research communications
Syntheses and crystal structures of hydrated and anhydrous 1:2 cocrystals of oxyresveratrol and zwitterionic proline
aDepartment of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, 90112, Thailand, bDivision of Physical Science and Center of Excellence for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat-Yai, Songkhla, 90112, Thailand, cMedical Science Research and Innovation Institute, Research and Development Office, Prince of Songkla University, Hat-Yai, 90112, Thailand, and dCenter of Excellence for Drug Delivery System and Department of Pharmaceutical, Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, 90112, Thailand
*Correspondence e-mail: vimon.t@psu.ac.th
The hydrated and anhydrous 1:2 cocrystals of oxyresveratrol (4-[(E)-2-(3,5-dihydroxyphenyl)ethenyl]benzene-1,3-diol; OXY; C14H12O4) and proline [(S)-pyrrolidine-2-carboxylic acid; PRO; C5H9NO2], namely, 4-[(E)-2-(3,5-dihydroxyphenyl)ethenyl]benzene-1,3-diol bis[(S)-pyrrolidin-1-ium-2-carboxylate] monohydrate, C14H12O4·2C5H9NO2·H2O, and the anhydrous form, C14H12O4·2C5H9NO2, were obtained by crystallization at different temperatures. Both of them crystallize with orthorhombic (P212121) symmetry. The structures display N—H⋯O and O—H⋯O hydrogen-bonding interactions between PRO and PRO, OXY and OXY, and OXY and PRO. In the hydrated cocrystal, these types of contacts are also observed between the OXY, PRO and water molecules. A combination of these interactions leads to a three-dimensional supramolecular assembly in each case. Hirshfeld surfaces were used to gain further insight into the intermolecular interactions in the packing, including the relative percentage contributions of the significant intermolecular H⋯H and H⋯O/O⋯H contacts.
Keywords: cocrystal structure; zwitterion; oxyresveratrol; resveratrol.
1. Chemical context
Oxyresveratrol (4-[(E)-2-(3,5-dihydroxyphenyl)ethenyl]benzene-1,3-diol; OXY; C14H12O4) is a natural stilbenoid found in various plants, such as Morus alba L. (Lu et al., 2017). It has several biological activities, including neuroprotective and hepatoprotective effects (Shah et al., 2019; Jia et al., 2018; Chao et al., 2008). As the aqueous solubility of OXY is low, there have been attempts to improve its solubility and oral bioavailability by cocrystallization with citric acid and glutaric acid (Suzuki et al., 2019). Proline [(S)-pyrrolidine-2-carboxylic acid; PRO,; C5H9NO2] is a natural amino acid that has a secondary amino group in the form of a pyrrolydinic ring. It is an osmoprotectant and is used frequently in many pharmacological and biotechnological applications (Panday, 2011). PRO has been used as a cocrystal former in various drugs and pharmacological active compounds because of its molecular rigidity and high solubility in water (Chesna et al., 2017; Surov et al., 2018; Tilborg et al., 2014). According to previous studies, the phenolic hydroxyl groups of are able to form charge-assisted hydrogen bonds with the carboxylate moiety of PRO (He et al., 2016). Moreover, PRO could form a cocrystal with resveratrol [(E)-5-(4-hydroxystyryl)benzene-1,3-diol; RES; C14H12O3], which is a close analogue of OXY (He et al., 2017). Therefore, PRO is a good candidate as a cocrystal former for cocrystallization with OXY and we now describe the syntheses and structures of hydrated and anhydrous 1:2 cocrystals of OXY and PRO, hereafter (I) and (II).
2. Structural commentary
Both cocrystals of OXY and PRO form a 1:2 stoichiometry in the orthorhombic system, P212121, with Z = 4. The of (I) contains two PRO, one OXY and one water molecule while the of (II) consists of only two PRO and one OXY molecules, as depicted in Fig. 1. The dihedral angle between the planes of the OXY C1–C6 and C9–C14 phenyl rings in (I) is 7.1 (2)°. This is slightly different from the previous report [9.39 (9)°] of the corresponding angle in OXY·2H2O (Deng et al., 2012). However, a more twisted dihedral angle between these phenyl rings is observed in (II), of 14.15 (19)°. It might be caused by the influence of hydrogen-bonding interactions in the crystal. In addition, the zwitterionic form of the PRO molecules of both cocrystals is confirmed by the C—O and C—N bond lengths.
3. Supramolecular features
The packing for (I) and (II) is shown in Fig. 2. The two PRO molecules (PRO 1 and PRO 2) are indicated in blue and red, respectively, whereas the OXY and water molecules are shown in green and yellow, respectively. The main architectures of (I) and (II) are quite similar but there are clearly differences regarding the water molecule in (I).
The PRO 1 and PRO 2 molecules form a three-dimensional network of N—H⋯O hydrogen bonds between the H atoms of NH2 groups and O atoms of carboxylate groups: N1—H1A⋯O6iii, N2—H2A⋯O8v and N2—H2B⋯O5vi for (I) and N1—H1B⋯O5iii, N1—H1A⋯O8iv and N2—H2B⋯O6vi for (II) (see Tables 1 and 2, where the symmetry codes are defined). The hydrogen-bonding interactions between PRO 1 and PRO 2 of both cocrystals viewed down [100] are shown in Fig. 3. The phenolic hydroxyl groups from the OXY molecule interact with O atoms of the carboxylate groups of the PRO molecules via O—H⋯O hydrogen bonds, namely O2—H2′⋯O6 and O1—H1′⋯O8 for (I) and O1—H1′⋯O8, O2—H2′⋯O6 and O4—H4′⋯O7ii for (II). In addition, one of the four hydroxyl groups of OXY accepts a hydrogen bond N1—H1B⋯O4iv from PRO at an N⋯O distance of 2.951 (4) Å in (I) while the equivalent bond in (II) is observed at 2.920 (4) Å for N2—H2A⋯O4v. Moreover, hydrogen-bonding contacts among the OXY molecules in both cocrystals are observed between phenolic hydroxyl groups, O3—H3′⋯O2i, for both cocrystals. Further hydrogen-bond interactions involving the water molecule are observed in (I): N1—H1B⋯O9iv between PRO and water [N⋯O = 3.105 (5) Å] and O4—H4′⋯O9 [2.575 (6) Å] and O9—H9A⋯O7ii [2.639 (5) Å] interactions between OXY and water molecules. Taken together, the hydrogen bonds in both cocrystals form complex three-dimensional supramolecular architectures.
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4. Hirshfeld surface analysis
Hirshfeld surface analysis and two dimensional fingerprint plots are used to provide the additional insight of the weak intermolecular contacts and intermolecular interactions in the crystal packing of molecules (McKinnon et al., 2004; 2007; Spackman & Jayatilaka, 2009). The blue, white and red areas in the dnorm-mapped Hirshfeld surfaces indicate interatomic contacts longer, equal to and shorter than the sum of the van der Waals radii, respectively. Analysis of (I) and (II) was performed by using Crystal Explorer 17.5 (Turner et al., 2017). The Hirshfeld surfaces are plotted for individual components, to examine the interactions of the main molecules (PRO and OXY) in the cocrystals.
The Hirshfeld surfaces around the PRO molecules mapped over dnorm are shown in Fig. 4 with selected atoms labelled (compare Tables 1 and 2). There are red spots on the surface close to H atoms of the amine group inside the surface of PRO molecules in both cocrystals, H1A and H1B for PRO 1 and H2A and H2B for PRO 2. The inside zones indicate hydrogen-bond donors to acceptor O atoms at outside surfaces of the nearby carboxylate groups of adjacent PRO molecules (N—H⋯O type), hydroxyl group of OXY (N—H⋯O type) and O atoms of water [only for (I), O—H⋯O and N—H⋯O forms]. Besides, the O atoms of the carboxylate groups of both PRO molecules acting as hydrogen-bond acceptors interact with the hydrogen-bond donor NH2 group of PRO molecules on the outside surfaces, as discussed in the Supramolecular features section.
