Novel multi-component crystals of berberine with improved pharmaceutical properties

As an extremely popular natural product, berberine (BER) is mainly used for gastroenteritis and diarrhoea caused by bacteria. Research has also revealed the potent and extensive pharmacological properties of BER including its anti-arrhythmic, anti-tumour, anti-inflammatory and hypoglycemic activities and so on; therefore, BER is a promising drug for further development. However, its commercial form with hydro­chloride exhibits poor stability and solubility, which are detrimental to its clinical therapeutic effects. For these purposes, the salt form was regulated via the reactive crystallization of 8-hy­droxy-7,8-di­hydro­berberine (8H-HBER) with five pharmaceutically suitable organic acids including malonic acid (MA), L-tartaric acid (LTA), D-tartaric acid (DTA), DL-tartaric acid (DLTA) and citric acid (CA), resulting in the six novel solid forms 1BER-1LTA-1W, 1BER-1DTA-1W, 1BER-1DLTA and 2BER-2CA as well as two rare multi-stoichiometric solid forms 1BER-1MA and 1BER-2MA-2W. The preparation of the multi-stoichiometric products was greatly influenced by both the crystallization solvent type and the molar ratio of reactants. The structures of these multi-component solid forms were determined using single-crystal X-ray diffraction and further characterized by powder X-ray diffraction, thermal analysis and Fourier transform infrared spectroscopy. Stability experiments showed that all samples prepared had superior physical stability under high temperature and high humidity. Furthermore, dissolution experiments demonstrated that the maximum apparent solubilities (MAS) of all the products were significantly improved compared with the commercial form of BER in dilute hydro­chloric solution (pH = 1.2). In particular, the MAS of 1BER-1MA in dilute hydro­chloric solution is as high as 34 times that of the commercial form. In addition, it is preliminarily confirmed that the MAS of the samples prepared in pure water and dilute hydro­chloric solution is primarily influenced by a combination of factors including the packing index, intermolecular interactions, affinity of the counter-ion to the solvent, the molar ratio of the drug to counter-ion in the product and the common ion effect. These novel solids are potential candidates for BER solid forms with improved oral dosage design and may prompt further development.

1. Introduction

Berberine (BER) extracted from Coptidis rhizoma (Huang et al., 2020) is an iso­quinoline alkaloid used in the clinical treatment of gastroenteritis and diarrhoea caused by bacteria (Shao et al., 2020; Vishnoi et al., 2021). Recently, BER has gained increasing attention and is the focus of hundreds of papers every year owing to its extensive pharmacological properties such as anti-arrhythmic failure (Chen et al., 2014), anti-platelet aggregation (Zhang et al., 2016), anti-cerebral ischemia (Chai et al., 2013), anti-tumour (Wang et al., 2020), anti-viral (Warowicka et al., 2020), anti-inflammatory (Wu et al., 2018) and hypoglycemic activities (Yin et al., 2017) etc. Hence great efforts have been devoted by researchers to exploit these properties, with new directions for clinical application.

The most common commercially available salt form of BER is its hydro­chloride [Fig. 1(a)]. It is reported that BER hydro­chloride exists in four solid forms: anhydrate, monohydrate, dihydrate (1BER-1HCl-2W) and tetrahydrate (1BER-1HCl-4W) (Nakagawa et al., 1978; Yoshimatsu et al., 1981). The anhydrate and monohydrate are remarkably hygroscopic and readily convert to the dihydrate at 12% humidity. Humidity >70% would further induce a phase transformation from the dihydrate to the tetrahydrate. Hence, the commercial form of BER hydro­chloride is usually a mixture (1BER-1HCl-M) of its dihydrate and tetrahydrate (Tong et al., 2009). Variation in the environment may also promote the solid-state transformation of commercially available BER. However, changes in the solid form would not be beneficial for its clinical effects. Moreover, bioavailability of 1BER-1HCl-M is extremely low (<1%), partly due to its poor solubility (Liu, et al., 2016; Sahibzada, et al., 2020), which hinders further development.

Figure 1 (a) Berberine hydro­chloride. (b) 8-hy­droxy-7,8-di­hydro­berberine.

To overcome the aforementioned drawbacks, one of the most effective strategies for ionizable BER is the modification of its salt form. A Cambridge Structural Database (CSD) search combined with a literature retrieval showed that there are more than 30 hits for BER, and these solid forms were mainly obtained from its hydro­chloride used as the reactant (Allen, 2002; Deng et al., 2018; Lu et al., 2018; Wang et al., 2016, 2020, 2021; Yang et al., 2020). As a result, the stability issue was indeed resolved, but no substantial improvement in solubility of the products was achieved compared with 1BER-1HCl-M; the solubilities of some of the products such as BER acesulfame and BER saccharine are lower than that of 1BER-1HCl-M (Wang et al., 2016).

The solubility of a drug is related to a wide variety of factors, leading to a limited understanding of the relationship between its structure and solubility. Recently, many attempts have been made to elucidate this relationship. To the best of our knowledge, the main influencing factors include the packing index (Zhang et al., 2020), intermolecular interactions (Zhao et al., 2020), lattice energy (Guo et al., 2018), the affinity of the counter-ion to the solvent (Ren et al., 2021), the pH of the solution (Alhalaweh, et al., 2012), the molar ratio of the drug to counter-ion in the product (Yu et al., 2021), the common ion effect (Devarapalli et al., 2021) and so on. A combination of these factors has frequently been found to affect the solubility of a drug.

To acquire a solid form of BER with the desired properties, we anticipated that the reactants would need to be altered. In view of the reversible transformation between the free BER quaternary amine base and 8-hy­droxy-7,8-di­hydro­berberine [8H-HBER, Fig. 1(b)], 8H-HBER serving as the stable solid form (Dostál et al., 2004), we selected to react 8H-HBER with a number of pharmaceutical acids for the first time. MA, possessing the optimum solubility of the eight common carb­oxy­lic acids reported, was also employed in the study by Apelblat & Manzurola (1987). Additionally, the effect of chirality of the counter-ion on solubility was investigated with TA, the model acids included L-TA, D-TA and racemic DLTA. Moreover, CA with a solubility that is almost equivalent to LTA was also employed to form a salt with BER in order to evaluate the impact of the counter-ion on the solubility of the resultant products.

The reactive crystallizations of 8H-HBER with the selected acids yielded six novel solid forms of BER including 1BER-1MA, 1BER-2MA-2W, 1BER-1LTA-1W, 1BER-1DTA-1W, 1BER-1DLTA and 2BER-2CA. All the multi-component solid forms with the exception of 1BER-1DLTA were confirmed by single-crystal X-ray diffraction (SCXRD), and further comprehensively characterized using powder X-ray diffraction (PXRD), thermal analysis and Fourier transform infrared spectroscopy (FT-IR). Moreover, stability and solubility of the samples obtained were evaluated and compared with 1BER-1HCl-M. Furthermore, the relationships between the structures of the products and their solubilities were tentatively clarified.

2. Methods

2.1. Materials

Commercial BER hydro­chloride and BER hydrogen sulfate were purchased from Baoji Fangsheng Biological Development Co. Ltd (Shanxi, China). 8H-HBER (dark yellow powder) was prepared in our laboratory, and its purification confirmed by HPLC was >98%. All other chemicals were of analytical grade and were provided by Sinopharm Chemical Reagent Company Ltd (Shanghai, China). Redistilled water was used throughout the study.

2.2. Crystallization

2.2.1. Preparation of 8H-HBER

After complete dissolution of 200 mg of BER hydrogensulfate in water (45 ml), a saturated aqueous solution of NaOH was added until no further precipitation occured. Then, the mixture was extracted three times with 20 ml di­ethyl ether. The di­ethyl ether was removed under reduced pressure to obtain the residual solid sample. Finally, the solid sample collected was dissolved in methanol at 323 K and left at ambient temperature to evaporate. After five days, 8H-HBER precipitated and was analyzed using FT-IR; the FT-IR spectrum was consistent with a previous report (Dostál et al., 2004).

2.2.2. Preparation of 1BER-1MA and 1BER-2MA-2W

After complete dissolution of 50 mg of the 8H-HBER and MA mixture (molar ratio 1:1 or 1:2) in the solvents listed in Table S1 of the supporting information at 323 K, the solution was filtered and cooled to room temperature. After five days, needle-like crystals were harvested.

2.2.3. Preparation of 1BER-1LTA-1W and 1BER-1DTA-1W

After complete dissolution of 50 mg of the 8H-HBER and acid mixture (molar ratio 1:1) in the mixed acetone–water solvent (v/v = 3 ml:4 ml) at 323 K, the solution was filtered and cooled to room temperature. After four days, needle-like crystals were harvested.

2.2.4. Preparation of 1BER-1DLTA

After complete dissolution of 50 mg of the 8H-HBER and DLTA mixture (molar ratio 1:1) in the acetone–water solvent (v/v = 5 ml:5 ml) at 323 K, the solution was filtered and cooled to room temperature. After four days, the product was prepared.

2.2.5. Preparation of 2BER-2CA

After complete dissolution of 50 mg of the 8H-HBER and CA mixture (molar ratio 1:1) in the acetone–water solvent (v/v = 1.5 ml:2.5 ml) at 323 K, the solution was filtered and cooled to room temperature. After two days, needle-like crystals were harvested.

2.3. Single crystal X-ray diffraction

SCXRD data for the harvested crystals were collected on a Bruker APEX-II D8 Venture area diffractometer (Bruker, Germany). The crystal structures were solved via direct methods and refined by a full-matrix least-squares procedure against F² using OLEX2 (Dolomanov et al., 2009) and SHELXTL (Sheldrick, 2008) with anisotropic displacement parameters (ADPs) for non-hydrogen atoms. Hydrogen atoms bonded to nitrogen or oxygen were determined by the experimental electron density map, and their isotropic displacement parameters and positions were refined freely. All other hydrogen atoms were located in geometrically calculated positions and refined using a riding model.

Hirshfeld surfaces formed by the equal electron density point between the investigated molecule and its surrounding molecules were obtained by Crystal Explorer (version 3.1; McKinnon et al., 2004) based on the SCXRD data. After, various intermolecular interactions among the different crystal structures were quantitatively explored and compared.

2.4. Powder X-ray diffraction

PXRD experiments were performed on a Rigaku D/max-2550 diffractometer with Cu Kα radiation (Rigaku, Tokyo, Japan) at 40 kV and 150 mA at 293 K. PXRD patterns were recorded at a constant 8° min⁻¹ scan rate in the 2θ range 5–60°.

2.5. Thermal analysis

Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were conducted on a ZCT-B DSC/TGA calorimeter (Jingyi Gaoke Instrument Co. Ltd, Beijing, China). The accurately weighed samples in open aluminium oxide cells were heated from 313 to 573 K at a constant rate of 10 K min⁻¹.

2.6. Fourier transform infrared spectroscopy analysis

FT-IR analysis was performed using a Nicolet Nexus IS5 FT-IR with an attenuated total reflectance (ATR) accessory (Thermo-Nicolet, Madison, USA). The scan range was set from 500 to 4000 cm⁻¹ with a 4 cm⁻¹ resolution.

2.7. Stability test

Samples were subjected to accelerated conditions of high temperature (313 K and/or 333 K, 40% ± 5%) and high humidity (298 K, 90% ± 5%) for 10 days according to the Chinese Pharmacopoeia (Pharmacopoeia committee of the People's Republic of China, 2020) and further analysed via FT-IR to determine whether the samples had changed.

2.8. Dissolution experiments

All solid-state samples were sieved through a 100-mesh screen before dissolution experiments were performed. Then, a dissolution experiment was conducted on a constant-temperature oscillator (ZWY-103B, Shanghai Zhicheng Analytical Instrument Manufacturing Co. Ltd, China). Approximately 5 mg of 1BER-1HCl-M (accurately weighed) was dissolved in 100 ml hydro­chloric acid solution (pH = 1.2). Seven primary standard solutions were prepared by suitably diluting the stock solutions to generate a calibration curve. Excess amounts of seven different samples including 1BER-1MA, 1BER-2MA-2W, 1BER-1LTA-1W, 1BER-1DTA-1W, 1BER-1DLTA, 2BER-2CA and 1BER-1HCl-1M were added to 30 ml pure water or dilute hydro­chloric acid solution (pH = 1.2). The solutions were shaken at 310 K for 48 h at a speed of 100 rpm. The suspensions were removed at 5, 10, 20, 30 and 45 min; and 1, 1.5, 2, 3, 24 and 48 h, and filtered through 0.2 µm membrane filters. Finally, the liquids were diluted appropriately and measured spectrophotometrically to determine the UV absorbance (L8, Shanghai Yidian Analytical Instrument Co. Ltd, China). The detection wavelength was set to 340 nm. Moreover, the undissolved samples were collected at 3 and 48 h for FT-IR analysis.

3. Results and discussion

3.1. Crystallization

The stoichiometric ratio of ionizable drug and counter-ion in the resulting product is commonly controlled by the molar ratio of reactants. As expected, 1BER-1MA is prepared via the reactive crystallization of 8H-HBER with MA in a 1:1 molar ratio in the ethanol and water mixed solvent system. However, the 1:2 molar ratio of 8H-HBER to MA also produces 1BER-1MA when the volume ratio of water and ethanol was below 1:9. 1BER-2MA-2W could be harvested from the mixed solvent system of acetone and water, regardless of the 1:1 or 1:2 molar ratio of 8H-HBER and MA. Crystallizations of 1BER-1MA and 1BER-2MA-2W were influenced by the crystallization solvent type as well as the molar ratio of reactants. Thus, preparation of the desired stoichiometric salt required the appropriate crystallization solvents as well as molar ratio of reactants.

3.2. Structural analysis

Five novel crystal structures were determined using SCXRD. The crystallographic parameters and strong hydrogen-bond geometries of the five crystals are listed in Tables 1 and 2. Loss of a proton derived from the acid occurred in each crystal. Hence, these samples were termed salts. However, an additional neutral MA molecule was also included in 1BER-2MA-2W, which can be classified as a salt cocrystal.

Table 1
Crystal data and structure refinement parameters for the BER solid forms obtained

Compound	1BER-1MA	1BER-1MA-1	1BER-2MA-2W	1BER-1LTA-1W	1BER-1DTA-1W	2BER-2CA
Chemical formula	C20H18NO4·C3H3O4	C20H18NO4·C3H3O4	C20H18NO4·C3H4O4·C3H3O4·2(H2O)	C20H18NO4·C4H5O6·H2O	C20H18NO4·C4H5O6·H2O	2C20H18NO4·2C6H7O7
Formula weight	439.41	439.41	579.50	503.45	503.45	1054.92
Crystal system	Monoclinic	Monoclinic	Triclinic	Monoclinic	Monoclinic	Triclinic
Space group	P21c	P21c	P1	P21	P21	P1
a (Å)	6.844 (1)	6.943 (1)	7.587 (1)	12.111 (1)	12.106 (1)	7.585 (1)
b (Å)	19.545 (1)	19.818 (2)	12.937 (1)	7.093 (1)	7.090 (1)	14.686 (1)
c (Å)	14.650 (1)	14.669 (2)	13.964 (1)	12.703 (1)	12.699 (1)	22.789 (1)
α (°)	90	90	71.32 (1)	90	90	101.25 (1)
β (°)	98.71 (1)	97.08 (1)	83.35 (1)	99.43 (1)	99.39 (1)	97.33 (1)
γ (°)	90	90	81.36 (1)	90	90	100.89 (1)
V (Å^3)	1937.2(1)	2003.1(3)	1280.4 (2)	1076.6 (1)	1075.5 (1)	2409.2 (2)
Z	4	4	2	2	2	2
ρcalc (g cm^−3)	1.507	1.457	1.503	1.553	1.555	1.451
Radiation	Mo Kα (λ = 0.71073)	Mo Kα (λ = 0.71073)	Mo Kα (λ = 0.71073)	Cu Kα (λ = 1.54178)	Cu Kα (λ = 1.54178)	Cu Kα (λ = 1.54178)
Measured reflections	4584	3526	5902	4170	4305	9389
Independent reflections	4584	2657	5902	4090	4305	9389
Flack parameter	–	–	–	0.05 (6)	0.11 (4)	–
Rint	0.0328	0.0419	0.0339	0.0251	0.0187	0.0463
R1 [I > 2σ(I)]	0.1341	0.0992	0.0545	0.0298	0.0257	0.080
wR2 [I > 2σ(I)]	0.2788	0.2330	0.1204	0.0831	0.0670	0.226
R1(all)	0.1417	0.1182	0.0760	0.0302	0.0262	0.1073
wR2(all)	0.2818	0.2413	0.1399	0.0836	0.0673	0.2353
Goodness of fit	1.049	1.081	1.038	1.076	1.050	1.03
Temperature (K)	100	293	100	100	100	100
Completeness (%)	100	99.0	99.9	95.7	98.8	95.7
CCDC code	2132141	2132142	2132143	2132145	2132144	2132146

Table 2
Hydrogen-bond geometry of the BER solid forms obtained

Compound	Hydrogen bond	D—H (Å)	H⋯A (Å)	D⋯A (Å)	D—H⋯A (°)	Symmetry codes
1BER-1MA	O5—H5A⋯O7	0.800 (10)	1.68 (7)	2.434 (6)	156 (19)
1BER-2MA-2W	O5—H5A⋯O13	1.00 (3)	1.61 (3)	2.5876 (19)	163 (3)	−x + 1, −y + 1, −z
	O8—H8A⋯O9	0.92 (3)	1.63 (3)	2.554 (2))	175 (3)
	O10—H12C⋯O12	1.20 (3)	1.23 (3)	2.4008 (17)	163 (3)
	O13—H13C⋯O11	0.86 (3)	1.94 (3)	2.792 (2)	173 (3)	−x + 1, −y + 1, −z − 1
	O13—H13D⋯O14	0.92 (3)	1.84 (3)	2.735 (2)	165 (2)	−x + 2, −y + 1, −z − 1
	O14—H14B⋯O6	0.82 (3)	2.03 (3)	2.833 (2)	166 (3)	−x + 2, −y, −z
	O14—H14C⋯O12	0.95 (4)	1.92 (4)	2.849 (2)	164 (3)	−x + 2, −y, −z − 1
1BER-1LTA-1W	O7—H7A⋯O11	0.87 (4)	1.79 (4)	2.650 (2)	171 (3)
	O8—H8A⋯O10	0.88 (4)	2.07 (4)	2.643 (2)	122 (3)
	O9—H9B⋯O6	0.813 (14)	1.654 (15)	2.463 (2)	173 (4)	x, y + 1, z
	O11—H11A⋯O5	0.99 (4)	1.83 (4)	2.816 (2)	173 (3)	x, y + 1, z
	O11 —H11B⋯O7	0.86 (3)	2.21 (3)	2.970 (2)	147 (3)	−x + 1, y + 1/2, −z + 2
1BER-1DTA-1W	O7—H7A⋯O11	0.89 (3)	1.76 (3)	2.650 (2)	175 (3)	−x, y + 1/2, −z
	O8—H8A⋯O10	0.89 (4)	2.06 (4)	2.642 (2)	122 (3)
	O9—H9B⋯O6	0.821 (14)	1.644 (15)	2.4593 (19)	172 (5)	x, y − 1, z
	O11—H11A⋯O5	0.89 (3)	1.93 (3)	2.816 (2)	171 (3)	x, y − 1, z
	O11—H11B⋯O7	0.84 (3)	2.23 (3)	2.9714 (19)	147 (3)	−x, y − 3/2, −z
2BER-2CA	O6A—H6A⋯O9A	0.872 (19)	1.62 (2)	2.481 (4)	167 (5)
	O6B—H6B⋯O9B	0.87 (2)	1.67 (2)	2.538 (4)	173 (8)
	O7A—H7A⋯O8A	0.86 (2)	2.18 (7)	2.613 (5)	111 (6)
	O7B—H7B⋯O8B	0.859 (19)	2.10 (4)	2.604 (3)	117 (4)
	O10A—H10A⋯O8A	0.85	1.92	2.758 (5)	166.6	x − 1, y, z
	O10B—H10B⋯O9B	0.853 (10)	1.693 (11)	2.545 (3)	176 (5)	x − 1, y, z

3.2.1. BER-1MA

1BER-1MA crystallized in the monoclinic space group P2₁/c with one BER cation and one MA anion in the asymmetric unit. The intramolecular hydrogen bond O₅—H⋯O₇ in the MA anion generates a ring-like structure [Fig. 2(a)]. However, no intermolecular hydrogen bonds were observed in 1BER-1MA. π–π interactions in 1BER-1MA were formed between two benzene rings (C₁—C₂—C₃—C₄—C₅ and C₁₀—C₁₁—C₁₄—C₁₅—C₁₆) [shortest centre-to-centre distance: 3.549 (3) Å] and between the six-membered rings (N₁—C₈—C₇—C₆—C₅—C₉) [shortest centre-to-centre distance: 3.795 (3) Å] to construct a layer-like structure [Fig. 2(b)]. The layer-like structures depend on van der Waals forces to create a three-dimensional structure with MA anions scattered in the voids [Fig. 2(c)].

Figure 2 (a) Hydrogen bonds between molecules in 1BER-1MA. (b) π–π interactions between molecules in 1BER-1MA (hydrogen atoms have been omitted). (c) Three-dimensional structure of 1BER-1MA (hydrogen atoms have been omitted).

The unit-cell parameters of 1BER-1MA were evidently affected by the measured temperature. The 6.844 (1) Å a axis and 19.545 (1) Å b axis at 100 K increased to 6.943 (1) Å and 19.818 (2) Å at 293 K, respectively, whereas the c axis showed almost no change. This implies that the peak positions of 1BER-1MA between the simulated PXRD pattern based on SCXRD data at 100 K and the experimental PXRD pattern collected at 293 K would be different.

