A copper(II) paddle-wheel structure of tranexamic acid: di-chloro-tetra-kis-[μ-4-(ammonio-meth-yl)cyclo-hexane-1-carboxyl-ato-O,O']dicopper(II) dichloride hexa-hydrate.

Tranexamic acid [systematic name: trans-4-(amino-meth-yl)cyclo-hexane-1-carb-oxy-lic acid], is an anti-fibrinolytic amino acid that exists as a zwitterion [trans-4-(ammonio-meth-yl)cyclo-hexane-1-carboxyl-ate] in the solid state. Its reaction with copper chloride leads to the formation of a compound with a copper(II) paddle-wheel structure that crystallizes as a hexa-hydrate, [Cu2Cl2(C8H15NO2)4]2+·2Cl-·6H2O. The asymmetric unit is composed of a copper(II) cation, two zwitterionic tranexamic acid units, a coordinating Cl- anion and a free Cl- anion, together with three water mol-ecules of crystallization. The whole structure is generated by inversion symmetry, with the Cu⋯Cu axle of the paddle-wheel dication being located about a center of symmetry. The cyclo-hexane rings of the zwitterionic tranexamic acid units have chair conformations. The carboxyl-ate groups that bridge the two copper(II) cations are inclined to one another by 88.4 (8)°. The copper(II) cation is ligated by four carboxyl-ate O atoms in the equatorial plane and by a Cl- ion in the axial position. Hence, it has a fivefold O4Cl coordination sphere with a perfect square-pyramidal geometry and a τ5 index of zero. In the crystal, the paddle-wheel dications are linked by a series of N-H⋯Cl hydrogen bonds, involving the coordinating and free Cl- ions, forming a three-dimensional network. This network is strengthened by a series of N-H⋯Owater, Owater-H⋯Cl and Owater-H⋯O hydrogen bonds.

Chemical context

Tranexamic acid (n class="Chemical">TA) is a derivative of the amino acid lysine. It has important anti­fibrinolytic activity and is used extensively in both trauma and normal surgery to prevent excessive blood loss (Napolitano et al., 2013 ▸; Melvin et al., 2015 ▸). It was first synthesized in the early 1960s by the Japanese husband and wife team Shosuke and Utako Okamato (1962 ▸). They showed amino-methyl-cyclo­hexane-carb­oxy­lic acid (AMCHA) to be a new inhibitor of fibrinolysis. Almost simultaneously with a Swedish group (Melander et al., 1965 ▸), they were able to show that the anti­fibrinolytic active isomer (Okamoto et al., 1964 ▸) has a trans-conformation (TA; Fig. 1 ▸) with the amino­methyl and carb­oxy­lic acid substituents on the cyclo­hexane ring occupying equatorial positions (Fig. 1 ▸). The cis-isomer (Fig. 1 ▸), in which the carb­oxy­lic acid moiety is axial, is almost inactive. The latter was shown to exist as the free acid in the solid state (Yamazaki et al., 1981 ▸), in contrast to the trans-isomer, which exists as a zwitterion in the solid state (Groth, 1968 ▸; Shahzadi et al., 2007 ▸). Recently, Tengborn et al. (2015 ▸) published an excellent review article, entitled ‘Tranexamic acid – an old drug still going strong and making a revival’, in which they recount the history of the development of TA and its mechanism of action, pharmokinetics and other details, including clinical uses. Herein, we report on the first crystal structure of a metal complex of tranexamic acid. The reaction of TA with copper(II) chloride leads to the formation of the title compound with a copper(II) paddle-wheel structure, that crystallizes as a hexa­hydrate. The reaction of TA with copper(II) bromide leads to the formation of an isotypical compound; however, the crystals were twinned and the subsequent X-ray analysis was of insufficient quality to be submitted or deposited.

Figure 1

The trans- and cis-isomers of 4-(amino­meth­yl)cyclo­hexane-1-carb­oxy­lic acid.