In addition, the two-dimensional fingerprint plots of the PRO molecules for (I) and (II) are illustrated in Figs. 5 and 6, showing the relative contributions of the various types of contacts to the Hirshfeld surface. The overall fingerprint plot for PRO 1 is shown in Fig. 5a and 6a and those delineated into the contacts of H⋯H, O⋯H/H⋯O and C⋯H/H⋯C interactions are displayed in Fig. 5b–d and 6b–d. Similarly, the overall fingerprint plot of PRO 2 of both cocrystals is presented in Fig. 5e and 6e and those delineated into individual contacts are shown in Fig. 5f–h and 6f–h. For cocrystals (I) and (II), the most significant interactions in terms to their relative percentage contributions are by H⋯H contacts with the second largest percentage attributed to H⋯O/O⋯H interactions in one PRO molecule and vice versa for the other PRO molecule. A pair of blue-colored spikes pointing towards the bottom left of the H⋯O/O⋯H contacts in Figs. 5 and 6 correlate with the important O—H⋯O and N—H⋯O hydrogen bonds associated with the deep-red spots shown in Fig. 4. The asymmetric pair of wings for H⋯C/C⋯H interactions in both cocrystals are also found, while other types of contact make a negligible contribution. The relative percentage contributions for the PRO 1 and PRO 2 molecules in both cocrystals are summarized in Table 3.
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The OXY Hirshfeld surface, including fingerprint plots for each cocrystal, is depicted in Fig. 7. The bright-red spots on the surfaces relate to the significant hydrogen bonds of the phenolic hydroxyl groups as O donors (O—H⋯O) and acceptors (N—H⋯O). In (I), the hydrogen-bond contacts are observed from the O atom of the water molecule linking with the OXY surface through one of the hydroxyl groups. In addition, it is found that this water molecule is connected with PRO molecule via a hydrogen-bonding interaction, as indicated in part of the PRO surfaces. The fingerprint plots for OXY are illustrated below the Hirshfeld surfaces in Fig. 7a–c for (I) and Fig. 7d–f for (II). The fingerprint plots Fig. 7a and Fig. 7d show the overall interactions (100%) of the OXY surface. The most significant interactions are H⋯H contacts [38.6% for (I) and 38.2% for (II)] and the second largest percentage [33.3% for (I) and 35.1% for (II)] can be attributed to H⋯O/O⋯H contacts, which are seen as red spots on the Hirshfeld surfaces and correlate with the O—H⋯O and N—H⋯O hydrogen bonds. The relative percentage contributions of OXY are also included in Table 3. Overall, there are few differences between the Hirshfeld surfaces, fingerprint patterns and the relative percentage contributions for (I) and (II).
5. Database survey
Based on the SciFinder (2020) database, there are no reports for cocrystal structures containing OXY. Only the of OXY dihydrate was previously reported (Deng et al., 2012; Cambridge Structural Database refcode ZAPDOL). The connecting C=C bond of OXY has a trans configuration and allows the setup of a throughout the OXY molecule. Furthermore, in the crystal, the OXY molecules are connected through O—H⋯O hydrogen bonds between the hydroxy groups of OXY and water molecules. The anhydrous and monohydrate crystals of PRO have been reported in numerous papers (Seijas et al., 2010; Janczak & Luger, 1997; Verbist et al., 1972; Caetano et al., 2018; Koenig et al., 2018) and PRO invariably crystallizes in the zwitterionic form.
A search for cocrystal structures of PRO gave 148 hits. PRO has been used as a cocrystal former of various active pharmaceutical ingredients (Tilborg et al., 2013; Tumanova et al., 2018; Song et al., 2019). The most relevant cocrystal structure to this work is the cocrystal of RES and PRO (He et al., 2017; refcode PEBZEE). RES and PRO form O—H⋯O hydrogen bonds in the cocrystal.
6. Synthesis and crystallization
OXY and PRO were purchased from Chengdu Biopurify Phytochemicals Ltd. (Sichuan, China) and Sigma Aldrich (St. Louis, MO, USA), respectively. All organic solvents used were of analytical grade and were purchased from RCI Labscan Ltd (Bangkok, Thailand). All chemicals and solvents were used as received without further purification. Solid OXY (122.10 mg, 0.50 mmol) and PRO (115.10 mg, 1.00 mmol) were added to a 20 ml transparent glass vial. To this was added a mixture of methanol and acetonitrile (1:1 v/v, 12 ml), followed by sonication until all solids were entirely dissolved. The mixture was divided into two portions, and each was covered with aluminum foil with a few small holes in it. Crystals of (I) in the form of colourless rods were obtained when the solution was placed on a hot plate at 323 K for 16 h. Single crystals of (II) (colourless blocks) were grown from a solution that was left at room temperature (303 K) for 16 h.
7. Refinement
