Hydrogen-bonding patterns in pyrimethaminium dinitrate

The title compound, 2,4-diamino-5-(4-chloro­phen­yl)-6-ethyl­pyrimidine-1,3-diium dinitrate, C₁₂H₁₅ClN₄²⁺·2NO₃⁻, contains two crystallographically independent pyrimethamine (PMN) mol­ecules, which differ in the relative orientations of the pyrimidine and benzene rings and of the eth­yl substitutents. In both pyrimethamine mol­ecules, all the pyrimidine N atoms are protonated, unlike most related compounds, in which only one pyrimidine N atom is protonated. The two pyrimethamine moieties are bridged by a variety of N—H...O(nitrate) inter­actions, including some three-centre hydrogen bonds.

S1. Comment

Pyrimethamine is an antifolate drug used in the treatment of malaria. In the chemotherapy of malaria and neoplastic diseases, substituted 2,4-diamino pyrimidines are widely employed as metabolic inhibitors of pathways leading to the synthesis of proteins and nucleic acids (Hitchings & Burchall, 1965). Pyrimethamine acts against malarial parasites by selectively inhibiting their dihydrofolate reductase–thymidylate synthase (Sardarian et al., 2003). Hydrogen bonding plays a key role in molecular recognition (Goswami & Ghosh, 1997) and crystal engineering (Goswami et al., 1999). The design of a number of supramolecular nanoarchitectures, such as layers, ribbons, rosettes, rods, tapes, tubes, sheets and spheres, can be achieved through N—H···O and O—H···O hydrogen bonds (Vishweshwar et al., 2002; Aitipamula et al., 2002). The crystal structure of pyrimethamine (PMN) itself has been reported from our laboratory (Sethuraman & Muthiah, 2002). The crystal structures of trimethoprim nitrate (Murugesan & Muthiah, 1997), PMN hydrogen maleate, PMN hydrogen succinate, PMN hydrogen phthalate and PMN fumarate (Sethuraman et al., 2003), and PMN hydrogen glutarate and PMN formate (Stanley et al., 2002), have also been reported from our laboratory. In this paper, the conformation and hydrogen-bonding patterns of pyrimethamine dinitrate (PMNN), (I), are reported.

The asymmetric unit of (I) contains two pyrimethamine cations and four nitrate anions (Fig. 1). Both the PMN moieties are protonated at N1, N3, N1A and N3A of the pyrimidine moiety, which is evident from the increase in the internal angles C2—N1—C6, C2—N3—C4, C2A—N1A—C6A and C2A—N3A—C4A at the corresponding N atoms. The angles (Table 1) are smaller than the values observed in neutral pyrimethamine [116.25 (18), 116.38 (17), 116.09 (18) and 116.47°, respectively; Sethuraman & Muthiah, 2002]. Usually, only one pyrimidine N atom (N1 or N1A) is protonated in the pyrimethamine molecule, but in (I) all the pyrimidine N atoms are protonated in both the pyrimethamine molecules.

The dihedral angle between the pyrimidine plane and the substituted phenyl plane is 82.5 (2)° in one molecule and 73.9 (2)° in the other. Similar dihedral angles are seen in the crystal structures of neutral pyrimethamine [74.4 (1)° in molecule A and 82.4 (1)° in molecule B; Sethuraman & Muthiah, 2002], 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidinium ethanesulfonate (71.1°; Cody, 1983) and metoprine (78.1° in molecule A and 91.6° in molecule B; De et al., 1989). The two torsion angles (C5—C6—C7—C8 and C5A—C6A—C7A—C8A) of the PMN moieties are −107.7 (5) and −100.9 (5)°, respectively. These values are close to those observed in modelling studies of dihydrofolate reductase–pyrimethamine complexes, which indicates that these angles play an important role in the proper docking of the drug molecule in the active site of the enzyme (Sansom et al., 1989). The lengths of the bonds connecting the pyrimidine and phenyl rings (Table 1) are in close agreement with those reported for metoprine (De et al., 1989). The different mutual arrangements of the p-chlorophenyl and ethyl substituents in the two independent molecules of (I) are illustrated in Fig. 2.

The protonated atom N1A and the 2-amino group are hydrogen bonded to the O atoms of the nitrate anion (O1C and O3C), leading to an eight-membered ring formed via N—H···O bonds (Fig. 3). The other protonation sites, atom N3A and the 4-amino group, are hydrogen bonded to the O atoms of the other nitrate anion (atoms O1D and O2D), forming a similar cyclic hydrogen-bonded ring. Both can be designated by graph-set notation R₂²(8) (Etter, 1990; Bernstein et al., 1995). This type of interaction is similar to the carboxylate–trimethoprim interaction observed in the trimethoprim cation–dihydrofolate reductase complex (Kuyper, 1990) and to the cyclic hydrogen-bonded motif observed in many organic crystal structures (Allan et al., 1998).

In the other pyrimethamine molecule, the protonated N atom (N1) of the pyrimidine ring forms a three-centre hydrogen bond with two O atoms of the nitrate ion (atoms O1E and O3E). The other protonated N atom (N3) forms a three-centre hydrogen bond, of similar type but weaker, with another nitrate ion (atoms O1B and O3B) (Table 2). The protonated N atom (N3), 2-amino group and 4-amino group are hydrogen bonded with two O atoms of the same nitrate ion (atoms O1B and O3B), forming both three-centre and bifurcated hydrogen bonds. The protonated N atom (donor; N1) and the 2-amino group form hydrogen bonds with the O atom of the nitrate ion (acceptor; O1E), leading to a six-membered ring which can be designated by graph-set notation R₂¹(6) (Fig.3). This type of packing is commonly observed in PMN hydrogen maleate, PMN hydrogen succinate and PMN hydrogenphthalate (Sethuraman et al., 2003).

