Two polymorphs of 2-ethyl-3-hy­droxy-6-methyl­pyridinium hydrogen N-acetyl-L-glutamate from powder diffraction data

The title salt, C₈H₁₂NO⁺·C₇H₁₀NO₅⁻, crystallizes in two polymorphic modifications, viz. monoclinic (M) and ortho­rhom­bic (O). The crystal structures of both polymorphic modifications have been established from laboratory powder diffraction data. The crystal packing motifs in the two polymorphs are different, but the conformations of the anions are generally similar. In M, the anions are linked by pairs of hydrogen bonds of the N—H...O and O—H...O types into chains along the b-axis direction, and neighbouring mol­ecules within the chain are related by the 2₁ screw axis. The cations link these chains via O—H...O and N—H...O hydrogen bonds into layers parallel to (001). In O, the anions are linked by O—H...O hydrogen bonds into helices along [001], and neighbouring mol­ecules within the helix are related by the 2₁ screw axis. The neighbouring helical turns are linked by N—H...O hydrogen bonds. The cations link the helices via O—H...O and N—H...O hydrogen bonds, thus forming a three-dimensional network.

S1. Introduction

3-Hy­droxy­pyridine derivatives are structural analogs of the compounds of the vitamin B6 family, which are involved in the metabolisms of humans and animals. One of the most effective drugs distributed in Russia belonging to this group is ethyl­methyl­hydroxy­pyridine succinate (Mexidol, manufactured by Pharmasoft Pharmaceutical, and Mexicor, manufactured by Ecopharminvest), which is used in neurology for acute and chronic brain circulatory insufficiency (Voronina, 1992, 2004). The crystal structures of two succinic acid derivatives of 2-ethyl-3-hy­droxy-6-methyl­pyridine have been reported (Lyakhov et al., 2012). Recently, in a search for new analogs of Mexidol, Yasnetsov et al. (2010) have obtained a new compound, namely 2-ethyl-3-hy­droxy-6-methyl­pyridinium hydrogen N-acetyl-L-glutamate, (I). It has been established that (I) exhibits anti­hypoxic activity on various models of acute hypoxia (hypoxia is a pathological condition in which the body, or a part of the body, is deprived of an adequate oxygen supply) in mice and produces an equal or larger effect than Mexidol (Yasnetsov et al., 2012). Herewith we report the crystal structures of monoclinic (M) and orthorhombic (O) polymorphs of (I) obtained in different solvent systems and determined from laboratory powder diffraction data.

S2. Experimental

S2.1. Synthesis and crystallization

The original synthetic procedure reported by Yasnetsov et al. (2010, 2012) was modified in order to increase the yield of crystalline product.

(a) For the preparation of the orthorhombic polymorph, 20% solutions of 2-ethyl-3-hy­droxy-6-methyl­pyridine and N-acetyl-L-glutamic acid in ethanol were mixed in equimolar amounts and stirred for 25 min at 313 K. The light-yellow solution was filtered and evaporated in vacuo at 313 K to a half of its initial volume. The resulting liquid was added dropwise to a threefold volume of acetone cooled to 263 K. The cold mixture was stirred for 3 h and kept for 12 h in a refrigerator. The crystalline precipitate was filtered off and dried in vacuo at 313 K.

b) For the preparation of the monoclinic polymorph, equimolar amounts of 20% solutions of 2-ethyl-3-hy­droxy-6-methyl­pyridine and N-acetyl-L-glutamic acid in ethanol were mixed and stirred for 25 min at 313 K. The light-yellow solution was filtered and the solvent was removed in vacuo at 313 K. The resulting oil was dissolved in the minimal amount of methanol and added dropwise to cold acetone at 263 K. The mixture was stirred in cold for 3 h and kept overnight in a refrigerator. The crystalline precipitate was filtered off and dried in vacuo at 313 K.