3.2.2. BER-2MA-2W

1BER-2MA-2W crystallized in the triclinic space group P1 with one BER cation, one MA anion, one neutral MA molecule and two water molecules in the asymmetric unit. Similar to the MA anion in 1BER-1MA, the intramolecular hydrogen bond O₈—H₈⋯O₉ in 1BER-2MA-2W was generated to form a ring motif [Fig. 3(a)]. Only one of the two MA molecules in the asymmetric unit was deprotonated. Thus, 1BER-2MA-2W was regarded as a salt cocrystal. Two water molecules, one MA anion and one MA molecule were connected via the hydrogen bonds O₅—H⋯O₁₃ (−x + 1, −y + 1, −z), O₁₃—H⋯O₁₁ (−x + 1, −y + 1, −z − 1), O₁₄—H⋯O₆ (−x + 2, −y, −z − 1) and O₁₄—H⋯O₁₂ (−x + 2, −y, −z − 1) to form a 12-membered ring motif. Moreover, two 12-membered ring motifs were bonded to each other via the hydrogen bond O₁₃—H⋯O₁₄ (−x + 2, −y + 1, −z − 1). Furthermore, the hydrogen-bonded network was extended via the hydrogen bond O₈—H⋯O₉ to generate a chain-like structure. π–π interactions in 1BER-2MA-2W [Fig. 3(b)] were formed between two benzene rings (C₁—C₂—C₃—C₄—C₅—C₆ and C₁₀—C₁₁—C₁₄—C₁₅—C₁₆—C₁₇) [shortest centre-to-centre distance: 3.6476 (10) Å] and between the six-membered ring (N₁—C₈—C₇—C₆—C₅—C₉) and the benzene ring (C₁—C₂—C₃—C₄—C₅—C₆) [shortest centre-to-centre distance: 3.8355 (10) Å] to construct a layer-like structure. Ultimately, the chain-like structures and layer-like structures that rely on van der Waals forces were assembled into a three-dimensional structure with hydro­phobic zones and hydro­philic zones in an alternate arrangement [Fig. 3(c)].

Figure 3 (a) Hydrogen bonds between molecules in 1BER-2MA-2W. (b) π–π interactions between molecules in 1BER-2MA-2W (hydrogen atoms have been omitted). (c) Three-dimensional structure of 1BER-2MA-2W (hydrogen atoms have been omitted).

3.2.3. BER-1LTA-1W and 1BER-1DTA-1W

TA molecules with distinct chirality were employed in the salt formation process. However, the products obtained with 1BER-1LTA-1W and 1BER-1DTA-1W have similar cell parameters and crystal structure. This indicates that the two samples would have almost the same PXRD pattern, FT-IR spectra and TGA/DSC curves. They crystallized in the triclinic space group P2₁ with one BER cation, one TA anion and one water molecule in the asymmetric unit. Flack parameters for 1BER-1LTA-1W and 1BER-1DTA-1W below 0.3 were 0.05 (6) and 0.11 (4), respectively. This implies that the absolute configuration of the two crystals could be determined. The intramolecular hydrogen bond O₈—H⋯O₁₀ in the TA anion generates a five-membered ring-like motif (Fig. 4). Each water molecule is bonded to three TA anions around it via three hydrogen bonds, O₇—H⋯O₁₁, O₁₁—H⋯O₅ and O₁₁—H⋯O₇ to form a chain-like structure. The connection is further strengthened via the hydrogen bond O₉—H⋯O₆ to form a 12-membered ring-like structure. π–π interactions in 1BER-1LTA-1W and 1BER-1DTA-1W (Fig. 5) exist between the two benzene rings (C₁—C₂—C₃—C₄—C₅—C₆ and C₁₀—C₁₁—C₁₄—C₁₅—C₁₆—C₁₇) [shortest centre-to-centre distances: 3.5772 (12) Å and 3.5744 (12)] to construct a layer-like structure. The layer-like structures assemble via van der Waals forces into a three-dimensional structure with hydro­philic chain-like structures scattered in the voids (Fig. 6).

Figure 4 Hydrogen bonds between molecules in (a) 1BER-1L-TA-1W and (b) 1BER-1DTA-1W.

Figure 5 π–π interactions among molecules in (a) 1BER-1LTA-1W and (b) 1BER-1DTA-1W (hydrogen atoms have been omitted).

Figure 6 Three-dimensional structures of (a) 1BER-1L-TA-1W and (b) 1BER-1DTA-1W (hydrogen atoms have been omitted).

3.2.4. BER-2CA

2BER-2CA crystallized in the triclinic space group P1 with two BER cations and two CA anions in the asymmetric unit. Both BER cations and CA anions could be divided into two types in 2BER-2CA. The C_12B—C_13B group in one type of BER cations is disordered over two positions with 0.53:0.47. The disordered O_11A is split over two positions with 0.54:0.46, also observed in one type of the CA anions. Similar intramolecular hydrogen bonds O₆—H⋯O₉ and O₇—H⋯O₈ form in both types of CA anions to construct five- and seven-membered ring-like motifs [Fig. 7(a)]. The intermolecular hydrogen bond was shaped to yield a chain-like structure among the same type of CA anions, but with O_10A—H⋯O_8A for one type CA anions and O_10B—H… O_9B for the other. π–π interactions in 2BER-2CA were generated between two benzene rings (C₁—C₂—C₃—C₄—C₅—C₆ and C₁₀—C₁₁—C₁₄—C₁₅—C₁₆—C₁₇) [shortest centre-to-centre distance: 3.797 (3) Å] resulting in a layer-like structure [Fig. 7(b)]. Similar to 1BER-1LTA-1W and 1BER-1DTA-1W, a three-dimensional structure with hydro­philic chain-like structures scattered in the voids assembled by the layer-like structures were formed [Fig. 7(c)].

Figure 7 (a) Hydrogen bonds between molecules in 2BER-2CA. (b) π–π interactions between molecules in 2BER-2CA (hydrogen atoms have been omitted). (c) Three-dimensional structure of 2BER-2CA (hydrogen atoms have been omitted).

3.2.5. Packing coefficient

The packing coefficient was calculated using the PLATON software (Spek, 2009) based on SCXRD data according to the following equation (Price et al., 2006): C_k = ZV_molV_cell⁻¹, where Z, V_mol and V_cell represent the number of molecules in the unit cell, the molecular volume (ų) and the volume of the unit cell (ų), respectively.

The percentage of void space in molecular crystals was negatively related to the packing coefficient. A large packing coefficient for the crystal indicates a tight packing among molecules, suggesting lower solubility. The packing coefficients for 1BER-1MA, 1BER-2MA-2W, 1BER-1LTA-1W, 1BER-1DTA-1W and 2BER-2CA were determined to be 73.8, 73.0, 75.3, 75.6 and 69.6%, respectively.

3.3. Hirshfeld surface analysis

The various intermolecular interactions quantitatively obtained from the Hirshfeld surface analysis could reveal the strength of the connection among molecules to some extent, which may be reflected in the solubility and used for rationalizing the solid-state formation of a drug (Sanphui et al., 2015). Intermolecular interactions of the samples obtained are summarized in Fig. 8. It is clear that the O⋯H, C⋯H, H⋯H and C⋯C interactions contribute significantly to the Hirshfeld surfaces. An increasing proportion of the strong O⋯H interactions – with 46.4% in 1BER-2MA-W – was observed because two water molecules and one additional MA molecule are incorporated into the crystal structure compared with 36.4% in 1BER-1MA, and there is no obvious difference in packing coefficient between 1BER-1MA and 1BER-2MA-2W. This implies a stronger connection between the molecules in 1BER-2MA-2W. Thus, it is favourable for the formation of 1BER-2MA-2W over 1BER-1MA when the water content in solution and molar ratio of MA to BER increase to a certain extent.

Figure 8 Summary of intermolecular interactions obtained from the Hirshfeld surface area for the five multi-component crystals.

3.4. PXRD analysis

Significant differences between the solid forms obtained could be effectively detected by PXRD, with the exception of 1BER-1LTA-1W and 1BER-1DTA-1W (Figs. S1–S6). The experimental powder patterns of the crystals were well matched with their theoretical powder patterns calculated using Mercury [version 3.0; Cambridge Crystallographic Data Centre, Cambridge, UK (Macrae et al., 2006)], implying high purity of samples. The main experimental peak positions observed were 7.500, 8.873, 10.752, 12.122, 17.278, 17.832, 18.773, 18.997, 19.960, 25.688, 26.895 and 27.548° for 1BER-1MA; 6.721, 7.249, 14.459, 17.583, 19.628, 21.758, 25.298 and 26.402° for 1BER-2MA-2W; 6.971, 7.352, 9.236, 13.986, 14.724, 15.194, 24.927 and 26.629° for 1BER-1DTA-1W; 7.028, 7.399, 9.297, 14.043, 14.784, 15.252, 24.952 and 26.670° for 1BER-1LTA-1W; 7.007, 8.356, 13.719, 15.109, 16.705, 23.294 and 25.193° for 1BER-1DL-TA; and 6.701, 8.074, 13.332, 14.761, 16.297, 16.829, 24.193 and 27.589° for 2BER-2CA.

The experimental peak positions of 1BER-2MA-2W, 1BER-1LTA-1W, 1BER-1DTA-1W and 2BER-2CA were essentially consistent with the calculated peak positions derived from the SCXRD data collected at 100 K. This suggests that there are no obvious differences in the unit-cell parameters of these crystals between 100 and 293 K. However, the a and b axes of 1BER-1MA at 100 K relative to 293 K were notably shortened, which caused some peak positions at 100 K to differ from those at 293 K.

3.5. Thermal analysis

DSC and TGA curves of the samples obtained are depicted in Figs. S7–S8. The proportions of water weight loss for 1BER-2MA-2W, 1BER-1LTA-1W and 1BER-1DTA-1W were 6.20, 3.55 and 3.65%, respectively. The calculated loss numbers of water for the asymmetric units based on the weight loss values were in accordance with the SCXRD data (Table 3).

Table 3
Water molecule loss numbers and dehydration temperature of six BER salts

	First peak (K)	Weight loss (%)	Second peak (K)	Weight loss (%)	Third peak (K)	Weight loss (%)	Fourth peak (K)	Weight loss (%)	Observed stoichiometry	Calculated stoichiometry
1BER-1MA	470.7	20.55	–	–	–	–	–	–	–	–
1BER-2MA-2W	352.0	6.20	391.5	17.80	418.8	–	467.7	16.6	1:2	1:2
1BER-1L-TA-1W	375.7	3.55	498.2	26.88	–	–	–	–	1:1	1:1
1BER-1D-TA-1W	379.9	3.65	497.8	27.78	–	–	–	–	1:1	1:1
1BER-1DL-TA	507.8	29.48	–	–	–	–	–	–	–	–
2BER-2CA	481.3	26.5	–	–	–	–	–	–	–	–

Only one endothermic peak corresponding to melting and decomposition in the DSC plots of 1BER-1MA, 1BER-1DL-TA and 2BER-2CA was observed. However, another endothermic peak was observed in both 1BER-1LTA-1W and 1BER-1DTA-1W that could be attributed to the crystalline water loss. Comparatively, there were four endothermic peaks for 1BER-2MA-2W, which were successively attributed to water molecule loss, uncharged malonic acid loss, solid-state transformation, and melting and decomposition, on the basis of analysing the TGA and PXRD data.

Although every water molecule in 1BER-2MA-2W (similar to that in BER-1LTA-1W and 1BER-1DTA-1W) was also bonded to molecules around it via three hydrogen bonds, the dehydration temperature of 1BER-2MA-2W was evidently lower than BER-1LTA-1W and 1BER-1DTA-1W. The reason for this phenomenon may be the lower melting point of the molecules including the water molecule and malonic acid in 1BER-2MA-2W (which form hydrogen bonds with water molecules), relative to those of the molecules of tartaric acid in BER-1LTA-1W and 1BER-1DTA-1W (which also form hydrogen bonds with water molecules).

After 10 min dehydration at 378 K for 1BER-1LTA-1W and 1BER-1DTA-1W and at 353 K for 1BER-2MA-2W, the samples were characterized by PXRD (Figs. S9–S11), and the results showed that only the sample derived from 1BER-2MA-2W had undergone obvious changes in peak positions before and after dehydration. This signified that the crystal of 1BER-2MA-2W had collapsed following the loss of water to form a new solid (1BER-2MA-2W-AH) with the main experimental peak positions 6.109, 6.397, 7.581, 7.888, 10.447, 12.368, 15.418, 15.950, 16.872, 17.177, 19.243, 22.660, 23.949, 24.273, 25.380, 26.179 and 26.424°, while both 1BER-1LTA-1W and 1BER-1DTA-1W only formed anhydrates without crystal collapse.

The second DSC peak of 1BER-2MA-2W corresponded to a 17.80% weight loss in the TGA curve, almost equivalent to the calculated uncharged malonic acid loss value of 17.94% based on the SCXRD data. A third endothermic peak appeared along with the weight loss of the uncharged malonic acid. We inferred that the weight loss is accompanied by transformation of the solid form. Thus, the 1BER-2MA-2W sample after heating for 10 min at 423 K was characterized by PXRD, and the results suggested that the residual solid was 1BER-1MA.

Melting and decomposition appear to induce the formation of the novel compounds, and the TGA curves of all investigated samples after melting and decomposition seem flat to support this, which suggests that the products may be pure solid phases. Hence, all the products after melting and decomposition were monitored using FT-IR and were found to correspond to berberrubine derived from 1BER-1HCl-M (Iwasa et al., 1996) when heated for 10 min at 483 K. Therefore, these novel salts could also be employed to prepare berberrubine.

No de-solvent peak was observed for 1BER-1DLTA. Moreover, the weight loss value attributed to melting and decomposition for 1BER-1DLTA was roughly equivalent to that for 1BER-1LTA-1W and 1BER-1DTA-1W. Thus, the components included in 1BER-1DLTA were determined to be BER cations and DLTA anions with the molar ratio 1:1.

3.6. FT-IR spectroscopic analysis

The peak position, number and shape in the regions 3200–3800 cm⁻¹ and 1700–1800 cm⁻¹ attributed to the characteristic OH and C=O absorptions were remarkably different among the samples obtained due to the distinct hydrogen interactions (Fig. S12), with the exception of 1BER-1LTA-1W and 1BER-1DTA-1W. FT-IR could effectively monitor the change in solid forms so was employed to analyse the recrystallization product, the stability of the obtained solid forms and the solid forms of the undissolved samples in the dissolution experiments.

3.7. Stability

In this study, the stability of the synthesized products against high humidity and high temperature over 10 days were evaluated. As presented in Table 4 and Figs. S13–S18, all the samples prepared retained their original solid form except for 1BER-2MA-2W. The sample derived from 1BER-2MA-2W at high temperature was characterized by PXRD and found to be the new solid form 1BER-2MA-2W-AH. Thus, we further investigated the stability of 1BER-2MA-2W at high temperature (313 K) and the results showed that 1BER-2MA-2W remained stable. In comparison with the commercial form of BER, significant enhancement in stability was achieved for the novel solid forms.

Table 4
Stability of the synthesized products kept at high humidity and high temperature

	HT-313K-10d	HT-333K-10d	HH-90%-10d
1BER-1MA	–	1BER-1MA	1BER-1MA
1BER-2MA-2W	1BER-2MA-2W	1BER-2MA-2W-AH	1BER-2MA-2W
1BER-1LTA-1W	–	1BER-1LTA-1W	1BER-1LTA-1W
1BER-1DTA-1W	–	1BER-1DTA-1W	1BER-1DTA-1W
1BER-1DLTA	–	1BER-1DLTA	1BER-1DLTA
1BER-1CA	–	1BER-1CA	1BER-1CA

3.8. Powder dissolution experiments

It is widely known that elucidation of the relationship between the solid form of a drug and its solubility is particularly difficult, but it is of great importance for screening an adequate solid form for prescription design. As stated in the introduction, the solubility of a salt is usually controlled by a wide variety of factors such as the packing index, intermolecular interactions, lattice energy, the affinity of the counter-ion to the solvent, the pH of the solution, the common ion effect and so on. Dissolution profiles of the newly obtained samples compared with 1BER-1HCl-M in pure water and dilute hydro­chloric solution (pH = 1.2) are depicted in Fig. 9.

Figure 9 Dissolution profiles of the solid forms obtained in (a) pure water and (b) dilute hydro­chloric acid solution.

As presented in Fig. 9(a), the order of maximum apparent solubility (MAS) observed in pure water for the investigated samples was 1BER-1MA with 149.5 µmol ml⁻¹ > 1BER-2MA-2W with 41.9 µmol ml⁻¹ > 2BER-2CA with 9.2 µmol ml⁻¹ > 1BER-1HCl-M with 6.5 µmol ml⁻¹ ≃ 1BER-1DTA-1W with 6.2 µmol ml⁻¹ ≃ 1BER-1LTA-1W with 6.1 µmol ml⁻¹ > 1BER-1DL-TA with 2.3 µmol ml⁻¹. Solubilities (the mole fraction solubility) of MA, CA, DTA/LTA and DLTA in water are reported to be 0.2445, 0.1617, 0.1583 and 0.0365, respectively (Apelblat & Manzurola, 1987; Tan et al., 2016). It is obvious that the MAS of the novel salts was markedly affected by the affinity of the counter-ion to water. Among these organic acids, MA exhibits the best solubility. Therefore, the MAS of BER malonate was significantly higher than that of the other BER salts. In addition, 1BER-1MA and 1BER-2MA-2W included the same type of counter-ion as malonic acid and had similar packing indexes, but the former displayed better solubility, which may be attributed to the weaker intermolecular interactions with a lower proportion of O⋯H interactions (36.4%) compared with 1BER-2MA-2W (46.4%). In particular, the effect of chirality of TA on the MAS of the final products was clearly related to their solubilities. This phenomenon was in accordance with Wallach's rule (Brock et al., 1991; Wang et al., 2012) which states that racemic crystals have a higher density relative to their chiral counterparts. Thus, the racemic crystals of 1BER-1DL-TA displayed a lower solubility compared with their chiral counterparts 1BER-1DTA-1W and 1BER-1LTA-1W. Solubility of CA was slightly greater than that of DTA/LTA. However, significant improvement in the MAS for 2BER-2CA was achieved compared with 1BER-1LTA-1W and 1BER-1DTA-1W, which resulted from a smaller packing coefficient of 2BER-2CA with 69.6% relative to that of 1BER-1LTA-1W with 75.3% and 1BER-1DTA-1W with 75.6%.

As presented in Fig. 9(b), 1BER-1HCl-M, 1BER-1MA, 1BER-2MA-2W, 1BER-1DTA-1W, 1BER-1LTA-1W, 1BER-1DL-TA and 2BER-2CA achieved MAS in dilute hydro­chloric solution at 2.1, 68.8, 34.8, 13.1, 12.5, 4.5 and 16.4 µmol ml⁻¹, respectively. The MAS order in dilute hydro­chloric solution for the samples was in agreement with that in pure water, except for 1BER-1HCl-M with the lowest MAS, which may be the result of the common ion effect. The MAS of all the samples obtained was notably higher than that of the commercial form (1BER-1HCl-M), especially 1BER-1MA with a 33-fold increase.

Given that the solid form is largely related to solubility, all the residual solid forms were analysed after 3 and 48 h by FT-IR (Table 5). As expected, all the residual solid forms derived from pure water (Figs. S19–S20) showed no difference from their original forms, except for the commercial form of BER, which underwent full conversion to 1BER-1HCl-4W. 1BER-2MA-2W did not convert to 1BER-1MA in pure water. Hence, the common ion effect was not the cause of the lower MAS of 1BER-2MA-2W compared with 1BER-1MA.

Table 5
Solid forms of undissolved samples in the solubility experiment

Pure water			Dilute hydro­chloric solution
0 h	3 h	48 h	0 h	3 h	48 h
1BER-1HCl-M	1BER-1HCl-4W	1BER-1HCl-4W	1BER-1HCl-M	1BER-1HCl-4W	1BER-1HCl-4W
1BER-1MA	1BER-1MA	1BER-1MA	1BER-1MA	1BER-1HCl-4W	1BER-1HCl-4W
1BER-2MA-2W	1BER-2MA-2W	1BER-2MA-2W	1BER-2MA-2W	1BER-1HCl-4W	1BER-1HCl-4W
1BER-1D-TA-1W	1BER-1D-TA-1W	1BER-1D-TA-1W	1BER-1D-TA-1W	1BER-1D-TA-1W + 1BER-1HCl-4W	1BER-1HCl-4W
1BER-1L-TA-1W	1BER-1L-TA-1W	1BER-1L-TA-1W	1BER-1L-TA-1W	1BER-1L-TA-1W + 1BER-1HCl-4W	1BER-1HCl-4W
1BER-1DL-TA	1BER-1DL-TA	1BER-1DL-TA	1BER-1DL-TA	1BER-1DL-TA	1BER-1HCl-4W
1BER-1CA	1BER-1CA	1BER-1CA	1BER-1CA	1BER-1HCl-4W	1BER-1HCl-4W

The solid form transformation occurred in all the residual solid forms that originated from the dilute hydro­chloric solution (Figs. S21 and S22), but the conversion rate of the solid forms is obviously different among the solid forms obtained. 1BER-1MA, 1BER-2MA-2W and 2BER-2CA underwent complete conversion to 1BER-1HCl-4W after 3 h. In comparison, small amounts of 1BER-1DTA-1W and 1BER-1LTA-1W were converted to 1BER-1HCl-4W after 3 h. No conversion of solid form was observed from the residual sample of 1BER-1DL-TA after 3 h. However, all the residual solid forms that originated from dilute hydro­chloric solution were finally converted to 1BER-1HCl-4W after 48 h. This signifies that there may be a positive correlation between the conversion rate and the MAS of the distinct salts. In addition, owing to solid-state transformation, the apparent solubilities at 48 h of 1BER-1MA, 1BER-2MA-2W, 2BER-2CA, 1BER-1DTA-1W, 1BER-1LTA-1W and 1BER-1DL-TA below their MAS in dilute hydro­chloric solution, were 18.3, 21.6, 4.6, 5.0, 4.1 and 5.1 µmol ml⁻¹, respectively. Note that all the investigated salts underwent transformation to 1BER-1HCl-4W, but their final apparent solubilities were different and significantly greater than that of 1BER-1HCl-4W derived from 1BER-1HCl-M. It is inferred that the organic acids replaced by hydro­chloric acid in solution may affect the apparent solubility of 1BER-1HCl-4W.

4. Conclusions

Six novel BER multi-component solid forms were successfully synthesized via the reactive crystallization of 8H-HBER with a number of pharmaceutical acids for the first time. Five of the multi-component solid forms including 1BER-1MA, 1BER-2MA-2W, 1BER-1DTA-1W, 1BER-1LTA-1W and 1BER-1CA were structurally elucidated by SCXRD. All the samples obtained were thoroughly characterized by PXRD, FT-IR and thermal analysis. It is inferred from TGA/DSC data of three BER tartrates that the components in 1BER-1DL-TA were determined to be BER cations and racemic TA anions with a molar ratio of 1:1. Among the six products, 1BER-2MA-2W was a salt cocrystal, the rest were classified as salts. The unit-cell parameters of 1BER-1MA were sensitive to temperature. Subsequently, the calculated characteristic diffraction peak positions of 1BER-1MA at 100 K clearly differ from those at 293 K.

