Crystal structure of metronidazolium tetra-chlorido-aurate(III).

Metronidazole (MET) [systematic names: 1-(2-hy-droxy-eth-yl)-2-methyl-5-nitro-1H-imidazole and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanol] is a medication that is used to treat infections from a variety of anaerobic organisms. As with other imidazole derivatives, metronidazole is also susceptible to protonation. However, there are few reports of the structures of metronidazolium derivatives. In the title compound, (C6H10N3O3)[AuCl4] [systematic name: 1-(2-hy-droxy-eth-yl)-2-methyl-5-nitro-1H-imidazol-3-ium tetra-chlorido-aur-ate(III)], the asymmetric unit consists of a metronidazolium cation, [H(MET)](+), and a tetra-chlorido-aurate(III) anion, [AuCl4](-), in which the Au(III) ion is in a slightly distorted square-planar coordination environment. In the cation, the nitro group is essentially coplanar with the imidazole ring, as indicated by an O N-C=C torsion angle of -0.2 (4)°, while the hy-droxy-ethyl group is in a coiled conformation, with an O(H)-C-C-N torsion angle of 62.3 (3)°. In the crystal, the anion and cation are linked by an inter-molecular O-H⋯Cl hydrogen bond. In addition, the N-H group of the metronidazolium ion serves as a hydrogen-bond donor to the O atom of the hy-droxy-ethyl group of a symmetry-related mol-ecule, leading to the formation of chains along [010].

Chemical context

Metronidazole (MET), marketed as flagyl, and also known by the systematic names 1-(2-hy­droxy­eth­yl)-2-methyl-5-nitro-1H-imidazole and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanol, is a medication that has been used for the treatment of parasitic infections, such as trichomoniasis, amoebiasis and giardiasis, and is also effective against anaerobic bacteria (Freeman et al., 1997 ▸; Miljkovic et al., 2014 ▸; Soares et al., 2012 ▸; Samuelson, 1999 ▸; Lofmark et al., 2010 ▸; Contreras et al., 2009 ▸). Metronidazole possesses a variety of functional groups, and the two-coordinate nitro­gen atom of the imidazole ring has been shown to be an effective ligand for a variety of metals (Contreras et al., 2009 ▸). This nitro­gen atom is also susceptible to protonation, but there are few structures of metronidazolium derivatives reported in the literature (Yang, 2008 ▸; Wang et al., 2010 ▸). We describe herein the structure of metronidazolium tetra­chlorido­aurate(III), which is obtained by the addition of MET to HAuCl4.

Structural commentary

The asymmetric unit of [H(MET)][AuCl4] consists of a metronidazolium cation, [H(MET)]+, hydrogen-bonded to a square-planar tetra­chlorido­aurate(III) anion, [AuCl4]−, by an O—H⋯Cl hydrogen bond as illustrated in Fig. 1 ▸. The O3⋯Cl3 distance of 3.169 (2) Å is comparable to the values in other tetra­chlorido­aurate(III) derivatives that exhibit O—H⋯Cl hydrogen bonds. As an illustration, bis­{2-[(2-hy­droxy­eth­yl)imino­meth­yl]phenolato}gold(III) tetra­chlorido­aurate(III) possesses an O—H⋯Cl hydrogen bond between a hy­droxy­ethyl group and [AuCl4]−, with an O(H)⋯Cl distance of 3.365 Å (Nockemann et al., 2007 ▸). For further reference, the average O⋯Cl distance in compounds that have O—H⋯Cl inter­actions is 3.196 (3) Å (Steiner, 2002 ▸). The nitro group is almost coplanar with the imidazole ring, as indicated by an O1—N3—C2—C1 torsion angle of −0.2 (4)°, while the hy­droxy­ethyl group exhibits an O3—C6—C5—N2 torsion angle of 62.3 (3)°, describing a coiled conformation.

Figure 1

The asymmetric unit of the title compound, shown with 20% probability displacement ellipsoids. The O3—H3⋯Cl3 hydrogen bond is shown as an open bond.

