Phenylmercury chloride: Its single-crystal X-ray structure and some aspects of its biological chemistry

Article abstract of DOI:10.1515/znb-2000-0107

A single crystal of phenylmercury chloride (PhHgCl) was obtained by serendipity from a solution of diphenylmercury (HgPh₂) and dihydrolipoic acid in tetrahydrofuran / carbon tetrachloride. The crystal structure of PhHgCl is pseudotetragonal. It is best described in the orthorhombic space group Cmma with a = 6.856(1), b = 6.882(1), c = 14.309(2) A (at 193 K), and Z = 4. The Cl-Hg-C moiety of the PhHgCl molecule is exactly linear. The bond lengths at the Hg atom are Hg-Cl 2.345(2) and Hg-C 2.044(9) A. In the crystal, the molecules are arranged in double layers parallel to the a,b plane. In a model medium for the gastric juice (0.1 M DCl in D₂O / [D₈]dioxan, 37 °C), HgPh₂ reacts to form PhHgCl. HgCl₂, which would result from complete dearylation, cannot be isolated from the reaction mixture. However, it appears that a small equilibrium concentration of HgCl₂ may be present, because on addition of 1,4,7-trithiacyclononane (ttcn) and diethyl ether, the dichloride can be trapped as solid [Hg(ttcn)₂][HgCl₄]. We estimate that after oral uptake of HgPh₂ 20 - 90% are transformed into PhHgCl in the stomach after 30 min.

Full text of DOI:10.1515/znb-2000-0107

Phenylmercury Chloride: Its Single-Crystal X-Ray Structure
and Some Aspects of its Biological Chemistry
Michaela Wilhelm, Wolfgang Saak, and Henry Strasdeit
Fachbereich Chemie, Universität Oldenburg, Carl-von-Ossietzky-Straße 9-11,
D-26129 Oldenburg, Germany
Reprint requests to Priv.-Doz. Dr. H. Strasdeit. E-mail: henry.strasdeit@uni-oldenburg.de
Z. Naturforsch. 55 b, 35-38 (2000); received October 18, 1999
Acidolysis, Bioinorganic Chemistry, Crystal Structure, Mercury, Organomercury Compounds
A single crystal of phenylmercury chloride (PhHgCl) was obtained by serendipity from
a solution of diphenylmercury (HgPh2) and dihydrolipoic acid in tetrahydrofuran / carbon
tetrachloride. The crystal structure of PhHgCl is pseudotetragonal. It is best described in the
orthorhombic space group Cmma with a = 6.856(1), b = 6.882(1), c = 14.309(2) A (at 193 K),
and Z = 4. The Cl-Hg-C moiety of the PhHgCl moleculeois exactly linear. The bond lengths
at the Hg atom are Hg-Cl 2.345(2) and Hg-C 2.044(9) Ä. In the crystal, the molecules are
arranged in double layers parallel to the a,b plane.
In a model medium for the gastric juice (0.1 M DC1 in D20 / [Dg]dioxan, 37 °C), HgPh2
reacts to form PhHgCl. HgCl2, which would result from complete dearylation, cannot be isolated
from the reaction mixture. However, it appears that a small equilibrium concentration of HgCl2
may be present, because on addition of 1,4,7-trithiacyclononane (ttcn) and diethyl ether, the
dichloride can be trapped as solid [Hg(ttcn)2][HgCl4]. We estimate that after oral uptake of
HgPh2 20 - 90% are transformed into PhHgCl in the stomach after 30 min.
Introduction
exposed to the gastric juice before they enter so-
matic cells. The gastric juice contains ca. 0.1 M
hydrochloric acid [91 and therefore might be able
to degradate phenylmercury compounds. Results of
model reactions are presented in this paper.
Phenylmercury chloride, PhHgCl, which was first
mentioned already in 1869 [1] is one of the sim-
plest organomercury compounds. There are conve-
nient methods for its preparation and crystalliza-
tion [2], but so far it has not been possible to grow
single crystals suitable for X-ray diffraction. Two
attempts at determining the crystal structure of Ph-
HgCl by powder methods were published [3, 4], In
both cases, however, the space group chosen was
not the appropriate one. This will be demonstrated
here on the basis of high-quality diffraction data of a
serendipitously obtained single crystal of PhHgCl.