S2. Experimental

To a hot methanolic solution of pyrimethamine (62 mg, Shah Pharma Chemicals, India), a few drops of nitric acid were added. The solution was warmed over a water bath for a few minutes. The resultant solution was allowed to cool slowly at room temperature. Crystals of (I) appeared from the mother liquor after a few days.

S3. Refinement

All the H atoms were fixed geometrically and were refined using a riding model. The refined N—H and C—H bond lengths are 0.85–0.86 Å and 0.92–0.96 Å, and with U_iso(H)=1.2Ueq.

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2000); cell refinement: CrysAlis RED (Oxford Diffraction, 2000); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976) and PLATON (Spek, 2003); software used to prepare material for publication: PLATON.

Figures

	Fig. 1. A view of the asymmetric unit of (I), showing 50% probability displacement ellipsoids and the atom-numbering scheme.
	Fig. 2. An orthogonal fit of the two PMN molecules in (I). The fitted atoms are those forming the pyrimidine moiety.
	Fig. 3. A view of the hydrogen-bonded supramolecular chain along the b axis (see Table 2). Other atoms, and H atoms not involved in the bonding, are omitted for clarity.

2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidine-1,3-diium dinitrate

Crystal data

C12H15ClN4^2+·2NO3^−	F(000) = 3104
Mr = 374.75	Dx = 1.516 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 7379 reflections
a = 32.700 (7) Å	θ = 3.4–25.7°
b = 12.926 (3) Å	µ = 0.28 mm^−1
c = 16.065 (3) Å	T = 295 K
β = 104.73 (3)°	Prismatic, colourless
V = 6567 (3) Å^3	0.4 × 0.3 × 0.2 mm
Z = 16

Data collection

Kuma KM4CCD κ-geometry diffractometer	6490 independent reflections
Radiation source: fine-focus sealed tube	3225 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.048
ω–scans	θmax = 26.1°, θmin = 2.6°
Absorption correction: multi-scan (XEMP, Siemens, 1990)	h = −21→40
Tmin = 0.893, Tmax = 0.952	k = −15→15
27180 measured reflections	l = −19→19

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.059	All H-atom parameters refined
wR(F^2) = 0.231	w = 1/[σ^2(Fo^2) + (0.0399P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max < 0.001
6490 reflections	Δρmax = 0.46 e Å^−3
451 parameters	Δρmin = −0.64 e Å^−3
0 restraints	Extinction correction: SHELXL, FC^*=KFC[1+0.001XFC^2Λ^3/SIN(2Θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.00014 (3)

