organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 68| Part 3| March 2012| Pages o667-o668

Clarithromycin monohydrate: a synchrotron X-ray powder study

aGraduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan, and bIndustrial Application Division, Japan Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo-gun, Hyogo 679-5198, Japan
*Correspondence e-mail: noguchis@u-shizuoka-ken.ac.jp

(Received 3 January 2012; accepted 5 February 2012; online 10 February 2012)

In the crystal structure of the title compound, clarithromycin (CAM) monohydrate, C38H69NO13·H2O, the water mol­ecule behaves as a proton donor and is hydrogen bonded to the hy­droxy O atom of the CAM cladinose ring. The hy­droxy O atom also behaves as a proton donor, forming an inter­molecular hydrogen bond with one of the hy­droxy groups of the 14-membered aglycone ring. The CAM mol­ecules are linked through these hydrogen bonds into chains running parallel to the c axis.

Related literature

For background to the title compound, see Avrutov et al. (2003[Avrutov, I., Lifshitz, I., Borochovitz, R., Masarwa, B. & Schwartz, E. (2003). US Patent No. 6599884.]); Noguchi, Fujiki et al. (2012[Noguchi, S., Fujiki, S., Iwao, Y., Miura, K. & Itai, S. (2012). In preparation.]). For information relating to the pharmaceutical properties of CAM, see: Yajima et al. (1999[Yajima, T., Umeki, N. & Itai, S. (1999). Chem. Pharm. Bull. 47, 220-225.], 2002[Yajima, T., Umeki, N. & Itai, S. (2002). Chem. Pharm. Bull. 50, 147-152.]); Fujiki et al. (2011[Fujiki, S., Iwao, Y., Kobayashi, M., Miyagishima, A. & Itai, S. (2011). Chem. Pharm. Bull. 59, 553-558.]); Liu et al. (1999[Liu, J.-H., Riley, D. A. & Spanton, S. G. (1999). US Patent No. 5 858 986.]). For related structures, see: Noguchi, Miura et al. (2012[Noguchi, S., Miura, K., Fujiki, S., Iwao, Y. & Itai, S. (2012). Acta Cryst. C68, o41-o44.]; form I, anhydrate); Jin et al. (2011[Jin, Z. M., Ma, L. L., Wei, W. X., Lin, C. S. & Li, W. Z. (2011). J. Struct. Chem. 50, 185-189.]; form 0, ethanol solvate); Stephenson et al. (1997[Stephenson, G. A., Stowell, J. G., Toma, P. H., Pfeiffer, R. R. & Byrn, S. R. (1997). J. Pharm. Sci. 86, 1239-1244.]; form II, anhydrate); Liang & Yao (2008[Liang, J. H. & Yao, G. W. (2008). J. Chem. Crystallogr. 38, 61-64.]; form III, acetonitrile solvate); Parvez et al. (2000[Parvez, M., Arayne, M. S., Sabri, R. & Sultana, N. (2000). Acta Cryst. C56, e398-e399.]; hydro­chloride salt); Iwasaki et al. (1993[Iwasaki, H., Sugawara, Y., Adachi, T., Morimoto, S. & Watanabe, Y. (1993). Acta Cryst. C49, 1227-1230.]; methanol solvate).

[Scheme 1]

Experimental

Crystal data
  • C38H69NO13·H2O

  • Mr = 765.97

  • Orthorhombic, P 21 21 21

  • a = 15.6999 (2) Å

  • b = 18.8817 (2) Å

  • c = 15.0267 (2) Å

  • V = 4454.53 (9) Å3

  • Z = 4

  • Synchrotron radiation, λ = 1.3000 Å

  • μ = 0.41 mm−1

  • T = 298 K

  • cylinder, 3.0 × 0.3 mm

Data collection
  • BL-19B2 Debye–Scherrer camera diffractometer

  • Specimen mounting: capilary

  • Data collection mode: transmission

  • Scan method: Stationary detector

  • 2θfixed = 65

Refinement
  • Rp = 0.038

  • Rwp = 0.052

  • Rexp = 0.016

  • RBragg = 0.059

  • R(F) = 0.076

  • R(F2) = 0.07617

  • χ2 = 11.020

  • 6201 data points

  • 188 parameters

  • 96 restraints

  • H-atom parameters not refined

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O6—H67⋯O7 0.83 2.30 2.68 (3) 108
O7—H68⋯O8 0.82 2.13 2.83 (3) 143
O12—H69⋯O11 0.83 2.34 2.75 (4) 111
O6—H67⋯O12i 0.83 2.39 2.73 (3) 105
O12—H69⋯O6ii 0.83 2.43 2.73 (3) 102
O14—H70⋯O12 0.97 1.70 2.65 (4) 168
O14—H71⋯O7ii 0.95 2.58 3.51 (4) 166
Symmetry codes: (i) x, y, z+1; (ii) x, y, z-1.