IR absorption spectra of M, O and the initial acid and base were recorded in the wavenumber range 3000–400 cm^-1 with a resolution of 2 cm^-1 using a Nicolet iS10 (Thermo Scientific) spectrometer with KBr pellets. Absorption maxima in the 1800–1300 cm^-1 region: M, 1715, 1650, 1587, 1543, 1452, 1426, 1400, 1371, 1352, 1319s h, 1300 cm^-1; O, 1713, 1647, 1587, 1547, 1452, 1420, 1402, 1373, 1354, 1313s h, 1301 cm^-1.

S2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. X-ray powder diffraction data were collected using a Panalytical EMPYREAN instrument with a linear X'celerator detector using nonmonochromated Cu Kα radiation. The unit-cell dimensions for both compounds were determined using three indexing programs: TREOR90 (Werner et al., 1985), ITO (Visser et al., 1969) and AUTOX (Zlokazov, 1992, 1995). Based on systematic extinctions, the space groups for M and O were determined as P2₁ and P2₁2₁2₁, respectively. The unit-cell parameters and space groups were further tested using a Pawley fit (Pawley, 1981), which gave R_p/R_wp of 0.023/0.031 for M and 0.029/0.039 for O, and confirmed by crystal structure solution.

The crystal structures were solved using a simulated annealing technique (Zhukov et al., 2001). The initial molecular models for the 2-ethyl-3-hy­droxy-6-methyl­pyridinium cation and hydrogen N-acetyl-L-glutamate anion were taken from the Cambridge Structural Database (CSD, Version 5.33; Allen et al., 2002). In the simulated annealing runs (without H atoms), the total number of the varied degrees of freedom (DOF) for O was 19 (six translational, six orientational and seven torsional). For M, the number of DOF was 18, because one translational parameter was fixed to fix the origin in P2₁. The solutions found were fitted with the MRIA program (Zlokazov & Chernyshev, 1992) in the bond-restrained Rietveld refinement using a split-type pseudo-Voigt peak profile function (Toraya, 1986). To correct the preferred orientation in the [001] direction for both compounds, the March–Dollase (Dollase, 1986) formalism was used. Restraints were applied to the intra­molecular bond lengths and contacts (<2.8 Å), the strength of the restraints was a function of inter­atomic separation and for intra­molecular bond lengths, corresponded to an r.m.s. deviation of 0.02 Å. Additional restraints were applied to the planarity of acetyl­amino fragment, the carb­oxy­lic acid and carboxyl­ate groups, and the pyridine ring with the attached atoms, with the maximal allowed deviation from the mean plane being 0.03 Å. All non-H atoms were refined isotropically. H atoms were positioned geometrically (C—H = 0.93–0.98 Å, N—H 0.86 Å and O—H 0.82 Å) and not refined. The diffraction profiles for all compounds after the final bond-restrained Rietveld refinements are shown in Fig. 4.

S3. Results and discussion

The IR spectra of the monoclinic (M) and orthorhombic (O) polymorphs of (I) were practically identical and in good agreement with the previously reported spectrum of salt (Yasnetsov et al., 2010). The intensive bands at 1543–1547 and 1647–1650 cm^-1 present in these spectra were assigned to vibration of the COO^- group of anion and the wag–stretch vibration of cation, respectively. Both these lines were absent from the IR spectra of the initial acid and base. It is impossible to predict a priori, which of two –COOH groups of the 2-acetyl­amino-1,5-di­penta­noic acid (N-acetyl-L-glutamic acid) transforms into the carboxyl­ate anion, because for these groups, the dissociation constants do not differ significantly (pK_a1 = 3.28; pK_a2 = 4.60; Academic Software, 2000). In the only known structure containing the N-acetyl-L-glutamate monoanion (Grell et al., 1998), the acidic H atom lies between two carboxyl­ate O atoms, with a very short O···O distance [2.474 (4) Å], being slightly closer to the 1-carboxyl­ate group.

