Crystal structure of (3E)-5-nitro-3-(2-phenyl-hydrazinyl-idene)-1H-indol-2(3H)-one.

The reaction between 5-nitro-isatin and phenyl-hydrazine in acidic ethanol yields the title compound, C14H10N4O3, whose mol-ecular structure deviates slightly from a planar geometry (r.m.s. deviation = 0.065 Å for the mean plane through all non-H atoms). An intra-molecular N-H⋯O hydrogen bond is present, forming a ring of graph-set motif S(6). In the crystal, mol-ecules are linked by N-H⋯O and C-H⋯O hydrogen-bonding inter-actions into a two-dimensional network along (120), and rings of graph-set motif R22(8), R22(26) and R44(32) are observed. Additionally, a Hirshfeld surface analysis suggests that the mol-ecules are stacked along [100] through C=O⋯Cg inter-actions and indicates that the most important contributions for the crystal structure are O⋯H (28.5%) and H⋯H (26.7%) inter-actions. An in silico evaluation of the title compound with the DHFR enzyme (di-hydro-folate reductase) was performed. The isatin-hydrazone derivative and the active site of the selected enzyme show N-H⋯O(ASP29), N-H⋯O(ILE96) and Cg⋯Cg(PHE33) inter-actions.

Chemical context

The first reports on isatin and the synthesis of isatin derivatives were published independently in Germany and France over 170 years ago (Erdmann, 1841a ▸,b ▸; Laurent, 1841 ▸). After the 19th Century, isatin chemistry changed rapidly into a major group of compounds with a wide range of applications in different scientific disciplines, with special attention to medicinal chemistry. For example, the synthesis, in silico evaluation and in vitro inhibition of Chikungunya virus replication by an isatin–thio­semicarbazone derivative was performed recently (Mishra et al., 2016 ▸). Other isatin derivatives synthesized in the 1950s (Campaigne & Archer, 1952 ▸) had their pharmacological properties in vitro successfully tested against Cruzain, Falcipain-2 and Rhodesian in the 2000s (Chiyanzu et al., 2003 ▸), and the crystal structure of one of the derivatives was determined by X-ray diffraction in the 2010s (Pederzolli et al., 2011 ▸). The crystal structure determination of isatin-based mol­ecules is an intensive research field, especially in medicinal chemistry. As part of our studies in this area, we now describe the synthesis and structure of the title compound, (I).

Structural commentary

For the title compound, the mol­ecular structure matches the asymmetric unit and one intra­molecular N4—H5⋯O1 inter­action of graph-set S(6) is observed (Fig. 1 ▸). The mol­ecule is nearly planar with an r.m.s. deviation from the mean plane of the non–H atoms of 0.065 Å and a maximum deviation of 0.1907 (9) Å for atom O2 of the nitro group. The dihedral angle between the indole unit and the phenyl ring is 0.9 (4)°. The plane through the nitro group is rotated by 6.21 (6)° with respect to the indole ring.

Figure 1

The mol­ecular structure of the title compound, showing displacement ellipsoids drawn at the 50% probability level. The intra­molecular hydrogen bond is shown as a dashed line.

Supra­molecular features

In the crystal, the mol­ecules are connected by centrosymmetric pairs of N1—H1⋯O1i inter­actions (Table 1 ▸) into dimers with graph-set motif (8). In addition, C10—H6⋯O3ii and C12—H8⋯O2iii inter­actions complete a two-dimensional hydrogen-bonded network with rings of graph-set motif (26) and (32) (Fig. 2 ▸, Table 1 ▸). As suggested by Hirshfeld surface analysis, the dimensionality of the structure increases to three-dimensional through the C=O⋯Cg inter­actions [C1⋯Cg = 3.5427 (7) Å, O1⋯Cg = 3.2004 (7) Å; Cg is the centroid of the C9–C14 ring], building a chain along [100] (Fig. 3 ▸). The separation between the C1 and C14 atoms of adjacent mol­ecules in the chain is 3.1744 (11) Å, which is shorter than the sum of the van der Waals radii for carbon atoms (Bondi, 1964 ▸; Rowland & Taylor, 1996 ▸).

