[(C3H4N2)2Au] Cl - A bis protic gold(i)-NHC

Article abstract of DOI:10.1039/c0dt01089h

The gold(i) bis-NHC (NHC = imidazol-2-ylidene) parent compound was synthesised in high yield by a three step reaction starting from imidazole. The compound is highly water soluble and stable in concentrated hydrochloric acid.

Full text of DOI:10.1039/c0dt01089h

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[(C3H4N2)2Au]Cl—a bis protic gold(I)-NHC†
Peter C. Kunz,*a Corinna Wetzel,a Susanne Ko¨gel,b Matthias U. Kassackb and Bernhard Spinglerc
Received 23rd August 2010, Accepted 18th October 2010
DOI: 10.1039/c0dt01089h
The gold(I) bis-NHC (NHC = imidazol-2-ylidene) parent
compound was synthesised in high yield by a three step
reaction starting from imidazole. The compound is highly
water soluble and stable in concentrated hydrochloric acid.
protected with triethyl orthoformate, subsequently lithiated in 2-
position and reacted with [(tht)AuCl] (tht = tetrahydrothiophene).
The resulting anionic gold(I) bis(imidazolid) was protonated by
CF3SO3H to give the N-protected bis-NHC (1, Fig. 1), which was
then deprotected in concentrated hydrochloric acid under reflux
for 6 h to give the parent bis-NHC gold(I) compound (2) in nearly
quantitative yield (Scheme 2) as a white microcrystalline solid.‡
Since the first synthesis of stable N-heterocyclic carbenes (NHCs)
as a “chemical curiosity” their application as versatile catalysts
has stimulated the field and numerous stable carbenes and metal
complexes have been prepared. The imidazol-2-ylidenes are the
most commonly used NHC, although other NHCs are known.1,2
The stability of the metal–carbon bond under physiological
conditions has recently allowed therapeutic investigations. Most
of them are related to their use as antimicrobials and anti-cancer
agents.3–10
Usually, both N-atoms of the imidazol-2-ylidene NHCs are
alkylated. A few examples exist where only one N-atom is
alkylated and one is protonated.11–13 Bis protic NHNH car-
benes have been reported in complexes of imidazolidin-2-ylidenes
and benzimidazol-2-ylidines.14–16 The parental NHC, imidazol-2-
ylidene, which is a tautomer of imidazole, and its metal complexes
have been explored theoretically to calculate structural and
electronic parameters of NHC complexes.11,17–24 These “NHNH”
NHCs can not be obtained using Arduengos route via deprotona-
tion of the imidazolium ion.
Scheme 2
We have developed a simple route towards a bis protic gold(I)-
NHC starting from imidazole (Scheme 1). Imidazole was first N-
The bis protic gold(I)-NHC complex 2 is with 185 g L-1 very
soluble in water. The distribution coefficient at pH 7.4 (logP7.4) in
a n-octanol/water has been determined to be -0.87 and therefore 2
is more hydrophilic than analogues gold(I) bis(NHC) chlorides.25 It
is thermally stable and decomposes at temperatures above 190 ◦C.
Scheme 1
Table 1 Selected experimentally determined structure parameters of
2 compared to calculated ones (HF/DFT (B3LPP/LANL2DZ and
BHANH/LANL2DZ) and DFT (BP86))11,17
aInstitut fu¨r Anorganische Chemie und Strukturchemie, Heinrich-Heine-
University Du¨sseldorf, Universita¨tsstr. 1, D-40225, Du¨sseldorf, Germany.
E-mail: peter.kunz@uni-duesseldorf.de; Fax: +49 (0)211 81-12287;
Tel: +49 (0)211 8112873
Exp.a
HF/DFT11,a
DFT19
˚
Distance/A
Au–Ccarbene
bInstitut fu¨r Pharmazeutische und Medizinische Chemie, Heinrich-Heine-
University Du¨sseldorf, Universita¨tsstr. 1, D-40225, Du¨sseldorf, Germany.