Supra­molecular features

In the crystal, the N—H group of the metronidazolium ion serves as a hydrogen-bond donor to the oxygen atom of the hy­droxy­ethyl group of a symmetry-related mol­ecule, forming a chain along [010] in which each O—H group is O—H⋯Cl hydrogen bonded to a [AuCl4]− ion (Table 1 ▸ and Fig. 2 ▸). The N⋯O distance of 2.729 (3) Å associated with the hydrogen bond is comparable to that observed for metronidazole [2.816 (2) Å] (Blaton et al., 1979 ▸; Galván-Tejada et al., 2002 ▸). However, an important difference between the hydrogen bonds in metronidazole and metronidazolium is that the alcohol O—H group is the hydrogen-bond donor for metronidazole (i.e. O—H⋯N), while the N—H group is the hydrogen-bond donor for metronidazolium (i.e. N—H⋯O).

Table 1

Hydrogen-bond geometry (, )

DHA	DH	HA	D A	DHA
N1H01O3i	0.94(4)	1.81(4)	2.729(3)	166(3)
O3H3Cl3	0.67(4)	2.54(4)	3.169(2)	158(4)

Symmetry code: (i) .

Figure 2

Part of the crystal structure showing a hydrogen-bonded chain (open bonds) along [010].

Database survey

Metronidazolium derivatives that feature other counter-ions, e.g. 3-carb­oxy-4-hy­droxy­benzene­sulfonate and perchlorate have been reported (Yang, 2008 ▸; Wang et al., 2010 ▸), as have a variety of tetra­chlorido­aurate(III) complexes (Johnson & Steed, 1998 ▸; Pluzhnik-Gladyr et al., 2014 ▸; Faza­eli et al., 2010 ▸).

Synthesis and crystallization

Crystals of composition [H(MET)][AuCl4] were obtained by combining HAuCl4·H2O (0.12 mmol) with MET (0.20 mmol) in MeOH (2 ml), followed by evaporation of MeOH, and crystallization from Et2O.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. H atoms bonded to C atoms were refined with a riding model, with C—H = 0.95–0.99 Å and U iso(H) = 1.2U eq(C) or 1.5U eq(Cmeth­yl). H atoms bonded to N and O atoms were refined independently with isotropic displacement parameters.

Table 2

Experimental details

Crystal data
Chemical formula	(C6H10N3O3)[AuCl4]
M r	510.94
Crystal system, space group	Monoclinic, P21/n
Temperature (K)	130
a, b, c ()	7.324(2), 11.972(4), 15.667(5)
()	94.384(4)
V (3)	1369.6(8)
Z	4
Radiation type	Mo K
(mm1)	11.52
Crystal size (mm)	0.23 0.04 0.02
Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2013 ▸)
T min, T max	0.426, 0.746
No. of measured, independent and observed [I > 2(I)] reflections	22024, 4214, 3673
R int	0.041
(sin /)max (1)	0.718
Refinement
R[F 2 > 2(F 2)], wR(F 2), S	0.021, 0.045, 1.16
No. of reflections	4214
No. of parameters	163
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
max, min (e 3)	1.30, 1.22

Computer programs: APEX2 and, SAINT (Bruker, 2013 ▸), SHELXS97 and SHELXTL (Sheldrick, 2008 ▸), SHELXL2014 (Sheldrick, 2015 ▸).

Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989015010798/lh5766sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015010798/lh5766Isup3.hkl

CCDC reference: 1404845

Additional supporting information: crystallographic information; 3D view; checkCIF report

(C6H10N3O3)[AuCl4]	F(000) = 952
Mr = 510.94	Dx = 2.478 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 7.324 (2) Å	Cell parameters from 9874 reflections
b = 11.972 (4) Å	θ = 2.6–30.6°
c = 15.667 (5) Å	µ = 11.52 mm−1
β = 94.384 (4)°	T = 130 K
V = 1369.6 (8) Å3	Plate, yellow
Z = 4	0.23 × 0.04 × 0.02 mm

Bruker APEXII CCD diffractometer	3673 reflections with I > 2σ(I)
φ and ω scans	Rint = 0.041
Absorption correction: multi-scan (SADABS; Bruker, 2013)	θmax = 30.7°, θmin = 2.1°
Tmin = 0.426, Tmax = 0.746	h = −10→10
22024 measured reflections	k = −17→17
4214 independent reflections	l = −22→22