The asymmetric parts of M and O are shown in Fig. 1. In M and O, the acidic H atoms have been positioned geometrically in order to obtain reasonable hydrogen-bonding patterns. In both polymorphs, the monoanions are linked by O—H···O hydrogen bonds, and thus the acidic H atom is located between two carboxyl­ate O atoms. In O, one of these O atoms (O17) is involved also in an N—H···O hydrogen bond as an H-atom acceptor, and that is why the H atom is positioned at the other O atom (O23). In M, the H atom is positioned at O22 instead of at O18; the latter is sterically unfavourable because of a close contact with the amide H atom. The conformations of the anions in the crystals of the monoclinic and orthorhombic polymorphs, being similar in general, differ only in the mutual orientation of the N-acetyl­amino fragment and the 1-carboxyl­ate group; the dihedral angles formed by the planes of these groups are 29.7 (5) and 67.4 (5)° for M and O, respectively.

In M, the N-acetyl-L-glutamate monoanions are linked by pairs of N—H···O and O—H···O hydrogen bonds into chains along the b-axis direction; neighbouring molecules within the chain are related by the 2₁ screw axis. The cations link these chains via O—H···O and N—H···O hydrogen bonds into layers parallel to (001) (Fig. 2). In O, the N-acetyl-L-glutamate monoanions are linked by O—H···O hydrogen bonds into helices along [001]; neighbouring molecules within the helix are related by the 2₁ screw axis. The neighbouring helical turns are linked by N—H···O hydrogen bonds. The cations link the helices by O—H···O and N—H···O hydrogen bonds, thus forming a three-dimensional network (Fig. 3).

Related literature

For related literature, see: Academic Software (2000); Allen (2002); Dollase (1986); Grell et al. (1998); Lyakhov et al. (2012); Pawley (1981); Toraya (1986); Visser (1969); Voronina (1992, 2004); Werner et al. (1985); Yasnetsov, Vic, Skachilova, Sernov, Voronina & Yasnetsov (2012); Yasnetsov, Vic, Skachilova, Voronina & Yasnetsov (2010); Zhukov et al. (2001); Zlokazov (1992, 1995); Zlokazov & Chernyshev (1992).

Computing details

For both compounds, data collection: DataCollector (PANalytical, 2010); cell refinement: MRIA (Zlokazov & Chernyshev, 1992). Data reduction: DataCollector (PANalytical, 2010) for M; DataCollector (PANalytical, 2010)' for O. For both compounds, program(s) used to solve structure: simulated annealing (Zhukov et al., 2001); program(s) used to refine structure: MRIA (Zlokazov & Chernyshev, 1992); molecular graphics: PLATON (Spek, 2009) and Mercury (Macrae et al., 2008); software used to prepare material for publication: MRIA (Zlokazov & Chernyshev, 1992) and SHELXL97 (Sheldrick, 2008).

Figures

	Fig. 1. The asymmetric units of M (top) and O (bottom), showing the atomic numbering. Displacement spheres are drawn at the 50% probability level. Dashed lines denote hydrogen bonds.
	Fig. 2. The hydrogen-bonded layer in M, viewed along [001]. Thin lines (green in the electronic version of the paper) denote intermolecular hydrogen bonds. The symmetry codes are as in Table 1.
	Fig. 3. A portion of the crystal packing of O, showing the intermolecular hydrogen bonds as thin dotted lines (blue in the electronic version of the paper). C-bound H atoms have been omitted for clarity. The symmetry codes are as in Table 2.
	Fig. 4. The final Rietveld plots for M (top) and O (bottom). The experimental diffraction profiles are indicated by dots (black in the electronic version of the paper). The calculated diffraction profiles are shown as the upper solid lines (red), the difference profiles are shown as the bottom solid line (blue) and the vertical bars (green) between the solid lines correspond to the positions of the Bragg peaks.