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All e.s.d.'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Cl1	−0.04072 (4)	0.38389 (12)	0.14099 (11)	0.0853 (6)
N1	0.16443 (10)	0.3660 (2)	−0.0622 (2)	0.0355 (11)
N2	0.23742 (11)	0.3728 (3)	−0.0214 (2)	0.0464 (12)
N3	0.19920 (10)	0.3713 (2)	0.0814 (2)	0.0357 (11)
N4	0.16403 (11)	0.3733 (3)	0.1880 (2)	0.0450 (11)
C2	0.20081 (12)	0.3704 (3)	−0.0022 (2)	0.0340 (12)
C4	0.16211 (12)	0.3728 (3)	0.1053 (2)	0.0331 (12)
C5	0.12343 (12)	0.3709 (3)	0.0403 (2)	0.0334 (12)
C6	0.12548 (12)	0.3651 (3)	−0.0429 (2)	0.0338 (12)
C7	0.08849 (13)	0.3525 (3)	−0.1182 (2)	0.0435 (14)
C8	0.08739 (14)	0.2438 (4)	−0.1555 (3)	0.0623 (19)
C9	0.08293 (12)	0.3726 (3)	0.0669 (2)	0.0365 (14)
C10	0.06674 (16)	0.4643 (4)	0.0862 (4)	0.071 (2)
C11	0.02905 (17)	0.4677 (4)	0.1102 (4)	0.085 (3)
C12	0.00726 (14)	0.3795 (4)	0.1141 (3)	0.0531 (17)
C13	0.02354 (14)	0.2866 (4)	0.0973 (3)	0.0549 (17)
C14	0.06131 (13)	0.2823 (4)	0.0737 (3)	0.0493 (17)
Cl1A	0.00876 (4)	0.14944 (12)	0.62715 (8)	0.0713 (5)
N1A	0.17211 (10)	0.1267 (2)	0.3201 (2)	0.0402 (11)
N2A	0.24307 (11)	0.1204 (3)	0.3232 (2)	0.0506 (14)
N3A	0.22203 (11)	0.1212 (2)	0.4515 (2)	0.0384 (11)
N4A	0.20396 (11)	0.1238 (3)	0.5789 (2)	0.0461 (13)
C2A	0.21302 (13)	0.1223 (3)	0.3637 (2)	0.0378 (14)
C4A	0.19163 (12)	0.1248 (3)	0.4957 (2)	0.0337 (12)
C5A	0.14851 (12)	0.1297 (3)	0.4484 (2)	0.0340 (12)
C6A	0.13952 (13)	0.1316 (3)	0.3602 (2)	0.0361 (12)
C7A	0.09640 (13)	0.1400 (3)	0.3002 (3)	0.0471 (14)
C8A	0.07890 (16)	0.0393 (4)	0.2610 (3)	0.074 (2)
C9A	0.11470 (12)	0.1338 (3)	0.4949 (2)	0.0354 (14)
C10A	0.10775 (14)	0.2238 (3)	0.5362 (3)	0.0485 (17)
C11A	0.07577 (15)	0.2283 (4)	0.5782 (3)	0.0558 (17)
C12A	0.05042 (13)	0.1421 (4)	0.5778 (3)	0.0464 (14)
C13A	0.05715 (13)	0.0518 (4)	0.5383 (3)	0.0482 (17)
C14A	0.08961 (13)	0.0473 (3)	0.4978 (3)	0.0432 (16)
O1B	0.30315 (12)	0.3803 (3)	0.1384 (2)	0.0810 (18)
O2B	0.33083 (10)	0.3773 (3)	0.2751 (2)	0.0723 (13)
O3B	0.26349 (10)	0.3648 (3)	0.22723 (19)	0.0580 (13)
N1B	0.29935 (12)	0.3739 (3)	0.2139 (2)	0.0481 (14)
O1C	0.21359 (11)	0.1298 (3)	0.1448 (2)	0.0724 (13)
O2C	0.16767 (10)	0.1279 (3)	0.02391 (19)	0.0609 (13)
O3C	0.14755 (10)	0.1242 (3)	0.14138 (19)	0.0582 (13)
N1C	0.17619 (12)	0.1263 (3)	0.1024 (2)	0.0422 (12)
O1D	0.19156 (10)	0.3948 (3)	0.48109 (18)	0.0618 (13)
O2D	0.20758 (10)	0.3579 (3)	0.3641 (2)	0.0701 (13)
O3D	0.14291 (10)	0.3885 (3)	0.3619 (2)	0.0621 (13)
N1D	0.18011 (11)	0.3814 (2)	0.4017 (2)	0.0397 (12)
O1E	0.19542 (13)	0.6211 (3)	0.2856 (2)	0.0939 (18)
O2E	0.16923 (10)	0.6060 (2)	0.14908 (18)	0.0526 (11)
O3E	0.12991 (14)	0.6023 (4)	0.2360 (3)	0.1038 (19)
N1E	0.16509 (14)	0.6105 (3)	0.2241 (2)	0.0498 (14)
H1	0.16510	0.36390	−0.11530	0.0430*
H2	0.26040	0.37550	0.01900	0.0560*
H3	0.23850	0.37160	−0.07440	0.0560*
H4	0.22260	0.37140	0.12090	0.0430*
H5	0.18820	0.37270	0.22520	0.0540*
H6	0.14110	0.37400	0.20500	0.0540*
H7	0.06270	0.36480	−0.10040	0.0520*
H7A	0.08990	0.40310	−0.16200	0.0520*
H8A	0.08600	0.19370	−0.11230	0.0750*
H8B	0.06300	0.23710	−0.20330	0.0750*
H8C	0.11250	0.23240	−0.17490	0.0750*
H10	0.08130	0.52540	0.08300	0.0860*
H11	0.01840	0.53080	0.12300	0.1020*
H13	0.00890	0.22580	0.10120	0.0660*
H14	0.07220	0.21880	0.06280	0.0590*
H1A	0.16600	0.12620	0.26480	0.0480*
H2A	0.26910	0.11760	0.35210	0.0610*
H2B	0.23680	0.12160	0.26790	0.0610*
H3A	0.24810	0.11850	0.48020	0.0460*
H4A	0.18570	0.12590	0.60900	0.0550*
H4B	0.23050	0.12130	0.60420	0.0550*
H10A	0.12450	0.28170	0.53540	0.0580*
H11A	0.07130	0.28860	0.60620	0.0670*
H13A	0.04030	−0.00580	0.53960	0.0570*
H14A	0.09470	−0.01400	0.47190	0.0520*
H71A	0.09760	0.18780	0.25440	0.0570*
H71B	0.07720	0.16860	0.33140	0.0570*