Structural commentary

The mol­ecular structure of the dication of the title compound is illustrated in Fig. 2 ▸. The asymmetric unit is composed of a copper(II) cation coordinated by the carboxyl­ate O atoms (O1–O4) of two zwitterionic tranexamic acid units and a Cl− anion, Cl1, together with a free Cl− anion, Cl2, and three water mol­ecules of crystallization. The whole structure is generated by inversion symmetry, with the Cu1⋯Cu1i axle [2.6649 (11) Å; symmetry code (i): −x + 1, −y + 1, −z + 1] of the paddle-wheel being located about a center of symmetry. Selected bond lengths and angles in the paddle-wheel dication are given in Table 1 ▸. Atom Cu1 is coordinated by four carboxyl­ate O atoms (O1–O4) in the equatorial plane and a Cl− ion, Cl1, in the axial position. The Cu—O distances vary from 1.950 (4) to 1.991 (3) Å, with a longer Cu1—Cl1 axial distance of 2.499 (1) Å (Table 1 ▸). The copper(II) cation, Cu1 (Cu1i), has a perfect square-pyramidal coordination sphere with a τ 5 index of 0.0 (τ 5 = 0 for an ideal square-pyramidal coordination sphere, and = 1 for an ideal trigonal–pyramidal coordination sphere; Addison et al., 1984 ▸).

Figure 2

A view of the mol­ecular structure of the title dication, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level. Unlabelled atoms are related to the labelled atoms by inversion symmetry (symmetry operation: −x + 1, −y + 1, −z + 1).

Table 1

Selected geometric parameters (Å, °)

Cu1—Cu1i	2.6649 (11)	Cu1—O4i	1.965 (4)
Cu1—O1	1.950 (4)	Cu1—O3	1.991 (3)
Cu1—O2i	1.955 (4)	Cu1—Cl1	2.4990 (12)
O1—Cu1—O2i	167.02 (15)	O4i—Cu1—Cl1	92.57 (11)
O1—Cu1—O4i	89.3 (2)	O3—Cu1—Cl1	100.08 (10)
O2i—Cu1—O4i	89.9 (2)	O1—Cu1—Cu1i	83.04 (11)
O1—Cu1—O3	88.33 (18)	O2i—Cu1—Cu1i	84.05 (11)
O2i—Cu1—O3	89.60 (18)	O4i—Cu1—Cu1i	80.24 (11)
O4i—Cu1—O3	167.27 (15)	O3—Cu1—Cu1i	87.06 (10)
O1—Cu1—Cl1	94.31 (11)	Cl1—Cu1—Cu1i	172.34 (4)
O2i—Cu1—Cl1	98.68 (11)

Symmetry code: (i) .

The conformations of the two zwitterionic n class="Chemical">tranexamic acid units differ slightly. The cyclo­hexane rings (C2–C7 and C10–C15) have chair conformations; puckering parameters for ring C2–C7 are Q = 0.569 (7) Å, θ = 176.3 (6)°, φ = 358 (13)°, and for ring C10–C15 are Q = 0.568 (6) Å, θ = 6.0 (6)°, φ = 137 (6)°. The carboxyl­ate groups (C1/O1/O2 and C9/O3/O4) are inclined to the mean planes of the four planar atoms of the respective cyclo­hexane rings (C3/C4/C6/C7 and C11/C12/C14/C15) by 67.5 (6) and 85.8 (7)°, while they are inclined to one another by 88.4 (8)°. The ammonio­methyl units, C5/C8/N1 and C13/C16/N2, are inclined to the mean planes of the four planar atoms of the respective cyclo­hexane rings (C3/C4/C6/C7 and C11/C12/C14/C15) by 34.9 (6) and 47.5 (6)°.

Supra­molecular features

In the crystal, the n class="Chemical">NH3 + groups of the zwitterionic tranexamic acid units and the coordinating and free Cl ions are linked by a series of N—H⋯Cl hydrogen bonds forming a three-dimensional framework (Table 2 ▸ and Fig. 3 ▸). This framework is strengthened by a series of N—H⋯Owater, Owater—H⋯Cl and Owater—H⋯O hydrogen bonds (Table 2 ▸ and Fig. 4 ▸). The packing index, or percentage of filled space, is 67.1 (Kitajgorodskij, 1973 ▸) and the unit cell contains no residual solvent-accessible voids.

Table 2

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯Cl1ii	0.91	2.63	3.316 (5)	133
N1—H1C⋯Cl1iii	0.91	2.52	3.394 (5)	160
N2—H2B⋯Cl1iv	0.91	2.25	3.123 (5)	160
N2—H2C⋯Cl2v	0.91	2.24	3.151 (6)	179
N1—H1B⋯O1W vi	0.91	1.90	2.760 (7)	156
N2—H2A⋯O2W vii	0.91	2.06	2.789 (9)	137
O1W—H1WA⋯Cl2v	0.89 (2)	2.57 (8)	3.218 (6)	130 (8)
O2W—H2WA⋯Cl2viii	0.90 (2)	2.46 (7)	3.176 (6)	137 (9)
O2W—H2WB⋯O3i	0.90 (2)	2.22 (8)	2.820 (6)	124 (8)
O3W—H3WA⋯Cl1ix	0.88 (2)	2.66 (6)	3.258 (5)	127 (6)
O3W—H3WB⋯Cl2x	0.88 (2)	2.35 (3)	3.182 (5)	158 (7)

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) ; (viii) ; (ix) ; (x) .