(M) 2-Ethyl-3-hydroxy-6-methylpyridinium hydrogen N-acetyl-L-glutamate

Crystal data

C8H12NO^+·C7H10NO5^−	F(000) = 348
Mr = 326.35	Dx = 1.319 Mg m^−3
Monoclinic, P21	Melting point = 392–393 K
Hall symbol: P 2yb	Cu Kα radiation, λ = 1.5418 Å
a = 12.7258 (14) Å	T = 298 K
b = 14.4642 (16) Å	Particle morphology: plate
c = 4.4683 (11) Å	colourless
β = 92.528 (17)°	flat sheet, 15 × 1 mm
V = 821.7 (2) Å^3	Specimen preparation: Prepared at 298 K and 101 kPa
Z = 2

Data collection

PANanalytical EMPYREAN diffractometer	Data collection mode: reflection
Radiation source: line-focus sealed tube	Scan method: continuous
Ni-filter monochromator	2θmin = 4.035°, 2θmax = 80.008°, 2θstep = 0.017°
Specimen mounting: thin layer on the non-diffracting silicon plate

Refinement

Refinement on Inet	Profile function: split-type pseudo-Voigt (Toraya, 1986)
Least-squares matrix: full with fixed elements per cycle	125 parameters
Rp = 0.027	59 restraints
Rwp = 0.037	0 constraints
Rexp = 0.036	H-atom parameters not refined
RBragg = 0.087	Weighting scheme based on measured s.u.'s
χ^2 = 1.023	(Δ/σ)max = 0.003
4470 data points	Background function: Chebyshev polynomial up to the 5th order
Excluded region(s): none	Preferred orientation correction: March–Dollase (1986) texture correction; direction of preferred orientation [001], parameter r = 1.05(1).

Special details

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.

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

	x	y	z	Uiso*/Ueq
N1	0.3965 (6)	0.5080	0.5779 (19)	0.069 (3)*
H1	0.3299	0.5107	0.5371	0.083*
C2	0.4538 (8)	0.4399 (8)	0.462 (2)	0.075 (5)*
C3	0.5660 (8)	0.4363 (8)	0.507 (2)	0.079 (5)*
C4	0.6117 (8)	0.5080 (7)	0.682 (2)	0.078 (5)*
H4	0.6845	0.5111	0.7087	0.094*
C5	0.5511 (8)	0.5726 (10)	0.812 (2)	0.081 (4)*
H5	0.5818	0.6174	0.9372	0.097*
C6	0.4422 (8)	0.5713 (9)	0.756 (2)	0.073 (4)*
O7	0.6281 (5)	0.3746 (5)	0.4043 (15)	0.071 (2)*
H7	0.6889	0.3866	0.4588	0.107*
C8	0.3925 (8)	0.3709 (8)	0.278 (2)	0.076 (4)*
H8A	0.4272	0.3642	0.0902	0.091*
H8B	0.3239	0.3979	0.2303	0.091*
C9	0.3741 (9)	0.2749 (8)	0.396 (3)	0.079 (4)*
H9A	0.3334	0.2400	0.2501	0.119*
H9B	0.3367	0.2788	0.5779	0.119*
H9C	0.4405	0.2449	0.4367	0.119*
C10	0.3719 (8)	0.6429 (7)	0.879 (3)	0.082 (5)*
H10A	0.3003	0.6299	0.8161	0.123*
H10B	0.3914	0.7027	0.8073	0.123*
H10C	0.3786	0.6420	1.0941	0.123*
C11	1.0301 (9)	0.4831 (7)	0.606 (2)	0.084 (5)*
H11	1.0023	0.4885	0.3989	0.101*
N12	0.9745 (6)	0.4081 (6)	0.7577 (18)	0.077 (3)*
H12	1.0086	0.3779	0.8965	0.093*
C13	0.8762 (9)	0.3845 (8)	0.694 (2)	0.082 (4)*
O14	0.8257 (5)	0.4251 (4)	0.5032 (15)	0.068 (3)*
C15	0.8331 (7)	0.3029 (7)	0.867 (2)	0.078 (4)*
H15A	0.7613	0.3148	0.9123	0.117*
H15B	0.8744	0.2946	1.0503	0.117*
H15C	0.8366	0.2479	0.7477	0.117*
C16	1.1452 (8)	0.4558 (7)	0.608 (2)	0.076 (4)*
O17	1.1975 (5)	0.5027 (4)	0.4444 (15)	0.076 (3)*
O18	1.1655 (5)	0.3881 (5)	0.7717 (14)	0.079 (3)*
C19	1.0217 (8)	0.5767 (9)	0.763 (2)	0.077 (4)*
H19A	1.0607	0.6221	0.6529	0.093*
H19B	1.0549	0.5718	0.9619	0.093*
C20	0.9091 (8)	0.6118 (7)	0.791 (2)	0.078 (5)*
H20A	0.8722	0.6081	0.5971	0.094*
H20B	0.8730	0.5718	0.9277	0.094*
C21	0.9042 (8)	0.7077 (8)	0.901 (2)	0.085 (4)*
O22	0.8377 (5)	0.7150 (4)	1.1060 (14)	0.071 (3)*
H22	0.8360	0.7687	1.1642	0.107*
O23	0.9520 (5)	0.7732 (5)	0.8196 (16)	0.072 (3)*