Simultaneous improvements in stability and MAS of BER were observed in comparison with the commercial form of BER. All the solid forms obtained were found to be stable under high temperature and high humidity. The MAS values of BER-1MA and 1BER-2MA-2W in pure water, which show an increase of 23- and 6-fold, respectively, are obviously superior to that of the commercial form of BER. The MAS in dilute hydro­chloric solution of all the samples was also far greater than that of the commercial form. Thus, these novel solid forms could be valuable candidates for addressing the low bioavailability and poor stability of BER.

The solubility of a drug relies significantly on its solid form. However, the intrinsic relationship between the solid form of a drug and its solubility is usually unclear and there is a lack of in-depth investigation. In the present study, the factors affecting solubility were determined to be cumulative contributions of the affinity of the counter-ion to the solvent, the packing index, intermolecular interactions, the molar ratio of drug to counter-ion in the product and the common ion effect.

Supporting information

Computing details

For all structures, program(s) used to refine structure: SHELXL2014/7 (Sheldrick, 2014).

(1BER-1MA)

Crystal data

C20H18NO4·C3H3O4	F(000) = 920
Mr = 439.41	Dx = 1.507 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 6.84431 (18) Å	Cell parameters from 4584 reflections
b = 19.5457 (5) Å	θ = 1.8–29.4°
c = 14.6506 (4) Å	µ = 0.12 mm^−1
β = 98.714 (2)°	T = 100 K
V = 1937.29 (8) Å^3	Needle, colourless
Z = 4	0.12 × 0.02 × 0.01 mm

Data collection

CCD diffractometer	4087 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.033
ωκ scans	θmax = 29.4°, θmin = 1.8°
Absorption correction: multi-scan Higashi, T. (1995)	h = −8→8
Tmin = 0.997, Tmax = 0.999	k = −26→26
25159 measured reflections	l = −19→17
4584 independent reflections

Refinement

Refinement on F^2	1 restraint
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.134	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.282	w = 1/[σ^2(Fo^2) + (0.0099P)^2 + 28.P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max < 0.001
4584 reflections	Δρmax = 0.78 e Å^−3
304 parameters	Δρmin = −0.64 e Å^−3

Special details

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. Refined as a 2-component twin.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.3614 (7)	0.5027 (2)	0.1815 (3)	0.0274 (10)
O2	0.3409 (6)	0.36242 (19)	0.1594 (3)	0.0207 (8)
O3	0.1766 (6)	0.68773 (19)	0.8313 (2)	0.0184 (8)
O4	0.1886 (8)	0.5697 (2)	0.8333 (3)	0.0295 (10)
O5	0.6204 (9)	0.6827 (3)	0.0714 (3)	0.0401 (12)
O6	0.9319 (9)	0.6599 (3)	0.0547 (3)	0.0446 (13)
O7	0.5024 (8)	0.6611 (2)	0.2173 (3)	0.0346 (11)
O8	0.7108 (9)	0.6194 (2)	0.3364 (3)	0.0414 (13)
N1	0.2448 (8)	0.5543 (3)	0.5014 (3)	0.0252 (11)
C1	0.3173 (9)	0.4597 (3)	0.2487 (4)	0.0189 (11)
C2	0.3104 (8)	0.3895 (3)	0.2418 (3)	0.0155 (10)
C3	0.2834 (8)	0.3496 (3)	0.3194 (3)	0.0160 (10)
H3A	0.2819	0.3011	0.3141	0.019*
C4	0.2591 (8)	0.3789 (3)	0.4024 (3)	0.0147 (10)
H4A	0.2372	0.3509	0.4529	0.018*
C5	0.2670 (7)	0.4506 (3)	0.4119 (3)	0.0131 (9)
C6	0.2906 (8)	0.4912 (3)	0.3334 (4)	0.0175 (10)
C7	0.2918 (10)	0.5620 (3)	0.3432 (4)	0.0254 (13)
H7A	0.3127	0.5899	0.2924	0.030*
C8	0.2644 (9)	0.5917 (2)	0.4222 (3)	0.0184 (11)
C9	0.2445 (8)	0.4844 (3)	0.4944 (3)	0.0147 (10)
H9A	0.2286	0.4578	0.5470	0.018*
C10	0.2261 (8)	0.5923 (3)	0.5861 (4)	0.0157 (10)
C11	0.2134 (8)	0.6635 (3)	0.5851 (4)	0.0170 (10)
C12	0.2169 (19)	0.7000 (4)	0.4960 (5)	0.063 (3)
H12A	0.0786	0.7073	0.4664	0.076*
H12B	0.2766	0.7457	0.5100	0.076*
C13A	0.3198 (16)	0.6675 (5)	0.4315 (6)	0.020 (3)	0.589 (19)
H13A	0.4639	0.6719	0.4519	0.024*	0.589 (19)
H13B	0.2873	0.6902	0.3707	0.024*	0.589 (19)
C13B	0.175 (2)	0.6639 (6)	0.4156 (8)	0.014 (3)	0.411 (19)
H13C	0.2269	0.6893	0.3658	0.017*	0.411 (19)
H13D	0.0301	0.6604	0.3985	0.017*	0.411 (19)
C14	0.2015 (9)	0.7007 (3)	0.6665 (4)	0.0207 (11)
H14A	0.1972	0.7493	0.6666	0.025*
C15	0.1965 (7)	0.6638 (3)	0.7448 (3)	0.0148 (10)
C16	0.2034 (8)	0.5931 (3)	0.7460 (4)	0.0181 (10)
C17	0.2179 (9)	0.5558 (3)	0.6685 (4)	0.0225 (12)
H17A	0.2224	0.5072	0.6700	0.027*
C18	0.2053 (9)	0.6286 (3)	0.8915 (4)	0.0209 (11)
H18A	0.3375	0.6301	0.9298	0.025*
H18B	0.1038	0.6274	0.9329	0.025*
C19	0.2446 (12)	0.4987 (3)	0.0922 (4)	0.0344 (15)
H19A	0.2925	0.5322	0.0511	0.052*
H19B	0.2549	0.4526	0.0669	0.052*
H19C	0.1062	0.5084	0.0972	0.052*
C20	0.3216 (9)	0.2895 (3)	0.1483 (4)	0.0194 (11)
H20A	0.3470	0.2766	0.0866	0.029*
H20B	0.4173	0.2666	0.1950	0.029*
H20C	0.1874	0.2756	0.1559	0.029*
C21	0.7934 (13)	0.6553 (3)	0.0976 (4)	0.0388 (18)
C22	0.8116 (15)	0.6158 (4)	0.1885 (5)	0.050 (2)
H22A	0.9464	0.6232	0.2224	0.060*
H22B	0.7990	0.5664	0.1737	0.060*
C23	0.6626 (12)	0.6334 (3)	0.2536 (4)	0.0343 (16)
H5A	0.55 (2)	0.673 (10)	0.110 (9)	0.21 (9)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.048 (3)	0.0197 (19)	0.0166 (19)	−0.0083 (19)	0.0120 (18)	0.0010 (16)
O2	0.033 (2)	0.0145 (17)	0.0155 (17)	0.0014 (16)	0.0062 (16)	−0.0012 (14)
O3	0.023 (2)	0.0175 (18)	0.0149 (17)	0.0001 (15)	0.0044 (15)	−0.0024 (14)
O4	0.061 (3)	0.0172 (19)	0.0133 (18)	0.006 (2)	0.0144 (19)	0.0012 (15)
O5	0.055 (3)	0.047 (3)	0.019 (2)	0.004 (3)	0.007 (2)	0.011 (2)
O6	0.065 (4)	0.046 (3)	0.025 (2)	0.004 (3)	0.015 (2)	0.004 (2)
O7	0.060 (3)	0.022 (2)	0.022 (2)	−0.005 (2)	0.009 (2)	0.0028 (17)
O8	0.080 (4)	0.025 (2)	0.021 (2)	0.014 (2)	0.011 (2)	0.0106 (18)
N1	0.027 (3)	0.026 (2)	0.023 (2)	0.007 (2)	0.005 (2)	0.005 (2)
C1	0.023 (3)	0.020 (3)	0.014 (2)	0.002 (2)	0.006 (2)	0.005 (2)
C2	0.014 (2)	0.018 (2)	0.014 (2)	−0.0014 (19)	0.0015 (18)	0.0001 (19)
C3	0.016 (2)	0.015 (2)	0.017 (2)	0.0005 (19)	0.0023 (19)	0.0000 (19)
C4	0.014 (2)	0.015 (2)	0.014 (2)	−0.0003 (19)	0.0001 (18)	0.0006 (18)
C5	0.010 (2)	0.015 (2)	0.014 (2)	−0.0005 (18)	0.0009 (17)	0.0018 (18)
C6	0.024 (3)	0.013 (2)	0.015 (2)	−0.003 (2)	0.003 (2)	0.0012 (19)
C7	0.048 (4)	0.016 (3)	0.015 (2)	0.004 (2)	0.011 (2)	0.005 (2)
C8	0.042 (3)	0.005 (2)	0.010 (2)	0.006 (2)	0.010 (2)	0.0034 (17)
C9	0.016 (2)	0.016 (2)	0.011 (2)	−0.0007 (19)	0.0013 (18)	0.0032 (18)
C10	0.020 (3)	0.012 (2)	0.015 (2)	0.0037 (19)	0.0045 (19)	0.0017 (18)
C11	0.018 (3)	0.014 (2)	0.019 (2)	0.001 (2)	0.0030 (19)	0.0033 (19)
C12	0.155 (10)	0.018 (3)	0.025 (3)	0.010 (5)	0.042 (5)	0.005 (3)
C13A	0.026 (7)	0.015 (4)	0.020 (5)	−0.002 (4)	0.006 (4)	0.002 (3)
C13B	0.015 (8)	0.008 (5)	0.017 (6)	0.006 (4)	−0.002 (5)	0.005 (4)
C14	0.027 (3)	0.013 (2)	0.023 (3)	−0.003 (2)	0.007 (2)	0.000 (2)
C15	0.011 (2)	0.018 (2)	0.016 (2)	−0.0009 (19)	0.0035 (18)	−0.0011 (19)
C16	0.024 (3)	0.017 (2)	0.014 (2)	0.003 (2)	0.005 (2)	0.0022 (19)
C17	0.036 (3)	0.017 (2)	0.016 (2)	0.008 (2)	0.006 (2)	0.004 (2)
C18	0.031 (3)	0.018 (3)	0.015 (2)	0.001 (2)	0.007 (2)	−0.001 (2)
C19	0.055 (4)	0.033 (3)	0.016 (3)	0.012 (3)	0.008 (3)	0.011 (2)
C20	0.026 (3)	0.015 (2)	0.016 (2)	0.002 (2)	0.001 (2)	−0.0025 (19)
C21	0.080 (6)	0.021 (3)	0.015 (3)	−0.001 (3)	0.007 (3)	−0.001 (2)
C22	0.090 (7)	0.035 (4)	0.029 (4)	0.026 (4)	0.024 (4)	0.010 (3)
C23	0.068 (5)	0.012 (2)	0.023 (3)	0.003 (3)	0.012 (3)	0.003 (2)

Geometric parameters (Å, º)

O1—C1	1.363 (6)	C9—H9A	0.9500
O1—C19	1.429 (8)	C10—C11	1.394 (7)
O2—C2	1.363 (6)	C10—C17	1.411 (7)
O2—C20	1.439 (6)	C11—C14	1.410 (7)
O3—C15	1.377 (6)	C11—C12	1.491 (8)
O3—C18	1.449 (6)	C12—C13B	1.366 (14)
O4—C16	1.376 (6)	C12—C13A	1.412 (12)
O4—C18	1.426 (6)	C12—H12A	0.9900
O5—C21	1.304 (10)	C12—H12B	0.9900
O5—H5A	0.800 (10)	C13A—H13A	0.9900
O6—C21	1.217 (9)	C13A—H13B	0.9900
O7—C23	1.265 (9)	C13B—H13C	0.9900
O8—C23	1.239 (8)	C13B—H13D	0.9900
N1—C9	1.371 (7)	C14—C15	1.361 (7)
N1—C8	1.396 (7)	C14—H14A	0.9500
N1—C10	1.469 (7)	C15—C16	1.384 (7)
C1—C2	1.375 (7)	C16—C17	1.366 (7)
C1—C6	1.421 (7)	C17—H17A	0.9500
C2—C3	1.414 (7)	C18—H18A	0.9900
C3—C4	1.376 (7)	C18—H18B	0.9900
C3—H3A	0.9500	C19—H19A	0.9800
C4—C5	1.409 (7)	C19—H19B	0.9800
C4—H4A	0.9500	C19—H19C	0.9800
C5—C9	1.405 (7)	C20—H20A	0.9800
C5—C6	1.427 (7)	C20—H20B	0.9800
C6—C7	1.393 (7)	C20—H20C	0.9800
C7—C8	1.332 (7)	C21—C22	1.528 (9)
C7—H7A	0.9500	C22—C23	1.538 (10)
C8—C13A	1.530 (10)	C22—H22A	0.9900
C8—C13B	1.535 (12)	C22—H22B	0.9900
C1—O1—C19	118.3 (5)	C8—C13A—H13A	109.5
C2—O2—C20	117.5 (4)	C12—C13A—H13B	109.5
C15—O3—C18	105.4 (4)	C8—C13A—H13B	109.5
C16—O4—C18	106.1 (4)	H13A—C13A—H13B	108.1
C21—O5—H5A	107 (10)	C12—C13B—C8	113.1 (9)
C9—N1—C8	117.3 (5)	C12—C13B—H13C	109.0
C9—N1—C10	124.7 (5)	C8—C13B—H13C	109.0
C8—N1—C10	118.0 (5)	C12—C13B—H13D	109.0
O1—C1—C2	124.8 (5)	C8—C13B—H13D	109.0
O1—C1—C6	115.8 (5)	H13C—C13B—H13D	107.8
C2—C1—C6	119.2 (5)	C15—C14—C11	116.9 (5)
O2—C2—C1	116.4 (5)	C15—C14—H14A	121.5
O2—C2—C3	123.6 (5)	C11—C14—H14A	121.5
C1—C2—C3	119.9 (5)	C14—C15—O3	128.0 (5)
C4—C3—C2	121.9 (5)	C14—C15—C16	122.3 (5)
C4—C3—H3A	119.0	O3—C15—C16	109.6 (4)
C2—C3—H3A	119.0	C17—C16—O4	128.4 (5)
C3—C4—C5	119.5 (5)	C17—C16—C15	122.0 (5)
C3—C4—H4A	120.2	O4—C16—C15	109.6 (5)
C5—C4—H4A	120.2	C16—C17—C10	117.3 (5)
C9—C5—C4	123.0 (5)	C16—C17—H17A	121.4
C9—C5—C6	118.2 (5)	C10—C17—H17A	121.4
C4—C5—C6	118.7 (5)	O4—C18—O3	106.8 (4)
C7—C6—C1	121.4 (5)	O4—C18—H18A	110.4
C7—C6—C5	118.0 (5)	O3—C18—H18A	110.4
C1—C6—C5	120.6 (5)	O4—C18—H18B	110.4
C8—C7—C6	121.6 (5)	O3—C18—H18B	110.4
C8—C7—H7A	119.2	H18A—C18—H18B	108.6
C6—C7—H7A	119.2	O1—C19—H19A	109.5
C7—C8—N1	122.6 (5)	O1—C19—H19B	109.5
C7—C8—C13A	115.7 (6)	H19A—C19—H19B	109.5
N1—C8—C13A	119.1 (5)	O1—C19—H19C	109.5
C7—C8—C13B	116.9 (6)	H19A—C19—H19C	109.5
N1—C8—C13B	116.5 (6)	H19B—C19—H19C	109.5
N1—C9—C5	122.3 (5)	O2—C20—H20A	109.5
N1—C9—H9A	118.9	O2—C20—H20B	109.5
C5—C9—H9A	118.9	H20A—C20—H20B	109.5
C11—C10—C17	120.3 (5)	O2—C20—H20C	109.5
C11—C10—N1	120.6 (5)	H20A—C20—H20C	109.5
C17—C10—N1	119.1 (5)	H20B—C20—H20C	109.5
C10—C11—C14	121.1 (5)	O6—C21—O5	124.1 (6)
C10—C11—C12	118.6 (5)	O6—C21—C22	121.3 (8)
C14—C11—C12	120.3 (5)	O5—C21—C22	114.5 (7)
C13B—C12—C11	118.6 (7)	C21—C22—C23	116.9 (6)
C13A—C12—C11	116.5 (7)	C21—C22—H22A	108.1
C13A—C12—H12A	108.2	C23—C22—H22A	108.1
C11—C12—H12A	108.2	C21—C22—H22B	108.1
C13A—C12—H12B	108.2	C23—C22—H22B	108.1
C11—C12—H12B	108.2	H22A—C22—H22B	107.3
H12A—C12—H12B	107.3	O8—C23—O7	126.2 (7)
C12—C13A—C8	110.7 (7)	O8—C23—C22	117.1 (7)
C12—C13A—H13A	109.5	O7—C23—C22	116.7 (6)

(1BER-1MA-1)

Crystal data

C20H18NO4·C3H3O4	F(000) = 920
Mr = 439.41	Dx = 1.457 Mg m^−3
Monoclinic, P21/c	Cu Kα radiation, λ = 1.54184 Å
a = 6.9433 (5) Å	Cell parameters from 3526 reflections
b = 19.8179 (16) Å	θ = 3.8–66.6°
c = 14.6693 (13) Å	µ = 0.94 mm^−1
β = 97.084 (8)°	T = 293 K
V = 2003.1 (3) Å^3	Needle, colourless
Z = 4	0.11 × 0.02 × 0.01 mm

Data collection

CCD diffractometer	3526 independent reflections
Radiation source: fine-focus sealed tube	2657 reflections with I > 2σ(I)
ωκ scans	θmax = 66.6°, θmin = 3.8°
Absorption correction: multi-scan	h = −8→8
Tmin = 0.978, Tmax = 0.991	k = −23→23
3526 measured reflections	l = −3→17

Refinement

Refinement on F^2	1 restraint
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.099	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.241	w = 1/[σ^2(Fo^2) + (0.030P)^2 + 8.P] where P = (Fo^2 + 2Fc^2)/3
S = 1.08	(Δ/σ)max < 0.001
3526 reflections	Δρmax = 0.47 e Å^−3
315 parameters	Δρmin = −0.25 e Å^−3