Figure 3

A view along the c axis of the crystal structure of the title compound with the water solvent mol­ecules omitted. The N—H⋯Cl hydrogen bonds are shown as dashed lines (see Table 2 ▸), and the C-bound H atoms have been omitted for clarity.

Figure 4

A view along the c axis of the crystal structure of the title compound, with the hydrogen bonds shown as dashed lines (see Table 2 ▸). The C-bound H atoms have been omitted for clarity.

Database survey

A search of the Cambridge Structural Database (CSD, Version 5.38, update May 2017; Groom et al., 2016 ▸) for the skeleton of amino-methyl-cyclo­hexane-carb­oxy­lic acid gave 13 hits, of which six structures concern the cis- and trans-isomers. The crystal structures of the hydro­bromide of the trans-isomer (CSD refcode: CHCAHB) and the hydro­chloride of the cis-isomer (CHCAHC) were reported in 1966 (Kadoya et al., 1966 ▸). The crystal structure of the hydro­bromide of the cis-isomer has also been reported (AMHCAC; Groth & Hassel, 1965 ▸), and that of the free cis-isomer (AMCHCA; Yamazaki et al., 1981 ▸), which does not exist as a zwitterion in the solid state. The room temperature analysis of the trans-isomer (TA), viz. tranexamic acid (AMMCHC10; Groth, 1968 ▸), and a low-temperature analysis at 173 K (AMMCHC11; Shahzadi et al., 2007 ▸) showed that it crystallizes in the chiral ortho­rhom­bic space group P212121 and exists as a zwitterion in the solid state. Inter­estingly, in the low-temperature structure it can be seen that the carboxyl­ate group (COO−) is inclined to the mean plane of the four planar atoms of the cyclo­hexane ring by 48.9 (2)°, compared to 67.5 (6) and 85.8 (7)° in the title compound. The plane of the ammonio­methyl unit (Car—C—N) is inclined to the same mean plane of the four planar atoms of the cyclo­hexane ring by 37.4 (2)°, compared to 34.9 (6) and 47.5 (6)° in the title compound. Hence, on complexation the cyclo­hexane rings are rotated about the Ccarboxyl­ate—Ccyclo­hexa­ne bonds (C1—C2 and C9—C10), most probably to minimize steric hindrance.

In the CSD over 1500 copper(II) paddle-wheel structures have been deposited. There are only 13 compounds in which the axial position is occupied by a Cl− anion (see Supporting information). The Cu⋯Cu disn class="Chemical">tances vary from ca 2.63 to 2.84 Å, with the carboxyl­ate groups being inclined to one another by ca 84.65–90°, and the Cu—Cl distances varying from ca 2.41 to 2.49 Å. The values observed for the title compound fall within these limits (see Section 2, Structural commentary). In all 13 compounds the copper atoms have perfect square-pyramidal geometry, with τ 5 = 0.0.

Synthesis and crystallization

Tranexamic acid (0.785 g, 0.5 mmol) dissolved in 10 ml of deionized n class="Chemical">water was added dropwise to a transparent blue solution of CuCl2·2H2O (0.426 g, 0.25 mmol) in 20 ml of aceto­nitrile at ambient temperature and the mixture was stirred for 30 min. The green solution obtained was filtered and the filtrate kept undisturbed at room temperature for slow evaporation. After five days green plate-like crystals of the title compound were obtained.

Refinement

Crystal dan class="Chemical">ta, data collection and structure refinement details are summarized in Table 3 ▸. The H atoms of the water mol­ecules were located in difference-Fourier maps and refined with distance restraints: O—H = 0.88 (2) Å with U iso(H) = 1.5U eq(O). The ammonium H atoms and the C-bound H atoms were included in calculated positions and treated as riding: N—H = 0.91 Å, C-H = 0.99–1.00 Å with U iso(H) = 1.5U eq(N-ammonium) and 1.2U eq(C) for other H atoms. In the final difference-Fourier map the residual density peaks [Δρmax, Δρmin 1.80, −0.93 e Å−3] are located at a distance of 1.2 and 0.9 Å, respectively, from the copper atoms.