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N4—H5⋯O1	0.88	2.03	2.7479 (10)	137
N1—H1⋯O1i	0.88	1.96	2.8310 (10)	171
C10—H6⋯O3ii	0.95	2.63	3.5542 (13)	166
C12—H8⋯O2iii	0.95	2.47	3.3943 (13)	163

Symmetry codes: (i) ; (ii) ; (iii) .

Figure 2

A packing diagram of the title compound, showing the N—H⋯O and C—H⋯O inter­actions (dashed lines) connecting the mol­ecules into a two-dimensional network in the (120) plane. The graph-set motifs for the crystal packing are: R1 = (8), R2 = (26) and R3 = (32).

Figure 3

A packing diagram of the title compound showning the C⋯Cg inter­actions (as dashed lines) building a chain along [100]. [Symmetry codes: (iv) x − 1, y, z; (v) x + 1, y, z.]

Hirshfeld surface analysis

The Hirshfeld surface analysis of the crystal structure indicates that the contribution of O⋯H inter­molecular inter­actions to the crystal packing amounts to 28.5% and the H⋯H inter­actions amount to 26.7%. Other important inter­molecular contacts for the cohesion of the structure are (in %): H⋯C = 17.7, H⋯N = 8.9, C⋯O = 8.2, C⋯C = 5.5 and C⋯N = 3.3. The Hirshfeld surface graphical representation with transparency and labelled atoms (Figs. 4 ▸ and 5 ▸) indicates, in magenta, the locations of the strongest inter­molecular contacts. The H1, H8, O1 and O2 atoms are the most important for the inter­molecular hydrogen bonding, while the C1 and C14 atoms are the most important for C⋯C inter­actions. The O⋯H contribution to the crystal packing is shown as a Hirshfeld surface fingerprint two-dimensional plot with cyan dots (Wolff et al., 2012 ▸). The d e (y axis) and d i (x axis) values are the closest external and inter­nal distances (in Å) from given points on the Hirshfeld surface (Fig. 6 ▸). The magenta colour on graphical representations of the Hirshfeld surface matches the N1—H1⋯O1, C10—H6⋯O3 and C12—H8⋯O2 inter­actions described above. In the same way, the C⋯Cg inter­actions can be seen more clearly on the C1=O1 and C14 atoms.

Figure 4

A Hirshfeld surface graphical representation (d norm) for the title compound. The surface is drawn with transparency and all atoms are labelled. The surface regions with strongest inter­molecular inter­actions for atoms H1, O1 and C14 are shown in magenta.

Figure 5

A Hirshfeld surface graphical representation (d norm) for the title compound. The surface is drawn with transparency and all atoms are labelled. The surface regions with strongest inter­molecular inter­actions for atoms H8, O2 and C1 are shown in magenta.

Figure 6

Hirshfeld surface fingerprint two-dimensional plot for the 5-nitro­isatin-3-phenyl­hydrazone crystal structure showing the O⋯H contacts in detail (cyan dots). The O⋯H contribution for the crystal packing amounts to 28.5%, being the most important inter­molecular connection. The d e (y axis) and d i (x axis) values are the closest external and inter­nal distances [in Å] from given points on the Hirshfeld surface.

Mol­ecular docking evaluation

Finally, for a lock-and-key supra­molecular analysis, a mol­ecular docking evaluation between the title compound and the DHFR enzyme (di­hydro­folate reductase) was carried out. Initially, the semi-empirical equilibrium energy of the small mol­ecule was obtained using the PM6 Hamiltonian, but the experimental bond lengths were conserved. The calculated parameters were: heat of formation = 149.41 kJ mol−1, gradient normal = 0.763, HOMO = −8.96 eV, LUMO =-1.66 eV and energy gap = 7.30 eV. The target prediction for 5-nitro­isatin-3-phenyl­hydrazone was calculated with the SwissTargetPrediction webserver based on the bioisosteric similarity to the isatin entity (Gfeller et al., 2013 ▸). As result of this screening, the title compound showed a promising theoretical structure–activity relationship to kinase proteins sites. The Frequency Target Class for kinases amounts to 44%, while the second best result for phosphatases amounts to 13%. The inter­actions with enzymes are important features for biologic­ally active mol­ecules, e.g. inhibition of tumor cell proliferation, activation of cell apoptosis mechanisms and blocking of bacterial membrane synthesis. Based on a search for a biological target with pharmacological background, the di­hydro­folate reductase was selected for the in silico evaluation (Chen, 2015 ▸; Dias et al., 2014 ▸; Verdonk et al., 2003 ▸), biological target code: DHFR (Protein Data Bank ID: 4KM0; Wei et al., 2005 ▸). The isatin–hydrazone derivative and the active site of the selected enzyme matches and the structure–activity relationship can be assumed by the following observed inter­molecular inter­actions: N1—H1⋯O(ASP29) (1.928 Å), N4—H5⋯O(ILE96) (1.925 Å) and Cg⋯Cg(PHE33) (3.567 Å) (Fig. 7 ▸).