Special details

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. Refined as a 2-component twin.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.1575 (9)	−0.0027 (2)	0.3177 (3)	0.0773 (16)
O2	0.1851 (7)	0.1361 (2)	0.3392 (3)	0.0643 (12)
O3	0.2979 (7)	−0.1888 (2)	−0.3354 (3)	0.0585 (11)
O4	0.2922 (8)	−0.0713 (2)	−0.3369 (3)	0.0647 (12)
O5	−0.1383 (12)	−0.1826 (4)	0.4238 (4)	0.107 (2)
O6	−0.4404 (11)	−0.1627 (4)	0.4431 (4)	0.127 (3)
O7	−0.0236 (9)	−0.1598 (3)	0.2779 (4)	0.0863 (16)
O8	−0.2296 (11)	−0.1187 (3)	0.1620 (3)	0.106 (2)
N1	0.2246 (7)	−0.0915 (2)	0.0745 (3)	0.0469 (12)
C1	0.2009 (9)	0.0388 (3)	0.2500 (4)	0.0467 (13)
C2	0.2100 (8)	0.1084 (3)	0.2567 (3)	0.0421 (12)
C3	0.2370 (8)	0.1471 (3)	0.1787 (4)	0.0477 (13)
H3A	0.2423	0.1939	0.1835	0.057*
C4	0.2556 (8)	0.1173 (3)	0.0958 (4)	0.0418 (12)
H4A	0.2752	0.1440	0.0456	0.050*
C5	0.2453 (7)	0.0466 (3)	0.0860 (3)	0.0379 (11)
C6	0.2185 (8)	0.0080 (2)	0.1650 (3)	0.0396 (12)
C7	0.2075 (9)	−0.0618 (3)	0.1539 (4)	0.0480 (14)
H7	0.1875	−0.0885	0.2041	0.058*
C8	0.2492 (7)	−0.0552 (2)	−0.0039 (3)	0.0370 (11)
C9	0.2588 (7)	0.0128 (3)	0.0030 (3)	0.0376 (11)
H9A	0.2747	0.0380	−0.0490	0.045*
C10	0.2607 (7)	−0.0935 (3)	−0.0896 (3)	0.0367 (11)
C11	0.2687 (9)	−0.1640 (3)	−0.0887 (4)	0.0465 (13)
C12A	0.296 (2)	−0.2003 (6)	0.0012 (8)	0.050 (3)	0.70 (2)
H12A	0.4310	−0.1991	0.0271	0.060*	0.70 (2)
H12B	0.2571	−0.2472	−0.0076	0.060*	0.70 (2)
C13A	0.172 (2)	−0.1665 (4)	0.0659 (6)	0.048 (3)	0.70 (2)
H13A	0.1939	−0.1878	0.1258	0.058*	0.70 (2)
H13B	0.0359	−0.1714	0.0425	0.058*	0.70 (2)
C12B	0.196 (5)	−0.1985 (12)	−0.0032 (17)	0.040 (6)	0.30 (2)
H12C	0.0574	−0.1916	−0.0037	0.049*	0.30 (2)
H12D	0.2214	−0.2466	−0.0033	0.049*	0.30 (2)
C13B	0.307 (5)	−0.1656 (9)	0.0801 (13)	0.041 (7)	0.30 (2)
H13C	0.4454	−0.1661	0.0766	0.049*	0.30 (2)
H13D	0.2810	−0.1877	0.1363	0.049*	0.30 (2)
C14	0.2804 (10)	−0.2002 (3)	−0.1704 (4)	0.0550 (15)
H14A	0.2854	−0.2471	−0.1706	0.066*
C15	0.2840 (8)	−0.1643 (3)	−0.2484 (4)	0.0445 (13)
C16	0.2793 (8)	−0.0946 (3)	−0.2498 (3)	0.0423 (12)
C17	0.2688 (8)	−0.0574 (3)	−0.1722 (4)	0.0467 (13)
H17A	0.2670	−0.0105	−0.1736	0.056*
C18	0.2792 (11)	−0.1300 (3)	−0.3939 (4)	0.0642 (18)
H18A	0.3817	−0.1295	−0.4332	0.077*
H18B	0.1553	−0.1307	−0.4325	0.077*
C19	0.2491 (15)	0.0024 (4)	0.4066 (5)	0.096 (3)
H19A	0.3868	0.0056	0.4055	0.143*
H19B	0.2203	−0.0368	0.4409	0.143*
H19C	0.2038	0.0420	0.4350	0.143*
C20	0.2022 (11)	0.2078 (3)	0.3489 (4)	0.0583 (16)
H20A	0.1043	0.2293	0.3068	0.087*
H20B	0.3283	0.2218	0.3357	0.087*
H20C	0.1856	0.2204	0.4106	0.087*
C21	−0.3113 (15)	−0.1578 (4)	0.3984 (5)	0.082 (2)
C22	−0.3363 (17)	−0.1219 (5)	0.3064 (6)	0.127 (4)
H22A	−0.4611	−0.1350	0.2741	0.152*
H22B	−0.3419	−0.0738	0.3180	0.152*
C23	−0.1851 (15)	−0.1337 (3)	0.2430 (5)	0.078 (2)
H5A	−0.056 (10)	−0.178 (4)	0.385 (5)	0.10 (3)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.138 (5)	0.052 (3)	0.044 (2)	−0.017 (3)	0.021 (3)	0.003 (2)
O2	0.102 (4)	0.043 (2)	0.049 (2)	0.000 (2)	0.014 (2)	−0.0063 (18)
O3	0.083 (3)	0.050 (2)	0.046 (2)	0.001 (2)	0.019 (2)	−0.0065 (18)
O4	0.107 (4)	0.047 (2)	0.042 (2)	0.002 (2)	0.020 (2)	−0.0011 (18)
O5	0.125 (6)	0.134 (6)	0.066 (4)	0.019 (5)	0.032 (4)	0.017 (4)
O6	0.122 (6)	0.173 (7)	0.093 (4)	−0.002 (5)	0.045 (4)	0.008 (5)
O7	0.110 (5)	0.071 (3)	0.081 (4)	0.005 (3)	0.026 (3)	0.010 (3)
O8	0.187 (7)	0.072 (3)	0.062 (3)	0.007 (4)	0.021 (4)	0.025 (3)
N1	0.072 (3)	0.030 (2)	0.040 (2)	0.002 (2)	0.014 (2)	0.0051 (19)
C1	0.060 (4)	0.041 (3)	0.040 (3)	−0.003 (3)	0.011 (3)	0.006 (2)
C2	0.043 (3)	0.044 (3)	0.038 (3)	0.000 (2)	0.001 (2)	−0.004 (2)
C3	0.054 (3)	0.036 (3)	0.053 (3)	0.001 (2)	0.005 (3)	0.001 (2)
C4	0.048 (3)	0.035 (3)	0.042 (3)	−0.001 (2)	0.001 (2)	0.007 (2)
C5	0.037 (3)	0.038 (3)	0.039 (3)	0.001 (2)	0.001 (2)	0.005 (2)
C6	0.046 (3)	0.034 (3)	0.039 (3)	−0.002 (2)	0.005 (2)	0.003 (2)
C7	0.065 (4)	0.040 (3)	0.041 (3)	0.000 (3)	0.010 (3)	0.005 (2)
C8	0.035 (3)	0.037 (3)	0.038 (3)	0.000 (2)	0.002 (2)	0.007 (2)
C9	0.039 (3)	0.039 (3)	0.034 (2)	−0.004 (2)	0.002 (2)	0.005 (2)
C10	0.033 (3)	0.039 (3)	0.038 (3)	0.002 (2)	0.004 (2)	0.002 (2)
C11	0.053 (3)	0.038 (3)	0.050 (3)	−0.003 (3)	0.010 (3)	0.003 (2)
C12A	0.055 (7)	0.039 (5)	0.061 (6)	0.006 (6)	0.023 (6)	0.012 (4)
C13A	0.058 (9)	0.030 (4)	0.058 (5)	0.000 (4)	0.016 (5)	0.008 (4)
C12B	0.051 (15)	0.027 (9)	0.048 (12)	0.001 (12)	0.026 (13)	0.003 (8)
C13B	0.048 (17)	0.033 (9)	0.043 (10)	0.004 (9)	0.014 (10)	0.009 (8)
C14	0.078 (4)	0.035 (3)	0.053 (3)	−0.004 (3)	0.014 (3)	−0.004 (3)
C15	0.045 (3)	0.042 (3)	0.047 (3)	0.000 (2)	0.006 (2)	−0.008 (2)
C16	0.042 (3)	0.047 (3)	0.038 (3)	0.000 (2)	0.005 (2)	0.003 (2)
C17	0.060 (4)	0.036 (3)	0.045 (3)	0.001 (3)	0.011 (3)	0.003 (2)
C18	0.091 (5)	0.057 (4)	0.048 (3)	−0.002 (4)	0.021 (3)	−0.008 (3)
C19	0.164 (9)	0.071 (5)	0.049 (4)	0.005 (6)	0.002 (5)	0.016 (4)
C20	0.082 (5)	0.041 (3)	0.051 (3)	0.003 (3)	0.008 (3)	−0.007 (3)
C21	0.104 (7)	0.088 (6)	0.057 (4)	0.008 (5)	0.023 (5)	−0.002 (4)
C22	0.167 (11)	0.132 (9)	0.092 (6)	0.073 (8)	0.057 (7)	0.041 (6)
C23	0.135 (8)	0.037 (3)	0.065 (4)	0.001 (4)	0.026 (5)	0.009 (3)

Geometric parameters (Å, º)

O1—C1	1.352 (6)	C10—C17	1.412 (7)
O1—C19	1.382 (8)	C11—C14	1.408 (8)
O2—C2	1.359 (6)	C11—C12A	1.495 (13)
O2—C20	1.432 (7)	C11—C12B	1.57 (2)
O3—C15	1.380 (6)	C12A—C13A	1.51 (2)
O3—C18	1.444 (7)	C12A—H12A	0.9700
O4—C16	1.372 (6)	C12A—H12B	0.9700
O4—C18	1.429 (7)	C13A—H13A	0.9700
O5—C21	1.309 (11)	C13A—H13B	0.9700
O5—H5A	0.86 (2)	C12B—C13B	1.51 (4)
O6—C21	1.178 (10)	C12B—H12C	0.9700
O7—C23	1.283 (10)	C12B—H12D	0.9700
O8—C23	1.227 (8)	C13B—H13C	0.9700
N1—C7	1.323 (7)	C13B—H13D	0.9700
N1—C8	1.384 (6)	C14—C15	1.352 (8)
N1—C13A	1.533 (9)	C14—H14A	0.9300
N1—C13B	1.574 (19)	C15—C16	1.381 (7)
C1—C2	1.384 (7)	C16—C17	1.366 (7)
C1—C6	1.407 (7)	C17—H17A	0.9300
C2—C3	1.409 (7)	C18—H18A	0.9700
C3—C4	1.372 (7)	C18—H18B	0.9700
C3—H3A	0.9300	C19—H19A	0.9600
C4—C5	1.409 (7)	C19—H19B	0.9600
C4—H4A	0.9300	C19—H19C	0.9600
C5—C9	1.404 (7)	C20—H20A	0.9600
C5—C6	1.419 (7)	C20—H20B	0.9600
C6—C7	1.395 (7)	C20—H20C	0.9600
C7—H7	0.9300	C21—C22	1.516 (11)
C8—C9	1.352 (7)	C22—C23	1.504 (12)
C8—C10	1.479 (7)	C22—H22A	0.9700
C9—H9A	0.9300	C22—H22B	0.9700
C10—C11	1.399 (7)
C1—O1—C19	122.0 (6)	H13A—C13A—H13B	108.2
C2—O2—C20	118.1 (4)	C13B—C12B—C11	106 (2)
C15—O3—C18	104.6 (4)	C13B—C12B—H12C	110.5
C16—O4—C18	105.3 (4)	C11—C12B—H12C	110.5
C21—O5—H5A	116 (6)	C13B—C12B—H12D	110.5
C7—N1—C8	122.3 (4)	C11—C12B—H12D	110.5
C7—N1—C13A	117.2 (5)	H12C—C12B—H12D	108.7
C8—N1—C13A	119.2 (5)	C12B—C13B—N1	102 (2)
C7—N1—C13B	116.0 (8)	C12B—C13B—H13C	111.3
C8—N1—C13B	116.6 (8)	N1—C13B—H13C	111.3
O1—C1—C2	124.5 (5)	C12B—C13B—H13D	111.3
O1—C1—C6	116.0 (5)	N1—C13B—H13D	111.3
C2—C1—C6	119.1 (5)	H13C—C13B—H13D	109.2
O2—C2—C1	117.1 (5)	C15—C14—C11	117.5 (5)
O2—C2—C3	123.2 (5)	C15—C14—H14A	121.3
C1—C2—C3	119.7 (5)	C11—C14—H14A	121.3
C4—C3—C2	121.4 (5)	C14—C15—O3	127.5 (5)
C4—C3—H3A	119.3	C14—C15—C16	122.4 (5)
C2—C3—H3A	119.3	O3—C15—C16	110.1 (5)
C3—C4—C5	120.6 (5)	C17—C16—O4	127.6 (5)
C3—C4—H4A	119.7	C17—C16—C15	122.1 (5)
C5—C4—H4A	119.7	O4—C16—C15	110.3 (5)
C9—C5—C4	123.7 (5)	C16—C17—C10	117.0 (5)
C9—C5—C6	118.7 (5)	C16—C17—H17A	121.5
C4—C5—C6	117.6 (5)	C10—C17—H17A	121.5
C7—C6—C1	121.6 (5)	O4—C18—O3	108.4 (4)
C7—C6—C5	116.8 (5)	O4—C18—H18A	110.0
C1—C6—C5	121.6 (5)	O3—C18—H18A	110.0
N1—C7—C6	122.3 (5)	O4—C18—H18B	110.0
N1—C7—H7	118.9	O3—C18—H18B	110.0
C6—C7—H7	118.9	H18A—C18—H18B	108.4
C9—C8—N1	117.7 (5)	O1—C19—H19A	109.5
C9—C8—C10	124.6 (4)	O1—C19—H19B	109.5
N1—C8—C10	117.7 (4)	H19A—C19—H19B	109.5
C8—C9—C5	122.2 (5)	O1—C19—H19C	109.5
C8—C9—H9A	118.9	H19A—C19—H19C	109.5
C5—C9—H9A	118.9	H19B—C19—H19C	109.5
C11—C10—C17	120.5 (5)	O2—C20—H20A	109.5
C11—C10—C8	120.7 (5)	O2—C20—H20B	109.5
C17—C10—C8	118.8 (5)	H20A—C20—H20B	109.5
C10—C11—C14	120.5 (5)	O2—C20—H20C	109.5
C10—C11—C12A	119.4 (7)	H20A—C20—H20C	109.5
C14—C11—C12A	119.4 (7)	H20B—C20—H20C	109.5
C10—C11—C12B	115.3 (10)	O6—C21—O5	123.0 (8)
C14—C11—C12B	121.1 (10)	O6—C21—C22	121.5 (9)
C11—C12A—C13A	108.7 (10)	O5—C21—C22	115.5 (8)
C11—C12A—H12A	109.9	C23—C22—C21	117.8 (8)
C13A—C12A—H12A	109.9	C23—C22—H22A	107.9
C11—C12A—H12B	109.9	C21—C22—H22A	107.9
C13A—C12A—H12B	109.9	C23—C22—H22B	107.9
H12A—C12A—H12B	108.3	C21—C22—H22B	107.9
C12A—C13A—N1	109.6 (10)	H22A—C22—H22B	107.2
C12A—C13A—H13A	109.8	O8—C23—O7	126.0 (8)
N1—C13A—H13A	109.8	O8—C23—C22	116.7 (9)
C12A—C13A—H13B	109.8	O7—C23—C22	117.3 (7)
N1—C13A—H13B	109.8
C19—O1—C1—C2	−49.7 (10)	C17—C10—C11—C14	−1.5 (9)
C19—O1—C1—C6	136.8 (7)	C8—C10—C11—C14	−179.8 (5)
C20—O2—C2—C1	177.4 (6)	C17—C10—C11—C12A	169.2 (8)
C20—O2—C2—C3	−5.0 (9)	C8—C10—C11—C12A	−9.1 (10)
O1—C1—C2—O2	4.2 (9)	C17—C10—C11—C12B	−162.0 (15)
C6—C1—C2—O2	177.6 (5)	C8—C10—C11—C12B	19.7 (16)
O1—C1—C2—C3	−173.5 (6)	C10—C11—C12A—C13A	41.3 (15)
C6—C1—C2—C3	−0.1 (9)	C14—C11—C12A—C13A	−147.9 (10)
O2—C2—C3—C4	−178.0 (5)	C11—C12A—C13A—N1	−55.9 (16)
C1—C2—C3—C4	−0.3 (9)	C7—N1—C13A—C12A	−148.7 (9)
C2—C3—C4—C5	0.9 (9)	C8—N1—C13A—C12A	44.0 (14)
C3—C4—C5—C9	178.5 (5)	C10—C11—C12B—C13B	−53 (3)
C3—C4—C5—C6	−1.0 (8)	C14—C11—C12B—C13B	146.9 (16)
O1—C1—C6—C7	−5.1 (9)	C11—C12B—C13B—N1	68 (3)
C2—C1—C6—C7	−179.0 (6)	C7—N1—C13B—C12B	144.9 (15)
O1—C1—C6—C5	173.9 (5)	C8—N1—C13B—C12B	−60 (2)
C2—C1—C6—C5	0.0 (9)	C10—C11—C14—C15	0.2 (9)
C9—C5—C6—C7	0.1 (8)	C12A—C11—C14—C15	−170.5 (9)
C4—C5—C6—C7	179.6 (5)	C12B—C11—C14—C15	159.6 (16)
C9—C5—C6—C1	−179.0 (5)	C11—C14—C15—O3	178.9 (6)
C4—C5—C6—C1	0.6 (8)	C11—C14—C15—C16	0.9 (9)
C8—N1—C7—C6	−1.8 (9)	C18—O3—C15—C14	175.4 (6)
C13A—N1—C7—C6	−168.7 (8)	C18—O3—C15—C16	−6.4 (7)
C13B—N1—C7—C6	152.1 (13)	C18—O4—C16—C17	−174.3 (6)
C1—C6—C7—N1	−179.7 (6)	C18—O4—C16—C15	7.6 (7)
C5—C6—C7—N1	1.2 (9)	C14—C15—C16—C17	−0.6 (10)
C7—N1—C8—C9	1.1 (8)	O3—C15—C16—C17	−179.0 (5)
C13A—N1—C8—C9	167.7 (8)	C14—C15—C16—O4	177.6 (6)
C13B—N1—C8—C9	−152.7 (13)	O3—C15—C16—O4	−0.7 (7)
C7—N1—C8—C10	−178.2 (5)	O4—C16—C17—C10	−178.6 (5)
C13A—N1—C8—C10	−11.6 (9)	C15—C16—C17—C10	−0.7 (9)
C13B—N1—C8—C10	28.1 (14)	C11—C10—C17—C16	1.7 (8)
N1—C8—C9—C5	0.2 (8)	C8—C10—C17—C16	180.0 (5)
C10—C8—C9—C5	179.4 (5)	C16—O4—C18—O3	−11.5 (7)
C4—C5—C9—C8	179.7 (5)	C15—O3—C18—O4	11.0 (7)
C6—C5—C9—C8	−0.8 (8)	O6—C21—C22—C23	−164.0 (10)
C9—C8—C10—C11	173.7 (5)	O5—C21—C22—C23	15.9 (14)
N1—C8—C10—C11	−7.1 (7)	C21—C22—C23—O8	162.5 (8)
C9—C8—C10—C17	−4.6 (8)	C21—C22—C23—O7	−15.9 (14)
N1—C8—C10—C17	174.5 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5A···O7	0.86 (2)	1.65 (5)	2.417 (8)	146 (9)

(1BER-2MA-2W)

Crystal data

C20H18NO4·C3H4O4·C3H3O4·2(H2O)	Z = 2
Mr = 579.50	F(000) = 608
Triclinic, P1	Dx = 1.503 Mg m^−3
a = 7.5871 (5) Å	Mo Kα radiation, λ = 0.71073 Å
b = 12.9376 (8) Å	Cell parameters from 5902 reflections
c = 13.9641 (9) Å	θ = 2.6–29.4°
α = 71.320 (6)°	µ = 0.12 mm^−1
β = 83.354 (5)°	T = 100 K
γ = 81.366 (5)°	Needle, colourless
V = 1280.43 (15) Å^3	0.15 × 0.02 × 0.02 mm

Data collection

CCD diffractometer	4363 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.034
ωκ scans	θmax = 29.4°, θmin = 2.6°
Absorption correction: multi-scan Higashi, T. (1995)	h = −9→10
Tmin = 0.997, Tmax = 0.998	k = −10→16
9732 measured reflections	l = −15→18
5902 independent reflections

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.055	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.140	w = 1/[σ^2(Fo^2) + (0.0623P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max < 0.001
5902 reflections	Δρmax = 0.33 e Å^−3
398 parameters	Δρmin = −0.36 e Å^−3

Special details

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.