Data collection: local software (Osaka et al., 2010[Osaka, K., Matsumoto, T., Miura, K., Sato, M., Hirosawa, I. & Watanabe, Y. (2010). AIP Conf. Proc. 1234, 9-12.]; Takata et al., 2002[Takata, M., Nishibori, E., Kato, K., Kubota, Y., Kuroiwa, Y. & Sakata, M. (2002). Adv. X-ray Anal. 45, 377-384.]); cell refinement: EXPO2009 (Altomare et al., 2009[Altomare, A., Camalli, M., Cuocci, C., Giacovazzo, C., Moliterni, A. & Rizzi, R. (2009). J. Appl. Cryst. 42, 1197-1202.]) and RIETAN-FP (Izumi & Momma, 2007[Izumi, F. & Momma, K. (2007). Solid State Phenom. 130, 15-20.]); data reduction: local software (Takata et al., 2002[Takata, M., Nishibori, E., Kato, K., Kubota, Y., Kuroiwa, Y. & Sakata, M. (2002). Adv. X-ray Anal. 45, 377-384.]); program(s) used to solve structure: CCP4 (Collaborative Computational Project, Number 4, 1994[Collaborative Computational Project, Number 4 (1994). Acta Cryst. D50, 760-763.]); program(s) used to refine structure: CCP4, RIETAN-FP and Jmol (Hanson, 2010[Hanson, R. M. (2010). J. Appl. Cryst. 43, 1250-1260.]); molecular graphics: CCP4MG (McNicholas et al., 2011[McNicholas, S., Potterton, E., Wilson, K. S. & Noble, M. E. M. (2011). Acta Cryst. D67, 386-394.]); software used to prepare material for publication: publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information


Comment top

CAM is a macrolide antibiotic containing a 14-membered ring. Current clinical formulations of CAM use crystals of the stable anhydrate form II in the treatment of infections caused by bacteria (Yajima et al., 1999, 2002; Fujiki et al., 2011). Another anhydrate crystal form of CAM, metastable form I, has a dissolution rate three times greater than that of form II (Liu et al., 1999), indicating its potential use for a new drug formulation. We recently found that CAM form I spontaneously transforms to CAM monohydrate form IV when stored under high-humidity conditions at room temperature (Noguchi, Fujiki et al., 2012). Although existence of form IV has been documented in the literature (Avrutov et al., 2003), its structure remains unknown. As form IV is believed to be a possible impurity of form I, crystallographic characterization of form IV is necessary to enable a new drug formulation using form I to progress into practical use. We report here the crystal structure of form IV as determined by synchrotron powder X-ray diffraction analysis. The asymmetric unit of form IV contains one CAM molecule and one water molecule. The O14 atom of the water molecule behaves as a proton donor and is hydrogen-bonded to the hydroxy O12 atom of the CAM cladinose ring. Furthermore, the hydroxy O12 atom acts as a proton acceptor, forming an intermolecular hydrogen bond with the hydroxy O6i atom of CAM aglycone ring (symmetry code in Table 1). Through this intermolecular O6i—O12 hydrogen bonding interaction, CAM molecules are linked into chains running parallel to the c axis, as shown in Fig. 2.

Related literature top

For background to the title compound, see Avrutov et al. (2003); Noguchi, Fujiki et al. (2012). For information relating to the pharmaceutical properties of CAM, see: Yajima et al. (1999, 2002); Fujiki et al. (2011). For related structures, see: Noguchi, Miura et al. (2012; form I, anhydrate); Jin et al. (2011; form 0, ethanol solvate); Stephenson et al. (1997; form II, anhydrate); Liang & Yao (2008; form III, acetonitrile solvate); Parvez et al. (2000; hydrochloride salt); Iwasaki et al. (1993; methanol solvate).

For related literature [on what topic?], see: Hanson (2010); Liu (1999).

Experimental top

Powders of CAM form I were prepared as described (Noguchi, Miura et al., 2012) and were converted to form IV by storing at greater than 90% relative humidity overnight in a hermetic glass container at 297 K. Relative humidity was measured by digital hygrometer AD-5683 (A&D, Tokyo, Japan). The powders of form IV thus obtained were enclosed in a 0.3 mm Lindemann glass capillary. The powder diffraction data were collected at SPring-8 BL19B2 (Osaka et al., 2010; Takata et al., 2002). The sample was rotated at 1 r min-1 to reduce the possible preferential orientation and was kept at 298 K.