Figure 7

Inter­molecular inter­actions between the title compound and the di­hydro­folate reductase enzyme. The inter­actions are shown as dashed lines and the figure is simplified for clarity.

Comparison with a related structure

A recently published article (Bittencourt et al., 2016 ▸) reports the structure of (3E)-5-nitro-3-(2-phenyl­hydrazinyl­idene)-1H-indol-2(3H)-one, which may be compared with that of the title compound. The mol­ecular structure deviates slightly from the ideal planar geometry and the C⋯C contacts between the planes are observed. The mol­ecules are linked by N—H⋯O and C—H⋯Cl inter­actions into a two-dimensional hydrogen-bonded polymer, a quite similar structure to the title compound. The in silico evaluation of 5-chloro­isatin-phenyl­hydrazone, a mol­ecule with similar crystal packing to the title compound, with and the DNA topoisomerase IIα enzyme was performed and the global free energy of −26.59 kJ mol−1 was found. The evaluation agrees with the literature data for mol­ecular docking and cytotoxic activity of hydrazone derivatives against breast cancer cells (Dandawate et al., 2012 ▸) and supports research on the structural determination of other isatin-based mol­ecules. The title compound is commercially available, but its structural analysis by X–ray single crystal diffraction, Hirshfeld surface calculation and mol­ecular docking evaluation are presented in this work for the first time.

Synthesis and crystallization

All starting materials are commercially available and were used without further purification. The synthesis of the title compound was adapted from a procedure reported previously (Fonseca et al., 2011 ▸). The glacial acetic acid-catalysed reaction of 5-nitro­isatin (2.6 mmol) and phenyl­hydrazine (2.6 mmol) in ethanol (40 mL) was refluxed for 4 h. After cooling and filtering, an irregular solid was isolated. Single crystals suitable for X-ray diffraction were obtained from a DMF/methanol solution (1:1 v/v) on slow evaporation of the solvent.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. Hydrogen atoms were located in a difference Fourier map, but were positioned with idealized geometry and refined isotropically using a riding model, with U iso(H) = 1.2U eq(C, N), and with C—H = 0.95 Å and N—H = 0.88 Å.

Table 2

Experimental details

Crystal data
Chemical formula	C14H10N4O3
M r	282.26
Crystal system, space group	Triclinic, P
Temperature (K)	200
a, b, c (Å)	5.7504 (4), 9.7190 (6), 12.1976 (7)
α, β, γ (°)	111.196 (2), 96.759 (2), 98.497 (2)
V (Å3)	617.69 (7)
Z	2
Radiation type	Mo Kα
μ (mm−1)	0.11
Crystal size (mm)	0.48 × 0.16 × 0.10
Data collection
Diffractometer	Bruker APEXII CCD area detector
Absorption correction	Multi-scan (SADABS; Bruker, 2013 ▸)
T min, T max	0.949, 0.989
No. of measured, independent and observed [I > 2σ(I)] reflections	11325, 3971, 3281
R int	0.017
(sin θ/λ)max (Å−1)	0.726
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.039, 0.117, 1.03
No. of reflections	3971
No. of parameters	190
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.37, −0.26

Computer programs: APEX2 and SAINT (Bruker, 2013 ▸), SHELXS97 and SHELXL97 (Sheldrick, 2008 ▸), DIAMOND (Brandenburg, 2006 ▸), GOLD (Verdonk et al., 2003 ▸), Crystal Explorer (Wolff, et al., 2012 ▸), publCIF (Westrip, 2010 ▸) and enCIFer (Allen et al., 2004 ▸).