Table 3

Experimental details

Crystal data
Chemical formula	[Cu2Cl2(C8H15NO2)4](Cl2)·6H2O
M r	1005.81
Crystal system, space group	Monoclinic, P21/n
Temperature (K)	153
a, b, c (Å)	14.7100 (11), 10.7163 (6), 14.9312 (12)
β (°)	91.828 (10)
V (Å3)	2352.5 (3)
Z	2
Radiation type	Mo Kα
μ (mm−1)	1.19
Crystal size (mm)	0.34 × 0.30 × 0.20
Data collection
Diffractometer	STOE IPDS 1
Absorption correction	Multi-scan (MULABS; Spek, 2009 ▸)
T min, T max	0.712, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	18018, 4545, 3172
R int	0.091
(sin θ/λ)max (Å−1)	0.615
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.067, 0.196, 1.02
No. of reflections	4545
No. of parameters	273
No. of restraints	9
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	1.80, −0.93

Computer programs: EXPOSE, CELL and INTEGRATE in IPDS-I (Stoe & Cie, 2004 ▸), SHELXS2016/6 (Sheldrick, 2008 ▸), Mercury (Macrae et al., 2008 ▸), SHELXL2016/6 (Sheldrick, 2015 ▸), PLATON (Spek, 2009 ▸) and publCIF (Westrip, 2010 ▸).

Crystal structure: conn class="Chemical">tains datablock(s) I, Global. DOI: 10.1107/S2056989017012543/wm5416sup1.cif

Structure factors: contains dan class="Chemical">tablock(s) I. DOI: 10.1107/S2056989017012543/wm5416Isup2.hkl

CSD search of axially Cl- ligated Cu-Cu paddle-wheel structures. DOI: 10.1107/S2056989017012543/wm5416sup3.pdf

CCDC reference: 1571897

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

[Cu2Cl2(C8H15NO2)4](Cl2)·6H2O	F(000) = 1060
Mr = 1005.81	Dx = 1.420 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 14.7100 (11) Å	Cell parameters from 8000 reflections
b = 10.7163 (6) Å	θ = 2.3–25.9°
c = 14.9312 (12) Å	µ = 1.19 mm−1
β = 91.828 (10)°	T = 153 K
V = 2352.5 (3) Å3	Plate, green
Z = 2	0.34 × 0.30 × 0.20 mm

STOE IPDS 1 diffractometer	4545 independent reflections
Radiation source: fine-focus sealed tube	3172 reflections with I > 2σ(I)
Plane graphite monochromator	Rint = 0.091
φ rotation scans	θmax = 25.9°, θmin = 2.3°
Absorption correction: multi-scan (MULABS; Spek, 2009)	h = −18→18
Tmin = 0.712, Tmax = 1.000	k = −13→13
18018 measured reflections	l = −18→18

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.067	Hydrogen site location: mixed
wR(F2) = 0.196	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	w = 1/[σ2(Fo2) + (0.1331P)2] where P = (Fo2 + 2Fc2)/3
4545 reflections	(Δ/σ)max < 0.001
273 parameters	Δρmax = 1.80 e Å−3
9 restraints	Δρmin = −0.93 e Å−3