Refinement top

The determination of cell parameters and space group and the extraction of the Bragg peak intensities from the powder diffraction data were carried out using EXPO2009. The initial structure was determined by the molecular replacement method using MOLREP implemented in CCP4. The search model employed was form 0 of the CAM crystal structure (Jin et al., 2011). All H atoms were excluded from the model and the isotropic atomic displacement parameters were fixed at a value of 0.089 Å2. Reflections between 12.1 and 2.50 Å d-spacings were used for the calculation. The structure solution of the molecular replacement was refined using REFMAC implemented in CCP4. The bond lengths and bond angles were restrained to those of the form 0 crystal structure. The crystallographic R factor converged at 0.245. In the difference Fourier map, the positive spherical density was found at a distance of approximately 2.7 Å from the hydroxy O12 atom of the CAM cladinose ring. The O atom of the water molecule was placed at this density and the model was further refined, resulting in the convergence of the R factor at 0.201. This partially refined structure provided the starting model for Rietveld refinement. The geometry of the CAM molecule was restrained as described above. H atoms were placed at their theoretical positions using EXPO2009 and Jmol and were refined as riding. The overall atomic displacement parameter was applied to all atoms including H atoms, and was refined isotropically. The observed and Rietveld refined calculated powder patterns are shown in Fig. 3. The r.m.s differences of the bond lengths and angles from their target values were 0.023 Å and 2.7 °, respectively.

Computing details top

Data collection: local software (Osaka et al., 2010; Takata et al., 2002); cell refinement: EXPO2009 (Altomare et al., 2009) and RIETAN-FP (Izumi & Momma, 2007); data reduction: local software (Takata et al., 2002); program(s) used to solve structure: CCP4 (Collaborative Computational Project, Number 4, 1994); program(s) used to refine structure: CCP4 (Collaborative Computational Project, Number 4, 1994) and RIETAN-FP (Izumi & Momma, 2007); molecular graphics: CCP4MG (McNicholas et al., 2011); software used to prepare material for publication: publCIF (Westrip, 2010).