H81A	0.09820	0.00950	0.23160	0.0890*
H82A	0.05200	0.05020	0.22090	0.0890*
H83A	0.07560	−0.00670	0.30570	0.0890*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0551 (9)	0.1048 (12)	0.1121 (12)	−0.0042 (8)	0.0508 (9)	−0.0107 (9)
N1	0.039 (2)	0.045 (2)	0.0253 (17)	−0.0022 (16)	0.0135 (15)	−0.0021 (15)
N2	0.034 (2)	0.063 (2)	0.045 (2)	−0.0015 (17)	0.0153 (17)	−0.0022 (18)
N3	0.0304 (18)	0.044 (2)	0.0312 (18)	−0.0006 (15)	0.0048 (14)	0.0018 (15)
N4	0.044 (2)	0.064 (2)	0.0268 (18)	−0.0046 (18)	0.0089 (16)	0.0008 (17)
C2	0.037 (2)	0.034 (2)	0.032 (2)	−0.0010 (18)	0.0108 (18)	−0.0013 (18)
C4	0.039 (2)	0.029 (2)	0.032 (2)	−0.0044 (17)	0.0101 (18)	−0.0013 (17)
C5	0.034 (2)	0.038 (2)	0.028 (2)	−0.0026 (18)	0.0077 (17)	−0.0021 (17)
C6	0.033 (2)	0.039 (2)	0.030 (2)	−0.0008 (18)	0.0090 (17)	−0.0005 (17)
C7	0.035 (2)	0.066 (3)	0.028 (2)	0.001 (2)	0.0053 (18)	−0.001 (2)
C8	0.054 (3)	0.088 (4)	0.043 (3)	−0.023 (3)	0.009 (2)	−0.014 (3)
C9	0.033 (2)	0.047 (3)	0.031 (2)	−0.0035 (19)	0.0108 (17)	−0.0044 (19)
C10	0.066 (3)	0.044 (3)	0.121 (5)	−0.010 (3)	0.055 (3)	−0.019 (3)
C11	0.073 (4)	0.053 (3)	0.152 (6)	−0.009 (3)	0.073 (4)	−0.029 (4)
C12	0.042 (3)	0.068 (3)	0.054 (3)	−0.002 (2)	0.021 (2)	−0.007 (2)
C13	0.044 (3)	0.058 (3)	0.067 (3)	−0.012 (2)	0.022 (2)	0.003 (3)
C14	0.045 (3)	0.047 (3)	0.059 (3)	0.002 (2)	0.019 (2)	0.003 (2)
Cl1A	0.0475 (8)	0.1116 (12)	0.0616 (8)	0.0097 (7)	0.0264 (6)	−0.0026 (7)
N1A	0.042 (2)	0.054 (2)	0.0241 (17)	0.0036 (17)	0.0076 (15)	−0.0032 (15)
N2A	0.043 (2)	0.073 (3)	0.039 (2)	0.0063 (19)	0.0165 (17)	−0.0041 (19)
N3A	0.0351 (19)	0.048 (2)	0.0295 (18)	0.0013 (16)	0.0034 (15)	−0.0022 (15)
N4A	0.037 (2)	0.073 (3)	0.0263 (18)	−0.0005 (18)	0.0043 (15)	−0.0015 (17)
C2A	0.044 (3)	0.037 (2)	0.032 (2)	0.0013 (19)	0.0089 (19)	−0.0040 (18)
C4A	0.037 (2)	0.037 (2)	0.027 (2)	0.0014 (18)	0.0077 (17)	0.0003 (17)
C5A	0.034 (2)	0.037 (2)	0.030 (2)	0.0012 (18)	0.0064 (17)	−0.0017 (18)
C6A	0.037 (2)	0.040 (2)	0.030 (2)	0.0012 (18)	0.0062 (18)	−0.0024 (18)
C7A	0.037 (2)	0.069 (3)	0.033 (2)	0.004 (2)	0.0045 (19)	0.002 (2)
C8A	0.062 (4)	0.087 (4)	0.065 (3)	−0.018 (3)	0.000 (3)	−0.016 (3)
C9A	0.034 (2)	0.047 (3)	0.0229 (19)	0.0046 (19)	0.0030 (17)	0.0006 (18)
C10A	0.046 (3)	0.050 (3)	0.052 (3)	−0.007 (2)	0.017 (2)	−0.011 (2)
C11A	0.057 (3)	0.058 (3)	0.057 (3)	0.000 (3)	0.023 (2)	−0.014 (2)
C12A	0.035 (2)	0.071 (3)	0.034 (2)	0.011 (2)	0.0100 (19)	0.005 (2)
C13A	0.044 (3)	0.055 (3)	0.047 (3)	−0.004 (2)	0.014 (2)	0.000 (2)
C14A	0.049 (3)	0.041 (3)	0.042 (2)	0.003 (2)	0.016 (2)	−0.0056 (19)
O1B	0.072 (3)	0.139 (4)	0.0337 (19)	0.000 (2)	0.0164 (17)	0.004 (2)
O2B	0.041 (2)	0.133 (3)	0.0385 (18)	−0.008 (2)	0.0018 (16)	0.003 (2)
O3B	0.0365 (18)	0.093 (3)	0.0436 (18)	−0.0011 (17)	0.0087 (14)	0.0041 (17)
N1B	0.048 (2)	0.062 (3)	0.035 (2)	0.0007 (19)	0.0121 (19)	0.0023 (18)
O1C	0.040 (2)	0.136 (3)	0.0401 (18)	−0.004 (2)	0.0081 (16)	0.000 (2)
O2C	0.062 (2)	0.091 (3)	0.0296 (17)	−0.0049 (18)	0.0112 (15)	0.0013 (16)
O3C	0.0454 (19)	0.094 (3)	0.0372 (17)	0.0004 (17)	0.0140 (15)	−0.0022 (16)
N1C	0.051 (2)	0.045 (2)	0.032 (2)	−0.0028 (18)	0.0130 (18)	−0.0016 (17)
O1D	0.057 (2)	0.100 (3)	0.0273 (17)	−0.0021 (18)	0.0086 (15)	−0.0033 (16)
O2D	0.0396 (19)	0.130 (3)	0.0408 (18)	0.0096 (19)	0.0103 (15)	−0.0155 (19)
O3D	0.0349 (19)	0.099 (3)	0.0499 (19)	0.0047 (17)	0.0061 (15)	0.0020 (18)
N1D	0.040 (2)	0.044 (2)	0.034 (2)	0.0004 (17)	0.0072 (17)	0.0044 (16)
O1E	0.088 (3)	0.156 (4)	0.0298 (19)	−0.042 (3)	0.0007 (19)	−0.004 (2)
O2E	0.054 (2)	0.076 (2)	0.0307 (16)	0.0017 (16)	0.0161 (14)	0.0009 (15)
O3E	0.091 (3)	0.143 (4)	0.101 (3)	0.022 (3)	0.068 (3)	0.009 (3)
N1E	0.064 (3)	0.047 (2)	0.047 (2)	−0.001 (2)	0.030 (2)	0.0012 (18)