Geometric parameters (Å, º)

N1—C6	1.329 (14)	C11—N12	1.475 (14)
N1—C2	1.344 (14)	C11—C16	1.517 (15)
N1—H1	0.86	C11—C19	1.530 (16)
C2—C3	1.434 (14)	C11—H11	0.98
C2—C8	1.490 (15)	N12—C13	1.316 (14)
C3—O7	1.289 (13)	N12—H12	0.86
C3—C4	1.409 (15)	C13—O14	1.199 (13)
C4—C5	1.359 (16)	C13—C15	1.526 (15)
C4—H4	0.93	C15—H15A	0.96
C5—C6	1.397 (15)	C15—H15B	0.96
C5—H5	0.93	C15—H15C	0.96
C6—C10	1.490 (16)	C16—O17	1.215 (13)
O7—H7	0.82	C16—O18	1.243 (13)
C8—C9	1.507 (16)	C19—C20	1.531 (14)
C8—H8A	0.97	C19—H19A	0.97
C8—H8B	0.97	C19—H19B	0.97
C9—H9A	0.96	C20—C21	1.473 (15)
C9—H9B	0.96	C20—H20A	0.97
C9—H9C	0.96	C20—H20B	0.97
C10—H10A	0.96	C21—O23	1.191 (13)
C10—H10B	0.96	C21—O22	1.278 (13)
C10—H10C	0.96	O22—H22	0.82
C6—N1—C2	120.4 (9)	N12—C11—C16	106.8 (8)
C6—N1—H1	119.8	N12—C11—C19	113.3 (9)
C2—N1—H1	119.8	C16—C11—C19	108.4 (9)
N1—C2—C3	121.7 (10)	N12—C11—H11	109.4
N1—C2—C8	115.1 (9)	C16—C11—H11	109.4
C3—C2—C8	123.2 (10)	C19—C11—H11	109.4
O7—C3—C4	117.5 (9)	C13—N12—C11	124.3 (9)
O7—C3—C2	126.7 (10)	C13—N12—H12	117.9
C4—C3—C2	115.8 (10)	C11—N12—H12	117.9
C5—C4—C3	121.1 (10)	O14—C13—N12	120.0 (10)
C5—C4—H4	119.5	O14—C13—C15	123.1 (10)
C3—C4—H4	119.4	N12—C13—C15	116.8 (9)
C4—C5—C6	119.4 (11)	C13—C15—H15A	109.5
C4—C5—H5	120.3	C13—C15—H15B	109.5
C6—C5—H5	120.3	H15A—C15—H15B	109.5
N1—C6—C5	121.4 (11)	C13—C15—H15C	109.5
N1—C6—C10	116.5 (9)	H15A—C15—H15C	109.5
C5—C6—C10	122.1 (11)	H15B—C15—H15C	109.5
C3—O7—H7	109.5	O17—C16—O18	133.5 (10)
C2—C8—C9	120.6 (9)	O17—C16—C11	114.0 (9)
C2—C8—H8A	107.2	O18—C16—C11	112.5 (9)
C9—C8—H8A	107.2	C11—C19—C20	114.6 (9)
C2—C8—H8B	107.2	C11—C19—H19A	108.7
C9—C8—H8B	107.1	C20—C19—H19A	108.6
H8A—C8—H8B	106.8	C11—C19—H19B	108.6
C8—C9—H9A	109.5	C20—C19—H19B	108.6
C8—C9—H9B	109.5	H19A—C19—H19B	107.5
H9A—C9—H9B	109.5	C21—C20—C19	113.2 (9)
C8—C9—H9C	109.5	C21—C20—H20A	109.0
H9A—C9—H9C	109.4	C19—C20—H20A	108.9
H9B—C9—H9C	109.5	C21—C20—H20B	108.9
C6—C10—H10A	109.5	C19—C20—H20B	108.9
C6—C10—H10B	109.5	H20A—C20—H20B	107.8
H10A—C10—H10B	109.5	O23—C21—O22	121.1 (10)
C6—C10—H10C	109.5	O23—C21—C20	128.1 (10)
H10A—C10—H10C	109.5	O22—C21—C20	110.8 (9)
H10B—C10—H10C	109.4	C21—O22—H22	109.5