Growing interest in the toxicity of organomer-
cury compounds stems from persistent ecological
concerns as well as from a recent case of lethal
dimethylmercury poisoning [5, 6], It is well known
that the symptoms of poisoning by phenylmercury
Results and Discussion
Crystal structure
PhHgCl has been described in the literature as
tetragonal (space group PMnmm\ a = 4.76, c =
1
4.32 A) [3] and as monoclinic (P2/n; a = b = 4.89,
c = 14.46 A; ß = 90.0°) [4], In the second work
the structure has been solved and refined from pow-
der data (Rp = 0.076). It is also mentioned there
that an appropriate description should be possible
in the orthorhombic space group Cmma with cell
dimensions a = b = 6.92 and c = 14.46 A.
We unintentionally obtained a diffraction-quality
single crystal of PhHgCl from an experiment
aiming at the growth of single crystals of
[Hg(PhHg)2(HlipS2)2] [10]. A solution of HgPh2
and dihydrolipoic acid [Hlip(SH)2] in tetrahydrofu-
ran had been prepared in a test tube. Carbon tetra-
(
(
PhHg+) resemble those of “inorganic” mercury
Hg2+) and differ strongly from those of methylmer-
cury (MeHg+) [7], These observations may be ex-
plained by the facile intracellular breaking of Hg-
phenyl bonds, probably by biological thiols [8 ].
On oral uptake, phenylmercury compounds are first chloride had been added to form a lower layer.
0
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M. Wilhelm et al. • Phenylmercury Chloride
Fig. 1. Molecular structure of PhHgCl drawn with 50%
probability ellipsoids. Both alternative orientations of
the phenyl group are shown. Selected bond lengths [A]
and angles [°]: Hg-Cl 2.345(2), Hg-Cl 2.044(9), C l-
C2 1.40(1), C2-C3 1.39(1), C3-C4 1.36(1); Cl-Hg-Cl
1
80.0, Hg-Cl-C2 120.3(5), C2-C1-C2' 119(1), C1-C2-
C3 119(1), C2-C3-C4 120(1), C3-C4-C3' 121(1).
After several months (initially under a protective
atmosphere of N2), most of the solvent had evap-
orated, and a yellow residue remained which con-
tained colourless crystals. At least some of these
crystals consisted of PhHgCl. It is not entirely clear
how this compound had formed. Razuvaev et al.
showed that HgPh2 reacts with CCI4 in the pres-
ence of tetrahydrofuran already at 100°C, the main
product being PhHgCl [11]. Possible organic prod-
ucts, e. g. PhCCl3, or products resulting therefrom
could not be detected in our reaction system. Ph-
HgCl, on the other hand, was clearly identified by
mass spectrometry [12]. This observation is impor-
tant for the interpretation of the crystallographic re-
sults, because it rules out the presence of PhHg(SH)
Fig. 2. Perspective view of a section of a PhHgCl double
layer. For one of the Hg atoms the van der Waals contacts
to four Cl neighbours are depicted as dashed lines.
gonal one having a = 4.857(1) and c = 14.309(2) A,
whereby one significant angular deviation, namely
7
= 89.79(2)°, must be neglected. Refinement in
the tetragonal space group PMnmm then leads to
very good residuals (R1 = 0.0175, wR2 = 0.0441,
S = 1.110 for all data). The Hg-Cl and Hg-C bond
lengths agree with those of the orthorhombic model
within less than \a . However, an additional disor-
der is imposed on the phenyl group as the molecule
is now situated on 4mm. The fact, that the two ring
positions are not exactly perpendicular to each other
[
13, 14], It is well known that the discrimination be-
tween SH and Cl is difficult or even impossible from
X-ray diffraction data alone (for a recent example
see ref. [15]).
The crystal structure of PhHgCl was solved by
direct methods and successfully refined in the or-
thorhombic space group Cmma [16], The final resid-
uals (for all data) are R \ = 0.0178 and wR2 = 0.0439.
The PhHgCl molecule lies on a crystallographic mm
position. Its phenyl group is disordered, adopting
two equally populated positions as shown in Fig. 1.
The two ring planes intersect at an angle of 86.7(3)°.
