crystallographically in-
(37) Harris, R. K.; Becker, E. D.; Cabral de Menezes, S. M.; Goodfellow,
R.; Granger, P. Pure Appl. Chem. 2001, 73, 1795–1818.
(38) Kidd, R. G.; Goodfellow, R. J. In NMR and the Periodic Table; Harris,
R. K., Mann, B. E., Eds.; Academic Press: New York, 1978; p 268.
dependent {[(ArCO )SHgEt]Na} formula units, each of which
2
Inorganic Chemistry, Vol. 47, No. 14, 2008 6425

Melnick et al.
3
3
Table 5. Crystal, Intensity Collection, and Refinement Data
CO): 1.29 [t, JH-H ) 8, JH-Hg ) 230, 3 H of NaO2CC6H4SHg-
3
3
CH2CH3], 1.47 [q, JH-H ) 8, JH-Hg ) 173, 2 H of NaO2CC6-
H4SHgCH2CH3], 6.91-7.01 [m, 2 H of NaO2CC6H4SHgCH2CH3],
7.37-7.42 [m, 2 H of NaO2CC6H4SHgCH2CH3]. 13C NMR (D2O):
15.9 [q, 1JC-H ) 126, 2JHg-c ) 74, 1 C of NaO2CC6H4SHgCH2CH3],
28.3 [t, 1JC-H ) 136, 1JHg-C ) 1316, 1 C of NaO2CC6H4SHgCH2CH3],
128.0 [d,1JC-H ) 163, 1 C of NaO2CC6H4SHgCH2CH3], 128.2
thimerosal
PhSHgMe
PhSHgEt
lattice
formula
formula weight
space group
a/Å
monoclinic
C9H9O2SHgNa
404.8
orthorhombic
C7H8HgS
324.8
monoclinic
C8H10HgS
338.8
P21/c
Pbcn
Cc
14.653(1)
25.455(2)
17.730(1)
90
103.418(1)
90
23.863(1)
9.8304(5)
6.9604(4)
90
90
90
22.122(2)
10.893(1)
7.5251(8)
90
102.619(2)
90
1769.6(3)
8
243(2)
0.71073
2.543
17.555
28.27
6174
2928
183
b/Å
c/Å
[d,1JC-H ) 163, 1 C of NaO2CC6H4SHgCH2CH3], 130.5 [d, 1JC-H
)
160,1CofNaO2CC6H4SHgCH2CH3], 132.5 [s,1CofNaO2CC6H4SHg-
CH2CH3], 137.6 [d, 1JC-H ) 162, 1 C of NaO2CC6H4SHgCH2CH3],
147.0 [s, 1 C of NaO2CC6H4SHgCH2CH3], 181.4 [s, 1 C of
NaO2CC6H4SHgCH2CH3]. IR Data (KBr, cm-1): 3042 (w), 2962 (w),
2917 (w), 2862 (w), 1610 (m), 1586 (s), 1569 (vs), 1547 (s), 1464
(w), 1454 (m), 1425 (m), 1410 (m), 1394 (s), 1387 (vs), 1373 (s),
1260 (m), 1246 (w), 1233 (w), 1177 (m), 1098 (br), 1054 (m), 1035
(m), 837 (m), 802 (m), 745 (s), 714 (m), 704 (m), 677 (m), 649 (m).
199Hg NMR (D2O): -784 [tq, 2JHg-H ) 176, 3JHg-H ) 250].
Synthesis of PhSHgMe. A mixture of PhSNa (211 mg, 1.60
mmol) and MeHgCl (400 mg, 1.59 mmol) was treated with CH2Cl2
(20 mL), resulting in the immediate deposition of a white precipitate.