Crystal data, data collection and structure and (II) are summarized in Table 4. The H atoms of PRO molecules of both cocrystals were included with calculated positions and isotropically refined with Uiso(H) = 1.2Ueq(N). However, two H atoms on phenolic hydroxyl groups for OXY [for (I) and (II)] and water [for (I)] were located in difference maps and isotropically refined with the distance restraint O—H = 0.82 (2)–0.89 (2) Å for OXY and O—H = 0.89 (2)–1.03 (2) Å for water. The other two H atoms of the OXY molecules were calculated and isotropically refined and the constraint with Uiso(H) = 1.5Ueq(O) was applied.
details for (I)
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Supporting information
https://doi.org/10.1107/S2056989020011536/hb7935sup1.cif
contains datablocks I, II, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989020011536/hb7935Isup2.hkl
Structure factors: contains datablock II. DOI: https://doi.org/10.1107/S2056989020011536/hb7935IIsup3.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989020011536/hb7935Isup4.cml
Supporting information file. DOI: https://doi.org/10.1107/S2056989020011536/hb7935IIsup5.cml
For both structures, data collection: APEX2 (Bruker, 2016); cell
SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: Mercury (Macrae et al., 2020); software used to prepare material for publication: WinGX (Farrugia, 2012) and publCIF (Westrip, 2010).C14H12O4·2C5H9NO2·H2O | Dx = 1.353 Mg m−3 |
Mr = 492.51 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, P212121 | Cell parameters from 9870 reflections |
a = 9.9759 (2) Å | θ = 3.3–27.2° |
b = 10.6052 (2) Å | µ = 0.10 mm−1 |
c = 22.8535 (4) Å | T = 297 K |
V = 2417.82 (8) Å3 | Rod, colourless |
Z = 4 | 0.33 × 0.23 × 0.11 mm |
F(000) = 1048 |
Bruker D8 VENTURE diffractometer | 4237 independent reflections |
Radiation source: Sealed x-ray tube | 4046 reflections with I > 2σ(I) |
GraphiteDouble Bounce Multilayer Mirror monochromator | Rint = 0.024 |
Detector resolution: 7.39 pixels mm-1 | θmax = 25.0°, θmin = 2.9° |
φ and ω scans | h = −11→11 |
Absorption correction: multi-scan (SADABS; Bruker, 2016) | k = −12→12 |
Tmin = 0.716, Tmax = 0.746 | l = −27→27 |
27568 measured reflections |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.044 | Hydrogen site location: mixed |
wR(F2) = 0.117 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.05 | w = 1/[σ2(Fo2) + (0.0603P)2 + 1.0192P] where P = (Fo2 + 2Fc2)/3 |
4237 reflections | (Δ/σ)max < 0.001 |
332 parameters | Δρmax = 0.35 e Å−3 |
4 restraints | Δρmin = −0.31 e Å−3 |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.1315 (3) | 0.6159 (2) | 0.61582 (10) | 0.0526 (7) | |
N1 | 0.7751 (3) | 0.3182 (3) | 0.47097 (13) | 0.0448 (7) | |
H1A | 0.821241 | 0.251273 | 0.483057 | 0.054* | |
H1B | 0.765150 | 0.313168 | 0.432344 | 0.054* | |
C1 | 0.1165 (3) | 0.6442 (3) | 0.55821 (13) | 0.0380 (7) | |
O2 | 0.2661 (2) | 0.5415 (2) | 0.42047 (10) | 0.0456 (6) | |
H2' | 0.323 (4) | 0.489 (4) | 0.4405 (11) | 0.068* | |
N2 | −0.0782 (3) | 0.4926 (2) | 0.79401 (11) | 0.0366 (6) | |
H2A | −0.032399 | 0.421409 | 0.799100 | 0.044* | |
H2B | −0.055795 | 0.546139 | 0.822364 | 0.044* | |
C2 | 0.0261 (4) | 0.7335 (3) | 0.53867 (14) | 0.0459 (8) | |
H2 | −0.026401 | 0.778272 | 0.565113 | 0.055* | |
O3 | −0.2666 (3) | 0.9933 (3) | 0.19900 (11) | 0.0567 (7) | |
C3 | 0.0150 (4) | 0.7553 (3) | 0.47947 (14) | 0.0484 (8) | |
H3 | −0.047640 | 0.814001 | 0.466565 | 0.058* | |
O4 | 0.0969 (5) | 0.7386 (4) | 0.13945 (13) | 0.0928 (13) | |
H4' | 0.190 (8) | 0.723 (8) | 0.1526 (16) | 0.139* | |
C4 | 0.0942 (3) | 0.6928 (3) | 0.43769 (13) | 0.0369 (7) | |
O5 | 0.5778 (3) | 0.4212 (3) | 0.41114 (10) | 0.0520 (6) | |
C5 | 0.1858 (3) | 0.6041 (3) | 0.45910 (12) | 0.0323 (6) | |
O6 | 0.4180 (2) | 0.3743 (2) | 0.47524 (11) | 0.0489 (6) | |
C6 | 0.1957 (3) | 0.5792 (3) | 0.51887 (13) | 0.0354 (6) | |
H6 | 0.255747 | 0.518732 | 0.532283 | 0.042* | |
O7 | −0.0442 (5) | 0.7425 (2) | 0.78719 (12) | 0.0891 (13) | |
C7 | 0.0819 (4) | 0.7181 (3) | 0.37485 (14) | 0.0426 (7) | |
H7 | 0.147494 | 0.684006 | 0.350660 | 0.051* | |
O8 | −0.0014 (3) | 0.7457 (2) | 0.69276 (10) | 0.0562 (7) | |
C8 | −0.0133 (4) | 0.7847 (4) | 0.34932 (14) | 0.0450 (8) | |
H8 | −0.078062 | 0.818540 | 0.374046 | 0.054* | |
O9 | 0.3312 (5) | 0.6407 (4) | 0.1266 (2) | 0.0987 (14) | |
C9 | −0.0299 (3) | 0.8120 (3) | 0.28670 (14) | 0.0391 (7) | |
C10 | −0.1353 (3) | 0.8902 (3) | 0.27012 (14) | 0.0418 (7) | |
H10 | −0.190263 | 0.925334 | 0.298660 | 0.050* | |
C11 | −0.1595 (3) | 0.9162 (3) | 0.21180 (14) | 0.0426 (7) | |
C12 | −0.0792 (4) | 0.8656 (4) | 0.16910 (15) | 0.0519 (9) | |
H12 | −0.094718 | 0.884207 | 0.129914 | 0.062* | |
C13 | 0.0242 (4) | 0.7874 (4) | 0.18468 (15) | 0.0548 (9) | |
C14 | 0.0517 (4) | 0.7593 (3) | 0.24318 (15) | 0.0472 (8) | |
H14 | 0.122696 | 0.706643 | 0.253042 | 0.057* | |
C15 | 0.5376 (3) | 0.3770 (3) | 0.45739 (13) | 0.0357 (7) | |
C16 | 0.6412 (3) | 0.3223 (3) | 0.50027 (14) | 0.0378 (7) | |
H16 | 0.614353 | 0.237957 | 0.513251 | 0.045* | |
C17 | 0.6655 (4) | 0.4086 (5) | 0.55262 (16) | 0.0623 (11) | |
H17A | 0.583267 | 0.450158 | 0.564463 | 0.075* | |
H17B | 0.700761 | 0.361392 | 0.585567 | 0.075* | |