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

	x	y	z	Uiso*/Ueq
Cu1	0.57200 (3)	0.53341 (6)	0.55087 (4)	0.0195 (2)
Cl1	0.69386 (7)	0.59126 (13)	0.66374 (7)	0.0253 (3)
O1	0.5727 (3)	0.3572 (4)	0.5833 (3)	0.0384 (10)
O2	0.4505 (3)	0.3014 (4)	0.5009 (3)	0.0369 (10)
O3	0.6477 (2)	0.4905 (4)	0.4471 (2)	0.0297 (9)
O4	0.5250 (2)	0.4381 (5)	0.3640 (3)	0.0445 (12)
N1	0.6876 (3)	−0.1791 (5)	0.8123 (3)	0.0339 (11)
H1A	0.715646	−0.207468	0.762784	0.051*
H1B	0.688742	−0.239545	0.855069	0.051*
H1C	0.717108	−0.110116	0.833690	0.051*
N2	0.6727 (3)	0.1961 (6)	−0.0237 (3)	0.0451 (14)
H2A	0.674668	0.130093	0.014673	0.068*
H2B	0.702133	0.175997	−0.074399	0.068*
H2C	0.613684	0.215079	−0.038025	0.068*
C1	0.5154 (3)	0.2771 (5)	0.5551 (3)	0.0244 (11)
C2	0.5225 (4)	0.1471 (5)	0.5916 (4)	0.0299 (12)
H2	0.490146	0.089283	0.548741	0.036*
C3	0.6224 (4)	0.1033 (6)	0.6034 (4)	0.0377 (14)
H3A	0.650187	0.098871	0.543974	0.045*
H3B	0.657016	0.165255	0.640008	0.045*
C4	0.6295 (4)	−0.0230 (6)	0.6482 (4)	0.0388 (14)
H4A	0.694444	−0.045681	0.657197	0.047*
H4B	0.600371	−0.086743	0.608849	0.047*
C5	0.5841 (3)	−0.0227 (5)	0.7379 (4)	0.0288 (12)
H5	0.614942	0.042295	0.776158	0.035*
C6	0.4837 (4)	0.0149 (6)	0.7258 (6)	0.0472 (18)
H6A	0.451049	−0.048267	0.688621	0.057*
H6B	0.455311	0.017746	0.784995	0.057*
C7	0.4754 (3)	0.1418 (6)	0.6811 (4)	0.0372 (14)
H7A	0.502404	0.205796	0.721666	0.045*
H7B	0.410239	0.162109	0.671203	0.045*
C8	0.5915 (4)	−0.1465 (6)	0.7881 (4)	0.0397 (14)
H8A	0.556328	−0.141231	0.843406	0.048*
H8B	0.564509	−0.213527	0.750187	0.048*
C9	0.6099 (3)	0.4514 (5)	0.3760 (3)	0.0244 (11)
C10	0.6679 (3)	0.4182 (5)	0.2966 (3)	0.0244 (11)
H10	0.733515	0.427604	0.315003	0.029*
C11	0.6461 (4)	0.5081 (6)	0.2187 (4)	0.0288 (12)
H11A	0.579838	0.507245	0.204844	0.035*
H11B	0.663545	0.593965	0.236560	0.035*
C12	0.6970 (4)	0.4710 (6)	0.1351 (3)	0.0299 (12)
H12A	0.681611	0.530032	0.085930	0.036*
H12B	0.763338	0.475985	0.147985	0.036*
C13	0.6722 (3)	0.3405 (5)	0.1063 (3)	0.0262 (12)
H13	0.604822	0.337427	0.095228	0.031*
C14	0.6965 (4)	0.2495 (6)	0.1830 (4)	0.0332 (13)
H14A	0.677871	0.164112	0.164965	0.040*
H14B	0.763281	0.249287	0.193720	0.040*
C15	0.6507 (4)	0.2838 (6)	0.2693 (4)	0.0319 (12)
H15A	0.584401	0.270120	0.261501	0.038*
H15B	0.673527	0.227990	0.317868	0.038*
C16	0.7174 (4)	0.3051 (6)	0.0196 (4)	0.0347 (14)
H16A	0.714618	0.376924	−0.022083	0.042*
H16B	0.782239	0.285487	0.032601	0.042*
Cl2	0.53120 (11)	0.73439 (19)	0.07190 (12)	0.0537 (5)
O1W	0.3515 (3)	0.3850 (6)	0.0849 (3)	0.0600 (14)
H1WA	0.385 (4)	0.405 (9)	0.038 (3)	0.090*
H1WB	0.393 (4)	0.383 (9)	0.130 (3)	0.090*
O2W	0.1694 (4)	0.5612 (6)	0.5040 (4)	0.0651 (15)
H2WA	0.134 (5)	0.589 (9)	0.548 (5)	0.098*
H2WB	0.222 (3)	0.602 (8)	0.514 (6)	0.098*
O3W	0.1194 (3)	0.1039 (6)	0.3118 (3)	0.0619 (15)
H3WA	0.104 (5)	0.075 (8)	0.259 (3)	0.093*
H3WB	0.073 (4)	0.148 (8)	0.329 (5)	0.093*