Geometric parameters (Å, º)

Cl1—C12	1.731 (5)	C5—C6	1.357 (5)
Cl1A—C12A	1.744 (5)	C5—C9	1.492 (6)
O1B—N1B	1.253 (5)	C6—C7	1.486 (5)
O2B—N1B	1.230 (5)	C7—C8	1.524 (6)
O3B—N1B	1.250 (5)	C9—C14	1.383 (6)
O1C—N1C	1.240 (5)	C9—C10	1.366 (7)
O2C—N1C	1.220 (4)	C10—C11	1.382 (8)
O3C—N1C	1.252 (5)	C11—C12	1.354 (7)
O1D—N1D	1.247 (4)	C12—C13	1.368 (7)
O2D—N1D	1.241 (5)	C13—C14	1.382 (7)
O3D—N1D	1.225 (5)	C7—H7A	0.9703
N1—C2	1.328 (5)	C7—H7	0.9700
N1—C6	1.385 (5)	C8—H8A	0.9587
O1E—N1E	1.217 (5)	C8—H8C	0.9608
N2—C2	1.310 (5)	C8—H8B	0.9601
O2E—N1E	1.248 (4)	C10—H10	0.9303
N3—C2	1.357 (4)	C11—H11	0.9302
N3—C4	1.362 (5)	C13—H13	0.9306
O3E—N1E	1.218 (7)	C14—H14	0.9289
N4—C4	1.314 (4)	C4A—C5A	1.423 (5)
N1—H1	0.8593	C5A—C9A	1.484 (5)
N2—H2	0.8597	C5A—C6A	1.372 (4)
N2—H3	0.8612	C6A—C7A	1.496 (6)
N3—H4	0.8610	C7A—C8A	1.495 (7)
N4—H6	0.8608	C9A—C10A	1.386 (6)
N4—H5	0.8612	C9A—C14A	1.395 (6)
N1A—C2A	1.344 (5)	C10A—C11A	1.382 (7)
N1A—C6A	1.380 (5)	C11A—C12A	1.388 (7)
N2A—C2A	1.309 (5)	C12A—C13A	1.373 (7)
N3A—C2A	1.366 (4)	C13A—C14A	1.380 (6)
N3A—C4A	1.361 (5)	C7A—H71A	0.9692
N4A—C4A	1.294 (4)	C7A—H71B	0.9706
N1A—H1A	0.8596	C8A—H81A	0.9599
N2A—H2B	0.8596	C8A—H82A	0.9594
N2A—H2A	0.8605	C8A—H83A	0.9593
N3A—H3A	0.8606	C10A—H10A	0.9294
N4A—H4A	0.8590	C11A—H11A	0.9299
N4A—H4B	0.8603	C13A—H13A	0.9296
C4—C5	1.421 (5)	C14A—H14A	0.9295
Cl1···O3D^i	3.331 (4)	N1D···H4B^viii	2.9488
Cl1A···C8^i	3.508 (5)	N1D···H5	2.9162
Cl1···H71B^i	3.1037	N1D···H3A^viii	2.6164
Cl1A···H8B^i	3.1220	N1E···H1^vii	2.6011
Cl1A···H82A^ii	3.1375	N1E···H2A^iv	2.7345
Cl1A···H8B^iii	3.0647	C2···O1E^x	3.370 (5)
Cl1A···H8A^i	3.1000	C2···O1D^x	3.055 (6)
O1B···N2	2.901 (5)	C2···O2C	3.377 (5)
O1B···C2A^iv	3.171 (6)	C2A···N1B^vi	3.431 (5)
O1B···O2C^v	2.998 (5)	C2A···O1B^vi	3.171 (6)
O1C···N2A	2.784 (4)	C2A···O2D	3.051 (6)
O1C···N2^v	2.848 (5)	C4···O3C	3.321 (5)
O1C···O1E^vi	2.902 (6)	C4···O3B	3.396 (5)
O1D···O2E^vii	2.970 (4)	C4···O2E	3.091 (5)
O1D···N3A^viii	2.765 (5)	C4···N1C	3.221 (6)
O1D···N1^vii	3.243 (5)	C4A···O2C^ii	3.416 (6)
O1D···C2^vii	3.055 (6)	C6A···O3D	3.322 (6)
O1E···N2^vii	3.056 (5)	C7···C14	3.537 (6)
O1E···N1^vii	2.880 (5)	C7···O3E^x	3.046 (6)
O1E···N2A^iv	2.981 (5)	C7A···O3C	3.394 (6)
O1E···O1C^iv	2.902 (6)	C7A···C14A	3.453 (6)
O1E···C2^vii	3.370 (5)	C8···O3E^x	3.188 (7)
O2B···N4A^viii	2.855 (5)	C8···Cl1A^i	3.508 (5)
O2C···C14A^ix	3.358 (6)	C10···N4	3.396 (7)
O2C···C4A^ix	3.416 (6)	C10···O3E	3.273 (8)
O2C···O1B^v	2.998 (5)	C10A···O2E^vii	3.212 (5)
O2C···N2^v	3.114 (5)	C10A···N4A	3.308 (6)
O2C···C2	3.377 (5)	C14···C7	3.537 (6)
O2D···N4	2.832 (4)	C14A···O3C^ii	3.406 (6)
O2D···N1A	3.219 (5)	C14A···C7A	3.453 (6)
O2D···O3B	3.198 (5)	C14A···O2C^ii	3.358 (6)
O2D···C2A	3.051 (6)	C8···H1	2.9069
O2D···N3A^viii	3.268 (5)	C8A···H1A	3.0478
O2D···N4A^viii	2.813 (5)	C9···H7	2.6014
O2E···N4	3.086 (5)	C9···H6	2.5288
O2E···O1D^x	2.970 (4)	C9A···H71B	2.6396
O2E···N2A^iv	2.794 (5)	C9A···H4A	2.5684
O2E···C4	3.091 (5)	C10···H6	2.9253
O2E···C10A^x	3.212 (5)	C10A···H4A	2.8197
O3B···O2D	3.198 (5)	C14···H71A	3.0944
O3B···N3	2.722 (4)	C14···H7	3.0044
O3B···N4A^viii	3.028 (4)	C14A···H71B	3.0360
O3B···N4	3.154 (5)	C14A···H83A	3.0825
O3B···C4	3.396 (5)	H1···N1E^x	2.6011
O3C···C14A^ix	3.406 (6)	H1···C8	2.9069
O3C···C4	3.321 (5)	H1···H3	2.3239
O3C···N1A	2.778 (4)	H1···H7A	2.4348
O3C···C7A	3.394 (6)	H1···H8C	2.4345
O3D···Cl1^i	3.331 (4)	H1···O1E^x	2.0876
O3D···C6A	3.322 (6)	H1···O3E^x	2.4133
O3D···N4	3.050 (5)	H1A···O3C	1.9203
O3E···C8^vii	3.188 (7)	H1A···N1C	2.7129