C18 | 0.7653 (6) | 0.5017 (6) | 0.5311 (3) | 0.0917 (17) | |
H18A | 0.720375 | 0.573782 | 0.513840 | 0.110* | |
H18B | 0.821256 | 0.530953 | 0.563023 | 0.110* | |
C19 | 0.8472 (5) | 0.4362 (5) | 0.4868 (3) | 0.0820 (15) | |
H19A | 0.935075 | 0.416595 | 0.502539 | 0.098* | |
H19B | 0.858597 | 0.489086 | 0.452511 | 0.098* | |
C20 | −0.0468 (3) | 0.5485 (3) | 0.73547 (12) | 0.0331 (6) | |
H20 | 0.035826 | 0.510986 | 0.720132 | 0.040* | |
C21 | −0.1645 (5) | 0.5115 (4) | 0.69655 (18) | 0.0650 (11) | |
H21A | −0.210407 | 0.586187 | 0.682371 | 0.078* | |
H21B | −0.133480 | 0.463214 | 0.663169 | 0.078* | |
C22 | −0.2580 (5) | 0.4327 (5) | 0.7340 (2) | 0.0784 (14) | |
H22A | −0.350908 | 0.452288 | 0.725335 | 0.094* | |
H22B | −0.243179 | 0.343458 | 0.727209 | 0.094* | |
C23 | −0.2245 (4) | 0.4669 (4) | 0.7956 (2) | 0.0656 (11) | |
H23A | −0.273919 | 0.541110 | 0.807923 | 0.079* | |
H23B | −0.244741 | 0.397964 | 0.822045 | 0.079* | |
C24 | −0.0301 (4) | 0.6913 (3) | 0.73993 (14) | 0.0455 (8) | |
H1' | 0.080 (4) | 0.660 (4) | 0.6361 (18) | 0.068* | |
H3' | −0.270 (5) | 1.004 (5) | 0.1623 (11) | 0.068* | |
H9A | 0.376 (4) | 0.670 (4) | 0.1576 (14) | 0.055* | |
H9B | 0.419 (3) | 0.644 (4) | 0.1031 (16) | 0.055* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0727 (17) | 0.0544 (15) | 0.0305 (11) | 0.0138 (13) | 0.0030 (11) | 0.0011 (11) |
N1 | 0.0333 (14) | 0.0529 (17) | 0.0481 (16) | 0.0065 (12) | 0.0018 (12) | 0.0036 (13) |
C1 | 0.0474 (18) | 0.0358 (16) | 0.0309 (15) | −0.0028 (14) | −0.0001 (13) | −0.0031 (12) |
O2 | 0.0475 (13) | 0.0572 (14) | 0.0322 (12) | 0.0176 (11) | −0.0042 (10) | −0.0039 (10) |
N2 | 0.0513 (16) | 0.0274 (12) | 0.0311 (13) | −0.0006 (11) | 0.0041 (11) | −0.0008 (10) |
C2 | 0.0532 (19) | 0.0458 (18) | 0.0388 (17) | 0.0128 (16) | 0.0072 (15) | −0.0022 (14) |
O3 | 0.0526 (15) | 0.0767 (18) | 0.0408 (14) | 0.0061 (14) | −0.0015 (11) | 0.0187 (14) |
C3 | 0.054 (2) | 0.0473 (19) | 0.0439 (18) | 0.0172 (16) | 0.0014 (16) | 0.0053 (15) |
O4 | 0.126 (3) | 0.097 (3) | 0.0546 (17) | 0.039 (2) | 0.0386 (19) | 0.0031 (18) |
C4 | 0.0368 (16) | 0.0379 (16) | 0.0359 (16) | 0.0031 (13) | −0.0006 (13) | −0.0006 (13) |
O5 | 0.0557 (14) | 0.0676 (16) | 0.0326 (11) | 0.0066 (12) | 0.0033 (11) | 0.0128 (11) |
C5 | 0.0310 (14) | 0.0343 (15) | 0.0316 (14) | −0.0030 (12) | −0.0022 (11) | −0.0052 (12) |
O6 | 0.0313 (12) | 0.0589 (15) | 0.0565 (14) | 0.0063 (11) | 0.0013 (10) | 0.0141 (12) |
C6 | 0.0351 (15) | 0.0371 (15) | 0.0339 (15) | 0.0014 (12) | −0.0054 (12) | 0.0003 (13) |
O7 | 0.191 (4) | 0.0338 (13) | 0.0430 (14) | −0.0075 (19) | 0.031 (2) | −0.0107 (12) |
C7 | 0.0484 (18) | 0.0435 (18) | 0.0358 (16) | 0.0078 (15) | 0.0034 (14) | 0.0017 (14) |
O8 | 0.099 (2) | 0.0303 (11) | 0.0394 (12) | −0.0038 (13) | 0.0118 (13) | 0.0020 (10) |
C8 | 0.0436 (18) | 0.056 (2) | 0.0360 (17) | 0.0085 (16) | 0.0019 (14) | 0.0033 (15) |
O9 | 0.109 (3) | 0.072 (2) | 0.115 (3) | 0.016 (2) | −0.056 (3) | −0.022 (2) |
C9 | 0.0418 (16) | 0.0414 (17) | 0.0341 (15) | −0.0007 (14) | 0.0015 (14) | 0.0045 (13) |
C10 | 0.0434 (17) | 0.0479 (18) | 0.0341 (16) | 0.0007 (15) | 0.0058 (13) | 0.0057 (14) |
C11 | 0.0456 (18) | 0.0458 (18) | 0.0363 (16) | −0.0069 (15) | −0.0001 (14) | 0.0074 (14) |
C12 | 0.072 (2) | 0.052 (2) | 0.0313 (16) | −0.0028 (19) | 0.0020 (16) | 0.0065 (15) |
C13 | 0.074 (2) | 0.0491 (19) | 0.0411 (19) | 0.0025 (19) | 0.0206 (18) | 0.0002 (16) |
C14 | 0.054 (2) | 0.0429 (18) | 0.0449 (18) | 0.0043 (15) | 0.0050 (16) | 0.0058 (15) |
C15 | 0.0348 (16) | 0.0383 (16) | 0.0340 (16) | 0.0034 (13) | −0.0010 (12) | 0.0005 (13) |
C16 | 0.0318 (15) | 0.0457 (18) | 0.0357 (15) | 0.0007 (13) | 0.0013 (13) | 0.0089 (13) |
C17 | 0.057 (2) | 0.095 (3) | 0.0356 (18) | 0.000 (2) | −0.0052 (16) | −0.005 (2) |
C18 | 0.092 (4) | 0.094 (4) | 0.088 (4) | −0.028 (3) | 0.004 (3) | −0.033 (3) |
C19 | 0.053 (2) | 0.058 (3) | 0.135 (5) | −0.012 (2) | 0.018 (3) | 0.000 (3) |
C20 | 0.0461 (17) | 0.0274 (13) | 0.0259 (13) | 0.0006 (12) | 0.0021 (12) | −0.0016 (11) |
C21 | 0.079 (3) | 0.065 (3) | 0.051 (2) | −0.018 (2) | −0.023 (2) | 0.003 (2) |
C22 | 0.062 (3) | 0.077 (3) | 0.096 (4) | −0.022 (2) | −0.018 (2) | 0.004 (3) |
C23 | 0.053 (2) | 0.069 (3) | 0.075 (3) | −0.005 (2) | 0.015 (2) | 0.007 (2) |
C24 | 0.073 (2) | 0.0290 (15) | 0.0341 (16) | 0.0016 (15) | 0.0058 (16) | −0.0039 (13) |
O1—C1 | 1.359 (4) | O9—H9A | 0.89 (2) |
O1—H1' | 0.84 (2) | O9—H9B | 1.03 (2) |
N1—C19 | 1.487 (6) | C9—C10 | 1.392 (5) |
N1—C16 | 1.495 (4) | C9—C14 | 1.401 (5) |
N1—H1A | 0.8900 | C10—C11 | 1.382 (4) |
N1—H1B | 0.8900 | C10—H10 | 0.9300 |
C1—C6 | 1.381 (5) | C11—C12 | 1.372 (5) |
C1—C2 | 1.382 (5) | C12—C13 | 1.370 (6) |
O2—C5 | 1.364 (4) | C12—H12 | 0.9300 |
O2—H2' | 0.92 (5) | C13—C14 | 1.397 (5) |
N2—C23 | 1.486 (5) | C14—H14 | 0.9300 |
N2—C20 | 1.496 (4) | C15—C16 | 1.538 (4) |
N2—H2A | 0.8900 | C16—C17 | 1.525 (5) |
N2—H2B | 0.8900 | C16—H16 | 0.9800 |
C2—C3 | 1.377 (5) | C17—C18 | 1.486 (7) |
C2—H2 | 0.9300 | C17—H17A | 0.9700 |