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

	x	y	z	Uiso*/Ueq
O1	0.50350 (17)	0.76587 (10)	0.06948 (9)	0.0202 (3)
O2	0.44369 (18)	0.62597 (11)	0.25729 (9)	0.0250 (3)
O3	1.23934 (19)	0.40309 (11)	−0.45064 (9)	0.0275 (3)
O4	1.13574 (19)	0.27022 (11)	−0.30910 (9)	0.0260 (3)
O5	0.63518 (18)	0.15989 (11)	0.24241 (10)	0.0255 (3)
O6	0.8165 (2)	0.00557 (13)	0.30282 (10)	0.0457 (5)
O7	0.96248 (18)	0.21600 (11)	0.09826 (10)	0.0263 (3)
O8	0.92066 (18)	0.16928 (12)	−0.03502 (9)	0.0236 (3)
O9	0.79095 (18)	0.02436 (11)	−0.08505 (9)	0.0250 (3)
O10	0.65301 (18)	−0.03680 (11)	−0.18361 (9)	0.0236 (3)
O11	0.7589 (2)	0.21146 (12)	−0.43711 (10)	0.0364 (4)
O12	0.6380 (2)	0.05732 (12)	−0.36169 (10)	0.0320 (4)
O13	0.4446 (2)	0.79517 (13)	−0.41111 (11)	0.0325 (4)
O14	1.2789 (2)	0.08147 (13)	−0.51275 (12)	0.0352 (4)
N1	0.78379 (19)	0.65261 (12)	−0.15731 (10)	0.0155 (3)
C1	0.5634 (2)	0.65633 (15)	0.09060 (13)	0.0168 (4)
C2	0.5288 (2)	0.58212 (15)	0.18561 (12)	0.0176 (4)
C3	0.5830 (2)	0.46907 (15)	0.20230 (13)	0.0185 (4)
H3A	0.5561	0.4196	0.2654	0.022*
C4	0.6745 (2)	0.43025 (15)	0.12782 (12)	0.0176 (4)
H4A	0.7088	0.3552	0.1408	0.021*
C5	0.7168 (2)	0.50406 (15)	0.03124 (12)	0.0159 (4)
C6	0.6568 (2)	0.61744 (14)	0.01288 (12)	0.0155 (4)
C7	0.6958 (2)	0.68928 (15)	−0.08411 (12)	0.0163 (4)
H7A	0.6594	0.7641	−0.0976	0.020*
C8	0.8499 (2)	0.54273 (14)	−0.14170 (12)	0.0149 (4)
C9	0.8154 (2)	0.46991 (15)	−0.04728 (12)	0.0175 (4)
H9A	0.8585	0.3960	−0.0350	0.021*
C10	0.9509 (2)	0.51118 (14)	−0.22626 (12)	0.0161 (4)
C11	1.0165 (2)	0.59118 (15)	−0.31140 (12)	0.0178 (4)
C12	0.9848 (2)	0.70927 (15)	−0.31228 (13)	0.0196 (4)
H12A	0.9914	0.7574	−0.3817	0.023*
H12B	1.0768	0.7238	−0.2771	0.023*
C13	0.8036 (3)	0.73247 (15)	−0.26124 (12)	0.0206 (4)
H13A	0.7889	0.8066	−0.2568	0.025*
H13B	0.7112	0.7273	−0.3015	0.025*
C14	1.1155 (2)	0.56136 (16)	−0.39189 (13)	0.0211 (4)
H14A	1.1586	0.6141	−0.4489	0.025*
C15	1.1463 (2)	0.45216 (16)	−0.38343 (13)	0.0195 (4)
C16	1.0837 (2)	0.37258 (15)	−0.29851 (13)	0.0189 (4)
C17	0.9853 (2)	0.39889 (15)	−0.21986 (13)	0.0190 (4)
H17A	0.9423	0.3449	−0.1639	0.023*
C18	1.2247 (3)	0.28811 (17)	−0.40788 (14)	0.0303 (5)
H18A	1.1570	0.2643	−0.4502	0.036*
H18B	1.3425	0.2464	−0.4035	0.036*
C19	0.6228 (3)	0.82618 (16)	0.09737 (15)	0.0267 (5)
H19A	0.5743	0.9022	0.0809	0.040*
H19B	0.6366	0.7969	0.1689	0.040*
H19C	0.7371	0.8197	0.0609	0.040*
C20	0.3908 (3)	0.55209 (16)	0.35420 (13)	0.0240 (4)
H20A	0.3325	0.5937	0.3973	0.036*
H20B	0.3099	0.5061	0.3452	0.036*
H20C	0.4946	0.5072	0.3848	0.036*
C21	0.7455 (3)	0.07520 (16)	0.23294 (13)	0.0230 (4)
C22	0.7782 (3)	0.07221 (15)	0.12520 (13)	0.0199 (4)
H22A	0.6648	0.0853	0.0950	0.024*
H22B	0.8351	0.0000	0.1249	0.024*
C23	0.8960 (2)	0.15816 (15)	0.06288 (13)	0.0188 (4)
C24	0.7422 (2)	0.03320 (15)	−0.16935 (13)	0.0181 (4)
C25	0.7858 (3)	0.13070 (15)	−0.25971 (13)	0.0212 (4)
H25A	0.7322	0.1972	−0.2446	0.025*
H25B	0.9143	0.1316	−0.2667	0.025*
C26	0.7264 (3)	0.13538 (16)	−0.36082 (13)	0.0242 (4)
H8A	0.867 (4)	0.119 (2)	−0.0530 (19)	0.054 (8)*
H13C	0.377 (4)	0.798 (2)	−0.457 (2)	0.055 (8)*
H14B	1.259 (4)	0.046 (2)	−0.453 (2)	0.061 (9)*
H13D	0.533 (4)	0.836 (2)	−0.4475 (19)	0.048 (8)*
H12C	0.635 (4)	−0.001 (2)	−0.273 (2)	0.067 (8)*
H14C	1.292 (5)	0.026 (3)	−0.546 (3)	0.112 (13)*
H5A	0.624 (4)	0.167 (3)	0.312 (2)	0.086 (10)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0205 (7)	0.0140 (7)	0.0245 (6)	0.0013 (5)	0.0000 (5)	−0.0058 (5)
O2	0.0322 (8)	0.0190 (7)	0.0210 (6)	−0.0016 (6)	0.0098 (6)	−0.0071 (5)
O3	0.0365 (9)	0.0227 (8)	0.0228 (7)	−0.0024 (6)	0.0089 (6)	−0.0107 (5)
O4	0.0340 (8)	0.0184 (7)	0.0260 (7)	−0.0021 (6)	0.0084 (6)	−0.0116 (5)
O5	0.0282 (8)	0.0254 (8)	0.0231 (7)	0.0023 (6)	0.0008 (6)	−0.0111 (6)
O6	0.0619 (11)	0.0414 (10)	0.0211 (7)	0.0221 (8)	−0.0021 (7)	−0.0048 (7)
O7	0.0270 (8)	0.0249 (8)	0.0319 (7)	−0.0072 (6)	0.0003 (6)	−0.0148 (6)
O8	0.0258 (8)	0.0250 (8)	0.0189 (7)	−0.0058 (6)	0.0006 (6)	−0.0048 (5)
O9	0.0335 (8)	0.0225 (8)	0.0187 (7)	−0.0016 (6)	−0.0044 (6)	−0.0058 (5)
O10	0.0312 (8)	0.0180 (7)	0.0224 (7)	−0.0078 (6)	−0.0008 (6)	−0.0056 (5)
O11	0.0579 (11)	0.0289 (9)	0.0200 (7)	−0.0153 (8)	−0.0018 (7)	0.0000 (6)
O12	0.0471 (9)	0.0287 (8)	0.0235 (7)	−0.0146 (7)	−0.0066 (6)	−0.0069 (6)
O13	0.0384 (9)	0.0379 (10)	0.0208 (7)	−0.0045 (8)	−0.0037 (7)	−0.0083 (6)
O14	0.0495 (10)	0.0292 (9)	0.0271 (8)	−0.0041 (8)	−0.0003 (7)	−0.0098 (7)
N1	0.0173 (8)	0.0131 (8)	0.0150 (7)	−0.0012 (6)	−0.0003 (6)	−0.0035 (6)
C1	0.0149 (9)	0.0141 (9)	0.0213 (9)	−0.0001 (7)	−0.0001 (7)	−0.0064 (7)
C2	0.0165 (9)	0.0191 (10)	0.0176 (8)	−0.0022 (7)	0.0026 (7)	−0.0075 (7)
C3	0.0199 (10)	0.0174 (10)	0.0156 (8)	−0.0034 (8)	0.0010 (7)	−0.0019 (7)
C4	0.0202 (10)	0.0126 (9)	0.0185 (8)	0.0001 (7)	−0.0017 (7)	−0.0035 (7)
C5	0.0157 (9)	0.0165 (9)	0.0147 (8)	−0.0019 (7)	−0.0005 (7)	−0.0041 (7)
C6	0.0134 (9)	0.0158 (9)	0.0177 (8)	−0.0023 (7)	−0.0021 (7)	−0.0053 (7)
C7	0.0171 (9)	0.0135 (9)	0.0184 (8)	0.0002 (7)	−0.0015 (7)	−0.0057 (7)
C8	0.0128 (9)	0.0149 (9)	0.0178 (8)	−0.0024 (7)	−0.0016 (7)	−0.0055 (7)
C9	0.0175 (9)	0.0148 (9)	0.0190 (8)	−0.0009 (7)	−0.0002 (7)	−0.0047 (7)
C10	0.0157 (9)	0.0170 (9)	0.0150 (8)	−0.0021 (7)	−0.0016 (7)	−0.0039 (7)
C11	0.0178 (9)	0.0178 (10)	0.0171 (8)	−0.0011 (7)	−0.0012 (7)	−0.0048 (7)
C12	0.0243 (10)	0.0158 (10)	0.0164 (8)	−0.0030 (8)	0.0013 (7)	−0.0026 (7)
C13	0.0289 (11)	0.0134 (9)	0.0151 (8)	−0.0002 (8)	−0.0009 (8)	0.0005 (7)
C14	0.0238 (10)	0.0209 (10)	0.0151 (8)	−0.0017 (8)	0.0011 (7)	−0.0021 (7)
C15	0.0190 (10)	0.0240 (10)	0.0167 (8)	−0.0012 (8)	0.0013 (7)	−0.0095 (7)
C16	0.0202 (10)	0.0168 (10)	0.0204 (9)	−0.0010 (8)	−0.0013 (7)	−0.0075 (7)
C17	0.0192 (10)	0.0175 (10)	0.0188 (9)	−0.0034 (8)	0.0007 (7)	−0.0037 (7)
C18	0.0416 (13)	0.0222 (11)	0.0250 (10)	0.0010 (9)	0.0082 (9)	−0.0101 (8)
C19	0.0265 (11)	0.0168 (10)	0.0387 (11)	−0.0055 (8)	−0.0005 (9)	−0.0105 (8)
C20	0.0276 (11)	0.0262 (11)	0.0163 (9)	−0.0035 (9)	0.0052 (8)	−0.0060 (7)
C21	0.0242 (10)	0.0199 (10)	0.0227 (10)	−0.0027 (8)	0.0031 (8)	−0.0054 (8)
C22	0.0204 (10)	0.0175 (10)	0.0219 (9)	−0.0024 (8)	0.0032 (7)	−0.0077 (7)
C23	0.0161 (9)	0.0169 (10)	0.0215 (9)	0.0034 (7)	−0.0012 (7)	−0.0057 (7)
C24	0.0156 (9)	0.0155 (9)	0.0227 (9)	0.0018 (7)	0.0014 (7)	−0.0079 (7)
C25	0.0241 (10)	0.0178 (10)	0.0218 (9)	−0.0041 (8)	−0.0002 (8)	−0.0058 (7)
C26	0.0275 (11)	0.0233 (11)	0.0207 (9)	−0.0005 (9)	0.0010 (8)	−0.0075 (8)

Geometric parameters (Å, º)

O1—C1	1.368 (2)	C6—C7	1.403 (2)
O1—C19	1.438 (2)	C7—H7A	0.9300
O2—C2	1.358 (2)	C8—C9	1.376 (2)
O2—C20	1.438 (2)	C8—C10	1.467 (2)
O3—C15	1.370 (2)	C9—H9A	0.9300
O3—C18	1.431 (2)	C10—C11	1.401 (2)
O4—C16	1.373 (2)	C10—C17	1.412 (2)
O4—C18	1.428 (2)	C11—C14	1.404 (2)
O5—C21	1.308 (2)	C11—C12	1.507 (2)
O5—H5A	1.00 (3)	C12—C13	1.508 (3)
O6—C21	1.211 (2)	C12—H12A	0.9700
O7—C23	1.211 (2)	C12—H12B	0.9700
O8—C23	1.322 (2)	C13—H13A	0.9700
O8—H8A	0.92 (3)	C13—H13B	0.9700
O9—C24	1.240 (2)	C14—C15	1.366 (3)
O10—C24	1.284 (2)	C14—H14A	0.9300
O10—H12C	1.20 (3)	C15—C16	1.388 (3)
O11—C26	1.227 (2)	C16—C17	1.361 (2)
O12—C26	1.297 (2)	C17—H17A	0.9300
O12—H12C	1.23 (3)	C18—H18A	0.9700
O13—H13C	0.86 (3)	C18—H18B	0.9700
O13—H13D	0.92 (3)	C19—H19A	0.9600
O14—H14B	0.82 (3)	C19—H19B	0.9600
O14—H14C	0.95 (4)	C19—H19C	0.9600
N1—C7	1.332 (2)	C20—H20A	0.9600
N1—C8	1.390 (2)	C20—H20B	0.9600
N1—C13	1.494 (2)	C20—H20C	0.9600
C1—C2	1.389 (2)	C21—C22	1.508 (2)
C1—C6	1.413 (2)	C22—C23	1.513 (3)
C2—C3	1.409 (2)	C22—H22A	0.9700
C3—C4	1.371 (2)	C22—H22B	0.9700
C3—H3A	0.9300	C24—C25	1.517 (3)
C4—C5	1.415 (2)	C25—C26	1.511 (3)
C4—H4A	0.9300	C25—H25A	0.9700
C5—C9	1.406 (2)	C25—H25B	0.9700
C5—C6	1.418 (2)
C1—O1—C19	113.05 (14)	C12—C13—H13B	109.5
C2—O2—C20	118.16 (14)	H13A—C13—H13B	108.1
C15—O3—C18	106.14 (14)	C15—C14—C11	117.61 (16)
C16—O4—C18	106.08 (14)	C15—C14—H14A	121.2
C21—O5—H5A	113.7 (18)	C11—C14—H14A	121.2
C23—O8—H8A	113.0 (16)	C14—C15—O3	128.47 (16)
C24—O10—H12C	102.4 (13)	C14—C15—C16	121.79 (16)
C26—O12—H12C	102.7 (13)	O3—C15—C16	109.73 (16)
H13C—O13—H13D	103 (2)	C17—C16—O4	128.28 (17)
H14B—O14—H14C	103 (3)	C17—C16—C15	122.03 (17)
C7—N1—C8	122.62 (14)	O4—C16—C15	109.68 (15)
C7—N1—C13	118.16 (14)	C16—C17—C10	117.61 (16)
C8—N1—C13	119.15 (14)	C16—C17—H17A	121.2
O1—C1—C2	121.42 (16)	C10—C17—H17A	121.2
O1—C1—C6	119.16 (15)	O4—C18—O3	108.01 (15)
C2—C1—C6	119.39 (16)	O4—C18—H18A	110.1
O2—C2—C1	116.00 (16)	O3—C18—H18A	110.1
O2—C2—C3	124.41 (15)	O4—C18—H18B	110.1
C1—C2—C3	119.59 (16)	O3—C18—H18B	110.1
C4—C3—C2	121.64 (16)	H18A—C18—H18B	108.4
C4—C3—H3A	119.2	O1—C19—H19A	109.5
C2—C3—H3A	119.2	O1—C19—H19B	109.5
C3—C4—C5	120.13 (16)	H19A—C19—H19B	109.5
C3—C4—H4A	119.9	O1—C19—H19C	109.5
C5—C4—H4A	119.9	H19A—C19—H19C	109.5
C9—C5—C4	122.91 (16)	H19B—C19—H19C	109.5
C9—C5—C6	118.65 (15)	O2—C20—H20A	109.5
C4—C5—C6	118.44 (16)	O2—C20—H20B	109.5
C7—C6—C1	121.47 (16)	H20A—C20—H20B	109.5
C7—C6—C5	117.78 (15)	O2—C20—H20C	109.5
C1—C6—C5	120.74 (15)	H20A—C20—H20C	109.5
N1—C7—C6	121.45 (16)	H20B—C20—H20C	109.5
N1—C7—H7A	119.3	O6—C21—O5	124.14 (17)
C6—C7—H7A	119.3	O6—C21—C22	122.47 (18)
C9—C8—N1	117.54 (15)	O5—C21—C22	113.40 (15)
C9—C8—C10	123.98 (16)	C21—C22—C23	111.02 (16)
N1—C8—C10	118.48 (14)	C21—C22—H22A	109.4
C8—C9—C5	121.87 (16)	C23—C22—H22A	109.4
C8—C9—H9A	119.1	C21—C22—H22B	109.4
C5—C9—H9A	119.1	C23—C22—H22B	109.4
C11—C10—C17	120.21 (16)	H22A—C22—H22B	108.0
C11—C10—C8	120.46 (16)	O7—C23—O8	120.62 (18)
C17—C10—C8	119.31 (15)	O7—C23—C22	123.26 (16)
C10—C11—C14	120.73 (17)	O8—C23—C22	116.10 (16)
C10—C11—C12	118.25 (15)	O9—C24—O10	122.47 (17)
C14—C11—C12	120.96 (16)	O9—C24—C25	119.64 (17)
C11—C12—C13	110.19 (15)	O10—C24—C25	117.89 (15)
C11—C12—H12A	109.6	C26—C25—C24	117.07 (17)
C13—C12—H12A	109.6	C26—C25—H25A	108.0
C11—C12—H12B	109.6	C24—C25—H25A	108.0
C13—C12—H12B	109.6	C26—C25—H25B	108.0
H12A—C12—H12B	108.1	C24—C25—H25B	108.0
N1—C13—C12	110.73 (14)	H25A—C25—H25B	107.3
N1—C13—H13A	109.5	O11—C26—O12	122.73 (18)
C12—C13—H13A	109.5	O11—C26—C25	120.36 (19)
N1—C13—H13B	109.5	O12—C26—C25	116.90 (16)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5A···O13^i	1.00 (3)	1.61 (3)	2.5876 (19)	163 (3)
O8—H8A···O9	0.92 (3)	1.63 (3)	2.554 (2)	175 (3)
O10—H12C···O12	1.20 (3)	1.23 (3)	2.4008 (17)	163 (3)
O13—H13C···O11^ii	0.86 (3)	1.94 (3)	2.792 (2)	173 (3)
O13—H13D···O14^iii	0.92 (3)	1.84 (3)	2.735 (2)	165 (2)
O14—H14B···O6^iv	0.82 (3)	2.03 (3)	2.833 (2)	166 (3)
O14—H14C···O12^v	0.95 (4)	1.92 (4)	2.849 (2)	164 (3)

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

(1BER-1DTA-1W)

Crystal data

C20H18NO4·C4H5O6·H2O	F(000) = 528
Mr = 503.45	Dx = 1.555 Mg m^−3
Monoclinic, P21	Cu Kα radiation, λ = 1.54184 Å
a = 12.10682 (12) Å	Cell parameters from 4305 reflections
b = 7.09040 (6) Å	θ = 3.5–76.0°
c = 12.69987 (11) Å	µ = 1.06 mm^−1
β = 99.3973 (9)°	T = 100 K
V = 1075.56 (2) Å^3	Needle, colourless
Z = 2	0.09 × 0.02 × 0.01 mm

Data collection

CCD diffractometer	4262 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.019
ωκ scans	θmax = 76.0°, θmin = 3.5°
Absorption correction: multi-scan Higashi, T. (1995)	h = −15→15
Tmin = 0.975, Tmax = 0.989	k = −8→8
11101 measured reflections	l = −15→12
4305 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.026	w = 1/[σ^2(Fo^2) + (0.0363P)^2 + 0.2827P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.067	(Δ/σ)max < 0.001
S = 1.05	Δρmax = 0.20 e Å^−3
4305 reflections	Δρmin = −0.18 e Å^−3
345 parameters	Absolute structure: Flack x determined using 1880 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
2 restraints	Absolute structure parameter: 0.11 (4)

Special details

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.

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

	x	y	z	Uiso*/Ueq
O1	−0.60275 (11)	−0.7274 (2)	−0.40530 (10)	0.0194 (3)
O2	−0.81884 (11)	−0.6088 (2)	−0.44105 (10)	0.0213 (3)
O3	−0.18576 (12)	−0.5884 (2)	0.37963 (11)	0.0246 (3)
O4	−0.36742 (12)	−0.6926 (2)	0.38015 (11)	0.0222 (3)
O10	−0.31929 (12)	−0.3962 (2)	−0.28480 (12)	0.0230 (3)
O9	−0.14154 (12)	−0.40203 (19)	−0.31657 (11)	0.0184 (3)
O8	−0.32254 (12)	−0.0248 (2)	−0.26856 (12)	0.0200 (3)
O7	−0.12596 (12)	−0.0984 (2)	−0.11403 (10)	0.0188 (3)
O5	−0.05199 (11)	0.2522 (2)	−0.14241 (10)	0.0177 (3)
O6	−0.13557 (11)	0.25129 (19)	−0.31336 (10)	0.0180 (3)
O11	−0.01753 (11)	−0.8820 (2)	0.07530 (11)	0.0177 (3)
N1	−0.41615 (12)	−0.6834 (2)	−0.10487 (12)	0.0137 (3)
C1	−0.65438 (16)	−0.6673 (3)	−0.32312 (15)	0.0162 (4)
C2	−0.76588 (16)	−0.6150 (3)	−0.33837 (15)	0.0165 (4)
C3	−0.81822 (15)	−0.5731 (3)	−0.24903 (15)	0.0174 (4)
H3A	−0.8949	−0.5373	−0.2602	0.021*
C4	−0.76027 (15)	−0.5832 (3)	−0.14633 (14)	0.0158 (3)
H4A	−0.7979	−0.5597	−0.0876	0.019*
C5	−0.64558 (15)	−0.6282 (3)	−0.12825 (15)	0.0145 (4)
C6	−0.59273 (15)	−0.6679 (3)	−0.21847 (15)	0.0145 (4)
C7	−0.47678 (15)	−0.6958 (3)	−0.20183 (14)	0.0147 (3)
H7B	−0.4407	−0.7241	−0.2610	0.018*
C8	−0.46438 (15)	−0.6533 (2)	−0.01366 (14)	0.0139 (4)
C9	−0.57788 (15)	−0.6282 (3)	−0.02650 (14)	0.0143 (3)
H9A	−0.6122	−0.6103	0.0349	0.017*
C10	−0.38771 (15)	−0.6412 (2)	0.08870 (14)	0.0140 (4)
C11	−0.27764 (15)	−0.5811 (3)	0.08913 (14)	0.0152 (3)
C12	−0.23974 (16)	−0.5481 (3)	−0.01651 (15)	0.0174 (4)
H12A	−0.1571	−0.5565	−0.0078	0.021*
H12B	−0.2626	−0.4205	−0.0434	0.021*
C13	−0.29233 (14)	−0.6956 (3)	−0.09503 (14)	0.0159 (4)
H13A	−0.2696	−0.6740	−0.1655	0.019*
H13B	−0.2666	−0.8227	−0.0698	0.019*
C14	−0.20343 (16)	−0.5552 (3)	0.18468 (16)	0.0179 (4)
H14A	−0.1289	−0.5128	0.1853	0.021*
C15	−0.24320 (15)	−0.5937 (3)	0.27728 (15)	0.0177 (4)
C16	−0.35208 (16)	−0.6561 (3)	0.27767 (15)	0.0167 (4)
C17	−0.42656 (15)	−0.6822 (3)	0.18541 (15)	0.0155 (4)
H17A	−0.5006	−0.7257	0.1863	0.019*
C18	−0.26796 (17)	−0.6241 (3)	0.44767 (15)	0.0225 (4)
H18A	−0.2847	−0.5067	0.4842	0.027*
H18B	−0.2397	−0.7194	0.5024	0.027*
C19	−0.56170 (17)	−0.5805 (3)	−0.46725 (15)	0.0227 (4)
H19A	−0.5264	−0.6373	−0.5238	0.034*
H19B	−0.6242	−0.5005	−0.4993	0.034*
H19C	−0.5066	−0.5038	−0.4208	0.034*
C20	−0.93636 (17)	−0.5654 (4)	−0.45993 (16)	0.0270 (5)
H20A	−0.9640	−0.5655	−0.5369	0.040*
H20B	−0.9770	−0.6604	−0.4253	0.040*
H20C	−0.9483	−0.4406	−0.4305	0.040*
C24	−0.23193 (16)	−0.3190 (3)	−0.29832 (14)	0.0152 (4)
C23	−0.22374 (14)	−0.1046 (3)	−0.29707 (14)	0.0143 (4)
H23A	−0.2164	−0.0604	−0.3704	0.017*
C22	−0.12023 (15)	−0.0415 (3)	−0.21978 (14)	0.0140 (4)
H22A	−0.0538	−0.1048	−0.2417	0.017*
C21	−0.10124 (15)	0.1725 (3)	−0.22358 (14)	0.0135 (3)
H7A	−0.079 (2)	−0.195 (5)	−0.098 (2)	0.034 (7)*
H11A	−0.039 (2)	−0.902 (4)	0.010 (2)	0.031 (7)*
H8A	−0.370 (3)	−0.121 (5)	−0.275 (3)	0.049 (9)*
H11B	0.002 (3)	−0.995 (5)	0.103 (2)	0.037 (8)*
H9B	−0.139 (4)	−0.517 (2)	−0.309 (3)	0.081 (14)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0209 (6)	0.0219 (7)	0.0165 (6)	0.0008 (6)	0.0062 (5)	−0.0032 (6)
O2	0.0143 (6)	0.0338 (8)	0.0153 (6)	0.0000 (6)	0.0005 (5)	0.0008 (6)
O3	0.0202 (7)	0.0337 (8)	0.0178 (7)	0.0017 (7)	−0.0028 (5)	−0.0012 (6)
O4	0.0223 (7)	0.0296 (7)	0.0144 (6)	−0.0004 (6)	0.0023 (5)	−0.0008 (6)
O10	0.0192 (7)	0.0200 (7)	0.0297 (8)	−0.0045 (6)	0.0033 (6)	0.0033 (6)
O9	0.0207 (7)	0.0123 (7)	0.0226 (7)	0.0000 (5)	0.0045 (5)	−0.0010 (5)
O8	0.0145 (6)	0.0195 (7)	0.0262 (8)	0.0017 (6)	0.0039 (5)	−0.0033 (5)
O7	0.0264 (7)	0.0157 (7)	0.0136 (6)	0.0031 (6)	0.0012 (5)	0.0023 (5)
O5	0.0179 (6)	0.0162 (6)	0.0182 (6)	−0.0017 (5)	0.0001 (5)	−0.0028 (5)
O6	0.0250 (7)	0.0137 (6)	0.0149 (6)	−0.0002 (5)	0.0020 (5)	0.0001 (5)
O11	0.0202 (7)	0.0171 (7)	0.0149 (7)	0.0006 (5)	0.0004 (5)	−0.0002 (5)
N1	0.0124 (7)	0.0122 (7)	0.0169 (7)	0.0006 (6)	0.0040 (6)	−0.0001 (6)
C1	0.0177 (8)	0.0147 (9)	0.0168 (9)	−0.0012 (7)	0.0041 (7)	−0.0018 (7)
C2	0.0172 (8)	0.0153 (9)	0.0165 (8)	−0.0021 (7)	0.0017 (7)	0.0012 (7)
C3	0.0126 (8)	0.0178 (9)	0.0220 (9)	−0.0002 (7)	0.0036 (7)	0.0012 (8)
C4	0.0153 (8)	0.0152 (9)	0.0176 (8)	−0.0008 (7)	0.0045 (6)	−0.0013 (7)
C5	0.0150 (8)	0.0111 (8)	0.0178 (9)	−0.0002 (6)	0.0038 (7)	0.0001 (7)
C6	0.0152 (8)	0.0111 (8)	0.0173 (9)	−0.0007 (7)	0.0031 (7)	−0.0003 (6)
C7	0.0170 (8)	0.0124 (8)	0.0153 (8)	0.0007 (7)	0.0044 (6)	0.0001 (7)
C8	0.0163 (8)	0.0106 (8)	0.0152 (8)	−0.0013 (7)	0.0043 (7)	−0.0008 (6)
C9	0.0154 (8)	0.0118 (8)	0.0167 (8)	−0.0003 (6)	0.0056 (7)	−0.0004 (7)
C10	0.0137 (8)	0.0120 (9)	0.0161 (9)	0.0021 (6)	0.0019 (7)	−0.0015 (6)
C11	0.0150 (8)	0.0119 (8)	0.0190 (9)	0.0016 (7)	0.0041 (7)	−0.0012 (7)
C12	0.0151 (8)	0.0179 (9)	0.0201 (9)	−0.0012 (7)	0.0053 (7)	0.0003 (7)
C13	0.0116 (8)	0.0193 (9)	0.0172 (8)	0.0017 (7)	0.0031 (6)	0.0007 (7)
C14	0.0127 (8)	0.0179 (9)	0.0225 (9)	0.0003 (7)	0.0014 (7)	−0.0006 (8)
C15	0.0161 (8)	0.0163 (9)	0.0188 (9)	0.0035 (8)	−0.0024 (7)	−0.0023 (8)
C16	0.0196 (9)	0.0147 (9)	0.0162 (9)	0.0036 (7)	0.0041 (7)	−0.0003 (7)
C17	0.0137 (8)	0.0152 (8)	0.0180 (9)	0.0006 (7)	0.0035 (7)	−0.0007 (7)
C18	0.0228 (9)	0.0283 (11)	0.0149 (9)	0.0026 (8)	−0.0013 (7)	−0.0019 (8)
C19	0.0218 (9)	0.0301 (11)	0.0174 (9)	−0.0005 (8)	0.0064 (7)	0.0000 (8)
C20	0.0155 (9)	0.0439 (13)	0.0203 (10)	−0.0003 (9)	−0.0006 (7)	0.0034 (9)
C24	0.0175 (9)	0.0163 (9)	0.0110 (8)	−0.0009 (7)	0.0000 (7)	0.0007 (7)
C23	0.0134 (8)	0.0159 (9)	0.0138 (8)	−0.0006 (7)	0.0031 (6)	−0.0004 (7)
C22	0.0154 (8)	0.0132 (9)	0.0131 (8)	0.0016 (7)	0.0018 (6)	0.0000 (6)
C21	0.0110 (8)	0.0147 (8)	0.0156 (9)	0.0009 (7)	0.0048 (6)	−0.0016 (7)