Figures top
[Figure 1] Fig. 1. The molecular structure of CAM with atoms represented as spheres of arbitrary radii. C, N, and O atoms are shown in yellow, blue and red, respectively. H atoms have been omitted for clarity. Hydrogen bonding between CAM and a water molecule is indicated by a dashed line.
[Figure 2] Fig. 2. Packing view of CAM. The molecular chains generated by hydrogen bonding between CAM molecules along the c axis are coloured as in Fig. 1. [Symmetry code: (i) x, y, z - 1, (ii) x, y, z + 1.] Molecules of symmetry codes (iii) x + 1/2, -y + 1/2, -z + 1, (iv) -x + 1/2, -y + 1, z + 1/2, and (v) -x + 1, y + 1/2, -z + 1/2 are shown in light green, light blue and cyan, respectively.
[Figure 3] Fig. 3. The final Rietveld plot. The experimental diffraction profile is indicated by red crosses. The calculated diffraction and difference profiles are depicted as solid green and blue lines, respectively. The vertical green bars correspond to the positions of the Bragg peaks.
(3R,4S,5S,6R,7R,9R, 11S,12R,13S,14S)- 6-{[(2S,3R,4S,6R)-4-dimethylamino- 3-hydroxy-6-methyloxan-2-yl]oxy}-14-ethyl-12,13-dihydroxy- 4-{[(2R,4S,5S,6S)-5-hydroxy-4-methoxy- 4,6-dimethyloxan-2-yl]oxy}-7-methoxy-3,5,7,9,11,13-hexamethyl-1- oxacyclotetradecane-2,10-dione top
Crystal data top
C38H69NO13·H2OF(000) = 1672.00
Mr = 765.97Dx = 1.142 Mg m3
Orthorhombic, P212121Synchrotron radiation, λ = 1.3000 Å
Hall symbol: P 2ac 2abµ = 0.41 mm1
a = 15.6999 (2) ÅT = 298 K
b = 18.8817 (2) ÅParticle morphology: powder
c = 15.0267 (2) Åwhite
V = 4454.53 (9) Å3cylinder, 3.0 × 0.3 mm
Z = 4Specimen preparation: Prepared at 298 K and 101 kPa
Data collection top
BL-19B2 Debye–Scherrer camera
diffractometer
Data collection mode: transmission
Radiation source: synchrotron, SPring-8 BL19B2Scan method: Stationary detector
Si(111) monochromator2θfixed = 65
Specimen mounting: capilary
Refinement top
Least-squares matrix: selected elements onlyProfile function: split pseudo-Voigt function
Rp = 0.038188 parameters
Rwp = 0.05296 restraints
Rexp = 0.0160 constraints
RBragg = 0.059H-atom parameters not refined
R(F) = 0.076Weighting scheme based on measured s.u.'s 1/[Yi]
R(F2) = 0.07617(Δ/σ)max = 0.011
χ2 = 11.020Background function: Legendre polynomials
6201 data points
Crystal data top
C38H69NO13·H2OV = 4454.53 (9) Å3
Mr = 765.97Z = 4
Orthorhombic, P212121Synchrotron radiation, λ = 1.3000 Å
a = 15.6999 (2) ŵ = 0.41 mm1
b = 18.8817 (2) ÅT = 298 K
c = 15.0267 (2) Åcylinder, 3.0 × 0.3 mm
Data collection top
BL-19B2 Debye–Scherrer camera
diffractometer
Scan method: Stationary detector
Specimen mounting: capilary2θfixed = 65
Data collection mode: transmission
Refinement top
Rp = 0.038χ2 = 11.020
Rwp = 0.0526201 data points
Rexp = 0.016188 parameters
RBragg = 0.05996 restraints
R(F) = 0.076H-atom parameters not refined
R(F2) = 0.07617
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.024 (1)0.1102 (8)0.205 (1)0.066 (5)*
C10.154 (2)0.074 (2)0.101 (2)0.066 (5)*
O20.108 (2)0.1127 (9)0.327 (1)0.066 (5)*
C20.217 (3)0.007 (2)0.026 (1)0.066 (5)*
O30.256 (1)0.079 (1)0.220 (2)0.066 (5)*
C30.156 (1)0.0568 (7)0.095 (1)0.066 (5)*
O40.051 (1)0.356 (1)0.609 (1)0.066 (5)*
C40.168 (1)0.065 (1)0.197 (1)0.066 (5)*
O50.166 (1)0.286 (1)0.638 (1)0.066 (5)*
C50.107 (1)0.119 (1)0.236 (1)0.066 (5)*
O60.089 (1)0.239 (1)0.8636 (9)0.066 (5)*
C60.0191 (8)0.1221 (7)0.111 (1)0.066 (5)*