O3—C11 | 1.378 (4) | C17—H17B | 0.9700 |
O3—H3' | 0.85 (2) | C18—C19 | 1.475 (8) |
C3—C4 | 1.405 (5) | C18—H18A | 0.9700 |
C3—H3 | 0.9300 | C18—H18B | 0.9700 |
O4—C13 | 1.365 (4) | C19—H19A | 0.9700 |
O4—H4' | 0.99 (8) | C19—H19B | 0.9700 |
C4—C5 | 1.400 (4) | C20—C21 | 1.525 (5) |
C4—C7 | 1.466 (4) | C20—C24 | 1.526 (4) |
O5—C15 | 1.224 (4) | C20—H20 | 0.9800 |
C5—C6 | 1.395 (4) | C21—C22 | 1.517 (6) |
O6—C15 | 1.262 (4) | C21—H21A | 0.9700 |
C6—H6 | 0.9300 | C21—H21B | 0.9700 |
O7—C24 | 1.217 (4) | C22—C23 | 1.492 (7) |
C7—C8 | 1.319 (5) | C22—H22A | 0.9700 |
C7—H7 | 0.9300 | C22—H22B | 0.9700 |
O8—C24 | 1.256 (4) | C23—H23A | 0.9700 |
C8—C9 | 1.469 (4) | C23—H23B | 0.9700 |
C8—H8 | 0.9300 | ||
C1—O1—H1' | 110 (3) | C13—C14—H14 | 120.6 |
C19—N1—C16 | 107.4 (3) | C9—C14—H14 | 120.6 |
C19—N1—H1A | 110.2 | O5—C15—O6 | 126.7 (3) |
C16—N1—H1A | 110.2 | O5—C15—C16 | 118.3 (3) |
C19—N1—H1B | 110.2 | O6—C15—C16 | 114.9 (3) |
C16—N1—H1B | 110.2 | N1—C16—C17 | 103.1 (3) |
H1A—N1—H1B | 108.5 | N1—C16—C15 | 109.0 (2) |
O1—C1—C6 | 117.2 (3) | C17—C16—C15 | 112.4 (3) |
O1—C1—C2 | 122.5 (3) | N1—C16—H16 | 110.7 |
C6—C1—C2 | 120.3 (3) | C17—C16—H16 | 110.7 |
C5—O2—H2' | 109.5 | C15—C16—H16 | 110.7 |
C23—N2—C20 | 107.5 (3) | C18—C17—C16 | 104.2 (3) |
C23—N2—H2A | 110.2 | C18—C17—H17A | 110.9 |
C20—N2—H2A | 110.2 | C16—C17—H17A | 110.9 |
C23—N2—H2B | 110.2 | C18—C17—H17B | 110.9 |
C20—N2—H2B | 110.2 | C16—C17—H17B | 110.9 |
H2A—N2—H2B | 108.5 | H17A—C17—H17B | 108.9 |
C3—C2—C1 | 119.0 (3) | C19—C18—C17 | 106.6 (4) |
C3—C2—H2 | 120.5 | C19—C18—H18A | 110.4 |
C1—C2—H2 | 120.5 | C17—C18—H18A | 110.4 |
C11—O3—H3' | 109 (3) | C19—C18—H18B | 110.4 |
C2—C3—C4 | 122.9 (3) | C17—C18—H18B | 110.4 |
C2—C3—H3 | 118.6 | H18A—C18—H18B | 108.6 |
C4—C3—H3 | 118.6 | C18—C19—N1 | 107.2 (4) |
C13—O4—H4' | 109.5 | C18—C19—H19A | 110.3 |
C5—C4—C3 | 116.5 (3) | N1—C19—H19A | 110.3 |
C5—C4—C7 | 121.3 (3) | C18—C19—H19B | 110.3 |
C3—C4—C7 | 122.2 (3) | N1—C19—H19B | 110.3 |
O2—C5—C6 | 120.0 (3) | H19A—C19—H19B | 108.5 |
O2—C5—C4 | 119.0 (3) | N2—C20—C21 | 105.0 (3) |
C6—C5—C4 | 121.0 (3) | N2—C20—C24 | 110.9 (2) |
C1—C6—C5 | 120.2 (3) | C21—C20—C24 | 112.2 (3) |
C1—C6—H6 | 119.9 | N2—C20—H20 | 109.6 |
C5—C6—H6 | 119.9 | C21—C20—H20 | 109.6 |
C8—C7—C4 | 126.2 (3) | C24—C20—H20 | 109.6 |
C8—C7—H7 | 116.9 | C22—C21—C20 | 106.6 (3) |
C4—C7—H7 | 116.9 | C22—C21—H21A | 110.4 |
C7—C8—C9 | 128.1 (3) | C20—C21—H21A | 110.4 |
C7—C8—H8 | 116.0 | C22—C21—H21B | 110.4 |
C9—C8—H8 | 116.0 | C20—C21—H21B | 110.4 |
H9A—O9—H9B | 89 (3) | H21A—C21—H21B | 108.6 |
C10—C9—C14 | 118.9 (3) | C23—C22—C21 | 105.1 (3) |
C10—C9—C8 | 117.9 (3) | C23—C22—H22A | 110.7 |
C14—C9—C8 | 123.2 (3) | C21—C22—H22A | 110.7 |
C11—C10—C9 | 120.9 (3) | C23—C22—H22B | 110.7 |
C11—C10—H10 | 119.6 | C21—C22—H22B | 110.7 |
C9—C10—H10 | 119.6 | H22A—C22—H22B | 108.8 |
C12—C11—O3 | 122.3 (3) | N2—C23—C22 | 104.0 (3) |
C12—C11—C10 | 120.4 (3) | N2—C23—H23A | 111.0 |
O3—C11—C10 | 117.3 (3) | C22—C23—H23A | 111.0 |
C13—C12—C11 | 119.4 (3) | N2—C23—H23B | 111.0 |
C13—C12—H12 | 120.3 | C22—C23—H23B | 111.0 |
C11—C12—H12 | 120.3 | H23A—C23—H23B | 109.0 |
O4—C13—C12 | 115.6 (3) | O7—C24—O8 | 125.7 (3) |
O4—C13—C14 | 122.7 (4) | O7—C24—C20 | 119.3 (3) |
C12—C13—C14 | 121.7 (3) | O8—C24—C20 | 115.0 (3) |
C13—C14—C9 | 118.7 (3) | ||
O1—C1—C2—C3 | −178.9 (3) | O4—C13—C14—C9 | −178.9 (4) |
C6—C1—C2—C3 | 0.9 (5) | C12—C13—C14—C9 | 0.6 (6) |
C1—C2—C3—C4 | −1.6 (6) | C10—C9—C14—C13 | 0.1 (5) |
C2—C3—C4—C5 | 0.8 (5) | C8—C9—C14—C13 | 177.5 (4) |
C2—C3—C4—C7 | −179.4 (4) | C19—N1—C16—C17 | −25.4 (4) |
C3—C4—C5—O2 | −179.4 (3) | C19—N1—C16—C15 | 94.1 (4) |
C7—C4—C5—O2 | 0.8 (5) | O5—C15—C16—N1 | −8.3 (4) |
C3—C4—C5—C6 | 0.7 (5) | O6—C15—C16—N1 | 173.7 (3) |
C7—C4—C5—C6 | −179.1 (3) | O5—C15—C16—C17 | 105.3 (4) |
O1—C1—C6—C5 | −179.7 (3) | O6—C15—C16—C17 | −72.7 (4) |
C2—C1—C6—C5 | 0.5 (5) | N1—C16—C17—C18 | 33.9 (4) |
O2—C5—C6—C1 | 178.7 (3) | C15—C16—C17—C18 | −83.3 (4) |
C4—C5—C6—C1 | −1.4 (5) | C16—C17—C18—C19 | −30.2 (6) |
C5—C4—C7—C8 | 169.2 (4) | C17—C18—C19—N1 | 14.5 (6) |
C3—C4—C7—C8 | −10.6 (6) | C16—N1—C19—C18 | 7.3 (6) |
C4—C7—C8—C9 | −179.7 (3) | C23—N2—C20—C21 | −19.7 (4) |
C7—C8—C9—C10 | −176.9 (4) | C23—N2—C20—C24 | 101.7 (3) |
C7—C8—C9—C14 | 5.8 (6) | N2—C20—C21—C22 | −1.4 (4) |
C14—C9—C10—C11 | −0.3 (5) | C24—C20—C21—C22 | −121.9 (4) |
C8—C9—C10—C11 | −177.7 (3) | C20—C21—C22—C23 | 21.6 (5) |
C9—C10—C11—C12 | −0.3 (5) | C20—N2—C23—C22 | 33.4 (4) |
C9—C10—C11—O3 | 179.3 (3) | C21—C22—C23—N2 | −33.4 (5) |
O3—C11—C12—C13 | −178.7 (3) | N2—C20—C24—O7 | −0.7 (5) |
C10—C11—C12—C13 | 1.0 (5) | C21—C20—C24—O7 | 116.3 (4) |
C11—C12—C13—O4 | 178.4 (4) | N2—C20—C24—O8 | 178.9 (3) |
C11—C12—C13—C14 | −1.1 (6) | C21—C20—C24—O8 | −64.1 (5) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1′···O8 | 0.84 (2) | 1.78 (3) | 2.597 (3) | 166 (5) |
O2—H2′···O6 | 0.92 | 1.74 | 2.647 (3) | 172 |
O3—H3′···O2i | 0.85 (2) | 1.93 (3) | 2.778 (3) | 175 (5) |
O4—H4′···O9 | 0.99 | 1.76 | 2.575 (6) | 137 |