Refinement on F2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.021	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.045	w = 1/[σ2(Fo2) + (0.0129P)2] where P = (Fo2 + 2Fc2)/3
S = 1.16	(Δ/σ)max = 0.001
4214 reflections	Δρmax = 1.30 e Å−3
163 parameters	Δρmin = −1.22 e Å−3

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

	x	y	z	Uiso*/Ueq
Au	0.36629 (2)	0.79983 (2)	0.58625 (2)	0.01868 (4)
Cl1	0.26070 (11)	0.84595 (7)	0.45047 (5)	0.03247 (17)
Cl2	0.44092 (10)	0.62541 (6)	0.54111 (5)	0.03012 (16)
Cl3	0.46029 (10)	0.75210 (6)	0.72389 (5)	0.02610 (15)
Cl4	0.29498 (10)	0.97418 (6)	0.63205 (5)	0.02831 (15)
O1	0.8047 (3)	0.7553 (2)	0.41611 (14)	0.0367 (5)
O2	0.9242 (3)	0.60835 (18)	0.47815 (14)	0.0331 (5)
O3	0.7450 (3)	0.55236 (18)	0.73360 (15)	0.0265 (5)
H3	0.684 (5)	0.591 (3)	0.719 (2)	0.042 (13)*
N1	0.8446 (3)	0.89061 (19)	0.65413 (15)	0.0175 (4)
H01	0.810 (5)	0.953 (3)	0.685 (2)	0.042 (10)*
N2	0.9387 (3)	0.72022 (17)	0.63739 (14)	0.0159 (4)
N3	0.8670 (3)	0.70319 (19)	0.47846 (15)	0.0223 (5)
C1	0.8127 (4)	0.8685 (2)	0.56913 (17)	0.0191 (5)
H1A	0.7604	0.9173	0.5261	0.023*
C2	0.8708 (3)	0.7626 (2)	0.55853 (17)	0.0158 (5)
C3	0.9200 (4)	0.8016 (2)	0.69521 (17)	0.0170 (5)
C4	0.9783 (4)	0.7982 (3)	0.78720 (19)	0.0272 (6)
H4A	0.9318	0.8643	0.8154	0.041*
H4B	1.1123	0.7972	0.7949	0.041*
H4C	0.9295	0.7307	0.8126	0.041*
C5	1.0107 (4)	0.6070 (2)	0.65912 (18)	0.0198 (5)
H5A	1.0863	0.6102	0.7142	0.024*
H5B	1.0904	0.5822	0.6145	0.024*
C6	0.8579 (4)	0.5230 (2)	0.66604 (18)	0.0227 (6)
H6A	0.7818	0.5199	0.6111	0.027*
H6B	0.9111	0.4479	0.6773	0.027*

	U11	U22	U33	U12	U13	U23
Au	0.01490 (5)	0.01746 (6)	0.02409 (6)	−0.00147 (4)	0.00416 (4)	−0.00253 (4)
Cl1	0.0438 (4)	0.0304 (4)	0.0234 (4)	0.0042 (3)	0.0037 (3)	−0.0009 (3)
Cl2	0.0286 (4)	0.0222 (3)	0.0400 (4)	0.0024 (3)	0.0057 (3)	−0.0092 (3)
Cl3	0.0255 (3)	0.0251 (3)	0.0272 (4)	0.0036 (3)	−0.0008 (3)	−0.0012 (3)
Cl4	0.0360 (4)	0.0193 (3)	0.0292 (4)	0.0033 (3)	0.0002 (3)	−0.0038 (3)
O1	0.0516 (15)	0.0375 (13)	0.0193 (11)	0.0047 (11)	−0.0090 (10)	−0.0008 (10)
O2	0.0468 (14)	0.0221 (11)	0.0309 (12)	0.0056 (10)	0.0058 (10)	−0.0077 (9)
O3	0.0250 (11)	0.0233 (11)	0.0327 (13)	0.0053 (9)	0.0109 (9)	0.0075 (9)
N1	0.0172 (10)	0.0152 (10)	0.0203 (11)	−0.0003 (9)	0.0023 (9)	−0.0003 (9)
N2	0.0146 (10)	0.0157 (10)	0.0175 (11)	0.0000 (8)	0.0021 (8)	0.0014 (8)
N3	0.0253 (12)	0.0233 (12)	0.0181 (12)	−0.0032 (10)	0.0010 (9)	−0.0019 (9)
C1	0.0217 (13)	0.0198 (13)	0.0157 (12)	0.0003 (10)	−0.0001 (10)	0.0012 (10)
C2	0.0184 (12)	0.0152 (11)	0.0138 (12)	−0.0023 (10)	0.0008 (9)	−0.0006 (9)
C3	0.0146 (12)	0.0188 (12)	0.0180 (13)	−0.0012 (10)	0.0038 (10)	0.0002 (10)
C4	0.0292 (16)	0.0355 (17)	0.0167 (14)	0.0031 (13)	0.0011 (12)	−0.0009 (12)
C5	0.0181 (12)	0.0170 (12)	0.0245 (14)	0.0051 (10)	0.0026 (10)	0.0064 (10)
C6	0.0254 (14)	0.0164 (13)	0.0271 (15)	0.0029 (11)	0.0072 (12)	0.0046 (11)