	U11	U22	U33	U12	U13	U23
Cu1	0.0152 (3)	0.0291 (4)	0.0144 (3)	0.0005 (2)	0.0036 (2)	0.0010 (2)
Cl1	0.0213 (6)	0.0352 (8)	0.0193 (6)	−0.0045 (5)	0.0001 (4)	0.0005 (5)
O1	0.035 (2)	0.039 (3)	0.041 (2)	−0.0092 (18)	−0.0129 (17)	0.0117 (19)
O2	0.035 (2)	0.033 (2)	0.041 (2)	0.0018 (17)	−0.0158 (17)	−0.0035 (19)
O3	0.0195 (16)	0.050 (3)	0.0195 (17)	−0.0029 (16)	0.0022 (13)	−0.0049 (17)
O4	0.0187 (18)	0.088 (4)	0.027 (2)	−0.0061 (19)	0.0057 (14)	−0.018 (2)
N1	0.031 (2)	0.032 (3)	0.038 (3)	0.007 (2)	−0.0064 (19)	0.001 (2)
N2	0.041 (3)	0.056 (4)	0.039 (3)	0.001 (3)	0.018 (2)	−0.019 (3)
C1	0.024 (2)	0.031 (3)	0.018 (2)	0.004 (2)	0.0067 (19)	0.004 (2)
C2	0.032 (3)	0.025 (3)	0.032 (3)	0.001 (2)	−0.008 (2)	−0.003 (2)
C3	0.032 (3)	0.048 (4)	0.034 (3)	0.015 (3)	0.016 (2)	0.011 (3)
C4	0.039 (3)	0.040 (4)	0.038 (3)	0.015 (3)	−0.001 (2)	0.003 (3)
C5	0.020 (2)	0.029 (3)	0.037 (3)	0.001 (2)	−0.002 (2)	0.004 (2)
C6	0.022 (3)	0.036 (4)	0.084 (5)	0.002 (2)	0.010 (3)	0.022 (4)
C7	0.019 (2)	0.037 (4)	0.056 (4)	0.007 (2)	0.010 (2)	0.019 (3)
C8	0.028 (3)	0.040 (4)	0.051 (4)	0.005 (3)	0.004 (2)	0.009 (3)
C9	0.022 (2)	0.030 (3)	0.022 (2)	0.001 (2)	0.0045 (19)	0.004 (2)
C10	0.014 (2)	0.039 (3)	0.021 (2)	0.001 (2)	0.0046 (17)	0.000 (2)
C11	0.034 (3)	0.029 (3)	0.024 (3)	0.002 (2)	0.008 (2)	−0.001 (2)
C12	0.032 (3)	0.037 (4)	0.021 (3)	0.004 (2)	0.010 (2)	0.004 (2)
C13	0.020 (2)	0.035 (3)	0.024 (2)	0.004 (2)	0.0101 (18)	−0.006 (2)
C14	0.031 (3)	0.030 (3)	0.039 (3)	0.002 (2)	0.011 (2)	0.000 (3)
C15	0.036 (3)	0.031 (3)	0.030 (3)	0.003 (2)	0.011 (2)	0.002 (2)
C16	0.029 (3)	0.047 (4)	0.028 (3)	0.003 (2)	0.013 (2)	−0.012 (3)
Cl2	0.0453 (9)	0.0647 (13)	0.0518 (10)	−0.0012 (8)	0.0122 (7)	0.0128 (9)
O1W	0.062 (3)	0.068 (4)	0.051 (3)	0.008 (3)	0.014 (2)	0.021 (3)
O2W	0.048 (3)	0.075 (4)	0.071 (4)	0.012 (3)	−0.008 (3)	−0.019 (3)
O3W	0.052 (3)	0.081 (4)	0.053 (3)	0.018 (3)	0.000 (2)	−0.034 (3)