O70.0338 (9)0.2408 (9)0.740 (2)0.066 (5)*
C70.064 (1)0.062 (1)0.068 (1)0.066 (5)*
O80.1207 (9)0.122 (1)0.670 (1)0.066 (5)*
C80.073 (1)0.117 (1)0.092 (2)0.066 (5)*
O90.032 (2)0.210 (1)0.484 (2)0.066 (5)*
C90.079 (1)0.176 (1)0.374 (1)0.066 (5)*
C100.150 (1)0.221 (1)0.422 (1)0.066 (5)*
C110.236 (1)0.213 (1)0.372 (2)0.066 (5)*
C120.121 (1)0.297 (1)0.419 (1)0.066 (5)*
C130.165 (1)0.341 (1)0.495 (1)0.066 (5)*
C140.170 (2)0.420 (1)0.473 (2)0.066 (5)*
C150.118 (1)0.329 (1)0.586 (1)0.066 (5)*
C160.1654 (9)0.2915 (7)0.737 (1)0.066 (5)*
C170.133 (1)0.3633 (7)0.763 (1)0.066 (5)*
C180.207 (2)0.411 (1)0.784 (3)0.066 (5)*
C190.1174 (8)0.2269 (6)0.7706 (8)0.066 (5)*
C200.179 (1)0.1663 (7)0.777 (2)0.066 (5)*
C210.0398 (9)0.205 (1)0.709 (1)0.066 (5)*
C220.0214 (9)0.1267 (8)0.708 (2)0.066 (5)*
C230.005 (2)0.095 (2)0.797 (2)0.066 (5)*
C240.0497 (8)0.109 (1)0.645 (1)0.066 (5)*
C250.028 (1)0.0617 (8)0.564 (1)0.066 (5)*
C260.012 (2)0.008 (1)0.599 (2)0.066 (5)*
C270.036 (1)0.095 (1)0.502 (2)0.066 (5)*
C280.003 (2)0.1505 (9)0.434 (1)0.066 (5)*
C290.060 (1)0.113 (2)0.371 (2)0.066 (5)*
N10.198 (1)0.0086 (9)0.071 (1)0.066 (5)*
C300.108 (2)0.245 (2)0.457 (3)0.066 (5)*
C310.096 (1)0.3798 (7)0.282 (1)0.066 (5)*
C320.147 (2)0.4097 (8)0.204 (2)0.066 (5)*
C330.144 (2)0.3696 (9)0.113 (2)0.066 (5)*
C340.181 (3)0.418 (2)0.044 (2)0.066 (5)*
C350.259 (2)0.288 (1)0.164 (2)0.066 (5)*
C360.050 (1)0.355 (2)0.089 (2)0.066 (5)*
C370.0039 (9)0.319 (2)0.166 (2)0.066 (5)*
C380.088 (1)0.309 (2)0.147 (2)0.066 (5)*
O100.148 (1)0.326 (1)0.322 (1)0.066 (5)*
O110.189 (1)0.301 (1)0.109 (2)0.066 (5)*
O120.040 (2)0.310 (1)0.013 (2)0.066 (5)*
O130.013 (1)0.357 (1)0.251 (1)0.066 (5)*
O140.108 (2)0.328 (1)0.069 (2)0.066 (5)*
H10.187520.114450.084650.066*
H20.148030.07240.164570.066*
H30.099360.076530.073540.066*
H40.165220.005350.05870.066*
H50.251910.032890.039530.066*
H60.247710.050050.041390.066*
H70.181590.095220.062360.066*
H80.153380.020440.22340.066*
H90.125610.164820.217950.066*
H100.043570.166090.092040.066*
H110.061590.069380.004060.066*
H120.035730.019070.082520.066*
H130.102420.154810.122780.066*
H140.082170.121970.029350.066*
H150.09440.072450.112070.066*
H160.059240.211740.333470.066*
H170.158660.204170.481940.066*
H180.225160.214230.309050.066*
H190.271910.252470.387710.066*
H200.262420.169850.388110.066*
H210.06070.302250.428370.066*
H220.221660.323060.501040.066*
H230.113380.439680.468830.066*
H240.201020.44450.518480.066*
H250.198350.426290.416720.066*
H260.220070.289540.764840.066*
H270.100260.383180.715590.066*
H280.098150.359080.815420.066*
H290.239050.419510.730170.066*
H300.185420.456210.80510.066*
H310.242740.390060.828330.066*
H320.149170.124510.795050.066*
H330.205860.159150.721050.066*
H340.221660.177690.82140.066*
H350.055220.218680.649640.066*
H360.075030.106240.69070.066*
H370.063120.107940.809890.066*
H380.000250.04470.795650.066*
H390.031080.113870.84370.066*
H400.080130.053860.532190.066*
H410.027960.032310.63740.066*
H420.027330.038130.550890.066*
H430.062420.002860.633870.066*
H440.078150.1180.537980.066*
H450.061970.057360.46870.066*
H460.085480.146650.331880.066*
H470.030380.077540.336670.066*
H480.103690.090030.405680.066*
H490.146750.210360.433560.066*
H500.13280.267880.50730.066*
H510.094140.278840.412130.066*
H520.081970.413890.327420.066*
H530.125290.4570.193850.066*
H540.204520.412090.223140.066*
H550.241590.424590.057030.066*