Geometric parameters (Å, º)

O1—C1	1.369 (2)	C7—H7B	0.9500
O1—C19	1.442 (2)	C8—C9	1.369 (3)
O2—C2	1.357 (2)	C8—C10	1.471 (2)
O2—C20	1.437 (2)	C9—H9A	0.9500
O3—C15	1.371 (2)	C10—C11	1.398 (2)
O3—C18	1.443 (3)	C10—C17	1.415 (3)
O4—C16	1.369 (2)	C11—C14	1.399 (3)
O4—C18	1.444 (2)	C11—C12	1.505 (2)
O10—C24	1.228 (2)	C12—C13	1.512 (3)
O9—C24	1.296 (2)	C12—H12A	0.9900
O9—H9B	0.821 (14)	C12—H12B	0.9900
O8—C23	1.422 (2)	C13—H13A	0.9900
O8—H8A	0.89 (4)	C13—H13B	0.9900
O7—C22	1.415 (2)	C14—C15	1.369 (3)
O7—H7A	0.89 (3)	C14—H14A	0.9500
O5—C21	1.240 (2)	C15—C16	1.391 (3)
O6—C21	1.277 (2)	C16—C17	1.369 (3)
O11—H11A	0.84 (3)	C17—H17A	0.9500
O11—H11B	0.89 (3)	C18—H18A	0.9900
N1—C7	1.330 (2)	C18—H18B	0.9900
N1—C8	1.396 (2)	C19—H19A	0.9800
N1—C13	1.486 (2)	C19—H19B	0.9800
C1—C2	1.383 (3)	C19—H19C	0.9800
C1—C6	1.414 (3)	C20—H20A	0.9800
C2—C3	1.418 (3)	C20—H20B	0.9800
C3—C4	1.378 (3)	C20—H20C	0.9800
C3—H3A	0.9500	C24—C23	1.524 (3)
C4—C5	1.407 (2)	C23—C22	1.527 (2)
C4—H4A	0.9500	C23—H23A	1.0000
C5—C9	1.413 (3)	C22—C21	1.537 (2)
C5—C6	1.429 (3)	C22—H22A	1.0000
C6—C7	1.399 (2)
C1—O1—C19	115.61 (15)	C12—C13—H13A	109.9
C2—O2—C20	117.84 (15)	N1—C13—H13B	109.9
C15—O3—C18	105.68 (15)	C12—C13—H13B	109.9
C16—O4—C18	105.76 (15)	H13A—C13—H13B	108.3
C24—O9—H9B	116 (3)	C15—C14—C11	116.92 (17)
C23—O8—H8A	104 (2)	C15—C14—H14A	121.5
C22—O7—H7A	108.2 (18)	C11—C14—H14A	121.5
H11A—O11—H11B	105 (3)	C14—C15—O3	127.87 (17)
C7—N1—C8	122.42 (15)	C14—C15—C16	122.19 (17)
C7—N1—C13	118.08 (14)	O3—C15—C16	109.86 (17)
C8—N1—C13	119.46 (15)	O4—C16—C17	127.97 (17)
O1—C1—C2	122.23 (17)	O4—C16—C15	109.82 (16)
O1—C1—C6	118.61 (17)	C17—C16—C15	122.13 (17)
C2—C1—C6	119.08 (16)	C16—C17—C10	116.69 (17)
O2—C2—C1	116.15 (16)	C16—C17—H17A	121.7
O2—C2—C3	124.01 (17)	C10—C17—H17A	121.7
C1—C2—C3	119.83 (17)	O3—C18—O4	107.06 (15)
C4—C3—C2	121.42 (17)	O3—C18—H18A	110.3
C4—C3—H3A	119.3	O4—C18—H18A	110.3
C2—C3—H3A	119.3	O3—C18—H18B	110.3
C3—C4—C5	120.17 (16)	O4—C18—H18B	110.3
C3—C4—H4A	119.9	H18A—C18—H18B	108.6
C5—C4—H4A	119.9	O1—C19—H19A	109.5
C4—C5—C9	124.00 (16)	O1—C19—H19B	109.5
C4—C5—C6	118.25 (17)	H19A—C19—H19B	109.5
C9—C5—C6	117.69 (16)	O1—C19—H19C	109.5
C7—C6—C1	120.33 (16)	H19A—C19—H19C	109.5
C7—C6—C5	118.46 (16)	H19B—C19—H19C	109.5
C1—C6—C5	121.09 (17)	O2—C20—H20A	109.5
N1—C7—C6	121.27 (16)	O2—C20—H20B	109.5
N1—C7—H7B	119.4	H20A—C20—H20B	109.5
C6—C7—H7B	119.4	O2—C20—H20C	109.5
C9—C8—N1	117.96 (17)	H20A—C20—H20C	109.5
C9—C8—C10	125.03 (16)	H20B—C20—H20C	109.5
N1—C8—C10	116.93 (16)	O10—C24—O9	126.44 (18)
C8—C9—C5	122.02 (16)	O10—C24—C23	119.99 (17)
C8—C9—H9A	119.0	O9—C24—C23	113.56 (16)
C5—C9—H9A	119.0	O8—C23—C24	110.08 (15)
C11—C10—C17	120.72 (16)	O8—C23—C22	110.85 (15)
C11—C10—C8	118.98 (16)	C24—C23—C22	110.12 (15)
C17—C10—C8	120.25 (16)	O8—C23—H23A	108.6
C10—C11—C14	121.33 (16)	C24—C23—H23A	108.6
C10—C11—C12	118.23 (16)	C22—C23—H23A	108.6
C14—C11—C12	120.43 (17)	O7—C22—C23	111.37 (15)
C11—C12—C13	108.86 (15)	O7—C22—C21	110.01 (15)
C11—C12—H12A	109.9	C23—C22—C21	112.35 (15)
C13—C12—H12A	109.9	O7—C22—H22A	107.6
C11—C12—H12B	109.9	C23—C22—H22A	107.6
C13—C12—H12B	109.9	C21—C22—H22A	107.6
H12A—C12—H12B	108.3	O5—C21—O6	125.84 (17)
N1—C13—C12	109.01 (14)	O5—C21—C22	118.56 (16)
N1—C13—H13A	109.9	O6—C21—C22	115.56 (16)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O7—H7A···O11^i	0.89 (3)	1.76 (3)	2.650 (2)	175 (3)
O8—H8A···O10	0.89 (4)	2.06 (4)	2.642 (2)	122 (3)
O9—H9B···O6^ii	0.82 (1)	1.64 (2)	2.4593 (19)	172 (5)
O11—H11A···O7^ii	0.84 (3)	2.23 (3)	2.9714 (19)	147 (3)
O11—H11B···O5^iii	0.89 (3)	1.93 (3)	2.816 (2)	171 (3)

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

(1BER-1LTA-1W)

Crystal data

C20H18NO4·C4H5O6·H2O	F(000) = 528
Mr = 503.45	Dx = 1.553 Mg m^−3
Monoclinic, P21	Cu Kα radiation, λ = 1.54178 Å
a = 12.1118 (1) Å	Cell parameters from 4170 reflections
b = 7.0931 (1) Å	θ = 3.5–75.7°
c = 12.7037 (1) Å	µ = 1.06 mm^−1
β = 99.436 (1)°	T = 100 K
V = 1076.61 (2) Å^3	Needle, colourless
Z = 2	0.08 × 0.02 × 0.01 mm

Data collection

CCD diffractometer	4090 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.025
ωκ scans	θmax = 75.7°, θmin = 3.5°
Absorption correction: multi-scan Higashi, T. (1995)	h = −15→15
Tmin = 0.975, Tmax = 0.989	k = −7→8
13053 measured reflections	l = −15→15
4170 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.030	w = 1/[σ^2(Fo^2) + (0.0571P)^2 + 0.115P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.084	(Δ/σ)max < 0.001
S = 1.08	Δρmax = 0.18 e Å^−3
4170 reflections	Δρmin = −0.23 e Å^−3
345 parameters	Absolute structure: Flack x determined using 1707 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
2 restraints	Absolute structure parameter: 0.05 (6)

Special details

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.

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

	x	y	z	Uiso*/Ueq
O10	0.18071 (13)	0.2640 (2)	0.71530 (13)	0.0251 (4)
O8	0.17767 (12)	−0.1075 (2)	0.73143 (13)	0.0217 (3)
O1	0.10274 (12)	0.0946 (2)	0.40522 (11)	0.0210 (3)
O7	0.37441 (13)	−0.0337 (2)	0.88586 (11)	0.0207 (3)
O9	0.35840 (12)	0.2697 (2)	0.68344 (12)	0.0201 (3)
O6	0.36445 (12)	−0.3831 (2)	0.68665 (11)	0.0195 (3)
O1AA	−0.31417 (13)	−0.0439 (3)	−0.37978 (11)	0.0259 (4)
O11	0.51747 (12)	0.2503 (2)	0.92467 (12)	0.0190 (3)
O2AA	−0.13244 (12)	0.0597 (3)	−0.38012 (11)	0.0234 (3)
O2	0.31875 (12)	−0.0235 (3)	0.44129 (11)	0.0230 (3)
O5	0.44804 (12)	−0.3840 (2)	0.85751 (11)	0.0193 (3)
N1	−0.08379 (13)	0.0511 (3)	0.10485 (13)	0.0150 (3)
C10	−0.11236 (16)	0.0087 (3)	−0.08871 (16)	0.0153 (4)
C5	0.14536 (17)	−0.0044 (3)	0.12833 (16)	0.0157 (4)
C17	−0.07364 (16)	0.0499 (3)	−0.18545 (16)	0.0168 (4)
H17A	−0.0013	0.0931	−0.1863	0.020*
C14	−0.29653 (17)	−0.0771 (3)	−0.18487 (17)	0.0191 (4)
H14A	−0.3695	−0.1184	−0.1855	0.023*
C1	0.15404 (17)	0.0345 (3)	0.32324 (16)	0.0175 (4)
C7	−0.02346 (16)	0.0633 (3)	0.20185 (15)	0.0161 (4)
H7B	−0.0589	0.0908	0.2597	0.019*
C16	−0.14782 (17)	0.0233 (3)	−0.27762 (16)	0.0180 (4)
C9	0.07789 (17)	−0.0045 (3)	0.02665 (16)	0.0158 (4)
H9A	0.1115	−0.0223	−0.0334	0.019*
C8	−0.03570 (17)	0.0210 (3)	0.01370 (15)	0.0155 (4)
C24	0.26821 (17)	0.1868 (3)	0.70183 (15)	0.0165 (4)
C4	0.26003 (16)	−0.0494 (3)	0.14633 (15)	0.0170 (4)
H4A	0.2968	−0.0726	0.0889	0.020*
C3	0.31800 (16)	−0.0593 (3)	0.24917 (16)	0.0186 (4)
H3A	0.3931	−0.0941	0.2601	0.022*
C2	0.26594 (17)	−0.0179 (3)	0.33840 (16)	0.0182 (4)
C12	−0.26017 (16)	−0.0844 (3)	0.01630 (17)	0.0186 (4)
H12A	−0.2377	−0.2093	0.0426	0.022*
H12B	−0.3411	−0.0763	0.0078	0.022*
C23	0.27621 (15)	−0.0272 (3)	0.70296 (15)	0.0154 (4)
H23A	0.2834	−0.0704	0.6311	0.018*
C11	−0.22241 (16)	−0.0512 (3)	−0.08921 (15)	0.0162 (4)
C15	−0.25690 (17)	−0.0389 (3)	−0.27737 (16)	0.0187 (4)
C13	−0.20768 (15)	0.0630 (3)	0.09486 (15)	0.0172 (4)
H13A	−0.2330	0.1875	0.0702	0.021*
H13B	−0.2299	0.0418	0.1639	0.021*
C22	0.37992 (16)	−0.0905 (3)	0.78033 (15)	0.0151 (4)
H22A	0.4450	−0.0285	0.7588	0.018*
C19	0.06202 (18)	−0.0520 (4)	0.46727 (17)	0.0248 (5)
H19A	0.0275	0.0037	0.5226	0.037*
H19B	0.0080	−0.1272	0.4219	0.037*
H19C	0.1234	−0.1301	0.4987	0.037*
C20	0.43631 (18)	−0.0667 (4)	0.46001 (17)	0.0280 (5)
H20A	0.4635	−0.0664	0.5354	0.042*
H20B	0.4480	−0.1889	0.4313	0.042*
H20C	0.4759	0.0264	0.4259	0.042*
C18	−0.23196 (19)	−0.0084 (4)	−0.44752 (17)	0.0245 (5)
H18A	−0.2596	0.0851	−0.5012	0.029*
H18B	−0.2157	−0.1234	−0.4834	0.029*
C6	0.09301 (17)	0.0353 (3)	0.21866 (16)	0.0158 (4)
C21	0.39883 (16)	−0.3042 (3)	0.77633 (15)	0.0152 (4)
H8A	0.130 (3)	−0.013 (6)	0.722 (3)	0.048 (10)*
H11A	0.496 (3)	0.377 (5)	0.896 (3)	0.036 (8)*
H7A	0.417 (3)	0.064 (6)	0.903 (3)	0.040 (9)*
H11B	0.539 (2)	0.271 (5)	0.992 (3)	0.034 (8)*
H9B	0.361 (4)	0.384 (2)	0.690 (3)	0.062 (13)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O10	0.0216 (7)	0.0209 (9)	0.0321 (8)	0.0053 (6)	0.0029 (6)	−0.0028 (7)
O8	0.0156 (7)	0.0198 (9)	0.0296 (8)	−0.0017 (6)	0.0037 (6)	0.0037 (6)
O1	0.0224 (7)	0.0226 (9)	0.0189 (7)	0.0008 (7)	0.0055 (5)	−0.0029 (6)
O7	0.0292 (8)	0.0161 (8)	0.0159 (6)	−0.0036 (7)	0.0009 (5)	−0.0021 (6)
O9	0.0226 (7)	0.0124 (8)	0.0254 (8)	−0.0003 (6)	0.0039 (6)	0.0012 (6)
O6	0.0268 (7)	0.0134 (8)	0.0177 (7)	0.0003 (6)	0.0017 (6)	−0.0002 (6)
O1AA	0.0206 (7)	0.0346 (10)	0.0200 (7)	0.0017 (7)	−0.0038 (6)	−0.0014 (7)
O11	0.0210 (7)	0.0176 (8)	0.0175 (7)	0.0007 (6)	0.0004 (6)	−0.0004 (6)
O2AA	0.0231 (7)	0.0298 (9)	0.0169 (7)	0.0002 (7)	0.0021 (5)	−0.0006 (6)
O2	0.0157 (7)	0.0349 (10)	0.0173 (7)	−0.0004 (7)	−0.0003 (5)	0.0004 (7)
O5	0.0189 (6)	0.0171 (8)	0.0205 (7)	0.0017 (6)	−0.0007 (5)	0.0033 (6)
N1	0.0133 (7)	0.0133 (9)	0.0184 (8)	0.0010 (6)	0.0031 (6)	−0.0004 (7)
C10	0.0148 (9)	0.0125 (11)	0.0181 (9)	0.0024 (7)	0.0016 (7)	−0.0020 (7)
C5	0.0159 (9)	0.0114 (10)	0.0197 (9)	−0.0011 (7)	0.0024 (7)	0.0001 (7)
C17	0.0138 (8)	0.0160 (10)	0.0204 (9)	0.0009 (7)	0.0023 (7)	−0.0009 (8)
C14	0.0136 (8)	0.0174 (11)	0.0252 (10)	0.0002 (8)	0.0003 (7)	−0.0014 (9)
C1	0.0184 (9)	0.0157 (11)	0.0186 (9)	−0.0010 (7)	0.0037 (8)	−0.0013 (8)
C7	0.0172 (9)	0.0131 (10)	0.0182 (9)	0.0011 (8)	0.0034 (7)	0.0005 (8)
C16	0.0200 (9)	0.0161 (11)	0.0180 (10)	0.0033 (8)	0.0037 (8)	−0.0005 (8)
C9	0.0164 (9)	0.0132 (10)	0.0185 (9)	0.0006 (7)	0.0053 (7)	−0.0009 (7)
C8	0.0170 (9)	0.0119 (11)	0.0179 (9)	−0.0008 (7)	0.0032 (7)	−0.0002 (7)
C24	0.0186 (10)	0.0165 (11)	0.0135 (8)	0.0017 (8)	0.0000 (7)	−0.0006 (7)
C4	0.0171 (9)	0.0148 (11)	0.0196 (9)	−0.0011 (8)	0.0043 (7)	−0.0017 (8)
C3	0.0138 (8)	0.0192 (11)	0.0229 (9)	0.0000 (8)	0.0030 (7)	0.0019 (9)
C2	0.0176 (9)	0.0169 (11)	0.0196 (9)	−0.0024 (8)	0.0011 (7)	0.0015 (8)
C12	0.0146 (8)	0.0181 (11)	0.0236 (10)	−0.0015 (8)	0.0048 (7)	0.0003 (8)
C23	0.0140 (9)	0.0160 (11)	0.0159 (8)	0.0008 (8)	0.0017 (7)	0.0005 (8)
C11	0.0155 (9)	0.0122 (10)	0.0208 (9)	0.0014 (8)	0.0029 (7)	−0.0012 (8)
C15	0.0181 (9)	0.0168 (11)	0.0190 (9)	0.0029 (8)	−0.0035 (7)	−0.0028 (8)
C13	0.0115 (8)	0.0212 (11)	0.0190 (9)	0.0025 (8)	0.0022 (7)	0.0018 (8)
C22	0.0154 (8)	0.0137 (11)	0.0156 (9)	−0.0013 (7)	0.0006 (7)	−0.0002 (7)
C19	0.0227 (10)	0.0325 (14)	0.0199 (9)	−0.0009 (9)	0.0056 (8)	0.0006 (10)
C20	0.0156 (9)	0.0441 (16)	0.0227 (10)	−0.0001 (10)	−0.0014 (8)	0.0039 (10)
C18	0.0241 (10)	0.0298 (13)	0.0177 (9)	0.0029 (9)	−0.0024 (8)	−0.0027 (9)
C6	0.0168 (9)	0.0111 (10)	0.0195 (9)	−0.0006 (7)	0.0028 (7)	0.0000 (7)
C21	0.0125 (8)	0.0164 (11)	0.0176 (9)	−0.0004 (7)	0.0045 (7)	0.0018 (7)

Geometric parameters (Å, º)