O9—H9A···O7ii | 0.89 (2) | 1.76 (3) | 2.639 (5) | 168 (4) |
N1—H1A···O6iii | 0.89 | 1.90 | 2.777 (4) | 168 |
N1—H1B···O4iv | 0.89 | 2.28 | 2.951 (4) | 132 |
N1—H1B···O9iv | 0.89 | 2.47 | 3.105 (5) | 129 |
N2—H2A···O8v | 0.89 | 1.90 | 2.753 (3) | 159 |
N2—H2B···O5vi | 0.89 | 2.07 | 2.829 (3) | 143 |
N2—H2B···O7 | 0.89 | 2.24 | 2.677 (4) | 110 |
C6—H6···O6 | 0.93 | 2.58 | 3.261 (4) | 130 |
C12—H12···O2i | 0.93 | 2.65 | 3.339 (5) | 131 |
Symmetry codes: (i) −x, y+1/2, −z+1/2; (ii) x+1/2, −y+3/2, −z+1; (iii) x+1/2, −y+1/2, −z+1; (iv) −x+1, y−1/2, −z+1/2; (v) −x, y−1/2, −z+3/2; (vi) −x+1/2, −y+1, z+1/2. |
C14H12O4·2C5H9NO2 | Dx = 1.330 Mg m−3 |
Mr = 474.50 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, P212121 | Cell parameters from 9885 reflections |
a = 9.8293 (2) Å | θ = 3.0–33.7° |
b = 10.4915 (2) Å | µ = 0.10 mm−1 |
c = 22.9863 (6) Å | T = 297 K |
V = 2370.44 (9) Å3 | Block, colourless |
Z = 4 | 0.46 × 0.33 × 0.19 mm |
F(000) = 1008 |
Bruker D8 VENTURE diffractometer | 4084 independent reflections |
Radiation source: Sealed x-ray tube | 4038 reflections with I > 2σ(I) |
GraphiteDouble Bounce Multilayer Mirror monochromator | Rint = 0.019 |
Detector resolution: 7.39 pixels mm-1 | θmax = 25.0°, θmin = 3.0° |
φ and ω scans | h = −11→11 |
Absorption correction: multi-scan (SADABS; Bruker, 2016) | k = −12→12 |
Tmin = 0.656, Tmax = 0.747 | l = −27→27 |
22887 measured reflections |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.047 | Hydrogen site location: mixed |
wR(F2) = 0.134 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.09 | w = 1/[σ2(Fo2) + (0.0845P)2 + 0.7969P] where P = (Fo2 + 2Fc2)/3 |
4084 reflections | (Δ/σ)max < 0.001 |
317 parameters | Δρmax = 0.62 e Å−3 |
2 restraints | Δρmin = −0.22 e Å−3 |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.1260 (3) | 0.6128 (3) | 0.61986 (10) | 0.0514 (7) | |
H1' | 0.071 (6) | 0.669 (5) | 0.6427 (14) | 0.077* | |
N1 | −0.0705 (3) | 0.4844 (2) | 0.79572 (11) | 0.0353 (6) | |
H1A | −0.014333 | 0.419063 | 0.801444 | 0.042* | |
H1B | −0.056256 | 0.541800 | 0.823585 | 0.042* | |
C1 | 0.1126 (3) | 0.6427 (3) | 0.56307 (13) | 0.0352 (7) | |
O2 | 0.2565 (2) | 0.5318 (3) | 0.42496 (9) | 0.0427 (6) | |
N2 | 0.7837 (3) | 0.3235 (3) | 0.46631 (12) | 0.0389 (6) | |
H2A | 0.772557 | 0.318253 | 0.427954 | 0.047* | |
H2B | 0.837980 | 0.260292 | 0.477681 | 0.047* | |
C2 | 0.0265 (4) | 0.7382 (4) | 0.54340 (14) | 0.0453 (8) | |
H2 | −0.024706 | 0.785813 | 0.569582 | 0.054* | |
O3 | −0.2495 (3) | 0.9798 (3) | 0.19378 (11) | 0.0495 (6) | |
H3' | −0.249 (3) | 0.987 (5) | 0.156 (3) | 0.074* | |
C3 | 0.0180 (4) | 0.7616 (4) | 0.48443 (14) | 0.0455 (8) | |
H3 | −0.041818 | 0.824262 | 0.471595 | 0.055* | |
O4 | 0.1637 (3) | 0.7502 (3) | 0.15416 (11) | 0.0599 (8) | |
C4 | 0.0949 (3) | 0.6957 (3) | 0.44306 (13) | 0.0356 (7) | |
O5 | 0.5729 (3) | 0.4173 (3) | 0.41022 (10) | 0.0533 (7) | |
C5 | 0.1812 (3) | 0.6002 (3) | 0.46420 (13) | 0.0309 (6) | |
O6 | 0.4198 (2) | 0.3686 (3) | 0.47823 (11) | 0.0466 (6) | |
C6 | 0.1903 (3) | 0.5733 (3) | 0.52325 (13) | 0.0329 (6) | |
H6 | 0.247994 | 0.509154 | 0.536261 | 0.039* | |
O7 | −0.0892 (3) | 0.7406 (2) | 0.78591 (10) | 0.0460 (6) | |
C7 | 0.0875 (4) | 0.7241 (3) | 0.38077 (13) | 0.0386 (7) | |
H7 | 0.156958 | 0.691646 | 0.357645 | 0.046* | |
O8 | −0.0296 (3) | 0.7428 (2) | 0.69242 (10) | 0.0506 (7) | |
C8 | −0.0076 (3) | 0.7910 (4) | 0.35402 (14) | 0.0398 (7) | |
H8 | −0.075927 | 0.825377 | 0.377158 | 0.048* | |
C9 | −0.0159 (3) | 0.8164 (3) | 0.29118 (14) | 0.0360 (7) | |
C10 | −0.1234 (3) | 0.8909 (3) | 0.27047 (14) | 0.0371 (7) | |
H10 | −0.185411 | 0.926232 | 0.296429 | 0.044* | |
C11 | −0.1378 (3) | 0.9121 (3) | 0.21109 (14) | 0.0366 (7) | |
C12 | −0.0429 (4) | 0.8644 (3) | 0.17235 (13) | 0.0411 (8) | |
H12 | −0.051837 | 0.880042 | 0.132705 | 0.049* | |
C13 | 0.0660 (4) | 0.7930 (3) | 0.19307 (14) | 0.0419 (7) | |
C14 | 0.0793 (4) | 0.7665 (3) | 0.25177 (14) | 0.0399 (7) | |
H14 | 0.150671 | 0.716115 | 0.265004 | 0.048* | |
C15 | 0.5388 (3) | 0.3722 (3) | 0.45688 (13) | 0.0329 (6) | |
C16 | 0.6496 (3) | 0.3150 (3) | 0.49651 (14) | 0.0378 (7) | |
H16 | 0.628213 | 0.226093 | 0.505799 | 0.045* | |
C17 | 0.6714 (5) | 0.3919 (6) | 0.55258 (16) | 0.0633 (12) | |
H17A | 0.588047 | 0.434238 | 0.564351 | 0.076* | |
H17B | 0.701960 | 0.337248 | 0.583990 | 0.076* | |
C18 | 0.7786 (8) | 0.4871 (8) | 0.5367 (3) | 0.108 (3) | |
H18A | 0.737801 | 0.570706 | 0.532318 | 0.130* | |
H18B | 0.845990 | 0.491800 | 0.567471 | 0.130* | |
C19 | 0.8440 (5) | 0.4497 (5) | 0.4825 (2) | 0.0664 (12) | |
H19A | 0.941535 | 0.442251 | 0.487748 | 0.080* | |
H19B | 0.826332 | 0.512272 | 0.452326 | 0.080* | |
C20 | −0.0456 (3) | 0.5426 (3) | 0.73720 (12) | 0.0326 (6) | |
H20 | 0.044694 | 0.517884 | 0.723075 | 0.039* | |
C21 | −0.1553 (5) | 0.4849 (4) | 0.69788 (18) | 0.0583 (10) | |
H21A | −0.208778 | 0.551754 | 0.679827 | 0.070* | |
H21B | −0.113911 | 0.433781 | 0.667490 | 0.070* | |
C22 | −0.2429 (6) | 0.4041 (6) | 0.7356 (2) | 0.0830 (17) | |
H22A | −0.338064 | 0.418173 | 0.726516 | 0.100* | |