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O17^i	0.86	1.72	2.577 (10)	173
O7—H7···O14	0.82	1.83	2.637 (9)	168
N12—H12···O18	0.86	2.10	2.446 (10)	103
N12—H12···O23^ii	0.86	2.02	2.845 (11)	159
O22—H22···O18^iii	0.82	1.75	2.563 (9)	171

Symmetry codes: (i) x−1, y, z; (ii) −x+2, y−1/2, −z+2; (iii) −x+2, y+1/2, −z+2.

(O) 2-Ethyl-3-hydroxy-6-methylpyridinium hydrogen N-acetyl-L-glutamate

Crystal data

C8H12NO^+·C7H10NO5^−	F(000) = 696
Mr = 326.35	Dx = 1.291 Mg m^−3
Orthorhombic, P212121	Melting point = 396–398 K
Hall symbol: P 2ac 2ab	Cu Kα radiation, λ = 1.5418 Å
a = 27.821 (2) Å	T = 298 K
b = 12.0939 (15) Å	Particle morphology: plate
c = 4.9917 (13) Å	colourless
V = 1679.5 (5) Å^3	flat sheet, 15 × 1 mm
Z = 4	Specimen preparation: Prepared at 298 K and 101 kPa

Data collection

PANanalytical EMPYREAN diffractometer	Data collection mode: reflection
Radiation source: line-focus sealed tube	Scan method: continuous
Ni-filter monochromator	2θmin = 4.020°, 2θmax = 79.993°, 2θstep = 0.017°
Specimen mounting: thin layer on the non-diffracting silicon plate

Refinement

Refinement on Inet	Profile function: split-type pseudo-Voigt (Toraya, 1986)
Least-squares matrix: full with fixed elements per cycle	126 parameters
Rp = 0.035	57 restraints
Rwp = 0.045	0 constraints
Rexp = 0.046	H-atom parameters not refined
RBragg = 0.071	Weighting scheme based on measured s.u.'s
χ^2 = 0.965	(Δ/σ)max = 0.002
4470 data points	Background function: Chebyshev polynomial up to the 5th order
Excluded region(s): none	Preferred orientation correction: March–Dollase (1986) texture correction; direction of preferred orientation [001], parameter r = 1.05(1).

Special details

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.