O10—C24	1.229 (3)	C14—H14A	0.9300
O8—C23	1.422 (2)	C1—C2	1.388 (3)
O8—H8A	0.88 (4)	C1—C6	1.410 (3)
O1—C1	1.365 (2)	C7—C6	1.406 (3)
O1—C19	1.440 (3)	C7—H7B	0.9300
O7—C22	1.412 (2)	C16—C15	1.393 (3)
O7—H7A	0.87 (4)	C9—C8	1.370 (3)
O9—C24	1.295 (3)	C9—H9A	0.9300
O9—H9B	0.813 (14)	C24—C23	1.521 (3)
O6—C21	1.277 (3)	C4—C3	1.380 (3)
O1AA—C15	1.371 (2)	C4—H4A	0.9300
O1AA—C18	1.441 (3)	C3—C2	1.415 (3)
O11—H11A	0.99 (4)	C3—H3A	0.9300
O11—H11B	0.86 (3)	C12—C11	1.504 (3)
O2AA—C16	1.370 (2)	C12—C13	1.512 (3)
O2AA—C18	1.443 (3)	C12—H12A	0.9700
O2—C2	1.358 (2)	C12—H12B	0.9700
O2—C20	1.438 (2)	C23—C22	1.530 (3)
O5—C21	1.240 (2)	C23—H23A	0.9800
N1—C7	1.328 (3)	C13—H13A	0.9700
N1—C8	1.395 (2)	C13—H13B	0.9700
N1—C13	1.487 (2)	C22—C21	1.535 (3)
C10—C11	1.398 (3)	C22—H22A	0.9800
C10—C17	1.416 (3)	C19—H19A	0.9600
C10—C8	1.472 (3)	C19—H19B	0.9600
C5—C4	1.407 (3)	C19—H19C	0.9600
C5—C9	1.411 (3)	C20—H20A	0.9600
C5—C6	1.427 (3)	C20—H20B	0.9600
C17—C16	1.367 (3)	C20—H20C	0.9600
C17—H17A	0.9300	C18—H18A	0.9700
C14—C15	1.367 (3)	C18—H18B	0.9700
C14—C11	1.400 (3)
C23—O8—H8A	103 (2)	C13—C12—H12A	109.9
C1—O1—C19	115.58 (18)	C11—C12—H12B	109.9
C22—O7—H7A	110 (2)	C13—C12—H12B	109.9
C24—O9—H9B	117 (3)	H12A—C12—H12B	108.3
C15—O1AA—C18	105.70 (16)	O8—C23—C24	110.31 (17)
H11A—O11—H11B	103 (3)	O8—C23—C22	110.75 (16)
C16—O2AA—C18	105.69 (16)	C24—C23—C22	110.06 (17)
C2—O2—C20	117.57 (16)	O8—C23—H23A	108.6
C7—N1—C8	122.60 (17)	C24—C23—H23A	108.6
C7—N1—C13	117.99 (15)	C22—C23—H23A	108.6
C8—N1—C13	119.37 (16)	C10—C11—C14	121.27 (18)
C11—C10—C17	120.67 (18)	C10—C11—C12	118.20 (17)
C11—C10—C8	119.00 (17)	C14—C11—C12	120.52 (18)
C17—C10—C8	120.29 (17)	C14—C15—O1AA	128.04 (19)
C4—C5—C9	123.85 (18)	C14—C15—C16	122.10 (18)
C4—C5—C6	118.10 (18)	O1AA—C15—C16	109.79 (18)
C9—C5—C6	117.98 (18)	N1—C13—C12	109.04 (16)
C16—C17—C10	116.75 (18)	N1—C13—H13A	109.9
C16—C17—H17A	121.6	C12—C13—H13A	109.9
C10—C17—H17A	121.6	N1—C13—H13B	109.9
C15—C14—C11	117.04 (18)	C12—C13—H13B	109.9
C15—C14—H14A	121.5	H13A—C13—H13B	108.3
C11—C14—H14A	121.5	O7—C22—C23	111.39 (16)
O1—C1—C2	122.27 (19)	O7—C22—C21	110.10 (16)
O1—C1—C6	118.91 (18)	C23—C22—C21	112.30 (17)
C2—C1—C6	118.74 (18)	O7—C22—H22A	107.6
N1—C7—C6	121.16 (17)	C23—C22—H22A	107.6
N1—C7—H7B	119.4	C21—C22—H22A	107.6
C6—C7—H7B	119.4	O1—C19—H19A	109.5
C17—C16—O2AA	127.98 (19)	O1—C19—H19B	109.5
C17—C16—C15	122.14 (18)	H19A—C19—H19B	109.5
O2AA—C16—C15	109.80 (17)	O1—C19—H19C	109.5
C8—C9—C5	121.96 (18)	H19A—C19—H19C	109.5
C8—C9—H9A	119.0	H19B—C19—H19C	109.5
C5—C9—H9A	119.0	O2—C20—H20A	109.5
C9—C8—N1	117.90 (18)	O2—C20—H20B	109.5
C9—C8—C10	125.01 (17)	H20A—C20—H20B	109.5
N1—C8—C10	117.00 (17)	O2—C20—H20C	109.5
O10—C24—O9	126.5 (2)	H20A—C20—H20C	109.5
O10—C24—C23	119.87 (19)	H20B—C20—H20C	109.5
O9—C24—C23	113.61 (18)	O1AA—C18—O2AA	107.22 (16)
C3—C4—C5	120.07 (18)	O1AA—C18—H18A	110.3
C3—C4—H4A	120.0	O2AA—C18—H18A	110.3
C5—C4—H4A	120.0	O1AA—C18—H18B	110.3
C4—C3—C2	121.55 (18)	O2AA—C18—H18B	110.3
C4—C3—H3A	119.2	H18A—C18—H18B	108.5
C2—C3—H3A	119.2	C7—C6—C1	120.10 (18)
O2—C2—C1	115.88 (18)	C7—C6—C5	118.22 (18)
O2—C2—C3	124.28 (18)	C1—C6—C5	121.55 (18)
C1—C2—C3	119.84 (18)	O5—C21—O6	125.7 (2)
C11—C12—C13	108.88 (17)	O5—C21—C22	118.53 (18)
C11—C12—H12A	109.9	O6—C21—C22	115.74 (18)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O7—H7A···O11	0.87 (4)	1.79 (4)	2.650 (2)	171 (3)
O8—H8A···O10	0.88 (4)	2.07 (4)	2.643 (2)	122 (3)
O9—H9B···O6^i	0.81 (1)	1.65 (2)	2.463 (2)	173 (4)
O11—H11A···O5^i	0.99 (4)	1.83 (4)	2.816 (2)	173 (3)
O11—H11B···O7^ii	0.86 (3)	2.21 (3)	2.970 (2)	147 (3)

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

(2BER-2CA)

Crystal data

2C20H18NO4·2C6H7O7	Z = 2
Mr = 1054.94	F(000) = 1104
Triclinic, P1	Dx = 1.454 Mg m^−3
a = 7.5857 (5) Å	Cu Kα radiation, λ = 1.54184 Å
b = 14.6861 (9) Å	Cell parameters from 9389 reflections
c = 22.7899 (11) Å	θ = 2.0–74.1°
α = 101.256 (5)°	µ = 0.98 mm^−1
β = 97.331 (5)°	T = 100 K
γ = 100.898 (5)°	Needle, colourless
V = 2409.2 (2) Å^3	0.06 × 0.02 × 0.01 mm

Data collection

CCD diffractometer	6783 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.046
ωκ scans	θmax = 74.1°, θmin = 2.0°
Absorption correction: multi-scan Higashi, T. (1995)	h = −6→9
Tmin = 0.977, Tmax = 0.990	k = −18→17
16809 measured reflections	l = −27→28
9389 independent reflections

Refinement

Refinement on F^2	7 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.080	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.226	w = 1/[σ^2(Fo^2) + (0.092P)^2 + 3.0612P] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max < 0.001
9389 reflections	Δρmax = 0.72 e Å^−3
729 parameters	Δρmin = −0.70 e Å^−3

Special details

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.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
N1A	0.6644 (3)	0.41661 (17)	0.39935 (11)	0.0251 (5)
N1B	0.3507 (4)	0.0716 (2)	0.08757 (13)	0.0414 (7)
O1A	0.6126 (3)	0.65030 (16)	0.33051 (10)	0.0369 (5)
O1B	0.4146 (4)	−0.15812 (18)	0.15869 (12)	0.0500 (7)
O2A	0.7033 (4)	0.82998 (15)	0.40563 (11)	0.0397 (6)
O2B	0.3128 (4)	−0.33814 (17)	0.08718 (11)	0.0484 (7)
O3A	0.6802 (4)	0.09391 (16)	0.55060 (11)	0.0439 (6)
O3B	0.2659 (6)	0.3929 (2)	−0.05899 (13)	0.0819 (13)
O4A	0.8456 (4)	0.23593 (17)	0.61348 (11)	0.0403 (6)
O4B	0.1591 (5)	0.2501 (2)	−0.12704 (13)	0.0592 (8)
O5B	0.8816 (5)	0.1387 (3)	0.15568 (13)	0.0651 (9)
O5A	0.0222 (4)	0.4537 (2)	0.36189 (11)	0.0519 (7)
O6A	0.2106 (4)	0.37863 (19)	0.31763 (13)	0.0488 (7)
H6A	0.266 (6)	0.379 (3)	0.2865 (16)	0.063 (15)*
O6B	1.0456 (5)	0.0431 (2)	0.18506 (13)	0.0539 (7)
H6B	1.078 (11)	0.023 (6)	0.218 (2)	0.16 (3)*
O7B	0.8681 (3)	0.14426 (17)	0.35760 (10)	0.0367 (5)
H7B	0.926 (5)	0.134 (3)	0.3899 (13)	0.057 (13)*
O7A	0.1644 (5)	0.5715 (2)	0.19476 (14)	0.0578 (8)
H7A	0.236 (9)	0.573 (6)	0.168 (3)	0.14 (3)*
O8A	0.4629 (4)	0.5101 (2)	0.18467 (14)	0.0624 (8)
O8B	1.1446 (3)	0.06948 (18)	0.38417 (11)	0.0393 (6)
O9A	0.4088 (4)	0.4066 (2)	0.24145 (12)	0.0489 (7)
O9B	1.1665 (3)	0.01530 (19)	0.28757 (11)	0.0421 (6)
O10A	−0.2184 (4)	0.4528 (3)	0.21589 (15)	0.0960 (16)
H10A	−0.3093	0.4725	0.2014	0.115*
O10B	0.4846 (3)	−0.01378 (17)	0.31339 (11)	0.0355 (5)
H10B	0.376 (3)	−0.006 (4)	0.305 (2)	0.072 (16)*
O11A	−0.2647 (18)	0.3987 (14)	0.1237 (4)	0.082 (6)	0.46 (2)
O11C	−0.1922 (11)	0.4381 (4)	0.1141 (2)	0.0342 (19)*	0.54 (2)
O11B	0.5385 (3)	0.07491 (18)	0.24628 (11)	0.0376 (5)
C1A	0.6811 (4)	0.6656 (2)	0.39101 (14)	0.0293 (6)
C1B	0.3342 (5)	−0.1748 (2)	0.09915 (15)	0.0337 (7)
C2A	0.7269 (5)	0.7547 (2)	0.43018 (15)	0.0315 (7)
C2B	0.2806 (5)	−0.2646 (2)	0.06217 (15)	0.0364 (7)
C3A	0.7904 (5)	0.7634 (2)	0.49248 (15)	0.0333 (7)
H3AA	0.8250	0.8236	0.5182	0.040*
C3B	0.1994 (6)	−0.2761 (3)	0.00105 (16)	0.0453 (9)
H3BA	0.1588	−0.3372	−0.0233	0.054*
C4A	0.8022 (4)	0.6856 (2)	0.51590 (14)	0.0313 (7)
H4AA	0.8428	0.6932	0.5572	0.038*
C4B	0.1790 (6)	−0.2000 (3)	−0.02315 (15)	0.0410 (8)
H4BA	0.1253	−0.2098	−0.0636	0.049*
C5A	0.7532 (4)	0.5940 (2)	0.47783 (14)	0.0274 (6)
C5B	0.2380 (4)	−0.1076 (2)	0.01231 (14)	0.0298 (6)
C6A	0.6954 (4)	0.5844 (2)	0.41469 (14)	0.0265 (6)
C6B	0.3137 (4)	−0.0957 (2)	0.07461 (14)	0.0309 (7)
C7A	0.6562 (4)	0.4933 (2)	0.37701 (14)	0.0277 (6)
H7AB	0.6236	0.4860	0.3353	0.033*
C7B	0.3668 (6)	−0.0035 (2)	0.11018 (17)	0.0463 (10)
H7BB	0.4149	0.0057	0.1511	0.056*
C8A	0.7120 (4)	0.4219 (2)	0.46118 (13)	0.0257 (6)
C8B	0.2843 (4)	0.0645 (2)	0.02680 (14)	0.0286 (6)
C9B	0.2273 (4)	−0.0249 (2)	−0.00959 (14)	0.0308 (7)
H9BA	0.1797	−0.0316	−0.0503	0.037*
C9A	0.7568 (4)	0.5106 (2)	0.49918 (14)	0.0283 (6)
H9AA	0.7909	0.5158	0.5406	0.034*
C10A	0.7072 (4)	0.3325 (2)	0.48118 (14)	0.0273 (6)
C10B	0.2803 (4)	0.1533 (2)	0.00642 (14)	0.0302 (7)
C11A	0.6076 (4)	0.2462 (2)	0.44291 (14)	0.0275 (6)
C11B	0.3454 (9)	0.2398 (3)	0.04666 (18)	0.0732 (17)
C12A	0.5197 (4)	0.2476 (2)	0.38034 (14)	0.0289 (6)
H12A	0.4001	0.2616	0.3816	0.035*
H12B	0.5050	0.1858	0.3534	0.035*
C12B	0.3349 (13)	0.2302 (5)	0.1126 (3)	0.037 (2)	0.466 (11)
H12C	0.3800	0.2911	0.1411	0.044*	0.466 (11)
H12D	0.2109	0.2045	0.1169	0.044*	0.466 (11)
C13B	0.4543 (15)	0.1629 (5)	0.1220 (4)	0.032 (2)	0.466 (11)
H13C	0.5677	0.1803	0.1073	0.039*	0.466 (11)
H13D	0.4816	0.1625	0.1647	0.039*	0.466 (11)
C12C	0.4740 (9)	0.2454 (4)	0.1100 (3)	0.0283 (18)	0.534 (11)
H12E	0.5904	0.2308	0.1034	0.034*	0.534 (11)
H12F	0.4944	0.3076	0.1370	0.034*	0.534 (11)
C13C	0.3616 (12)	0.1698 (4)	0.1342 (3)	0.0294 (17)	0.534 (11)
H13E	0.2407	0.1816	0.1362	0.035*	0.534 (11)
H13F	0.4190	0.1687	0.1745	0.035*	0.534 (11)
C13A	0.6374 (4)	0.3226 (2)	0.35669 (14)	0.0278 (6)
H13A	0.7543	0.3066	0.3530	0.033*
H13B	0.5790	0.3254	0.3168	0.033*
C14A	0.5903 (5)	0.1610 (2)	0.46310 (15)	0.0322 (7)
H14A	0.5256	0.1034	0.4381	0.039*
C14B	0.3503 (12)	0.3253 (3)	0.0282 (2)	0.114 (3)
H14B	0.3987	0.3837	0.0551	0.137*
C15A	0.6730 (5)	0.1666 (2)	0.52125 (15)	0.0341 (7)
C15B	0.2811 (8)	0.3197 (3)	−0.03109 (18)	0.0593 (12)
C16A	0.7714 (4)	0.2520 (2)	0.55894 (14)	0.0310 (7)
C16B	0.2181 (5)	0.2343 (3)	−0.07147 (15)	0.0360 (7)
C17A	0.7923 (4)	0.3360 (2)	0.54083 (14)	0.0298 (6)
H17A	0.8590	0.3928	0.5664	0.036*
C17B	0.2152 (5)	0.1506 (3)	−0.05451 (17)	0.0426 (8)
H17B	0.1713	0.0929	−0.0825	0.051*
C18A	0.7535 (6)	0.1409 (3)	0.61281 (17)	0.0458 (9)
H18A	0.6562	0.1423	0.6365	0.055*
H18B	0.8380	0.1073	0.6301	0.055*
C18B	0.2170 (6)	0.3494 (3)	−0.12207 (17)	0.0501 (10)
H18C	0.1194	0.3742	−0.1406	0.060*
H18D	0.3208	0.3623	−0.1424	0.060*
C19A	0.7238 (6)	0.6974 (3)	0.29432 (16)	0.0479 (9)
H19A	0.6619	0.6814	0.2530	0.072*
H19B	0.7465	0.7650	0.3096	0.072*
H19C	0.8374	0.6775	0.2961	0.072*
C19B	0.3039 (8)	−0.1970 (3)	0.19777 (18)	0.0707 (15)
H19D	0.3718	−0.1817	0.2383	0.106*
H19E	0.1973	−0.1707	0.1978	0.106*
H19F	0.2681	−0.2649	0.1836	0.106*
C20A	0.7723 (6)	0.9239 (2)	0.44308 (17)	0.0450 (9)
H20A	0.7468	0.9700	0.4205	0.067*
H20B	0.7146	0.9306	0.4783	0.067*
H20C	0.9015	0.9338	0.4555	0.067*
C20B	0.2580 (9)	−0.4324 (3)	0.0498 (2)	0.0749 (16)
H20D	0.2885	−0.4770	0.0729	0.112*
H20E	0.1288	−0.4471	0.0359	0.112*
H20F	0.3200	−0.4363	0.0155	0.112*
C21A	0.1217 (5)	0.4477 (2)	0.32439 (14)	0.0355 (7)
C21B	0.9534 (5)	0.1109 (3)	0.19683 (16)	0.0435 (9)
C22B	0.9491 (5)	0.1544 (2)	0.26210 (15)	0.0349 (7)
H22A	0.8532	0.1897	0.2623	0.042*
H22B	1.0633	0.2004	0.2780	0.042*
C22A	0.1549 (5)	0.5220 (2)	0.28703 (14)	0.0333 (7)
H22C	0.2639	0.5689	0.3079	0.040*
H22D	0.0543	0.5541	0.2876	0.040*
C23B	0.9198 (4)	0.0890 (2)	0.30740 (13)	0.0283 (6)
C23A	0.1775 (5)	0.4918 (2)	0.22031 (15)	0.0337 (7)
C24B	0.7701 (4)	−0.0017 (2)	0.28108 (14)	0.0296 (6)
H24A	0.7870	−0.0311	0.2408	0.035*
H24B	0.7773	−0.0469	0.3067	0.035*
C24A	0.0343 (5)	0.4044 (2)	0.18235 (15)	0.0363 (7)
H24C	0.0758	0.3804	0.1450	0.044*
H24D	0.0210	0.3546	0.2048	0.044*
C25B	0.5861 (4)	0.0238 (2)	0.27775 (13)	0.0291 (6)
C25A	−0.1455 (6)	0.4288 (4)	0.16755 (19)	0.0630 (13)
C26A	0.3658 (5)	0.4687 (3)	0.21553 (16)	0.0421 (8)
C26B	1.0925 (4)	0.0571 (2)	0.32944 (14)	0.0302 (6)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1A	0.0268 (13)	0.0210 (12)	0.0243 (12)	−0.0001 (9)	0.0040 (9)	0.0031 (10)
N1B	0.0547 (18)	0.0266 (14)	0.0335 (16)	−0.0077 (12)	−0.0115 (13)	0.0126 (12)
O1A	0.0501 (14)	0.0266 (11)	0.0277 (12)	−0.0029 (10)	−0.0027 (10)	0.0082 (9)
O1B	0.0705 (18)	0.0328 (13)	0.0360 (14)	−0.0060 (12)	−0.0148 (12)	0.0149 (11)
O2A	0.0613 (16)	0.0196 (11)	0.0342 (13)	0.0038 (10)	0.0017 (11)	0.0058 (9)
O2B	0.085 (2)	0.0269 (12)	0.0330 (13)	0.0148 (12)	0.0054 (13)	0.0072 (10)
O3A	0.0688 (17)	0.0258 (12)	0.0351 (13)	0.0057 (11)	0.0011 (12)	0.0123 (10)
O3B	0.180 (4)	0.0418 (17)	0.0343 (16)	0.048 (2)	0.0093 (19)	0.0173 (13)
O4A	0.0527 (15)	0.0342 (12)	0.0322 (12)	0.0025 (10)	−0.0008 (10)	0.0157 (10)
O4B	0.086 (2)	0.0437 (16)	0.0419 (16)	0.0019 (14)	−0.0155 (14)	0.0236 (13)
O5B	0.079 (2)	0.083 (2)	0.0376 (16)	0.0153 (17)	0.0038 (14)	0.0285 (16)
O5A	0.0492 (16)	0.0621 (18)	0.0305 (13)	−0.0158 (13)	0.0091 (11)	0.0030 (12)
O6A	0.0649 (18)	0.0385 (14)	0.0429 (16)	0.0083 (12)	0.0035 (13)	0.0153 (12)
O6B	0.076 (2)	0.0551 (17)	0.0331 (15)	0.0170 (15)	0.0173 (13)	0.0088 (13)
O7B	0.0440 (14)	0.0371 (13)	0.0257 (12)	0.0111 (10)	0.0025 (10)	−0.0004 (10)
O7A	0.099 (2)	0.0410 (15)	0.0478 (17)	0.0259 (15)	0.0269 (16)	0.0250 (13)
O8A	0.0606 (19)	0.070 (2)	0.0494 (17)	−0.0061 (15)	0.0281 (14)	0.0045 (15)
O8B	0.0438 (14)	0.0419 (13)	0.0301 (12)	0.0094 (10)	−0.0007 (10)	0.0080 (10)
O9A	0.0442 (15)	0.0580 (17)	0.0417 (15)	0.0208 (13)	0.0020 (11)	−0.0012 (12)
O9B	0.0394 (14)	0.0528 (15)	0.0357 (13)	0.0190 (11)	0.0089 (10)	0.0042 (11)
O10A	0.0441 (18)	0.168 (4)	0.052 (2)	0.042 (2)	−0.0094 (14)	−0.038 (2)
O10B	0.0303 (12)	0.0400 (13)	0.0403 (13)	0.0075 (10)	0.0103 (10)	0.0159 (10)
O11A	0.049 (6)	0.137 (12)	0.038 (5)	0.037 (8)	−0.020 (4)	−0.029 (6)
O11B	0.0376 (13)	0.0450 (14)	0.0327 (12)	0.0084 (10)	0.0030 (10)	0.0173 (11)
C1A	0.0354 (17)	0.0246 (15)	0.0242 (15)	0.0018 (12)	0.0012 (12)	0.0044 (12)
C1B	0.0404 (18)	0.0286 (16)	0.0288 (16)	0.0003 (13)	0.0010 (13)	0.0091 (13)
C2A	0.0394 (17)	0.0233 (15)	0.0304 (16)	0.0032 (12)	0.0054 (13)	0.0068 (12)
C2B	0.051 (2)	0.0305 (17)	0.0304 (17)	0.0096 (14)	0.0117 (15)	0.0096 (13)
C3A	0.0431 (19)	0.0258 (15)	0.0285 (16)	0.0044 (13)	0.0082 (13)	0.0015 (12)
C3B	0.076 (3)	0.0314 (18)	0.0274 (18)	0.0139 (17)	0.0088 (17)	0.0022 (14)
C4A	0.0361 (17)	0.0298 (16)	0.0247 (15)	0.0022 (13)	0.0068 (12)	0.0025 (12)
C4B	0.065 (2)	0.0359 (18)	0.0226 (16)	0.0143 (16)	0.0071 (15)	0.0050 (14)
C5A	0.0302 (16)	0.0270 (15)	0.0243 (15)	0.0027 (12)	0.0081 (12)	0.0052 (12)
C5B	0.0333 (16)	0.0314 (16)	0.0269 (16)	0.0060 (12)	0.0094 (12)	0.0098 (13)
C6A	0.0299 (15)	0.0222 (14)	0.0253 (15)	0.0004 (11)	0.0047 (11)	0.0052 (12)
C6B	0.0329 (16)	0.0280 (16)	0.0285 (16)	−0.0023 (12)	0.0016 (12)	0.0095 (13)
C7A	0.0328 (16)	0.0235 (14)	0.0238 (15)	0.0002 (11)	0.0030 (12)	0.0050 (12)
C7B	0.063 (2)	0.0290 (18)	0.0339 (19)	−0.0100 (16)	−0.0171 (16)	0.0134 (15)
C8A	0.0247 (14)	0.0277 (15)	0.0235 (14)	0.0008 (11)	0.0063 (11)	0.0063 (12)
C8B	0.0274 (15)	0.0325 (16)	0.0268 (15)	0.0034 (12)	0.0055 (12)	0.0115 (13)
C9B	0.0371 (17)	0.0350 (17)	0.0225 (15)	0.0087 (13)	0.0064 (12)	0.0100 (13)
C9A	0.0337 (16)	0.0273 (15)	0.0219 (14)	0.0019 (12)	0.0046 (12)	0.0055 (12)
C10A	0.0317 (16)	0.0244 (15)	0.0259 (15)	0.0029 (12)	0.0073 (12)	0.0077 (12)
C10B	0.0321 (16)	0.0353 (17)	0.0290 (16)	0.0103 (13)	0.0108 (12)	0.0142 (13)
C11A	0.0287 (15)	0.0270 (15)	0.0258 (15)	0.0032 (11)	0.0066 (12)	0.0051 (12)
C11B	0.167 (5)	0.037 (2)	0.0238 (19)	0.046 (3)	0.010 (2)	0.0084 (16)
C12A	0.0329 (16)	0.0237 (14)	0.0275 (15)	0.0018 (12)	0.0050 (12)	0.0043 (12)
C12B	0.055 (6)	0.026 (4)	0.025 (4)	0.003 (3)	0.004 (3)	0.002 (3)
C13B	0.041 (5)	0.024 (4)	0.027 (4)	0.004 (3)	−0.002 (3)	0.003 (3)
C12C	0.035 (4)	0.023 (3)	0.024 (3)	0.001 (2)	0.002 (2)	0.008 (2)
C13C	0.039 (4)	0.023 (3)	0.024 (3)	0.006 (3)	0.002 (3)	0.002 (2)
C13A	0.0340 (16)	0.0231 (14)	0.0243 (15)	0.0032 (12)	0.0070 (12)	0.0022 (12)
C14A	0.0399 (18)	0.0226 (15)	0.0299 (16)	0.0025 (12)	0.0033 (13)	0.0018 (12)
C14B	0.275 (10)	0.038 (2)	0.032 (2)	0.061 (4)	−0.001 (4)	0.005 (2)
C15A	0.0460 (19)	0.0267 (16)	0.0321 (17)	0.0074 (13)	0.0099 (14)	0.0110 (13)
C15B	0.116 (4)	0.039 (2)	0.037 (2)	0.039 (2)	0.018 (2)	0.0183 (17)
C16A	0.0337 (16)	0.0316 (16)	0.0274 (16)	0.0028 (12)	0.0068 (12)	0.0091 (13)
C16B	0.0376 (18)	0.0440 (19)	0.0319 (17)	0.0111 (14)	0.0059 (13)	0.0192 (15)
C17A	0.0332 (16)	0.0270 (15)	0.0275 (16)	0.0014 (12)	0.0044 (12)	0.0074 (12)
C17B	0.049 (2)	0.0345 (18)	0.0375 (19)	−0.0046 (15)	−0.0076 (15)	0.0151 (15)
C18A	0.068 (3)	0.0310 (18)	0.0357 (19)	0.0036 (16)	−0.0008 (17)	0.0141 (15)
C18B	0.077 (3)	0.039 (2)	0.037 (2)	0.0128 (19)	0.0029 (18)	0.0194 (16)
C19A	0.068 (3)	0.042 (2)	0.0274 (18)	−0.0034 (18)	0.0037 (16)	0.0088 (15)
C19B	0.117 (4)	0.053 (3)	0.027 (2)	−0.010 (3)	−0.001 (2)	0.0095 (18)
C20A	0.073 (3)	0.0210 (16)	0.038 (2)	0.0035 (16)	0.0112 (18)	0.0051 (14)
C20B	0.149 (5)	0.029 (2)	0.043 (2)	0.029 (3)	0.000 (3)	−0.0004 (18)
C21A	0.0361 (18)	0.0358 (18)	0.0239 (16)	−0.0093 (13)	0.0001 (13)	0.0012 (13)
C21B	0.052 (2)	0.048 (2)	0.0288 (18)	0.0002 (17)	0.0060 (15)	0.0156 (16)
C22B	0.0378 (18)	0.0291 (16)	0.0346 (18)	−0.0015 (13)	0.0039 (13)	0.0096 (13)
C22A	0.0382 (18)	0.0303 (16)	0.0275 (16)	0.0028 (13)	0.0065 (13)	0.0010 (13)
C23B	0.0337 (16)	0.0263 (15)	0.0218 (14)	0.0031 (12)	0.0038 (12)	0.0022 (12)
C23A	0.049 (2)	0.0274 (15)	0.0277 (16)	0.0091 (14)	0.0108 (14)	0.0095 (13)
C24B	0.0371 (17)	0.0263 (15)	0.0245 (15)	0.0066 (12)	0.0044 (12)	0.0050 (12)
C24A	0.0426 (19)	0.0378 (18)	0.0283 (17)	0.0125 (15)	0.0058 (14)	0.0038 (14)
C25B	0.0319 (16)	0.0292 (15)	0.0228 (15)	0.0028 (12)	0.0031 (12)	0.0027 (12)
C25A	0.064 (3)	0.080 (3)	0.035 (2)	0.039 (2)	−0.0106 (19)	−0.021 (2)
C26A	0.042 (2)	0.044 (2)	0.0296 (18)	−0.0047 (15)	0.0135 (14)	−0.0087 (14)
C26B	0.0316 (16)	0.0279 (15)	0.0297 (16)	0.0024 (12)	0.0056 (12)	0.0068 (12)