H22B | −0.222303 | 0.314678 | 0.729493 | 0.100* | |
C23 | −0.2149 (4) | 0.4400 (4) | 0.7970 (2) | 0.0583 (10) | |
H23A | −0.225509 | 0.367342 | 0.822688 | 0.070* | |
H23B | −0.275284 | 0.507642 | 0.809722 | 0.070* | |
C24 | −0.0559 (3) | 0.6875 (3) | 0.74016 (13) | 0.0350 (7) | |
H2' | 0.311 (4) | 0.484 (4) | 0.4408 (18) | 0.052* | |
H4' | 0.234 (3) | 0.736 (5) | 0.1775 (16) | 0.052* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0627 (15) | 0.0674 (16) | 0.0241 (11) | 0.0127 (14) | 0.0039 (11) | 0.0043 (11) |
N1 | 0.0470 (15) | 0.0298 (11) | 0.0291 (12) | 0.0001 (11) | 0.0021 (11) | −0.0007 (10) |
C1 | 0.0366 (15) | 0.0449 (17) | 0.0242 (14) | −0.0039 (13) | 0.0001 (12) | −0.0004 (12) |
O2 | 0.0439 (13) | 0.0569 (15) | 0.0272 (11) | 0.0194 (11) | −0.0044 (10) | −0.0057 (10) |
N2 | 0.0297 (13) | 0.0499 (15) | 0.0372 (14) | 0.0040 (12) | 0.0003 (11) | 0.0029 (12) |
C2 | 0.0494 (18) | 0.0534 (19) | 0.0330 (16) | 0.0142 (16) | 0.0088 (14) | −0.0023 (15) |
O3 | 0.0459 (13) | 0.0668 (16) | 0.0357 (12) | 0.0036 (12) | −0.0028 (10) | 0.0172 (12) |
C3 | 0.0517 (19) | 0.0494 (18) | 0.0355 (17) | 0.0193 (17) | 0.0019 (14) | 0.0031 (15) |
O4 | 0.0617 (17) | 0.082 (2) | 0.0356 (13) | 0.0123 (16) | 0.0113 (12) | 0.0022 (14) |
C4 | 0.0369 (15) | 0.0426 (16) | 0.0274 (14) | 0.0044 (13) | −0.0007 (12) | 0.0021 (12) |
O5 | 0.0467 (13) | 0.0819 (19) | 0.0311 (11) | 0.0097 (13) | 0.0015 (10) | 0.0159 (12) |
C5 | 0.0261 (13) | 0.0385 (15) | 0.0281 (14) | −0.0001 (12) | 0.0009 (11) | −0.0053 (12) |
O6 | 0.0301 (11) | 0.0578 (14) | 0.0517 (14) | 0.0071 (11) | 0.0051 (10) | 0.0140 (11) |
C6 | 0.0318 (14) | 0.0375 (15) | 0.0294 (15) | 0.0028 (12) | −0.0035 (12) | 0.0009 (12) |
O7 | 0.0643 (16) | 0.0357 (11) | 0.0382 (12) | −0.0033 (11) | 0.0102 (11) | −0.0075 (10) |
C7 | 0.0435 (16) | 0.0425 (16) | 0.0297 (14) | 0.0083 (14) | 0.0031 (13) | 0.0020 (13) |
O8 | 0.0834 (19) | 0.0336 (11) | 0.0347 (12) | −0.0046 (12) | 0.0123 (12) | 0.0041 (10) |
C8 | 0.0374 (16) | 0.0523 (18) | 0.0295 (15) | 0.0059 (14) | 0.0017 (12) | 0.0023 (14) |
C9 | 0.0381 (16) | 0.0403 (15) | 0.0297 (15) | −0.0020 (13) | 0.0008 (13) | 0.0034 (13) |
C10 | 0.0366 (16) | 0.0436 (16) | 0.0310 (15) | 0.0000 (14) | 0.0020 (12) | 0.0030 (13) |
C11 | 0.0376 (16) | 0.0406 (16) | 0.0315 (15) | −0.0057 (13) | −0.0039 (13) | 0.0090 (13) |
C12 | 0.0518 (19) | 0.0478 (17) | 0.0236 (14) | −0.0086 (16) | −0.0010 (13) | 0.0062 (13) |
C13 | 0.0485 (19) | 0.0450 (17) | 0.0324 (16) | −0.0022 (15) | 0.0075 (14) | −0.0001 (13) |
C14 | 0.0417 (16) | 0.0448 (17) | 0.0333 (15) | 0.0014 (14) | 0.0018 (13) | 0.0040 (13) |
C15 | 0.0305 (15) | 0.0389 (15) | 0.0294 (15) | 0.0020 (13) | −0.0008 (12) | 0.0029 (12) |
C16 | 0.0323 (15) | 0.0458 (17) | 0.0354 (17) | 0.0018 (13) | 0.0001 (13) | 0.0105 (14) |
C17 | 0.058 (2) | 0.103 (3) | 0.0294 (17) | 0.004 (2) | −0.0044 (16) | −0.002 (2) |
C18 | 0.111 (5) | 0.121 (5) | 0.093 (4) | −0.052 (4) | 0.023 (4) | −0.062 (4) |
C19 | 0.054 (2) | 0.063 (3) | 0.083 (3) | −0.018 (2) | 0.005 (2) | −0.003 (2) |
C20 | 0.0404 (15) | 0.0294 (13) | 0.0280 (14) | −0.0022 (12) | 0.0035 (12) | −0.0017 (11) |
C21 | 0.078 (3) | 0.053 (2) | 0.043 (2) | −0.014 (2) | −0.0174 (19) | −0.0079 (17) |
C22 | 0.073 (3) | 0.089 (3) | 0.088 (4) | −0.044 (3) | −0.027 (3) | 0.008 (3) |
C23 | 0.049 (2) | 0.057 (2) | 0.069 (3) | −0.0053 (18) | 0.0188 (19) | 0.012 (2) |
C24 | 0.0420 (16) | 0.0321 (14) | 0.0309 (14) | −0.0060 (13) | 0.0039 (13) | −0.0023 (12) |
O1—C1 | 1.349 (4) | C8—H8 | 0.9300 |
O1—H1' | 0.96 (6) | C9—C10 | 1.398 (5) |
N1—C23 | 1.495 (5) | C9—C14 | 1.403 (5) |
N1—C20 | 1.497 (4) | C10—C11 | 1.390 (4) |
N1—H1A | 0.8900 | C10—H10 | 0.9300 |
N1—H1B | 0.8900 | C11—C12 | 1.383 (5) |
C1—C2 | 1.387 (5) | C12—C13 | 1.391 (5) |
C1—C6 | 1.397 (5) | C12—H12 | 0.9300 |
O2—C5 | 1.369 (4) | C13—C14 | 1.384 (4) |
O2—H2' | 0.82 (2) | C14—H14 | 0.9300 |
N2—C16 | 1.492 (4) | C15—C16 | 1.541 (4) |
N2—C19 | 1.498 (5) | C16—C17 | 1.535 (5) |
N2—H2A | 0.8900 | C16—H16 | 0.9800 |
N2—H2B | 0.8900 | C17—C18 | 1.497 (8) |
C2—C3 | 1.380 (5) | C17—H17A | 0.9700 |
C2—H2 | 0.9300 | C17—H17B | 0.9700 |
O3—C11 | 1.367 (4) | C18—C19 | 1.456 (8) |
O3—H3' | 0.87 (6) | C18—H18A | 0.9700 |
C3—C4 | 1.398 (5) | C18—H18B | 0.9700 |
C3—H3 | 0.9300 | C19—H19A | 0.9700 |
O4—C13 | 1.387 (4) | C19—H19B | 0.9700 |
O4—H4' | 0.89 (2) | C20—C24 | 1.526 (4) |
C4—C5 | 1.400 (4) | C20—C21 | 1.531 (5) |
C4—C7 | 1.464 (4) | C20—H20 | 0.9800 |
O5—C15 | 1.219 (4) | C21—C22 | 1.488 (7) |
C5—C6 | 1.389 (4) | C21—H21A | 0.9700 |
O6—C15 | 1.269 (4) | C21—H21B | 0.9700 |
C6—H6 | 0.9300 | C22—C23 | 1.485 (7) |
O7—C24 | 1.234 (4) | C22—H22A | 0.9700 |
C7—C8 | 1.320 (5) | C22—H22B | 0.9700 |
C7—H7 | 0.9300 | C23—H23A | 0.9700 |
O8—C24 | 1.268 (4) | C23—H23B | 0.9700 |
C8—C9 | 1.471 (4) | ||
C1—O1—H1' | 109.5 | C13—C14—H14 | 120.3 |
C23—N1—C20 | 107.4 (3) | C9—C14—H14 | 120.3 |
C23—N1—H1A | 110.2 | O5—C15—O6 | 127.2 (3) |
C20—N1—H1A | 110.2 | O5—C15—C16 | 118.5 (3) |
C23—N1—H1B | 110.2 | O6—C15—C16 | 114.3 (3) |