Cu1—Cu1i	2.6649 (11)	C6—H6A	0.9900
Cu1—O1	1.950 (4)	C6—H6B	0.9900
Cu1—O2i	1.955 (4)	C7—H7A	0.9900
Cu1—O4i	1.965 (4)	C7—H7B	0.9900
Cu1—O3	1.991 (3)	C8—H8A	0.9900
Cu1—Cl1	2.4990 (12)	C8—H8B	0.9900
O1—C1	1.265 (7)	C9—C10	1.526 (6)
O2—C1	1.258 (6)	C10—C15	1.516 (8)
O3—C9	1.255 (6)	C10—C11	1.536 (7)
O4—C9	1.264 (6)	C10—H10	1.0000
N1—C8	1.489 (7)	C11—C12	1.527 (7)
N1—H1A	0.9100	C11—H11A	0.9900
N1—H1B	0.9100	C11—H11B	0.9900
N1—H1C	0.9100	C12—C13	1.505 (8)
N2—C16	1.479 (8)	C12—H12A	0.9900
N2—H2A	0.9100	C12—H12B	0.9900
N2—H2B	0.9100	C13—C16	1.522 (7)
N2—H2C	0.9100	C13—C14	1.538 (8)
C1—C2	1.499 (8)	C13—H13	1.0000
C2—C7	1.526 (8)	C14—C15	1.518 (7)
C2—C3	1.547 (7)	C14—H14A	0.9900
C2—H2	1.0000	C14—H14B	0.9900
C3—C4	1.512 (9)	C15—H15A	0.9900
C3—H3A	0.9900	C15—H15B	0.9900
C3—H3B	0.9900	C16—H16A	0.9900
C4—C5	1.515 (8)	C16—H16B	0.9900
C4—H4A	0.9900	O1W—H1WA	0.89 (2)
C4—H4B	0.9900	O1W—H1WB	0.90 (2)
C5—C8	1.526 (8)	O2W—H2WA	0.90 (2)
C5—C6	1.536 (7)	O2W—H2WB	0.90 (2)
C5—H5	1.0000	O3W—H3WA	0.88 (2)
C6—C7	1.518 (9)	O3W—H3WB	0.88 (2)
O1—Cu1—O2i	167.02 (15)	C5—C6—H6B	109.6
O1—Cu1—O4i	89.3 (2)	H6A—C6—H6B	108.1
O2i—Cu1—O4i	89.9 (2)	C6—C7—C2	112.7 (5)
O1—Cu1—O3	88.33 (18)	C6—C7—H7A	109.0
O2i—Cu1—O3	89.60 (18)	C2—C7—H7A	109.0
O4i—Cu1—O3	167.27 (15)	C6—C7—H7B	109.0
O1—Cu1—Cl1	94.31 (11)	C2—C7—H7B	109.0
O2i—Cu1—Cl1	98.68 (11)	H7A—C7—H7B	107.8
O4i—Cu1—Cl1	92.57 (11)	N1—C8—C5	112.0 (5)
O3—Cu1—Cl1	100.08 (10)	N1—C8—H8A	109.2
O1—Cu1—Cu1i	83.04 (11)	C5—C8—H8A	109.2
O2i—Cu1—Cu1i	84.05 (11)	N1—C8—H8B	109.2
O4i—Cu1—Cu1i	80.24 (11)	C5—C8—H8B	109.2
O3—Cu1—Cu1i	87.06 (10)	H8A—C8—H8B	107.9
Cl1—Cu1—Cu1i	172.34 (4)	O3—C9—O4	124.6 (5)
C1—O1—Cu1	125.2 (3)	O3—C9—C10	119.4 (4)
C1—O2—Cu1i	123.8 (4)	O4—C9—C10	116.0 (4)
C9—O3—Cu1	119.4 (3)	C15—C10—C9	109.8 (4)
C9—O4—Cu1i	128.7 (3)	C15—C10—C11	111.3 (4)
C8—N1—H1A	109.5	C9—C10—C11	109.5 (4)
C8—N1—H1B	109.5	C15—C10—H10	108.7
H1A—N1—H1B	109.5	C9—C10—H10	108.7
C8—N1—H1C	109.5	C11—C10—H10	108.7
H1A—N1—H1C	109.5	C12—C11—C10	111.1 (4)
H1B—N1—H1C	109.5	C12—C11—H11A	109.4
C16—N2—H2A	109.5	C10—C11—H11A	109.4
C16—N2—H2B	109.5	C12—C11—H11B	109.4
H2A—N2—H2B	109.5	C10—C11—H11B	109.4
C16—N2—H2C	109.5	H11A—C11—H11B	108.0
H2A—N2—H2C	109.5	C13—C12—C11	110.8 (4)
H2B—N2—H2C	109.5	C13—C12—H12A	109.5
O2—C1—O1	123.9 (5)	C11—C12—H12A	109.5
O2—C1—C2	118.0 (5)	C13—C12—H12B	109.5
O1—C1—C2	118.1 (4)	C11—C12—H12B	109.5
C1—C2—C7	108.9 (5)	H12A—C12—H12B	108.1
C1—C2—C3	112.2 (5)	C12—C13—C16	111.5 (5)
