Crystal structure of 7-phenyl-7-(2,4,5-trimethyl-3,6-dioxo­cyclo­hexa-1,4-dien-1-yl)hepta­noate 1,3-dihy­droxy-2-(hy­droxy­meth­yl)propan-2-aminium monohydrate: a new solid form of seratrodast

In the title compound, seratrodast has crystallized with trometamol to form a monohydrated salt. The carb­oxy­lic acid group of seratrodast has transferred its proton to the amino N atom of trometamol.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.074
• wR factor = 0.288
• Data-to-parameter ratio = 18.1

checkCIF/PLATON results

No syntax errors found



Alert level C
RFACR01_ALERT_3_C  The value of the weighted R factor is > 0.25
            Weighted R factor given   0.288
PLAT029_ALERT_3_C _diffrn_measured_fraction_theta_full Low .......      0.977 Note
PLAT084_ALERT_3_C High wR2 Value (i.e. > 0.25) ...................       0.29 Report
PLAT230_ALERT_2_C Hirshfeld Test Diff for    C11    --  C12     ..        5.2 su
PLAT241_ALERT_2_C High      Ueq as Compared to Neighbors for .....        C12 Check
PLAT250_ALERT_2_C Large U3/U1 Ratio for Average U(i,j) Tensor ....        2.2 Note
PLAT340_ALERT_3_C Low Bond Precision on  C-C Bonds ...............     0.0054 Ang.
PLAT412_ALERT_2_C Short Intra XH3 .. XHn     H7     ..  H20A    ..       1.82 Ang.
PLAT414_ALERT_2_C Short Intra D-H..H-X       H7A    ..  H25A    ..       1.95 Ang.
PLAT906_ALERT_3_C Large K value in the Analysis of Variance ......     28.094 Check
PLAT906_ALERT_3_C Large K value in the Analysis of Variance ......      4.458 Check
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600         68 Report
PLAT913_ALERT_3_C Missing # of Very Strong Reflections in FCF ....          1 Note
PLAT918_ALERT_3_C Reflection(s) with I(obs) much smaller I(calc) .         12 Check
PLAT939_ALERT_3_C Large Value of Not (SHELXL) Weight Optimized S .      28.29

Alert level G
PLAT005_ALERT_5_G No _iucr_refine_instructions_details  in the CIF     Please Do !
PLAT007_ALERT_5_G Number of Unrefined Donor-H Atoms ..............          8 Report
PLAT042_ALERT_1_G Calc. and Reported MoietyFormula Strings  Differ     Please Check
PLAT072_ALERT_2_G SHELXL First  Parameter in WGHT Unusually Large.       0.16 Report
PLAT199_ALERT_1_G Reported _cell_measurement_temperature ..... (K)        293 Check
PLAT200_ALERT_1_G Reported   _diffrn_ambient_temperature ..... (K)        293 Check
PLAT333_ALERT_2_G Check Large Av C6-Ring C-C Dist. C14    -C19           1.44 Ang.
PLAT793_ALERT_4_G The Model has Chirality at C7      .............          R Verify
PLAT899_ALERT_4_G SHELXL97   is Deprecated and Succeeded by SHELXL       2014 Note
PLAT910_ALERT_3_G Missing # of FCF Reflections Below Th(Min) .....          3 Report
PLAT912_ALERT_4_G Missing # of FCF Reflections Above STh/L=  0.600         64 Note

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
  15 ALERT level C = Check. Ensure it is not caused by an omission or oversight
  11 ALERT level G = General information/check it is not something unexpected

   3 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   7 ALERT type 2 Indicator that the structure model may be wrong or deficient
  11 ALERT type 3 Indicator that the structure quality may be low
   3 ALERT type 4 Improvement, methodology, query or suggestion
   2 ALERT type 5 Informative message, check

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S1. Chemical context

Seratrodast is the first thromboxane A2 receptor antagonist to have been developed as an anti-asthmatic drug (Samara, 1996). This drug molecule with a carb­oxy­lic group is practically insoluble in water. Its new solid forms have been scarcely exploited and only a polymorphic transition was ever investigated (Urakami & Beezer, 2003). Tris(hy­droxy­methyl)­amino methane, commonly called trometamol, is often used as a buffer in biochemical studies. It has been successfully exploited for improving properties of APIs such as ketoprofen (Zippel & Wagenitz, 2006). In this study, trometamol was employed to co-crystallize with seratrodast to give rise to a new crystalline form. To the best of our knowledge, the title salt is the first multi-component crystalline form of seratrodast to be reported.

S2. Structural commentary

The molecular structure of the title salt is illustrated in Fig. 1. It was clear from a difference Fourier map that the carb­oxy­lic group of seratrodast had transferred its proton to the amino N atom of trometamol. The bond distances C1—O1 and C1—O2 of the carboxyl­ate group of the seratrodast anion are 1.258 (4) and 1.232 (4) Å, respectively. The phenyl ring is normal to the dioxo­cyclo­hexadiene ring, with a dihedral angle of 89.95 (19)°, and the alkyl chain has an extended conformation.