O3E···C10	3.273 (8)	H1A···C8A	3.0478
O3E···N1^vii	3.177 (6)	H1A···H2B	2.3038
O3E···C7^vii	3.046 (6)	H1A···H71A	2.3398
O1B···H2	2.0673	H1A···O1C	2.7687
O1B···H4	2.5795	H2···O2C^v	2.6142
O1C···H3^v	2.1529	H2···O1B	2.0673
O1C···H2B	1.9326	H2···H4	2.2890
O1C···H1A	2.7687	H2A···O1D^viii	2.6662
O1D···H2A^viii	2.6662	H2A···O2E^vi	2.0271
O1D···H3A^viii	1.9198	H2A···N1E^vi	2.7345
O1E···H2A^iv	2.7472	H2A···H3A	2.3292
O1E···H1^vii	2.0876	H2A···O1E^vi	2.7472
O1E···H2B^iv	2.5729	H2B···O1E^vi	2.5729
O1E···H3^vii	2.3325	H2B···O1C	1.9326
O2B···H81A^iv	2.9059	H2B···N1C	2.8846
O2B···H4A^viii	2.0670	H2B···H1A	2.3038
O2C···H14A^ix	2.7469	H3···O1C^v	2.1529
O2C···H2^v	2.6142	H3···N1C^v	2.9365
O2D···H4B^viii	1.9766	H3···H1	2.3239
O2D···H5	2.1676	H3···O1E^x	2.3325
O2D···H3A^viii	2.5703	H3A···N1D^viii	2.6164
O2D···H6	2.9114	H3A···O2D^viii	2.5703
O2E···H2A^iv	2.0271	H3A···H2A	2.3292
O2E···H10A^x	2.4947	H3A···H4B	2.2099
O3B···H5	2.4560	H3A···O1D^viii	1.9198
O3B···H4B^viii	2.6709	H4···N1B	2.5739
O3B···H4A^viii	2.7339	H4···H5	2.2431
O3B···H4	1.8846	H4···O3B	1.8846
O3C···H1A	1.9203	H4···H2	2.2890
O3C···H71A	2.8546	H4···O1B	2.5795
O3C···H14	2.7528	H4A···N1B^viii	2.7616
O3C···H81A	2.8447	H4A···C10A	2.8197
O3D···H6	2.5132	H4A···O2B^viii	2.0670
O3E···H10	2.7513	H4A···O3B^viii	2.7339
O3E···H1^vii	2.4133	H4A···C9A	2.5684
O3E···H7A^vii	2.3435	H4B···O2D^viii	1.9766
O3E···H11A^x	2.8245	H4B···O3B^viii	2.6709
O3E···H8C^vii	2.7116	H4B···H3A	2.2099
N1···O3E^x	3.177 (6)	H4B···N1D^viii	2.9488
N1···O1E^x	2.880 (5)	H5···H4	2.2431
N1···O1D^x	3.243 (5)	H5···O2D	2.1676
N1A···O3C	2.778 (4)	H5···N1D	2.9162
N1A···O2D	3.219 (5)	H5···O3B	2.4560
N1B···C2A^iv	3.431 (5)	H6···O2D	2.9114
N1C···C4	3.221 (6)	H6···C9	2.5288
N1C···N3	3.292 (5)	H6···O3D	2.5132
N1E···N2A^iv	3.282 (6)	H6···C10	2.9253
N1E···N4	3.119 (6)	H7···C9	2.6014
N2···O1E^x	3.056 (5)	H7···C14	3.0044
N2···O2C^v	3.114 (5)	H7A···O3E^x	2.3435
N2···O1C^v	2.848 (5)	H7A···H1	2.4348
N2···O1B	2.901 (5)	H8A···Cl1A^i	3.1000
N2A···O2E^vi	2.794 (5)	H8B···Cl1A^i	3.1220
N2A···N1E^vi	3.282 (6)	H8B···Cl1A^xi	3.0647
N2A···O1C	2.784 (4)	H8C···H1	2.4345
N2A···O1E^vi	2.981 (5)	H8C···N1	2.7532
N3···O3B	2.722 (4)	H8C···O3E^x	2.7116
N3···N1C	3.292 (5)	H10···O3E	2.7513
N3A···O2D^viii	3.268 (5)	H10···H11A^x	2.4674
N3A···O1D^viii	2.765 (5)	H10A···O2E^vii	2.4947
N4···O2D	2.832 (4)	H11A···O3E^vii	2.8245
N4···N1E	3.119 (6)	H11A···H10^vii	2.4674
N4···C10	3.396 (7)	H14···O3C	2.7528
N4···O3D	3.050 (5)	H14A···O2C^ii	2.7469
N4···O3B	3.154 (5)	H14A···H83A	2.5845
N4···O2E	3.086 (5)	H71A···C14	3.0944
N4A···O3B^viii	3.028 (4)	H71A···H1A	2.3398
N4A···O2B^viii	2.855 (5)	H71A···O3C	2.8546
N4A···C10A	3.308 (6)	H71B···C9A	2.6396
N4A···O2D^viii	2.813 (5)	H71B···C14A	3.0360
N1···H8C	2.7532	H71B···Cl1^i	3.1037
N1A···H81A	2.9000	H81A···O3C	2.8447
N1B···H4A^viii	2.7616	H81A···N1A	2.9000
N1B···H4	2.5739	H81A···O2B^vi	2.9059
N1C···H2B	2.8846	H82A···Cl1A^ix	3.1375
N1C···H3^v	2.9365	H83A···C14A	3.0825
N1C···H1A	2.7129	H83A···H14A	2.5845
C2—N1—C6	122.9 (3)	C8—C7—H7	109.37
C2—N3—C4	122.7 (3)	C6—C7—H7	109.31
C2—N1—H1	118.52	H7—C7—H7A	107.97
C6—N1—H1	118.61	C8—C7—H7A	109.69
C2—N2—H2	119.92	C7—C8—H8A	109.80
C2—N2—H3	120.12	H8A—C8—H8C	109.45
H2—N2—H3	119.96	C7—C8—H8C	109.40
C4—N3—H4	118.71	C7—C8—H8B	109.23
C2—N3—H4	118.58	H8B—C8—H8C	109.35
C4—N4—H6	119.95	H8A—C8—H8B	109.60
H5—N4—H6	119.98	C9—C10—H10	119.40
C4—N4—H5	120.07	C11—C10—H10	119.57
C2A—N1A—C6A	122.9 (3)	C12—C11—H11	119.80
C2A—N3A—C4A	123.0 (3)	C10—C11—H11	120.00
C6A—N1A—H1A	118.60	C14—C13—H13	119.69