Crystal structure: contains datablock(s) I, publication_text. DOI: 10.1107/S2056989016020375/rz5203sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016020375/rz5203Isup2.hkl

SwissTargetPrediction Report for 5-nitroisatin-3-phenylhydrazone. DOI: 10.1107/S2056989016020375/rz5203sup3.pdf

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989016020375/rz5203Isup4.cml

CCDC reference: 1524161

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

C14H10N4O3	Z = 2
Mr = 282.26	F(000) = 292
Triclinic, P1	Dx = 1.518 Mg m−3
a = 5.7504 (4) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.7190 (6) Å	Cell parameters from 2154 reflections
c = 12.1976 (7) Å	θ = 2.3–31.0°
α = 111.196 (2)°	µ = 0.11 mm−1
β = 96.759 (2)°	T = 200 K
γ = 98.497 (2)°	Prism, yellow
V = 617.69 (7) Å3	0.48 × 0.16 × 0.10 mm

Bruker APEXII CCD area detector diffractometer	3971 independent reflections
Radiation source: fine-focus sealed tube, Bruker APEX2 CCD	3281 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.017
φ and ω scans	θmax = 31.1°, θmin = 1.8°
Absorption correction: multi-scan (SADABS; Bruker, 2013)	h = −8→8
Tmin = 0.949, Tmax = 0.989	k = −14→14
11325 measured reflections	l = −17→17

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)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.117	H-atom parameters constrained
S = 1.03	w = 1/[σ2(Fo2) + (0.0693P)2 + 0.1171P] where P = (Fo2 + 2Fc2)/3
3971 reflections	(Δ/σ)max < 0.001
190 parameters	Δρmax = 0.37 e Å−3
0 restraints	Δρmin = −0.26 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.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) 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.

	x	y	z	Uiso*/Ueq
C1	0.74444 (16)	0.10997 (10)	0.47144 (8)	0.01734 (17)
C2	0.58388 (16)	0.19030 (10)	0.42434 (8)	0.01692 (17)
C3	0.63293 (16)	0.17378 (10)	0.30690 (8)	0.01701 (17)
C4	0.53990 (17)	0.22036 (10)	0.21904 (8)	0.01863 (18)
H2	0.4130	0.2737	0.2283	0.022*
C5	0.64117 (17)	0.18525 (11)	0.11683 (8)	0.02053 (19)
C6	0.8299 (2)	0.10968 (12)	0.10014 (9)	0.0255 (2)
H3	0.8968	0.0921	0.0299	0.031*
C7	0.92000 (19)	0.06009 (12)	0.18685 (9)	0.0240 (2)
H4	1.0462	0.0062	0.1767	0.029*
C8	0.81885 (16)	0.09218 (10)	0.28844 (8)	0.01844 (17)
C9	0.26077 (16)	0.34671 (10)	0.65458 (8)	0.01776 (17)
C10	0.25473 (19)	0.34151 (12)	0.76695 (9)	0.0244 (2)
H6	0.3603	0.2920	0.7976	0.029*
C11	0.0939 (2)	0.40895 (13)	0.83359 (9)	0.0296 (2)
H7	0.0883	0.4047	0.9099	0.036*
C12	−0.0597 (2)	0.48282 (13)	0.78973 (10)	0.0284 (2)
H8	−0.1711	0.5280	0.8354	0.034*
C13	−0.04899 (19)	0.49000 (11)	0.67893 (9)	0.0248 (2)
H9	−0.1521	0.5418	0.6494	0.030*
C14	0.11070 (18)	0.42243 (11)	0.61027 (9)	0.02091 (19)
H10	0.1173	0.4278	0.5344	0.025*
N1	0.87794 (14)	0.05403 (9)	0.38620 (7)	0.01994 (17)
H1	0.9867	0.0010	0.3923	0.024*
N2	0.54638 (17)	0.23011 (10)	0.02105 (8)	0.02622 (19)
N3	0.43091 (14)	0.26487 (9)	0.47905 (7)	0.01813 (16)
N4	0.41836 (15)	0.27045 (9)	0.58791 (7)	0.01990 (17)
H5	0.5115	0.2250	0.6195	0.024*
O1	0.75650 (12)	0.09474 (8)	0.56864 (6)	0.02078 (15)
O2	0.36881 (18)	0.28657 (11)	0.03076 (8)	0.0393 (2)
O3	0.64526 (18)	0.20633 (12)	−0.06636 (8)	0.0416 (2)