E-mail: matthias.kassack@uni-duesseldorf.de; Fax: +49 (0)211 81-10801;
Tel: +49 (0)211 8114587
2.015
1.344
1.375
1.360
2.027
1.360
1.393
1.364
2.030
1.357
1.385
1.361
C
carbene–N
N–C
C–C
cAnorganisch-Chemisches Institut, Universita¨t Zu¨rich-Irchel, Winterthur-
erstr. 190, CH-8057, Zu¨rich, Switzerland. E-mail: spingler@aci.uzh.ch;
Fax: +41 (0)44 6356803; Tel: +41 (0)44 6354656
Angle/◦
† Electronic supplementary information (ESI) available: Experimental
details of the cell toxicity tests of 2. CCDC reference numbers 775874–
775875. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c0dt01089h
N–C–N
104.1
106.2
103.3
a Averaged.
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Fig. 1 Molecular structure of 1 with partial labelling. Displacement
ellipsoids are drawn at 50%. Hydrogen bonds are◦ indicated by
Fig. 2 Molecular structure of 2 with partial labelling. Displacement
˚
dashed lines. Selected bond lengths (A) and angles ( ): Au(1)–C(1)
ellipsoids are drawn at 50%. Hydrogen◦bonds are indicated by dashed lines.
1.999(10), Au(1)–C(4) 2.007(9), C(1)–N(1) 1.359(10), C(1)–N(2)
1.361(12), C(4)–N(3) 1.384(11), C(4)–N(4) 1.323(12); C(1)–Au(1)–C(4)
179.1(4), Au(1)–C(1)–N(1) 130.8(7), Au(1)–C(1)–N(2) 126.0(6),
Au(1)–C(4)–N(3) 129.5(7), Au(1)–C(4)–N(4) 125.5(7), N(1)–C(1)–N(2)
103.1(7), N(3)–C(4)–N(4) 105.0(8).
˚
Selected bond lengths (A) and angles ( ): Au(1)–C(1) 2.013(4), Au(1)–C(4)
2.018(4), Au(2)–C(7) 2.015(4), C(1)–N(1) 1.345(4), C(1)–N(2) 1.337(4),
C(4)–N(3) 1.358(4), C(4)–N(4) 1.346(4), C(7)–N(7) 1.342(5), C(7)–N(8)
1.341(4); C(1)–Au(1)–C(4) 176.67(13), C(7)–Au(2)–C(7¢) 178.31(18),
N(1)–C(1)–N(2) 104.1(3), N(3)–C(4)–N(4) 103.7(3), N(7)–C(7)–N(8)
104.2(3).
The structural parameters of 2 are in good agreement
with those calculated by Raubenheimer et al.11 at HF/DFT
(B3LPP/LANL2DZ and BHANH/LANL2DZ) and Frenking
et al.19 at the DFT (BP86) level of theory (Table 1), although
calculated for the gas phase and in the solid state the structure of
2 is determined by hydrogen bonds towards the chloride counter
ions (Fig. 2).
of the Au atoms are a result of the before mentioned formation of
hydrogen bonding networks. Therefore no aurophilic contacts are
observed.27 The absence of aurophilic contacts is also reflected
by the absorption spectrum of 2 in water which shows only
three bands in the UV regime (223, 252, 276 nm) for to the
imidazolydene ligands. Upon irradiation at 270–240 nm no
emission was observed in methanolic solution or the solid state.
A preliminary cytotoxicity screening at K562 and A2780sens.
cancer cell lines showed no cytotoxicity of compound 2 up to
10-5 M.† Interestingly, a significantly higher cytotoxicity of 2
In the solid state of 2 isosceles Au3-triangles are found (dAu–Au
=
◦
4.346 and 4.904 A, ∠(Au3) = 55.62 and 68.75◦, Fig. 3). The
metric parameters found in 2 are within the range of previously
described linear gold(I) bis(NHC) complexes.25,26 The separation
˚
Fig. 3 Packing of 2 in the solid state, only one layer shown; left: view along C–Au–C axis, right: view along a-axis. Gold atoms are shown in space filling
model, all others as capped sticks.
36 | Dalton Trans., 2011, 40, 35–37
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is found in cells in which the copper transporter CTR1 is over
expressed.
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Therefore, such “NHNH” NHCs may find applications in
biomedical applications as water soluble delocalised cations or
in supramolecular assemblies as hydrogen bond directing units.
Overall the work illustrates a simple and efficient route towards
water soluble metal complexes of “NHNH” NHCs. Currently, we
are exploring the scope of this reaction.
We acknowledge the support of Dr R. Linder with the fluores-
cence spectroscopy.