Geometric parameters (Å, º)

N1A—C7A	1.331 (4)	C9B—H9BA	0.9300
N1A—C8A	1.392 (4)	C9A—H9AA	0.9300
N1A—C13A	1.487 (4)	C10A—C11A	1.406 (4)
N1B—C7B	1.325 (4)	C10A—C17A	1.415 (4)
N1B—C8B	1.389 (4)	C10B—C11B	1.375 (5)
N1B—C13B	1.437 (8)	C10B—C17B	1.403 (5)
N1B—C13C	1.597 (7)	C11A—C14A	1.404 (4)
O1A—C1A	1.369 (4)	C11A—C12A	1.501 (4)
O1A—C19A	1.432 (4)	C11B—C14B	1.396 (6)
O1B—C1B	1.370 (4)	C11B—C12B	1.547 (8)
O1B—C19B	1.426 (5)	C11B—C12C	1.614 (7)
O2A—C2A	1.364 (4)	C12A—C13A	1.511 (4)
O2A—C20A	1.434 (4)	C12A—H12A	0.9700
O2B—C2B	1.362 (4)	C12A—H12B	0.9700
O2B—C20B	1.431 (5)	C12B—C13B	1.488 (13)
O3A—C15A	1.371 (4)	C12B—H12C	0.9700
O3A—C18A	1.438 (4)	C12B—H12D	0.9700
O3B—C15B	1.366 (4)	C13B—H13C	0.9700
O3B—C18B	1.424 (5)	C13B—H13D	0.9700
O4A—C16A	1.380 (4)	C12C—C13C	1.504 (10)
O4A—C18A	1.434 (4)	C12C—H12E	0.9700
O4B—C16B	1.367 (4)	C12C—H12F	0.9700
O4B—C18B	1.419 (5)	C13C—H13E	0.9700
O5B—C21B	1.203 (5)	C13C—H13F	0.9700
O5A—C21A	1.211 (4)	C13A—H13A	0.9700
O6A—C21A	1.315 (5)	C13A—H13B	0.9700
O6A—H6A	0.873 (19)	C14A—C15A	1.372 (5)
O6B—C21B	1.326 (5)	C14A—H14A	0.9300
O6B—H6B	0.87 (2)	C14B—C15B	1.367 (6)
O7B—C23B	1.412 (4)	C14B—H14B	0.9300
O7B—H7B	0.862 (19)	C15A—C16A	1.390 (5)
O7A—C23A	1.420 (4)	C15B—C16B	1.364 (6)
O7A—H7A	0.87 (2)	C16A—C17A	1.363 (4)
O8A—C26A	1.240 (4)	C16B—C17B	1.355 (5)
O8B—C26B	1.226 (4)	C17A—H17A	0.9300
O9A—C26A	1.249 (5)	C17B—H17B	0.9300
O9B—C26B	1.281 (4)	C18A—H18A	0.9700
O10A—C25A	1.312 (5)	C18A—H18B	0.9700
O10A—H10A	0.8500	C18B—H18C	0.9700
O10B—C25B	1.316 (4)	C18B—H18D	0.9700
O10B—H10B	0.854 (10)	C19A—H19A	0.9600
O11A—C25A	1.207 (8)	C19A—H19B	0.9600
O11C—C25A	1.265 (7)	C19A—H19C	0.9600
O11B—C25B	1.206 (4)	C19B—H19D	0.9600
C1A—C2A	1.386 (4)	C19B—H19E	0.9600
C1A—C6A	1.418 (4)	C19B—H19F	0.9600
C1B—C2B	1.375 (5)	C20A—H20A	0.9600
C1B—C6B	1.410 (4)	C20A—H20B	0.9600
C2A—C3A	1.413 (5)	C20A—H20C	0.9600
C2B—C3B	1.414 (5)	C20B—H20D	0.9600
C3A—C4A	1.365 (5)	C20B—H20E	0.9600
C3A—H3AA	0.9300	C20B—H20F	0.9600
C3B—C4B	1.365 (5)	C21A—C22A	1.515 (5)
C3B—H3BA	0.9300	C21B—C22B	1.507 (5)
C4A—C5A	1.404 (4)	C22B—C23B	1.550 (4)
C4A—H4AA	0.9300	C22B—H22A	0.9700
C4B—C5B	1.395 (5)	C22B—H22B	0.9700
C4B—H4BA	0.9300	C22A—C23A	1.539 (4)
C5A—C9A	1.408 (4)	C22A—H22C	0.9700
C5A—C6A	1.421 (4)	C22A—H22D	0.9700
C5B—C9B	1.411 (4)	C23B—C26B	1.532 (4)
C5B—C6B	1.426 (4)	C23B—C24B	1.539 (4)
C6A—C7A	1.397 (4)	C23A—C24A	1.541 (5)
C6B—C7B	1.391 (5)	C23A—C26A	1.541 (5)
C7A—H7AB	0.9300	C24B—C25B	1.509 (4)
C7B—H7BB	0.9300	C24B—H24A	0.9700
C8A—C9A	1.371 (4)	C24B—H24B	0.9700
C8A—C10A	1.467 (4)	C24A—C25A	1.489 (5)
C8B—C9B	1.367 (5)	C24A—H24C	0.9700
C8B—C10B	1.472 (4)	C24A—H24D	0.9700
C7A—N1A—C8A	122.5 (3)	N1A—C13A—H13A	109.8
C7A—N1A—C13A	119.1 (2)	C12A—C13A—H13A	109.8
C8A—N1A—C13A	118.2 (2)	N1A—C13A—H13B	109.8
C7B—N1B—C8B	122.8 (3)	C12A—C13A—H13B	109.8
C7B—N1B—C13B	117.4 (4)	H13A—C13A—H13B	108.3
C8B—N1B—C13B	117.2 (4)	C15A—C14A—C11A	117.1 (3)
C7B—N1B—C13C	117.9 (3)	C15A—C14A—H14A	121.4
C8B—N1B—C13C	117.7 (3)	C11A—C14A—H14A	121.4
C1A—O1A—C19A	117.1 (3)	C15B—C14B—C11B	117.3 (4)
C1B—O1B—C19B	115.7 (3)	C15B—C14B—H14B	121.4
C2A—O2A—C20A	117.9 (3)	C11B—C14B—H14B	121.4
C2B—O2B—C20B	118.1 (3)	O3A—C15A—C14A	128.2 (3)
C15A—O3A—C18A	104.5 (3)	O3A—C15A—C16A	109.7 (3)
C15B—O3B—C18B	105.0 (3)	C14A—C15A—C16A	122.1 (3)
C16A—O4A—C18A	104.2 (3)	C16B—C15B—O3B	110.5 (3)
C16B—O4B—C18B	106.1 (3)	C16B—C15B—C14B	121.6 (4)
C21A—O6A—H6A	110 (3)	O3B—C15B—C14B	127.9 (4)
C21B—O6B—H6B	111 (5)	C17A—C16A—O4A	127.8 (3)
C23B—O7B—H7B	107 (3)	C17A—C16A—C15A	122.5 (3)
C23A—O7A—H7A	108 (5)	O4A—C16A—C15A	109.7 (3)
C25A—O10A—H10A	101.8	C17B—C16B—C15B	121.8 (3)
C25B—O10B—H10B	110 (3)	C17B—C16B—O4B	129.2 (3)
O1A—C1A—C2A	123.6 (3)	C15B—C16B—O4B	108.9 (3)
O1A—C1A—C6A	117.2 (3)	C16A—C17A—C10A	116.6 (3)
C2A—C1A—C6A	119.1 (3)	C16A—C17A—H17A	121.7
O1B—C1B—C2B	122.7 (3)	C10A—C17A—H17A	121.7
O1B—C1B—C6B	118.0 (3)	C16B—C17B—C10B	118.3 (3)
C2B—C1B—C6B	119.2 (3)	C16B—C17B—H17B	120.9
O2A—C2A—C1A	116.8 (3)	C10B—C17B—H17B	120.9
O2A—C2A—C3A	123.4 (3)	O4A—C18A—O3A	107.5 (3)
C1A—C2A—C3A	119.7 (3)	O4A—C18A—H18A	110.2
O2B—C2B—C1B	116.9 (3)	O3A—C18A—H18A	110.2
O2B—C2B—C3B	123.7 (3)	O4A—C18A—H18B	110.2
C1B—C2B—C3B	119.4 (3)	O3A—C18A—H18B	110.2
C4A—C3A—C2A	121.6 (3)	H18A—C18A—H18B	108.5
C4A—C3A—H3AA	119.2	O4B—C18B—O3B	107.0 (3)
C2A—C3A—H3AA	119.2	O4B—C18B—H18C	110.3
C4B—C3B—C2B	121.8 (3)	O3B—C18B—H18C	110.3
C4B—C3B—H3BA	119.1	O4B—C18B—H18D	110.3
C2B—C3B—H3BA	119.1	O3B—C18B—H18D	110.3
C3A—C4A—C5A	120.2 (3)	H18C—C18B—H18D	108.6
C3A—C4A—H4AA	119.9	O1A—C19A—H19A	109.5
C5A—C4A—H4AA	119.9	O1A—C19A—H19B	109.5
C3B—C4B—C5B	120.5 (3)	H19A—C19A—H19B	109.5
C3B—C4B—H4BA	119.8	O1A—C19A—H19C	109.5
C5B—C4B—H4BA	119.8	H19A—C19A—H19C	109.5
C4A—C5A—C9A	123.2 (3)	H19B—C19A—H19C	109.5
C4A—C5A—C6A	118.8 (3)	O1B—C19B—H19D	109.5
C9A—C5A—C6A	118.0 (3)	O1B—C19B—H19E	109.5
C4B—C5B—C9B	124.1 (3)	H19D—C19B—H19E	109.5
C4B—C5B—C6B	118.1 (3)	O1B—C19B—H19F	109.5
C9B—C5B—C6B	117.8 (3)	H19D—C19B—H19F	109.5
C7A—C6A—C1A	121.5 (3)	H19E—C19B—H19F	109.5
C7A—C6A—C5A	118.1 (3)	O2A—C20A—H20A	109.5
C1A—C6A—C5A	120.4 (3)	O2A—C20A—H20B	109.5
C7B—C6B—C1B	121.2 (3)	H20A—C20A—H20B	109.5
C7B—C6B—C5B	117.8 (3)	O2A—C20A—H20C	109.5
C1B—C6B—C5B	121.0 (3)	H20A—C20A—H20C	109.5
N1A—C7A—C6A	121.5 (3)	H20B—C20A—H20C	109.5
N1A—C7A—H7AB	119.2	O2B—C20B—H20D	109.5
C6A—C7A—H7AB	119.2	O2B—C20B—H20E	109.5
N1B—C7B—C6B	121.9 (3)	H20D—C20B—H20E	109.5
N1B—C7B—H7BB	119.0	O2B—C20B—H20F	109.5
C6B—C7B—H7BB	119.0	H20D—C20B—H20F	109.5
C9A—C8A—N1A	117.4 (3)	H20E—C20B—H20F	109.5
C9A—C8A—C10A	124.7 (3)	O5A—C21A—O6A	120.2 (3)
N1A—C8A—C10A	118.0 (3)	O5A—C21A—C22A	121.1 (3)
C9B—C8B—N1B	117.2 (3)	O6A—C21A—C22A	118.6 (3)
C9B—C8B—C10B	125.0 (3)	O5B—C21B—O6B	119.6 (4)
N1B—C8B—C10B	117.8 (3)	O5B—C21B—C22B	121.6 (4)
C8B—C9B—C5B	122.4 (3)	O6B—C21B—C22B	118.7 (3)
C8B—C9B—H9BA	118.8	C21B—C22B—C23B	119.4 (3)
C5B—C9B—H9BA	118.8	C21B—C22B—H22A	107.5
C8A—C9A—C5A	122.4 (3)	C23B—C22B—H22A	107.5
C8A—C9A—H9AA	118.8	C21B—C22B—H22B	107.5
C5A—C9A—H9AA	118.8	C23B—C22B—H22B	107.5
C11A—C10A—C17A	121.1 (3)	H22A—C22B—H22B	107.0
C11A—C10A—C8A	119.9 (3)	C21A—C22A—C23A	119.7 (3)
C17A—C10A—C8A	118.8 (3)	C21A—C22A—H22C	107.4
C11B—C10B—C17B	119.5 (3)	C23A—C22A—H22C	107.4
C11B—C10B—C8B	120.1 (3)	C21A—C22A—H22D	107.4
C17B—C10B—C8B	120.4 (3)	C23A—C22A—H22D	107.4
C14A—C11A—C10A	120.6 (3)	H22C—C22A—H22D	106.9
C14A—C11A—C12A	121.0 (3)	O7B—C23B—C26B	108.8 (2)
C10A—C11A—C12A	118.4 (3)	O7B—C23B—C24B	109.3 (3)
C10B—C11B—C14B	121.5 (4)	C26B—C23B—C24B	106.9 (2)
C10B—C11B—C12B	110.9 (4)	O7B—C23B—C22B	105.6 (2)
C14B—C11B—C12B	123.2 (4)	C26B—C23B—C22B	113.0 (3)
C10B—C11B—C12C	119.4 (4)	C24B—C23B—C22B	113.2 (3)
C14B—C11B—C12C	116.4 (5)	O7A—C23A—C22A	105.7 (3)
C11A—C12A—C13A	109.5 (3)	O7A—C23A—C24A	109.1 (3)
C11A—C12A—H12A	109.8	C22A—C23A—C24A	115.0 (3)
C13A—C12A—H12A	109.8	O7A—C23A—C26A	108.8 (3)
C11A—C12A—H12B	109.8	C22A—C23A—C26A	111.3 (3)
C13A—C12A—H12B	109.8	C24A—C23A—C26A	106.8 (3)
H12A—C12A—H12B	108.2	C25B—C24B—C23B	109.3 (2)
C13B—C12B—C11B	103.1 (7)	C25B—C24B—H24A	109.8
C13B—C12B—H12C	111.1	C23B—C24B—H24A	109.8
C11B—C12B—H12C	111.1	C25B—C24B—H24B	109.8
C13B—C12B—H12D	111.1	C23B—C24B—H24B	109.8
C11B—C12B—H12D	111.1	H24A—C24B—H24B	108.3
H12C—C12B—H12D	109.1	C25A—C24A—C23A	111.3 (3)
N1B—C13B—C12B	104.7 (7)	C25A—C24A—H24C	109.4
N1B—C13B—H13C	110.8	C23A—C24A—H24C	109.4
C12B—C13B—H13C	110.8	C25A—C24A—H24D	109.4
N1B—C13B—H13D	110.8	C23A—C24A—H24D	109.4
C12B—C13B—H13D	110.8	H24C—C24A—H24D	108.0
H13C—C13B—H13D	108.9	O11B—C25B—O10B	123.5 (3)
C13C—C12C—C11B	101.5 (5)	O11B—C25B—C24B	123.2 (3)
C13C—C12C—H12E	111.5	O10B—C25B—C24B	113.3 (3)
C11B—C12C—H12E	111.5	O11A—C25A—O10A	109.3 (7)
C13C—C12C—H12F	111.5	O11C—C25A—O10A	128.9 (5)
C11B—C12C—H12F	111.5	O11A—C25A—C24A	131.3 (5)
H12E—C12C—H12F	109.3	O11C—C25A—C24A	117.5 (5)
C12C—C13C—N1B	105.7 (6)	O10A—C25A—C24A	112.6 (3)
C12C—C13C—H13E	110.6	O8A—C26A—O9A	123.8 (4)
N1B—C13C—H13E	110.6	O8A—C26A—C23A	118.4 (4)
C12C—C13C—H13F	110.6	O9A—C26A—C23A	117.7 (3)
N1B—C13C—H13F	110.6	O8B—C26B—O9B	125.5 (3)
H13E—C13C—H13F	108.7	O8B—C26B—C23B	119.0 (3)
N1A—C13A—C12A	109.3 (2)	O9B—C26B—C23B	115.4 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O6A—H6A···O9A	0.87 (2)	1.63 (2)	2.481 (4)	164 (5)
O6B—H6B···O9B	0.87 (2)	1.68 (3)	2.536 (4)	165 (9)
O7A—H7A···O8A	0.87 (2)	2.13 (7)	2.611 (5)	115 (6)
O7B—H7B···O8B	0.86 (2)	2.07 (4)	2.604 (3)	120 (4)
O10A—H10A···O8A^i	0.85	1.93	2.761 (5)	167
O10B—H10B···O9B^i	0.85 (1)	1.69 (1)	2.545 (3)	176 (5)

Symmetry code: (i) x−1, y, z.