C2A—N1A—H1A	118.50	C12—C13—H13	119.70
C2A—N2A—H2A	119.80	C9—C14—H14	120.17
H2A—N2A—H2B	120.11	C13—C14—H14	119.96
C2A—N2A—H2B	120.08	N1A—C2A—N3A	117.6 (4)
C4A—N3A—H3A	118.50	N2A—C2A—N3A	121.4 (4)
C2A—N3A—H3A	118.55	N1A—C2A—N2A	121.0 (3)
H4A—N4A—H4B	119.82	N4A—C4A—C5A	123.9 (4)
C4A—N4A—H4A	120.16	N3A—C4A—N4A	117.5 (4)
C4A—N4A—H4B	120.02	N3A—C4A—C5A	118.6 (3)
O2B—N1B—O3B	119.8 (3)	C6A—C5A—C9A	121.8 (3)
O1B—N1B—O3B	120.0 (4)	C4A—C5A—C9A	119.8 (3)
O1B—N1B—O2B	120.2 (4)	C4A—C5A—C6A	118.4 (4)
O2C—N1C—O3C	120.9 (4)	C5A—C6A—C7A	125.9 (4)
O1C—N1C—O2C	120.1 (4)	N1A—C6A—C7A	114.6 (3)
O1C—N1C—O3C	119.0 (3)	N1A—C6A—C5A	119.5 (4)
O1D—N1D—O2D	117.8 (4)	C6A—C7A—C8A	113.9 (4)
O1D—N1D—O3D	121.6 (4)	C5A—C9A—C14A	120.5 (3)
O2D—N1D—O3D	120.6 (3)	C5A—C9A—C10A	120.3 (4)
O1E—N1E—O3E	119.3 (4)	C10A—C9A—C14A	119.2 (4)
O1E—N1E—O2E	121.6 (4)	C9A—C10A—C11A	120.4 (4)
O2E—N1E—O3E	119.1 (4)	C10A—C11A—C12A	119.3 (4)
N1—C2—N3	117.7 (4)	C11A—C12A—C13A	121.3 (4)
N1—C2—N2	122.2 (3)	Cl1A—C12A—C11A	119.3 (4)
N2—C2—N3	120.0 (3)	Cl1A—C12A—C13A	119.5 (4)
N3—C4—C5	118.9 (3)	C12A—C13A—C14A	119.1 (4)
N4—C4—C5	123.2 (4)	C9A—C14A—C13A	120.8 (4)
N3—C4—N4	117.9 (3)	C8A—C7A—H71A	108.68
C4—C5—C6	117.8 (4)	C8A—C7A—H71B	108.70
C6—C5—C9	123.6 (3)	C6A—C7A—H71B	108.81
C4—C5—C9	118.6 (3)	C6A—C7A—H71A	108.78
N1—C6—C7	115.0 (3)	H71A—C7A—H71B	107.79
C5—C6—C7	125.0 (4)	H81A—C8A—H83A	109.44
N1—C6—C5	119.9 (3)	H82A—C8A—H83A	109.59
C6—C7—C8	110.7 (3)	H81A—C8A—H82A	109.50
C5—C9—C10	120.1 (4)	C7A—C8A—H81A	109.12
C10—C9—C14	118.6 (4)	C7A—C8A—H82A	110.02
C5—C9—C14	121.3 (4)	C7A—C8A—H83A	109.16
C9—C10—C11	121.0 (5)	C9A—C10A—H10A	120.01
C10—C11—C12	120.2 (5)	C11A—C10A—H10A	119.63
Cl1—C12—C13	120.1 (4)	C10A—C11A—H11A	120.19
C11—C12—C13	119.6 (5)	C12A—C11A—H11A	120.53
Cl1—C12—C11	120.3 (4)	C12A—C13A—H13A	120.33
C12—C13—C14	120.6 (5)	C14A—C13A—H13A	120.54
C9—C14—C13	119.9 (5)	C13A—C14A—H14A	119.59
C6—C7—H7A	109.72	C9A—C14A—H14A	119.65
C6—N1—C2—N2	−178.9 (4)	C10—C9—C14—C13	1.8 (6)
C6—N1—C2—N3	1.7 (5)	C5—C9—C10—C11	179.4 (5)
C2—N1—C6—C5	1.3 (5)	C9—C10—C11—C12	−0.7 (9)
C2—N1—C6—C7	−175.9 (3)	C10—C11—C12—C13	2.4 (8)
C4—N3—C2—N1	−3.2 (5)	C10—C11—C12—Cl1	−178.1 (5)
C4—N3—C2—N2	177.5 (4)	C11—C12—C13—C14	−2.1 (7)
C2—N3—C4—N4	179.8 (4)	Cl1—C12—C13—C14	178.4 (4)
C2—N3—C4—C5	1.5 (5)	C12—C13—C14—C9	0.0 (7)
C2A—N1A—C6A—C7A	177.8 (3)	N3A—C4A—C5A—C6A	−0.6 (5)
C6A—N1A—C2A—N2A	−178.2 (4)	N3A—C4A—C5A—C9A	−179.9 (3)
C6A—N1A—C2A—N3A	1.0 (5)	N4A—C4A—C5A—C6A	179.2 (4)
C2A—N1A—C6A—C5A	−1.5 (5)	N4A—C4A—C5A—C9A	−0.1 (6)
C4A—N3A—C2A—N2A	178.9 (4)	C4A—C5A—C6A—N1A	1.3 (6)
C2A—N3A—C4A—N4A	−179.7 (4)	C4A—C5A—C6A—C7A	−178.0 (4)
C2A—N3A—C4A—C5A	0.1 (5)	C9A—C5A—C6A—N1A	−179.4 (3)
C4A—N3A—C2A—N1A	−0.3 (5)	C9A—C5A—C6A—C7A	1.3 (6)
N3—C4—C5—C9	−180.0 (3)	C4A—C5A—C9A—C14A	−106.0 (4)
N3—C4—C5—C6	1.6 (5)	C6A—C5A—C9A—C10A	−105.4 (5)
N4—C4—C5—C9	1.8 (6)	C6A—C5A—C9A—C14A	74.7 (5)
N4—C4—C5—C6	−176.6 (4)	C4A—C5A—C9A—C10A	73.9 (5)
C4—C5—C6—N1	−2.9 (6)	N1A—C6A—C7A—C8A	79.8 (5)
C6—C5—C9—C14	81.8 (5)	C5A—C6A—C7A—C8A	−100.9 (5)
C4—C5—C9—C14	−96.5 (5)	C14A—C9A—C10A—C11A	−1.3 (6)
C6—C5—C9—C10	−99.0 (5)	C5A—C9A—C14A—C13A	−177.7 (4)
C4—C5—C9—C10	82.6 (5)	C5A—C9A—C10A—C11A	178.8 (4)
C4—C5—C6—C7	174.0 (4)	C10A—C9A—C14A—C13A	2.5 (6)
C9—C5—C6—C7	−4.4 (6)	C9A—C10A—C11A—C12A	−0.7 (7)
C9—C5—C6—N1	178.7 (3)	C10A—C11A—C12A—Cl1A	−177.5 (4)
N1—C6—C7—C8	69.4 (4)	C10A—C11A—C12A—C13A	1.6 (7)
C5—C6—C7—C8	−107.7 (5)	C11A—C12A—C13A—C14A	−0.4 (7)
C5—C9—C14—C13	−179.1 (4)	Cl1A—C12A—C13A—C14A	178.6 (4)
C14—C9—C10—C11	−1.4 (8)	C12A—C13A—C14A—C9A	−1.6 (7)