C7—C2—C3	110.2 (4)	C12—C13—C14	109.2 (4)
C1—C2—H2	108.5	C16—C13—C14	112.2 (5)
C7—C2—H2	108.5	C12—C13—H13	107.9
C3—C2—H2	108.5	C16—C13—H13	107.9
C4—C3—C2	112.0 (5)	C14—C13—H13	107.9
C4—C3—H3A	109.2	C15—C14—C13	112.3 (5)
C2—C3—H3A	109.2	C15—C14—H14A	109.1
C4—C3—H3B	109.2	C13—C14—H14A	109.1
C2—C3—H3B	109.2	C15—C14—H14B	109.1
H3A—C3—H3B	107.9	C13—C14—H14B	109.1
C3—C4—C5	111.3 (5)	H14A—C14—H14B	107.9
C3—C4—H4A	109.4	C10—C15—C14	112.5 (5)
C5—C4—H4A	109.4	C10—C15—H15A	109.1
C3—C4—H4B	109.4	C14—C15—H15A	109.1
C5—C4—H4B	109.4	C10—C15—H15B	109.1
H4A—C4—H4B	108.0	C14—C15—H15B	109.1
C4—C5—C8	113.9 (5)	H15A—C15—H15B	107.8
C4—C5—C6	110.2 (5)	N2—C16—C13	111.6 (5)
C8—C5—C6	109.8 (5)	N2—C16—H16A	109.3
C4—C5—H5	107.5	C13—C16—H16A	109.3
C8—C5—H5	107.5	N2—C16—H16B	109.3
C6—C5—H5	107.5	C13—C16—H16B	109.3
C7—C6—C5	110.5 (5)	H16A—C16—H16B	108.0
C7—C6—H6A	109.6	H1WA—O1W—H1WB	102 (3)
C5—C6—H6A	109.6	H2WA—O2W—H2WB	103 (3)
C7—C6—H6B	109.6	H3WA—O3W—H3WB	106 (3)
Cu1i—O2—C1—O1	1.1 (7)	Cu1—O3—C9—O4	1.0 (8)
Cu1i—O2—C1—C2	178.1 (4)	Cu1—O3—C9—C10	−179.8 (4)
Cu1—O1—C1—O2	0.9 (7)	Cu1i—O4—C9—O3	−2.3 (9)
Cu1—O1—C1—C2	−176.1 (4)	Cu1i—O4—C9—C10	178.5 (4)
O2—C1—C2—C7	−94.2 (6)	O3—C9—C10—C15	122.8 (5)
O1—C1—C2—C7	82.9 (6)	O4—C9—C10—C15	−57.9 (6)
O2—C1—C2—C3	143.5 (5)	O3—C9—C10—C11	−114.7 (5)
O1—C1—C2—C3	−39.4 (7)	O4—C9—C10—C11	64.5 (6)
C1—C2—C3—C4	174.7 (5)	C15—C10—C11—C12	−53.7 (6)
C7—C2—C3—C4	53.1 (7)	C9—C10—C11—C12	−175.2 (4)
C2—C3—C4—C5	−56.3 (7)	C10—C11—C12—C13	58.9 (6)
C3—C4—C5—C8	−178.1 (5)	C11—C12—C13—C16	176.2 (4)
C3—C4—C5—C6	57.9 (7)	C11—C12—C13—C14	−59.3 (5)
C4—C5—C6—C7	−57.2 (8)	C12—C13—C14—C15	56.5 (6)
C8—C5—C6—C7	176.5 (6)	C16—C13—C14—C15	−179.4 (5)
C5—C6—C7—C2	55.9 (8)	C9—C10—C15—C14	172.3 (4)
C1—C2—C7—C6	−176.8 (5)	C11—C10—C15—C14	50.9 (6)
C3—C2—C7—C6	−53.3 (7)	C13—C14—C15—C10	−52.9 (6)
C4—C5—C8—N1	63.3 (7)	C12—C13—C16—N2	−162.4 (5)
C6—C5—C8—N1	−172.5 (5)	C14—C13—C16—N2	74.9 (6)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···Cl1ii	0.91	2.63	3.316 (5)	133
N1—H1C···Cl1iii	0.91	2.52	3.394 (5)	160
N2—H2B···Cl1iv	0.91	2.25	3.123 (5)	160
N2—H2C···Cl2v	0.91	2.24	3.151 (6)	179
N1—H1B···O1Wvi	0.91	1.90	2.760 (7)	156
N2—H2A···O2Wvii	0.91	2.06	2.789 (9)	137
O1W—H1WA···Cl2v	0.89 (2)	2.57 (8)	3.218 (6)	130 (8)
O2W—H2WA···Cl2viii	0.90 (2)	2.46 (7)	3.176 (6)	137 (9)
O2W—H2WB···O3i	0.90 (2)	2.22 (8)	2.820 (6)	124 (8)
O3W—H3WA···Cl1ix	0.88 (2)	2.66 (6)	3.258 (5)	127 (6)
O3W—H3WB···Cl2x	0.88 (2)	2.35 (3)	3.182 (5)	158 (7)