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Notes and references
‡ Syntheses: [(C8H14N2O2)2Au]Cl (1): a solution of n-butyl lithium in
hexane (1.6 M, 1.25 mL, 2.0 mmol) was added to a solution of
1-diethoxymethylimidazole (0.34 g, 2.0 mmol) in THF (50 mL) at
-78 ◦C. The solution was kept at -78 ◦C, after 45 min a solution of
[(tht)AuCl] (0.32 g, 1.0 mmol) in THF (5 mL) and after further 30 min
CF3SO3H (0.18 mL, 2.0 mmol) were added. The solution was slowly
warmed to ambient temperature. A precipitate formed after a few minutes,
which was collected by filtration, washed with diethyl ether, dried in vacuo
and recrystallised from methanol–CH2Cl2. Yield 0.41 g (72%). Crystals
suitable for single crystal structure analysis were grown by slow evaporation
of a solution of 1 in methanol. 1H NMR (methanol-d4) d/ppm: 1.25 (t, J =
7.1 Hz, 12 H, OCH2CH3), 3.57 (m, 8 H, OCH2CH3), 6.61 (s, 2 H, CH),
7.35 (d, J = 2 Hz, 2 H, Him), 7.57 (d, J = 2 Hz, 2 H, Him). MALDI-TOF
(MeOH): m/z = 537 [M - Cl]+, 435 [M - Cl - CH(OEt)2]+, 333 [M -
Cl - 2CH(OEt)2]+. ESI+ (MeOH): m/z = 333.5 [M - Cl - 2CH(OEt)2]+.
C16H28N4AuClO4·CH2Cl2 (656.77): calcd C 32.21, H 4.75, N 9.11; found
C 32.49, H 4.82, N 9.20. Crystal data of 1. C16H27AuClN4O4 M = 571.83
10 P. J. Barnard, M. V. Baker, S. J. Berners-Price and D. A. Day, J. Inorg.
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˚
g/mol, monoclinic, a = 7.4555(3), b = 13.2831(8), c = 22.2966(7) A, b =
◦
3
˚
18 G. Frenking, M. Sola˛ and S. Vyboishchikov, J. Organomet. Chem.,
96.996(3) , V = 2191.64(18) A , T = 183 K, space group P21/n, Z = 4,
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12 129 reflections measured, 4842 unique (Rint = 0.0375). The final wR was
0.0657 (I > 2s(I)) and wR2 was 0.1290 (all data).
19 D. Nemcsok, K. Wichmann and G. Frenking, Organometallics, 2004,
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[(C3H4N2)2Au]Cl (2): a suspension of 1 (0.35 g, 0.6 mmol) in 15 mL
hydrochloric acid (3.5 M) was heated to reflux for 5 h. All volatiles
were removed in vacuo to give 2 as a white micro-crystalline solid in
quantitative yield. Crystals suitable for single crystal structure analysis
were grown by slow diffusion of diethyl ether into a solution of 2 in
methanol. Yield 0.21 g (93%). 1H NMR (methanol-d4): d/ppm: 7.35
(pseudo t, 4 H, Him), 12.58 (s, br, 4 H, NH). MALDI-TOF (MeOH):
m/z = 332.86 [(C3N2H4)2Au]+. ESI+ (MeOH): m/z = 333.5 [M - Cl]+,
283.1 [(C3H4N2)Au(H2O)]+. C6H8N4AuCl·H2O (386.59): calcd C 18.64,
H 2.61, N 14.49; found C 18.97, H 2.77, N 14.55. Crystal data of
2. C6H8AuClN4 M = 368.59 g/mol, monoclinic, a = 8.51512(18), b =
20 C. Boehme and G. Frenking, Organometallics, 1998, 17, 5801–5809.
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Hickey, B. W. Skelton and A. H. White, Dalton Trans., 2006, 3708–
3715.
◦
3
˚
˚
14.1757(2), c = 23.3727(5) A, b = 97.774(2) , V = 2795.35(9) A , T =
183 K, space group C2/c, Z = 12, 24 088 reflections measured, 6769 unique
(Rint = 0.0338). The final wR was 0.0279 (I > 2s(I)) and wR2 was 0.0642
(all data).
26 A. Rit, T. Pape and F. E. Hahn, J. Am. Chem. Soc., 2010, 132, 4572–
4573.
27 H. Schmidbaur and A. Schier, Chem. Soc. Rev., 2008, 37, 1931–1951.
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The Royal Society of Chemistry 2011
Dalton Trans., 2011, 40, 35–37 | 37
©