The lattice parameters a and b differ by only 0.4%,
which is, however, significant as judged by their es-
timated standard deviations. To a good approxima-
tion they result from the a axis of the earlier tetrag-
(
see above), results in a twofold splitting of each of
them. Taking all this together, the structure must be
regarded as pseudotetragonal, and the description in
Cmma appears more appropriate.
The molecular structure of PhHgCl is unexcep-
tional. The Hg atom is exactly linearly coordinated
with the Hg-Cl bond being slightly (0.01 A) longer
than the longest Hg-Cl bonds found in compara-
ble aryl-Hg-Cl compounds [17]. The Hg-Cl bond
length is at the lower end of the usual range for Hg-
C(aryl). In the crystal, the PhHgCl molecules are ar-
ranged as sheets which are parallel to the a,b plane.
onal description [3] by multiplication with \[ l. The
orthorhombic cell can be transformed into a tetra-
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M. Wilhelm et al. ■Phenylmercury Chloride
37
These sheets partly interpenetrate to form double
layers (see Fig. 2). Each double layer bears phenyl
groups above and below, while its inner part consists
of the Hg and Cl atoms. Each Hg atom is surrounded
by four Cl atoms of neighbouring molecules, and
vice versa. The corresponding H g -C l distances are
of the HgPh2 are transformed into PhHgCl within
15 min (80% within 60 min, 90% within 120 min).
The interpretation of these data must take into ac-
count that the concentration of DC1 decreases from
initially 130 mM to 80 mM (40 mM) when 50%
(90%) of the HgPh2 has reacted. Consequently, the
reaction slows down due to a decrease in concen-
3
.43 and 3.45 A - too long for even weak (“sec-
ondary”) covalent interactions, because the sum of tration of both reaction partners. From the starting
the van der Waals radii of Hg and Cl probably falls
in the range 3.4 - 3.5 A [18]. Within each single
layer, only edge-to-face arrangements of the phenyl
groups, as found in crystals of benzene [19], are
possible. The resulting alternating orientations can
easily be recognized in the lower part of Fig. 2. Any
phase of the reaction the half-time can be roughly
estimated at ca. 10 min. This value is very similar
to the one obtained for the half-time of the aci-
dolysis of HgPh2 by perchloric acid (water, pH 1,
25 °C) [22], In conclusion, we can estimate that in
the stomach 20 - 90% of the HgPh2 are transformed
phenyl group that adopts the “wrong” disorder posi- into PhHgCl within the first 30 min.
tion would form four intermolecular H H contacts
of less than 1.0 A !Thus, the disorder can occur from
one single layer to the next along the c axis, but not
within a single layer. There are no indications that
this disorder is not statistical.
Even at an initial DCl-to-HgPh2 ratio of ca. 2.6:1,
no further reaction of PhHgCl to HgCl2 was ob-
served (see Experimental Part). After 14 d at 37 °C,
PhHgCl was isolated as the only product. Addi-
tion of 1,4,7-trithiacyclononane (ttcn) has no effect,
i. e. there is no donor activation of PhHgCl by ttcn.
Ttcn serves as a model for biological thioethers like
methionine which are potential ligands for PhHgCl
even in strongly acidic media. However, when di-
ethyl ether is allowed to diffuse via the gas phase
into the ttcn containing reaction mixture, the poorly
soluble complex salt [Hg(ttcn)2][HgCl4] crystal-
lizes. It was identified by X-ray structure determina-
tion [23]. This result indicates that a low equilibrium
concentration of HgCl2 may be present also in the
ttcn free system.
Protonolysis o f H gPh2 by hydrochloric acid under
near-physiological conditions
After oral uptake, HgPh2 remains in the stomach
for a maximum period of 1 - 3 h. During this time,
it is in contact with the gastric juice which typi-
cally contains ca. 120 mM hydrochloric acid [9].
We have modelled this situation in a HgPh2 / DC1
/
D2O / [Dgjdioxan reaction system (for details see
Experimental Part). The use of [D8]dioxan was nec-
essary to dissolve HgPh2 which is poorly soluble in
water alone. The reaction rate of the formation of
PhHgCl according to
Experimental Part
Caution! Phenylmercury compounds are highly toxic.