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

	x	y	z	Uiso*/Ueq
N1	0.5406 (2)	0.5139 (6)	0.5614 (16)	0.072 (3)*
H1	0.5684	0.4873	0.5994	0.086*
C2	0.5362 (3)	0.5884 (8)	0.3652 (19)	0.076 (4)*
C3	0.4912 (3)	0.6422 (8)	0.308 (2)	0.080 (4)*
C4	0.4517 (3)	0.6060 (8)	0.462 (2)	0.083 (3)*
H4	0.4217	0.6379	0.4349	0.100*
C5	0.4568 (3)	0.5251 (7)	0.649 (2)	0.077 (4)*
H5	0.4302	0.4996	0.7436	0.093*
C6	0.5022 (3)	0.4806 (9)	0.699 (2)	0.080 (4)*
O7	0.4862 (2)	0.7204 (5)	0.1222 (13)	0.074 (2)*
H7	0.4581	0.7407	0.1172	0.111*
C8	0.5811 (4)	0.6214 (8)	0.2253 (19)	0.083 (4)*
H8A	0.5781	0.6005	0.0385	0.100*
H8B	0.6073	0.5786	0.3001	0.100*
C9	0.5951 (4)	0.7428 (9)	0.236 (2)	0.092 (4)*
H9A	0.6245	0.7537	0.1395	0.138*
H9B	0.5995	0.7647	0.4195	0.138*
H9C	0.5701	0.7867	0.1567	0.138*
C10	0.5113 (3)	0.3940 (8)	0.899 (2)	0.084 (4)*
H10A	0.5449	0.3757	0.8999	0.126*
H10B	0.4929	0.3294	0.8557	0.126*
H10C	0.5021	0.4204	1.0733	0.126*
C11	0.6788 (3)	0.2813 (7)	0.628 (2)	0.077 (3)*
H11	0.6852	0.2860	0.8205	0.093*
N12	0.6792 (3)	0.1649 (5)	0.5534 (16)	0.078 (3)*
H12	0.6774	0.1488	0.3859	0.094*
C13	0.6822 (3)	0.0827 (8)	0.7252 (19)	0.087 (4)*
O14	0.68400 (19)	0.1031 (5)	0.9736 (11)	0.063 (2)*
C15	0.6827 (3)	−0.0307 (7)	0.615 (2)	0.079 (3)*
H15A	0.7151	−0.0510	0.5705	0.119*
H15B	0.6630	−0.0337	0.4576	0.119*
H15C	0.6703	−0.0812	0.7469	0.119*
C16	0.6307 (3)	0.3325 (7)	0.577 (2)	0.081 (4)*
O17	0.6235 (2)	0.4277 (5)	0.6686 (12)	0.069 (2)*
O18	0.59940 (19)	0.2753 (5)	0.4521 (12)	0.073 (2)*
C19	0.7154 (3)	0.3526 (8)	0.485 (2)	0.090 (4)*
H19A	0.7129	0.4279	0.5506	0.108*
H19B	0.7084	0.3532	0.2950	0.108*
C20	0.7662 (4)	0.3110 (8)	0.529 (2)	0.085 (4)*
H20A	0.7731	0.3116	0.7191	0.102*
H20B	0.7682	0.2350	0.4677	0.102*
C21	0.8033 (3)	0.3771 (8)	0.388 (2)	0.084 (4)*
O22	0.8300 (2)	0.3331 (4)	0.2340 (11)	0.066 (2)*
O23	0.8073 (2)	0.4816 (5)	0.4410 (13)	0.072 (2)*
H23	0.8300	0.5074	0.3557	0.108*

Geometric parameters (Å, º)