	U11	U22	U33	U12	U13	U23
C1	0.0163 (4)	0.0189 (4)	0.0187 (4)	0.0066 (3)	0.0039 (3)	0.0081 (3)
C2	0.0171 (4)	0.0202 (4)	0.0165 (4)	0.0077 (3)	0.0050 (3)	0.0084 (3)
C3	0.0160 (4)	0.0198 (4)	0.0176 (4)	0.0072 (3)	0.0050 (3)	0.0081 (3)
C4	0.0187 (4)	0.0222 (4)	0.0182 (4)	0.0089 (3)	0.0055 (3)	0.0091 (3)
C5	0.0229 (5)	0.0257 (4)	0.0165 (4)	0.0093 (4)	0.0049 (3)	0.0103 (3)
C6	0.0278 (5)	0.0344 (5)	0.0206 (4)	0.0158 (4)	0.0107 (4)	0.0125 (4)
C7	0.0242 (5)	0.0326 (5)	0.0217 (4)	0.0162 (4)	0.0100 (4)	0.0121 (4)
C8	0.0183 (4)	0.0217 (4)	0.0179 (4)	0.0084 (3)	0.0047 (3)	0.0085 (3)
C9	0.0181 (4)	0.0201 (4)	0.0169 (4)	0.0075 (3)	0.0053 (3)	0.0071 (3)
C10	0.0269 (5)	0.0326 (5)	0.0187 (4)	0.0138 (4)	0.0066 (4)	0.0120 (4)
C11	0.0357 (6)	0.0389 (6)	0.0195 (4)	0.0163 (5)	0.0127 (4)	0.0117 (4)
C12	0.0293 (5)	0.0329 (5)	0.0256 (5)	0.0152 (4)	0.0133 (4)	0.0085 (4)
C13	0.0250 (5)	0.0260 (4)	0.0274 (5)	0.0138 (4)	0.0085 (4)	0.0107 (4)
C14	0.0235 (5)	0.0236 (4)	0.0208 (4)	0.0112 (3)	0.0076 (3)	0.0111 (3)
N1	0.0203 (4)	0.0257 (4)	0.0196 (4)	0.0133 (3)	0.0068 (3)	0.0111 (3)
N2	0.0310 (5)	0.0332 (4)	0.0206 (4)	0.0144 (4)	0.0074 (3)	0.0136 (3)
N3	0.0184 (4)	0.0215 (3)	0.0171 (3)	0.0076 (3)	0.0056 (3)	0.0085 (3)
N4	0.0216 (4)	0.0265 (4)	0.0172 (3)	0.0130 (3)	0.0069 (3)	0.0108 (3)
O1	0.0218 (3)	0.0259 (3)	0.0201 (3)	0.0108 (3)	0.0059 (3)	0.0122 (3)
O2	0.0468 (5)	0.0577 (6)	0.0299 (4)	0.0370 (5)	0.0134 (4)	0.0241 (4)
O3	0.0475 (5)	0.0687 (6)	0.0280 (4)	0.0299 (5)	0.0198 (4)	0.0305 (4)