Symmetry codes: (i) −x, y, −z+1/2; (ii) x, −y, z+1/2; (iii) x, y, z+1; (iv) −x+1/2, y+1/2, −z+1/2; (v) −x+1/2, −y+1/2, −z; (vi) −x+1/2, y−1/2, −z+1/2; (vii) x, −y+1, z+1/2; (viii) −x+1/2, −y+1/2, −z+1; (ix) x, −y, z−1/2; (x) x, −y+1, z−1/2; (xi) x, y, z−1.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1E^x	0.86	2.09	2.880 (5)	153
N1—H1···O3E^x	0.86	2.41	3.177 (6)	148
N1A—H1A···O3C	0.86	1.92	2.778 (4)	175
N2—H2···O1B	0.86	2.07	2.901 (5)	163
N2A—H2A···O2E^vi	0.86	2.03	2.794 (5)	148
N2A—H2B···O1C	0.86	1.93	2.784 (4)	171
N2—H3···O1E^x	0.86	2.33	3.056 (5)	142
N2—H3···O1C^v	0.86	2.15	2.848 (5)	138
N3A—H3A···O1D^viii	0.86	1.92	2.765 (5)	167
N3—H4···O1B	0.86	2.58	3.290 (5)	141
N3—H4···O3B	0.86	1.88	2.722 (4)	164
N4A—H4A···O2B^viii	0.86	2.07	2.855 (5)	152
N4A—H4B···O2D^viii	0.86	1.98	2.813 (5)	164
N4—H5···O2D	0.86	2.17	2.832 (4)	134
N4—H5···O3B	0.86	2.46	3.154 (5)	139
N4—H6···O3D	0.86	2.51	3.050 (5)	121

Symmetry codes: (v) −x+1/2, −y+1/2, −z; (vi) −x+1/2, y−1/2, −z+1/2; (viii) −x+1/2, −y+1/2, −z+1; (x) x, −y+1, z−1/2.