H560.176310.395940.013180.066*
H570.153250.462670.044790.066*
H580.249940.306590.222270.066*
H590.270450.238380.16690.066*
H600.308030.311410.138020.066*
H610.026180.401020.074670.066*
H620.030890.273170.171690.066*
H630.095860.271160.104680.066*
H640.118280.297640.200710.066*
H650.111270.351980.122180.066*
H660.287010.067790.178280.066*
H670.045990.264220.865130.066*
H680.076620.216610.731700.066*
H690.072040.275400.017970.066*
H700.058540.319670.032280.066*
H710.091980.311470.126510.066*
Geometric parameters (Å, º) top
O1—C51.39 (2)C5—H90.96
O1—C61.43 (2)O6—H670.82
C1—N11.49 (4)C6—H100.96
O2—C51.37 (2)O7—H680.82
O2—C91.46 (3)C7—H120.96
C2—N11.49 (2)C7—H110.96
O3—C41.45 (2)C8—H140.96
C3—N11.45 (2)C8—H130.96
C3—C71.50 (2)C8—H150.96
C3—C41.55 (2)C9—H160.96
O4—C151.22 (2)C10—H170.96
C4—C51.52 (2)C11—H200.96
O5—C151.36 (2)C11—H190.96
O5—C161.49 (2)C11—H180.96
O6—C191.485 (18)C12—H210.96
C6—C81.48 (2)C13—H220.96
C6—C71.48 (2)C14—H250.96
O7—C211.42 (2)C14—H240.96
O8—C241.20 (2)C14—H230.96
O9—C301.42 (4)C16—H260.96
O9—C281.46 (3)C17—H270.96
C9—C281.57 (3)C17—H280.96
C9—C101.58 (2)C18—H310.96
C10—C121.51 (3)C18—H300.96
C10—C111.55 (3)C18—H290.96
C12—C131.57 (2)C20—H330.96
C13—C141.53 (3)C20—H320.96
C13—C151.57 (2)C20—H340.96
C16—C171.500 (19)C21—H350.96
C16—C191.520 (18)C22—H360.96
C17—C181.50 (3)C23—H380.96
C19—C201.501 (19)C23—H370.96
C19—C211.585 (19)C23—H390.96
C21—C221.51 (2)C25—H400.96
C22—C241.50 (3)C26—H420.96
C22—C231.52 (4)C26—H430.96
C24—C251.55 (2)C26—H410.96
C25—C271.51 (3)C27—H440.96
C25—C261.55 (3)C27—H450.96
C27—C281.55 (3)C29—H460.96
C28—C291.54 (4)C29—H470.96
C31—O101.44 (2)C29—H480.96
C31—O131.45 (2)C30—H500.96
C31—C321.53 (3)C30—H510.96
C32—C331.56 (4)C30—H490.96
C33—O111.48 (3)C31—H520.96
C33—C341.50 (4)C32—H540.96
C33—C361.54 (4)C32—H530.96
C35—O111.40 (4)C34—H570.96
C36—O121.43 (4)C34—H560.96
C36—C371.53 (4)C34—H550.98
C37—O131.47 (4)C35—H580.96
C37—C381.48 (2)C35—H590.96
C1—H10.96C35—H600.96
C1—H30.96C36—H610.96
C1—H20.96C37—H620.96
C2—H40.96C38—H640.96
C2—H50.96C38—H650.96
C2—H60.96C38—H630.96
O3—H660.82O12—H690.82
C3—H70.96O14—H700.96
C4—H80.96O14—H710.96
C5—O1—C6111.2 (13)H15—C8—C6109.3
C5—O2—C9114.0 (16)C28—O9—H51114.2
N1—C3—C7115.3 (13)H16—C9—O2111.4
N1—C3—C4106.0 (13)H16—C9—C28109.9
C7—C3—C4112.1 (13)H17—C10—C12112.2
O3—C4—C5112.8 (16)H17—C10—C11107.7
O3—C4—C3111.7 (16)H17—C10—C9111.0
C5—C4—C3111.8 (13)C11—C10—H16107.1
C15—O5—C16122.0 (15)H20—C11—H19109.8
O2—C5—O1109.5 (18)H20—C11—H18111.0
O2—C5—C4108.6 (16)H20—C11—C10109.8
O1—C5—C4112.4 (14)H19—C11—H18109.0
O1—C6—C8103.5 (16)H19—C11—C10109.0
O1—C6—C7106.5 (12)H18—C11—C10109.3
C8—C6—C7109.3 (14)H21—C12—C10112.4
C6—C7—C3112.9 (13)H21—C12—C13106.1
C30—O9—C28122 (3)H21—C12—O10110.8
O2—C9—C28105.3 (16)H22—C13—C14109.0
O2—C9—C10116.2 (17)H22—C13—C15108.2
C28—C9—C10116.1 (13)H22—C13—C12107.1
C12—C10—C11109.9 (14)H25—C14—H24110.0
C12—C10—C9106.6 (13)H25—C14—H23109.2
C11—C10—C9109.9 (14)H25—C14—C13109.6
C10—C12—C13110.4 (13)H24—C14—H23109.1
C10—C12—O10105.7 (13)H24—C14—C13109.5
C13—C12—O10111.2 (14)H23—C14—C13109.3
C14—C13—C15110.7 (17)H26—C16—O5115.5
C14—C13—C12112.4 (16)H26—C16—C17102.6
C15—C13—C12110.5 (13)H26—C16—C19105.4
O4—C15—O5124.5 (16)H27—C17—H28109.1
O4—C15—C13126.3 (16)H27—C17—C18109.7
O5—C15—C13109.1 (14)H27—C17—C16109.9
O5—C16—C17109.0 (13)H28—C17—C18108.6
O5—C16—C19106.2 (12)H28—C17—C16109.4
C17—C16—C19118.1 (12)H28—C17—H26109.2