Any swallowing, contact to skin or inhalation of dusts
must strictly be avoided. When solutions of these com-
pounds are handled, it is recommended to wear the special
combination of gloves specified in ref. [5, 6].
HgPh2 + HC1 -»> PhHgCl + C6H6
is probably no more than one order of magnitude
larger in our 80% dioxan system than in purely
aqueous solution. This can be inferred from the
results of early investigations on the acidolysis of
HgPh2 which, however, did not have any biological
background [20, 21]. The substitution of HC1 by
DC1 should have only a small effect on the reaction
rate [20]. Thus the conditions in our model system
are not very different from the physiological ones,
except for the high concentration of HgPh2 neces-
sary for NMR detection.
Crystal structure determination
A suitable single crystal of PhHgCl was obtained as de-
scribed in the previous section. It was mounted on the top
of a glass capillary on a STOEIPDS area detector diffrac-
tometer. MoÄa radiation (A = 0.71073 A) was used for
intensity data collection. Crystal data: CöHsClHg, Mr =
3
13.15, orthorhombic, space group Cmma\ a = 6.856(1),
b = 6.882(1), c = 14.309(2) A; V = 675.1(2) A3, Z = 4,
Pcaic = 3.081 gem-3 , n(M oKa) = 230.8 cm-1, crystal
size: 0.44 x 0.38 x 0.03 mm, T = 193 K, 178 expo-
sures, A^p = 1.8°, 5.7 <2<9 < 52.0°, completeness to
The main results from a typical experiment (see
Experimental Part) are the following. At 37 °C, 50%
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2
8
M. Wilhelm et al. ■Phenylmercury Chloride
(9 = 52.0°: 97.2%; reflections: 4093 collected, 385 in-
The initial concentrations were ca. 130 mM DC1 and
100 mM HgPh2. Starting immediately after the addition
of the DC1, a series of l3C NMR spectra was recorded at
37 °C over a period of 3 h. The relative concentrations of
HgPh2 and the reaction product PhHgCl were estimated
from the peak heights of the signals of the ortho-C atoms.
HgPh2: 6 = 128.36 ip-C), 128.91 (m-C), 138.44 (o-C),
171.54 (ipso-C)\ PhHgCl: 6 = 129.35 (p-C), 129.49 (m-
C), 137.24 (o-C), 150.74 (ipso-C)\ [Dg]dioxan as internal
standard at 6 = 66.50.
In a further experiment, an analogous sample was pre-
pared which contained, however, twice the amount of
DC1. Hence, the ratio of DC1 to HgPh2 was sufficiently
high to allow the hypothetical transformation of HgPh2
to HgCl2 to proceed completely. After the sample had
stood at 37 °C for 14 d, HgPh2 was no longer detectable
by NMR spectroscopy. The solvent was evaporated, and
the white solid residue was dried in vacuo. Cl analysis:
calcd for HgCl2: 26.1%, for PhHgCl: 11.3%; found for
the residue: 10.9%.
dependent (/?int = 0.0503), 376 observed [I > 2cr(/)]; nu-
merical absorption correction, min./max. transmission:
0
0
.0351/0.5444, refinement on F2, 36 parameters, R 1 =
.0173 [/ > 2cr(/)], wR2 = 0.0439 (all data), max./min.
residual electron density: +1.62/—0.61 eA- \ All non-
hydrogen atoms were anisotropically refined. The hy-
drogen atoms were included on idealized positions. Pro-
grams used were the SHELX-97 program package [16]
and DIAMOND [24], Further details of the structure
determination have been deposited with the Cambridge
Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK (fax: (+44)1223-336-033; e-mail:
deposit@ccdc.cam.ac.uk), and may be obtained by quot-
ing the deposition no. CCDC 135477, the authors' names
and the literature citation.
Reaction o f diphenylmercury with hydrochloric acid
A typical experiment, in which the time course of the
reaction between HgPh2 and DC1 was studied, was con-
ducted as follows. HgPh2 (44 mg, 125 /imol) was dis-
solved in D20 / [Da]dioxan (0.20 ml /1.00 ml) in an NMR
sample tube. An initial l3C NMR spectrum (75 MHz) was
recorded at 37 °C. After addition of a 20% solution of DC1
in D20 (24.4 p\, 157 /imol), the sample was kept at 37 °C.