C1—O1	1.2421 (11)	C9—C14	1.3942 (12)
C1—N1	1.3669 (11)	C9—N4	1.4029 (11)
C1—C2	1.4848 (12)	C10—C11	1.3845 (14)
C2—N3	1.3119 (11)	C10—H6	0.9500
C2—C3	1.4490 (12)	C11—C12	1.3913 (16)
C3—C4	1.3882 (12)	C11—H7	0.9500
C3—C8	1.4144 (12)	C12—C13	1.3863 (15)
C4—C5	1.3900 (13)	C12—H8	0.9500
C4—H2	0.9500	C13—C14	1.3919 (13)
C5—C6	1.3923 (13)	C13—H9	0.9500
C5—N2	1.4631 (12)	C14—H10	0.9500
C6—C7	1.3902 (13)	N1—H1	0.8800
C6—H3	0.9500	N2—O2	1.2267 (12)
C7—C8	1.3838 (13)	N2—O3	1.2316 (12)
C7—H4	0.9500	N3—N4	1.3202 (11)
C8—N1	1.3915 (11)	N4—H5	0.8800
C9—C10	1.3939 (13)
O1—C1—N1	126.00 (8)	C14—C9—N4	121.93 (8)
O1—C1—C2	127.42 (8)	C11—C10—C9	119.56 (9)
N1—C1—C2	106.58 (7)	C11—C10—H6	120.2
N3—C2—C3	126.40 (8)	C9—C10—H6	120.2
N3—C2—C1	126.92 (8)	C10—C11—C12	120.53 (9)
C3—C2—C1	106.67 (7)	C10—C11—H7	119.7
C4—C3—C8	119.72 (8)	C12—C11—H7	119.7
C4—C3—C2	134.01 (8)	C13—C12—C11	119.47 (9)
C8—C3—C2	106.26 (7)	C13—C12—H8	120.3
C3—C4—C5	116.83 (8)	C11—C12—H8	120.3
C3—C4—H2	121.6	C12—C13—C14	120.93 (9)
C5—C4—H2	121.6	C12—C13—H9	119.5
C4—C5—C6	123.62 (9)	C14—C13—H9	119.5
C4—C5—N2	118.74 (8)	C13—C14—C9	118.93 (9)
C6—C5—N2	117.64 (8)	C13—C14—H10	120.5
C7—C6—C5	119.64 (9)	C9—C14—H10	120.5
C7—C6—H3	120.2	C1—N1—C8	110.92 (7)
C5—C6—H3	120.2	C1—N1—H1	124.5
C8—C7—C6	117.46 (9)	C8—N1—H1	124.5
C8—C7—H4	121.3	O2—N2—O3	123.29 (9)
C6—C7—H4	121.3	O2—N2—C5	118.18 (8)
C7—C8—N1	127.81 (8)	O3—N2—C5	118.50 (9)
C7—C8—C3	122.66 (8)	C2—N3—N4	116.98 (8)
N1—C8—C3	109.53 (8)	N3—N4—C9	121.85 (8)
C10—C9—C14	120.56 (9)	N3—N4—H5	119.1
C10—C9—N4	117.49 (8)	C9—N4—H5	119.1
O1—C1—C2—N3	2.70 (16)	C14—C9—C10—C11	1.64 (16)
N1—C1—C2—N3	−177.67 (9)	N4—C9—C10—C11	−176.92 (9)
O1—C1—C2—C3	−178.71 (9)	C9—C10—C11—C12	−0.59 (17)
N1—C1—C2—C3	0.91 (10)	C10—C11—C12—C13	−0.70 (18)
N3—C2—C3—C4	−2.73 (17)	C11—C12—C13—C14	0.97 (17)
C1—C2—C3—C4	178.67 (10)	C12—C13—C14—C9	0.06 (16)
N3—C2—C3—C8	176.72 (9)	C10—C9—C14—C13	−1.37 (15)
C1—C2—C3—C8	−1.87 (10)	N4—C9—C14—C13	177.12 (9)
C8—C3—C4—C5	−1.17 (14)	O1—C1—N1—C8	−179.93 (9)
C2—C3—C4—C5	178.23 (10)	C2—C1—N1—C8	0.44 (10)
C3—C4—C5—C6	−1.17 (15)	C7—C8—N1—C1	177.81 (10)
C3—C4—C5—N2	179.09 (8)	C3—C8—N1—C1	−1.68 (11)
C4—C5—C6—C7	2.57 (17)	C4—C5—N2—O2	−5.61 (15)
N2—C5—C6—C7	−177.69 (9)	C6—C5—N2—O2	174.63 (10)
C5—C6—C7—C8	−1.48 (16)	C4—C5—N2—O3	175.99 (10)
C6—C7—C8—N1	179.74 (10)	C6—C5—N2—O3	−3.77 (15)
C6—C7—C8—C3	−0.83 (16)	C3—C2—N3—N4	−177.84 (8)
C4—C3—C8—C7	2.21 (15)	C1—C2—N3—N4	0.47 (14)
C2—C3—C8—C7	−177.34 (9)	C2—N3—N4—C9	−179.85 (8)
C4—C3—C8—N1	−178.26 (8)	C10—C9—N4—N3	177.74 (9)
C2—C3—C8—N1	2.18 (10)	C14—C9—N4—N3	−0.80 (15)

D—H···A	D—H	H···A	D···A	D—H···A
N4—H5···O1	0.88	2.03	2.7479 (10)	137
N1—H1···O1i	0.88	1.96	2.8310 (10)	171
C10—H6···O3ii	0.95	2.63	3.5542 (13)	166
C12—H8···O2iii	0.95	2.47	3.3943 (13)	163