The mixture was stirred for 2 h, allowed to settle for 30 min and
filtered. The volatile components were removed in vacuo to give
PhSHgMe as a white powder (325 mg, 63% yield). Crystals of
composition PhSHgMe suitable for X-ray diffraction were obtained
from CH2Cl2. Mass spectrum: m/z ) 326.1{M }+. 1H NMR (C6D6):
0.19 [s, JHg-H ) 163, PhSHgCH3], 6.91 [t, JH-H ) 8,
p-C6H5SHgMe], 7.00 [t, 3JH-H ) 8, m-C6H5SHgMe], 7.46 [d, 3JH-H
) 8, o-C6H5SHgMe]. IR Data (KBr pellet, cm-1): 3062 (w), 2991
(w), 2908 (w), 1578 (m), 1473 (vs), 1445 (w), 1432 (m), 1324
(w), 1265 (w), 1161 (w), 1084 (s), 1067 (m), 1023 (s), 886 (w),
775 (m), 730 (vs), 694 (m), 686 (s).
Synthesis of PhSHgEt. A mixture of PhSNa (150 mg, 1.14
mmol) and EtHgCl (301 mg, 1.14 mmol) was treated with CH2Cl2
(25 mL), resulting in the immediate deposition of a white precipitate.
The mixture was stirred for 2 h, allowed to settle for 30 min and
filtered. The volatile components were removed in vacuo to give
PhSHgEt as a white powder (260 mg, 68% yield). Crystals of
composition PhSHgMe suitable for X-ray diffraction were obtained
from CH3CN. Mass spectrum: m/z ) 340.1{M }+. 1H NMR (C6D6):
0.75 [t, 3JH-H ) 8, 3JH-Hg ) 228, PhSHgCH2CH3], 0.95 [q, 3JH-H
R/deg
ꢀ/deg
γ/deg
V/Å3
6432.7(8)
24
1632.8(2)
8
Z
temperature (K)
radiation (λ, Å)
F(calcd.), g cm-3
µ(Mo KR), mm-1
θ max, deg
no. of data collected
no. of data used
no. of parameters
R1 [I > 2σ(I)]
wR2 [I > 2σ(I)]
GOF
125(2)
0.71073
2.508
14.559
31.69
108850
21546
758
243(2)
0.71073
2.642
19.019
28.34
10681
1971
83
0.0611
0.1126
1.037
0.0263
0.0523
1.031
0.0272
0.0720
1.092
or a Bruker P4 diffractometer equipped with a SMART CCD
detector. Crystal data, data collection, and refinement parameters
are summarized in Table 5. The structures were solved using direct
methods and standard difference map techniques and were refined
by full-matrix least-squares procedures on F2 with SHELXTL
(Versions 5.10 and 6.1).39 Powder diffraction data for thimerosal
were collected on a Bruker Apex II diffractometer, and the powder
diffraction pattern based on the single crystal data was calculated
with Mercury (Version 1.4.2).40
2
3
Acknowledgment. We thank the National Institutes of
Health (GM046502) for support of this research. The
National Science Foundation (CHE-0619638) is thanked for
acquisition of an X-ray diffractometer.
Supporting Information Available: Experimental details, com-
putational data, and crystallographic data in CIF format. This
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
3
3
) 8, JH-Hg ) 162, PhSHgCH2CH3], 6.89 [t, JH-H ) 8,
p-C6H5SHgEt], 6.97 [t, 3JH-H ) 8, m-C6H5SHgEt], 7.42 [d, 3JH-H
) 8, o-C6H5SHgEt]. IR Data (KBr pellet, cm-1): 3064 (w), 2965
(w), 2911 (w), 2856 (w), 1575 (m), 1473 (s), 1443 (w), 1433 (m),
1325 (w), 1229 (w), 1176 (w), 1161 (w), 1118 (w), 1083 (m), 1023
(m), 947 (w), 889 (w), 733 (vs), 692 (m), 687 (s), 677 (m).
X-ray Structure Determinations. Single crystal X-ray diffrac-
tion data were collected on either a Bruker Apex II diffractometer
IC8005426
(39) (a) Sheldrick, G. M. SHELXTL, An Integrated System for SolVing,
Refining and Displaying Crystal Structures from Diffraction Data;
University of Go¨ttingen: Go¨ttingen, Federal Republic of Germany,
1981. (b) Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112–122.
(40) http://www.ccdc.cam.ac.uk/mercury/, May 2008.
6426 Inorganic Chemistry, Vol. 47, No. 14, 2008