N1—C6	1.331 (12)	C11—N12	1.456 (11)
N1—C2	1.337 (12)	C11—C16	1.497 (13)
N1—H1	0.8601	C11—C19	1.512 (14)
C2—C3	1.439 (13)	C11—H11	0.9799
C2—C8	1.485 (13)	N12—C13	1.315 (12)
C3—O7	1.333 (12)	N12—H12	0.8598
C3—C4	1.410 (13)	C13—O14	1.265 (11)
C4—C5	1.361 (14)	C13—C15	1.478 (13)
C4—H4	0.9299	C15—H15A	0.9600
C5—C6	1.395 (13)	C15—H15B	0.9600
C5—H5	0.9301	C15—H15C	0.9600
C6—C10	1.471 (15)	C16—O17	1.255 (11)
O7—H7	0.8199	C16—O18	1.275 (11)
C8—C9	1.519 (14)	C19—C20	1.515 (14)
C8—H8A	0.9693	C19—H19A	0.9708
C8—H8B	0.9707	C19—H19B	0.9691
C9—H9A	0.9595	C20—C21	1.483 (14)
C9—H9B	0.9608	C20—H20A	0.9702
C9—H9C	0.9599	C20—H20B	0.9708
C10—H10A	0.9602	C21—O22	1.193 (12)
C10—H10B	0.9600	C21—O23	1.297 (11)
C10—H10C	0.9600	O23—H23	0.8205
C6—N1—C2	120.5 (8)	N12—C11—C16	111.3 (8)
C6—N1—H1	119.8	N12—C11—C19	115.2 (8)
C2—N1—H1	119.7	C16—C11—C19	106.6 (8)
N1—C2—C3	121.9 (8)	N12—C11—H11	107.8
N1—C2—C8	116.7 (8)	C16—C11—H11	107.8
C3—C2—C8	121.1 (8)	C19—C11—H11	107.8
O7—C3—C4	121.2 (8)	C13—N12—C11	124.4 (8)
O7—C3—C2	123.3 (8)	C13—N12—H12	117.8
C4—C3—C2	115.5 (9)	C11—N12—H12	117.8
C5—C4—C3	121.0 (9)	O14—C13—N12	119.6 (8)
C5—C4—H4	119.5	O14—C13—C15	122.9 (9)
C3—C4—H4	119.5	N12—C13—C15	117.4 (8)
C4—C5—C6	119.6 (9)	C13—C15—H15A	109.5
C4—C5—H5	120.2	C13—C15—H15B	109.4
C6—C5—H5	120.2	H15A—C15—H15B	109.5
N1—C6—C5	121.2 (9)	C13—C15—H15C	109.5
N1—C6—C10	115.3 (8)	H15A—C15—H15C	109.5
C5—C6—C10	123.4 (9)	H15B—C15—H15C	109.5
C3—O7—H7	109.5	O17—C16—O18	124.6 (8)
C2—C8—C9	117.3 (8)	O17—C16—C11	117.4 (8)
C2—C8—H8A	108.0	O18—C16—C11	118.0 (8)
C9—C8—H8A	108.0	C11—C19—C20	111.8 (8)
C2—C8—H8B	107.9	C11—C19—H19A	109.2
C9—C8—H8B	108.0	C20—C19—H19A	109.2
H8A—C8—H8B	107.2	C11—C19—H19B	109.3
C8—C9—H9A	109.5	C20—C19—H19B	109.3
C8—C9—H9B	109.5	H19A—C19—H19B	107.9
H9A—C9—H9B	109.4	C21—C20—C19	113.7 (8)
C8—C9—H9C	109.5	C21—C20—H20A	108.9
H9A—C9—H9C	109.5	C19—C20—H20A	108.9
H9B—C9—H9C	109.4	C21—C20—H20B	108.8
C6—C10—H10A	109.5	C19—C20—H20B	108.8
C6—C10—H10B	109.5	H20A—C20—H20B	107.6
H10A—C10—H10B	109.5	O22—C21—O23	120.9 (9)
C6—C10—H10C	109.5	O22—C21—C20	119.9 (8)
H10A—C10—H10C	109.5	O23—C21—C20	119.2 (9)
H10B—C10—H10C	109.5	C21—O23—H23	109.3

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O17	0.86	1.73	2.587 (8)	177
O7—H7···O18^i	0.82	1.69	2.500 (8)	170
N12—H12···O14^ii	0.86	2.14	2.992 (10)	172
O23—H23···O17^iii	0.82	1.78	2.600 (8)	176

Symmetry codes: (i) −x+1, y+1/2, −z+1/2; (ii) x, y, z−1; (iii) −x+3/2, −y+1, z−1/2.