C18—C17—C16109.5 (15)H31—C18—H30110.0
O6—C19—C20104.5 (15)H31—C18—H29109.6
O6—C19—C16109.8 (12)H31—C18—C17110.2
O6—C19—C21111.0 (11)H30—C18—H29108.5
C20—C19—C16108.3 (11)H30—C18—C17109.6
C20—C19—C21109.5 (13)H29—C18—C17108.9
C16—C19—C21113.4 (11)C16—C19—H67104.0
O7—C21—C22108.4 (13)H33—C20—H32110.3
O7—C21—C19108.1 (15)H33—C20—H34109.5
C22—C21—C19114.2 (14)H33—C20—C19109.5
C24—C22—C21111.6 (16)H32—C20—H34109.3
C24—C22—C23105.3 (16)H32—C20—C19109.4
C21—C22—C23115 (2)H34—C20—C19108.9
O8—C24—C22116.6 (16)H35—C21—O7113.0
O8—C24—C25124.6 (15)H35—C21—C22107.0
C22—C24—C25117.4 (13)H35—C21—C19106.5
C27—C25—C24113.1 (14)H35—C21—H68112.6
C27—C25—C26107.1 (16)H68—C21—H36113.9
C24—C25—C26108.2 (15)H36—C22—C24113.0
C25—C27—C28117.8 (16)H36—C22—C21103.2
O9—C28—C29115 (3)H36—C22—C23108.8
O9—C28—C27107.9 (17)H38—C23—H37110.1
O9—C28—C9110.2 (17)H38—C23—H39109.5
C29—C28—C27108.0 (19)H38—C23—C22109.8
C29—C28—C9106.0 (14)H37—C23—H39109.0
C27—C28—C9109 (2)H37—C23—C22109.3
C3—N1—C2108.6 (19)H39—C23—C22109.0
C3—N1—C1115.0 (18)H40—C25—C27108.6
C2—N1—C1114 (2)H40—C25—C24107.1
O10—C31—O13115.8 (14)H40—C25—C26112.5
O10—C31—C32106.6 (15)H42—C26—H43110.0
O13—C31—C32109.5 (16)H42—C26—H41109.9
C31—C32—C33118.4 (17)H42—C26—C25110.5
O11—C33—C34109 (3)H43—C26—H41108.1
O11—C33—C36107 (2)H43—C26—C25109.0
O11—C33—C32117 (2)H41—C26—C25109.3
C34—C33—C36109 (3)H44—C27—H45109.4
C34—C33—C32107.3 (19)H44—C27—C25107.1
C36—C33—C32109 (2)H44—C27—C28107.9
O12—C36—C37107 (3)H45—C27—C25106.6
O12—C36—C33113 (2)H45—C27—C28107.5
C37—C36—C33111 (2)H46—C29—H47110.0
O13—C37—C38109 (2)H46—C29—H48109.5
O13—C37—C36113 (3)H46—C29—C28109.3
C38—C37—C36112 (2)H47—C29—H48109.4
C31—O10—C12118.0 (13)H47—C29—C28109.6
C35—O11—C33120 (2)H48—C29—C28109.1
C31—O13—C37120.7 (14)H50—C30—H51110.6
H1—C1—H3110.1H50—C30—H49109.6
H1—C1—H2109.6H50—C30—O9109.3
H1—C1—N1109.5H51—C30—H49109.6
H3—C1—H2109.5H51—C30—O9108.9
H3—C1—N1109.3H49—C30—O9108.7
H2—C1—N1108.8H52—C31—O10107.6
H4—C2—H5110.2H52—C31—O13103.1
H4—C2—H6109.0H52—C31—C32114.4
H4—C2—N1110.3H54—C32—H53109.6
H5—C2—H6108.4H54—C32—C31106.8
H5—C2—N1110.0H54—C32—C33108.1
H6—C2—N1108.8H53—C32—C31106.4
H66—O3—C4110.0H53—C32—C33107.5
H66—O3—H8111.6H57—C34—H56111.2
H7—C3—N1108.6H57—C34—H55109.4
H7—C3—C7102.0H57—C34—C33110.3
H7—C3—C4112.3H56—C34—H55108.4
H8—C4—O3106.6H56—C34—C33109.0
H8—C4—C5106.2H55—C34—C33108.3
H8—C4—C3107.4H58—C35—H59110.7
H8—C4—H66108.7H58—C35—H60108.8
H9—C5—O2110.6H58—C35—O11110.8
H9—C5—O1106.9H59—C35—H60108.8
H9—C5—C4107.9H59—C35—O11110.0
O1—C5—H8101.8H60—C35—O11107.7
H67—O6—C19111.0H61—C36—O12108.6
H10—C6—O1114.5H61—C36—C37112.7
H10—C6—C8112.5H61—C36—C33105.1
H10—C6—C7109.4H62—C37—O13108.1
H68—O7—C21110.8H62—C37—C38109.4
H68—O7—H35110.4H62—C37—C36105.2
H12—C7—H11109.5H64—C38—H63109.3
H12—C7—C6109.0H64—C38—H65109.3
H12—C7—C3108.7H64—C38—C37110.3
H11—C7—C6108.5H63—C38—H65108.9
H11—C7—C3108.6H63—C38—C37109.7
C6—C7—H7103.0H65—C38—C37109.3
H14—C8—H13109.6C33—O11—H60111.0
H14—C8—H15109.5H69—O12—C36109.7
H14—C8—C6109.5C36—O12—H70110.3
H13—C8—H15109.5C31—O13—H62107.2
H13—C8—C6109.4H70—O14—H71104.5
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O6—H67···O70.832.302.68 (3)108
O7—H68···O80.822.132.83 (3)143
O12—H69···O110.832.342.75 (4)111
O6—H67···O12i0.832.392.73 (3)105
O12—H69···O6ii0.832.432.73 (3)102
O14—H70···O120.971.702.65 (4)168
O14—H71···O7ii0.952.583.51 (4)166
Symmetry codes: (i) x, y, z+1; (ii) x, y, z1.