Acknowledgements
We are grateful to the Deutsche Forschungsgemein-
schaft (DFG) and the Fonds der Chemischen Industrie
for financial support.
[1] E. Dreher, R. Otto, Ber. Dt. Chem. Ges. 2, 542 (1869);
R. Otto, Ber. Dt. Chem. Ges. 2, 641 (1869).
[13] Dihydrolipoic acid can be regarded as a potential SH-
source.
[
2] See for example: “Synthetic Methods of Organometallic
and Inorganic Chemistry (Hermann/Brauer)”, Ed. W. A.
Herrmann, Vol. 5, p. 233ff, Thieme, Stuttgart (1999).
3] V. I. Pakhomov, Zh. Strukt. Khim. 4, 594 (1963); C. A. 59,
[14] PhHg(SH) appears to be an isolable compound: M. Döring,
G. Hahn, M. Stoll, A. C. Wolski, Organometallics 16, 1879
(1997); I. A. Koten, R. Adams, J. Am. Chem. Soc. 46,
2764 (1924). For the first structurally characterized mer-
cury complex with a terminal SH~ ligand see: U. Brand,
J. R. Shapley, Inorg. Chem. 37, 5697 (1998).
[15] B. M. Segal, H. R. Hoveyda, R. H. Holm, Inorg. Chem.
37, 3440(1998).
[
1
0839c (1963).
4] J. Fayos, G. Artioli, R. Torres, J. Crystallogr. Spectrosc.
Res. 23, 595 (1993).
5] D. W. Nierenberg, R. E. Nordgren, M. B. Chang, R. W.
[
[
Siegler, M. B. Blayney, F. Hochberg, T. Y. Toribara, E. Cer-
nichiari, T. Clarkson, New England J. Med. 338, 1672
[16] G. M. Sheldrick, SHELX-97, University of Göttingen
(1997).
(
1998).
6] H. Strasdeit, Nachr. Chem. Tech. Lab. 46, 846 (1998).
7] L. W. Chang in “Toxicology of Metals”, Ed. L. W. Chang,
p. 512f, CRC Press, Boca Raton, FL (1996).
[17] Cambridge Structural Database (CSD), Version 5.15
(April 1998, 181309 entries); F. H. Allen, O. Kennard,
Chem. Des. Autom. News 8, 1 and 31 (1993).
[18] J. G. Wright, M. J. Natan, F. M. MacDonnell, D. M. Ral-
ston, T. V. O’Halloran, Prog. Inorg. Chem. 38, 323 (1990)
and literature cited therein.
[
[
[
8] H. Strasdeit, A. von Döllen, W. Saak, M. Wilhelm, Angew.
Chem., in press.
[
9] J. G. Forte in “Comprehensive Human Physiology”, Eds.
R. Greger, U. Windhorst, Vol. 2, Chapter 61, Springer,
Berlin (1996).
[19] G. A. Jeffrey, J. R. Ruble, R. K. McMullan, J. A. Pople,
Proc. R. Soc. Lond. A 414, 47 (1987).
[20] R. E. Dessy, G. F. Reynolds, J.-Y. Kim, J. Am. Chem. Soc.
[10] The crystal structure of this trinuclear complex is described
81,2683 (1959).
in [8],
[21] F. Kaufman, A. H. Corwin, J. Am. Chem. Soc. 77,
6280(1955).
[22] N. L. Wolfe, R. G. Zepp, J. A. Gordon, G. L. Baughman,
Chemosphere 1, 273 (1972).
[
11] G. A. Razuvaev, S. F. Zhil’tsov, G. I. Anikanova, T. V.
Guseva, Dokl. Akad. Nauk SSSR 225, 336 (1975); Engl,
transl.: Dokl. Chem. 225, 637 (1976).
[
12] El mass spectra of PhHgCl are available on the Internet via
[23] M. Wilhelm, W. Saak, H. Strasdeit, manuscript in prepa-
ration.
the following URLs:
a) http://webbook.nist.gov/chemistry/name-ser.htm;
b) http://www.aist.go.jp/RIODB/SDBS/menu-e.html.
[24] DIAMOND - Visual Crystal Structure Information Sys-
tem, Version 2.1, CRYSTAL IMPACT, Bonn (1999).
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