Au—Cl1	2.2752 (10)	N2—C5	1.485 (3)
Au—Cl4	2.2807 (9)	N3—C2	1.441 (3)
Au—Cl2	2.2844 (9)	C1—C2	1.351 (4)
Au—Cl3	2.2855 (10)	C1—H1A	0.9500
O1—N3	1.218 (3)	C3—C4	1.472 (4)
O2—N3	1.210 (3)	C4—H4A	0.9800
O3—C6	1.436 (3)	C4—H4B	0.9800
O3—H3	0.67 (4)	C4—H4C	0.9800
N1—C3	1.341 (3)	C5—C6	1.515 (4)
N1—C1	1.360 (3)	C5—H5A	0.9900
N1—H01	0.94 (4)	C5—H5B	0.9900
N2—C3	1.345 (3)	C6—H6A	0.9900
N2—C2	1.392 (3)	C6—H6B	0.9900
Cl1—Au—Cl4	90.14 (3)	N1—C3—N2	108.2 (2)
Cl1—Au—Cl2	90.27 (3)	N1—C3—C4	124.7 (2)
Cl4—Au—Cl2	179.36 (3)	N2—C3—C4	127.0 (2)
Cl1—Au—Cl3	177.66 (3)	C3—C4—H4A	109.5
Cl4—Au—Cl3	89.52 (3)	C3—C4—H4B	109.5
Cl2—Au—Cl3	90.09 (3)	H4A—C4—H4B	109.5
C6—O3—H3	108 (3)	C3—C4—H4C	109.5
C3—N1—C1	110.4 (2)	H4A—C4—H4C	109.5
C3—N1—H01	120 (2)	H4B—C4—H4C	109.5
C1—N1—H01	129 (2)	N2—C5—C6	111.8 (2)
C3—N2—C2	106.6 (2)	N2—C5—H5A	109.3
C3—N2—C5	124.1 (2)	C6—C5—H5A	109.3
C2—N2—C5	129.3 (2)	N2—C5—H5B	109.3
O2—N3—O1	125.9 (3)	C6—C5—H5B	109.3
O2—N3—C2	118.9 (2)	H5A—C5—H5B	107.9
O1—N3—C2	115.2 (2)	O3—C6—C5	111.1 (2)
C2—C1—N1	105.7 (2)	O3—C6—H6A	109.4
C2—C1—H1A	127.1	C5—C6—H6A	109.4
N1—C1—H1A	127.1	O3—C6—H6B	109.4
C1—C2—N2	109.1 (2)	C5—C6—H6B	109.4
C1—C2—N3	125.8 (2)	H6A—C6—H6B	108.0
N2—C2—N3	125.1 (2)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H01···O3i	0.94 (4)	1.81 (4)	2.729 (3)	166 (3)
O3—H3···Cl3	0.67 (4)	2.54 (4)	3.169 (2)	158 (4)