Experimental details

Crystal data
Chemical formulaC38H69NO13·H2O
Mr765.97
Crystal system, space groupOrthorhombic, P212121
Temperature (K)298
a, b, c (Å)15.6999 (2), 18.8817 (2), 15.0267 (2)
V3)4454.53 (9)
Z4
Radiation typeSynchrotron, λ = 1.3000 Å
µ (mm1)0.41
Specimen shape, size (mm)Cylinder, 3.0 × 0.3
Data collection
DiffractometerBL-19B2 Debye–Scherrer camera
diffractometer
Specimen mountingCapilary
Data collection modeTransmission
Scan methodStationary detector
2θ values (°)2θfixed = 65
Refinement
R factors and goodness of fitRp = 0.038, Rwp = 0.052, Rexp = 0.016, RBragg = 0.059, R(F) = 0.076, R(F2) = 0.07617, χ2 = 11.020
No. of data points6201
No. of parameters188
No. of restraints96
H-atom treatmentH-atom parameters not refined

Computer programs: local software (Osaka et al., 2010; Takata et al., 2002), EXPO2009 (Altomare et al., 2009) and RIETAN-FP (Izumi & Momma, 2007), local software (Takata et al., 2002), CCP4 (Collaborative Computational Project, Number 4, 1994) and RIETAN-FP (Izumi & Momma, 2007), CCP4MG (McNicholas et al., 2011), publCIF (Westrip, 2010).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O6—H67···O70.832.302.68 (3)108
O7—H68···O80.822.132.83 (3)143
O12—H69···O110.832.342.75 (4)111
O6—H67···O12i0.832.392.73 (3)105
O12—H69···O6ii0.832.432.73 (3)102
O14—H70···O120.971.702.65 (4)168
O14—H71···O7ii0.952.583.51 (4)166
Symmetry codes: (i) x, y, z+1; (ii) x, y, z1.
 

Acknowledgements

This study was partly supported by a grant from the Pharmaceutical and Medical Device Regulatory Science Society of Japan. The synchrotron radiation experiment at BL19B2 was performed under the approval of the Japan Synchrotron Radiation Research Institute (JASRI; proposal Nos. 2011B1791 and 2011B1912).

References

First citationAltomare, A., Camalli, M., Cuocci, C., Giacovazzo, C., Moliterni, A. & Rizzi, R. (2009). J. Appl. Cryst. 42, 1197–1202.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationAvrutov, I., Lifshitz, I., Borochovitz, R., Masarwa, B. & Schwartz, E. (2003). US Patent No. 6599884.  Google Scholar
First citationCollaborative Computational Project, Number 4 (1994). Acta Cryst. D50, 760–763.  CrossRef IUCr Journals Google Scholar
First citationFujiki, S., Iwao, Y., Kobayashi, M., Miyagishima, A. & Itai, S. (2011). Chem. Pharm. Bull. 59, 553–558.  CrossRef CAS PubMed Google Scholar
First citationHanson, R. M. (2010). J. Appl. Cryst. 43, 1250–1260.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationIwasaki, H., Sugawara, Y., Adachi, T., Morimoto, S. & Watanabe, Y. (1993). Acta Cryst. C49, 1227–1230.  CSD CrossRef CAS Web of Science IUCr Journals Google Scholar
First citationIzumi, F. & Momma, K. (2007). Solid State Phenom. 130, 15–20.  CrossRef CAS Google Scholar
First citationJin, Z. M., Ma, L. L., Wei, W. X., Lin, C. S. & Li, W. Z. (2011). J. Struct. Chem. 50, 185–189.  Web of Science CrossRef Google Scholar
First citationLiang, J. H. & Yao, G. W. (2008). J. Chem. Crystallogr. 38, 61–64.  Web of Science CSD CrossRef CAS Google Scholar
First citationLiu, J.-H., Riley, D. A. & Spanton, S. G. (1999). US Patent No. 5 858 986.  Google Scholar
First citationMcNicholas, S., Potterton, E., Wilson, K. S. & Noble, M. E. M. (2011). Acta Cryst. D67, 386–394.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationNoguchi, S., Fujiki, S., Iwao, Y., Miura, K. & Itai, S. (2012). In preparation.  Google Scholar
First citationNoguchi, S., Miura, K., Fujiki, S., Iwao, Y. & Itai, S. (2012). Acta Cryst. C68, o41–o44.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
First citationOsaka, K., Matsumoto, T., Miura, K., Sato, M., Hirosawa, I. & Watanabe, Y. (2010). AIP Conf. Proc. 1234, 9–12.  CrossRef Google Scholar
First citationParvez, M., Arayne, M. S., Sabri, R. & Sultana, N. (2000). Acta Cryst. C56, e398–e399.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
First citationStephenson, G. A., Stowell, J. G., Toma, P. H., Pfeiffer, R. R. & Byrn, S. R. (1997). J. Pharm. Sci. 86, 1239–1244.  Web of Science CSD CrossRef CAS PubMed Google Scholar
First citationTakata, M., Nishibori, E., Kato, K., Kubota, Y., Kuroiwa, Y. & Sakata, M. (2002). Adv. X-ray Anal. 45, 377–384.  CAS Google Scholar
First citationWestrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationYajima, T., Umeki, N. & Itai, S. (1999). Chem. Pharm. Bull. 47, 220–225.  Web of Science CrossRef PubMed CAS Google Scholar
First citationYajima, T., Umeki, N. & Itai, S. (2002). Chem. Pharm. Bull. 50, 147–152.  Web of Science CrossRef PubMed CAS Google Scholar

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Volume 68| Part 3| March 2012| Pages o667-o668
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