C20—N1—H1B | 110.2 | N2—C16—C17 | 103.7 (3) |
H1A—N1—H1B | 108.5 | N2—C16—C15 | 109.0 (3) |
O1—C1—C2 | 122.9 (3) | C17—C16—C15 | 113.0 (3) |
O1—C1—C6 | 117.4 (3) | N2—C16—H16 | 110.3 |
C2—C1—C6 | 119.8 (3) | C17—C16—H16 | 110.3 |
C5—O2—H2' | 112 (3) | C15—C16—H16 | 110.3 |
C16—N2—C19 | 106.6 (3) | C18—C17—C16 | 104.1 (3) |
C16—N2—H2A | 110.4 | C18—C17—H17A | 110.9 |
C19—N2—H2A | 110.4 | C16—C17—H17A | 110.9 |
C16—N2—H2B | 110.4 | C18—C17—H17B | 110.9 |
C19—N2—H2B | 110.4 | C16—C17—H17B | 110.9 |
H2A—N2—H2B | 108.6 | H17A—C17—H17B | 109.0 |
C3—C2—C1 | 119.0 (3) | C19—C18—C17 | 109.8 (4) |
C3—C2—H2 | 120.5 | C19—C18—H18A | 109.7 |
C1—C2—H2 | 120.5 | C17—C18—H18A | 109.7 |
C11—O3—H3' | 109.5 | C19—C18—H18B | 109.7 |
C2—C3—C4 | 123.2 (3) | C17—C18—H18B | 109.7 |
C2—C3—H3 | 118.4 | H18A—C18—H18B | 108.2 |
C4—C3—H3 | 118.4 | C18—C19—N2 | 106.0 (4) |
C13—O4—H4' | 102 (3) | C18—C19—H19A | 110.5 |
C3—C4—C5 | 116.5 (3) | N2—C19—H19A | 110.5 |
C3—C4—C7 | 122.5 (3) | C18—C19—H19B | 110.5 |
C5—C4—C7 | 121.0 (3) | N2—C19—H19B | 110.5 |
O2—C5—C6 | 120.2 (3) | H19A—C19—H19B | 108.7 |
O2—C5—C4 | 118.3 (3) | N1—C20—C24 | 110.8 (2) |
C6—C5—C4 | 121.5 (3) | N1—C20—C21 | 104.7 (3) |
C5—C6—C1 | 120.0 (3) | C24—C20—C21 | 111.9 (3) |
C5—C6—H6 | 120.0 | N1—C20—H20 | 109.7 |
C1—C6—H6 | 120.0 | C24—C20—H20 | 109.7 |
C8—C7—C4 | 126.8 (3) | C21—C20—H20 | 109.7 |
C8—C7—H7 | 116.6 | C22—C21—C20 | 106.8 (3) |
C4—C7—H7 | 116.6 | C22—C21—H21A | 110.4 |
C7—C8—C9 | 126.4 (3) | C20—C21—H21A | 110.4 |
C7—C8—H8 | 116.8 | C22—C21—H21B | 110.4 |
C9—C8—H8 | 116.8 | C20—C21—H21B | 110.4 |
C10—C9—C14 | 119.5 (3) | H21A—C21—H21B | 108.6 |
C10—C9—C8 | 118.5 (3) | C23—C22—C21 | 107.6 (3) |
C14—C9—C8 | 122.0 (3) | C23—C22—H22A | 110.2 |
C11—C10—C9 | 120.0 (3) | C21—C22—H22A | 110.2 |
C11—C10—H10 | 120.0 | C23—C22—H22B | 110.2 |
C9—C10—H10 | 120.0 | C21—C22—H22B | 110.2 |
O3—C11—C12 | 122.8 (3) | H22A—C22—H22B | 108.5 |
O3—C11—C10 | 116.8 (3) | C22—C23—N1 | 103.7 (3) |
C12—C11—C10 | 120.4 (3) | C22—C23—H23A | 111.0 |
C11—C12—C13 | 119.6 (3) | N1—C23—H23A | 111.0 |
C11—C12—H12 | 120.2 | C22—C23—H23B | 111.0 |
C13—C12—H12 | 120.2 | N1—C23—H23B | 111.0 |
C14—C13—O4 | 119.9 (3) | H23A—C23—H23B | 109.0 |
C14—C13—C12 | 121.0 (3) | O7—C24—O8 | 125.8 (3) |
O4—C13—C12 | 119.1 (3) | O7—C24—C20 | 120.3 (3) |
C13—C14—C9 | 119.5 (3) | O8—C24—C20 | 113.8 (3) |
O1—C1—C2—C3 | −179.3 (4) | O4—C13—C14—C9 | 176.4 (3) |
C6—C1—C2—C3 | 0.9 (5) | C12—C13—C14—C9 | −2.3 (5) |
C1—C2—C3—C4 | −1.7 (6) | C10—C9—C14—C13 | 0.7 (5) |
C2—C3—C4—C5 | 1.4 (6) | C8—C9—C14—C13 | 179.7 (3) |
C2—C3—C4—C7 | −178.2 (4) | C19—N2—C16—C17 | −31.3 (4) |
C3—C4—C5—O2 | 178.9 (3) | C19—N2—C16—C15 | 89.3 (3) |
C7—C4—C5—O2 | −1.5 (5) | O5—C15—C16—N2 | −2.2 (4) |
C3—C4—C5—C6 | −0.4 (5) | O6—C15—C16—N2 | 179.3 (3) |
C7—C4—C5—C6 | 179.3 (3) | O5—C15—C16—C17 | 112.5 (4) |
O2—C5—C6—C1 | −179.6 (3) | O6—C15—C16—C17 | −66.0 (4) |
C4—C5—C6—C1 | −0.3 (5) | N2—C16—C17—C18 | 27.9 (5) |
O1—C1—C6—C5 | −179.7 (3) | C15—C16—C17—C18 | −89.9 (5) |
C2—C1—C6—C5 | 0.1 (5) | C16—C17—C18—C19 | −14.9 (8) |
C3—C4—C7—C8 | −15.6 (6) | C17—C18—C19—N2 | −4.2 (8) |
C5—C4—C7—C8 | 164.8 (3) | C16—N2—C19—C18 | 22.5 (6) |
C4—C7—C8—C9 | −178.4 (3) | C23—N1—C20—C24 | 99.1 (3) |
C7—C8—C9—C10 | −179.2 (4) | C23—N1—C20—C21 | −21.8 (4) |
C7—C8—C9—C14 | 1.8 (6) | N1—C20—C21—C22 | 3.7 (5) |
C14—C9—C10—C11 | 1.8 (5) | C24—C20—C21—C22 | −116.5 (4) |
C8—C9—C10—C11 | −177.2 (3) | C20—C21—C22—C23 | 15.9 (6) |
C9—C10—C11—O3 | 176.4 (3) | C21—C22—C23—N1 | −29.0 (5) |
C9—C10—C11—C12 | −2.8 (5) | C20—N1—C23—C22 | 31.5 (4) |
O3—C11—C12—C13 | −178.0 (3) | N1—C20—C24—O7 | −4.1 (4) |
C10—C11—C12—C13 | 1.1 (5) | C21—C20—C24—O7 | 112.4 (4) |
C11—C12—C13—C14 | 1.4 (5) | N1—C20—C24—O8 | 176.9 (3) |
C11—C12—C13—O4 | −177.3 (3) | C21—C20—C24—O8 | −66.5 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1′···O8 | 0.96 | 1.70 | 2.642 (4) | 169 |
O2—H2′···O6 | 0.82 (2) | 1.83 (3) | 2.647 (3) | 175 (5) |
O3—H3′···O2i | 0.87 | 1.92 | 2.784 (3) | 171 |
O4—H4′···O7ii | 0.89 (2) | 1.95 (3) | 2.794 (4) | 159 (4) |
N1—H1B···O5iii | 0.89 | 2.04 | 2.827 (3) | 146 |
N1—H1A···O8iv | 0.89 | 1.90 | 2.733 (4) | 154 |
N2—H2A···O4v | 0.89 | 2.11 | 2.920 (4) | 150 |
N2—H2B···O6vi | 0.89 | 1.87 | 2.734 (4) | 163 |
C6—H6···O6 | 0.93 | 2.61 | 3.282 (4) | 130 |
Symmetry codes: (i) −x, y+1/2, −z+1/2; (ii) x+1/2, −y+3/2, −z+1; (iii) −x+1/2, −y+1, z+1/2; (iv) −x, y−1/2, −z+3/2; (v) −x+1, y−1/2, −z+1/2; (vi) x+1/2, −y+1/2, −z+1. |
Contacts | PRO 1 | PRO 2 | OXY |
(I) | |||
H···H | 47.9 | 36.6 | 38.6 |
H···O/O···H | 31.4 | 43.6 | 33.3 |
H···C/C···H | 14.6 | 18.8 | – |
(II) | |||
H···H | 32.3 | 49.4 | 38.2 |
H···O/O···H | 47.8 | 34.7 | 35.1 |
H···C/C···H | 19.3 | 15.0 | – |
Funding information
The authors thank the Thailand Research Fund for financial support through the Royal Golden Jubilee PhD Program (grant No. PHD/0160/2558) and the Integrated Research and Development of Medicine Project (grant No. PHA610372S).
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