S3. Supra­molecular features

In the crystal, the trometamol cations are linked to the water molecules and to each other by N—H···O and O—H···O hydrogen bonds, forming sheets parallel to (100); see Table 1 and Fig 2. The seratrodast anions are linked to both sides of these sheets by O—H···O and C—H···O hydrogen bonds, forming a three-layer two-dimensional structure (Fig. 3 and Table 1). Further details of the hydrogen bonding are given below and in Table 1. The carboxyl­ate anion inter­acts with one hydroxyl group of trometamol through strong hydrogen bonding [O6···O1 = 2.662 (3) Å]. There also exist hydrogen-bonding inter­actions between carboxyl­ate anion and water molecule [O8···O2 = 2.617 (3) Å, O8···O1ⁱ = 2.667 (3) Å]. The protonated trometamol cation inter­acts with each other through three kinds of hydrogen-bonding inter­actions. An R₂²(11) heterosynthon is formed through hydrogen-bonding inter­actions between the hydroxyl groups [O5···O7ⁱⁱⁱ = 2.714 (3) Å] and between the hydroxyl group and the amino group [N1···O6ⁱⁱⁱ = 2.779 (3) Å]. Along the c axis, the R₂²(11) heterosynthon gives rise to a hydrogen-bonded chain of trometamol cations, which is further linked into a two-dimensional structure by hydrogen-bonding inter­actions between the amino and the hydroxyl groups [N1···O5ⁱⁱ = 2.935 (3) Å]. There also exist hydrogen-bonding inter­actions between water and trometamol [N1···O8ⁱ = 2.800 (4) Å; O7···O8ⁱⁱⁱ = 2.686 (3) Å]. The various hydrogen-bonding inter­actions result in a two-dimensional layer structure in which the seratrodast anions are spread around two sides of the layer in an orderly manner (Table 1 and Fig. 3).

S4. Database survey

To the best of our knowledge, the title salt is the first multi-component crystalline form of seratrodast to be reported.

S5. Synthesis and crystallization

Seratrodast (354 mg, 1 mmol) and trometamol (121 mg, 1 mmol) were dissolved in methanol (15 ml). The resulting solution was kept in air and after several days yellow block-like crystals of the title salt were obtained.

S6. Solubility Studies

Excess amounts of seratrodast and the title salt were suspended in 10 ml of water in screw-capped glass vials, respectively. These vials were kept at 310 K and were stirred at 100 r.p.m. using a magnetic stirrer. After 72 h, the suspensions were filtered through a 0.2 µm syringe filter. The filtered aliquots were sufficiently diluted, and the absorbances were measured at 268 nm in triplicate. Finally, the concentration of seratrodast after 72 h in each sample was determined from the previously made standard graph. A standard graph was made by measuring the absorbance of varied concentrations of seratrodast (2–16 mg/L) in water/methanol (9:1) solution using a UV-2500 spectrophotometer at 268 nm. The calibrated plot showed a good correlation coefficient (y = 0.04997x + 0.00459, R² = 0.9991). After forming the title salt, the solubility of seratrodast was found to be greatly improved.

S7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The C-bound H atoms were positioned geometrically and refined as riding atoms: C—H = 0.95–1.00 Å with U_iso(H) = 1.2U_eq(C). The OH and NH₃⁺ H atoms were located in difference Fourier maps and refined as riding atoms with U_iso(H) = 1.2U_eq(O,N).

Related literature

For related literature, see: Samara (1996); Urakami & Beezer (2003); Zippel & Wagenitz (2006).

Computing details

Data collection: CrystalClear (Rigaku, 2000); cell refinement: CrystalClear (Rigaku, 2000); data reduction: CrystalClear (Rigaku, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009) and publCIF (Westrip, 2010).

Figures

	Fig. 1. A view of the molecular structure of the title salt, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen bonds are shown as dashed lines (see Table 1 for details).
	Fig. 2. A view along the a axis of the two-dimensional hydrogen-bonded structure of the trometamol cations and the water molecules (hydrogen bonds are shown as dashed lines; see Table 1 for details).
	Fig. 3. A view along the c axis of the crystal packing of the title compound (hydrogen bonds are shown as dashed lines; see Table 1 for details). H atoms not involved in hydrogen bonding have been omitted for clarity

7-Phenyl-7-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)heptanoate 1,3-dihydroxy-2-(hydroxymethyl)propan-2-aminium monohydrate

Crystal data

C4H12NO3^+·C22H25O4^−·H2O	F(000) = 1064
Mr = 493.58	Dx = 1.276 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 6295 reflections
a = 23.506 (9) Å	θ = 2.1–27.5°
b = 9.665 (4) Å	µ = 0.09 mm^−1
c = 11.344 (5) Å	T = 293 K
β = 94.223 (7)°	Prism, yellow
V = 2570.0 (17) Å^3	0.20 × 0.20 × 0.20 mm
Z = 4

Data collection

Rigaku Mercury CCD diffractometer	5762 independent reflections
Radiation source: fine-focus sealed tube	3564 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.062
Detector resolution: 28.5714 pixels mm^-1	θmax = 27.5°, θmin = 2.6°
CCD_Profile_fitting scans	h = −30→30
Absorption correction: multi-scan (CrystalClear; Rigaku, 2000)	k = −12→12
Tmin = 0.549, Tmax = 1.000	l = −12→14
20028 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.074	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.288	H-atom parameters constrained
S = 1.10	w = 1/[σ^2(Fo^2) + (0.1567P)^2] where P = (Fo^2 + 2Fc^2)/3
5762 reflections	(Δ/σ)max < 0.001
319 parameters	Δρmax = 0.55 e Å^−3
0 restraints	Δρmin = −0.42 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
O1	0.38025 (10)	0.4145 (2)	0.4397 (2)	0.0447 (6)
O2	0.38047 (12)	0.4204 (3)	0.6328 (2)	0.0537 (7)
O3	0.09684 (12)	0.0531 (3)	0.8988 (3)	0.0749 (9)
O4	0.25430 (13)	−0.0713 (4)	1.2339 (3)	0.0789 (10)
O5	0.44774 (10)	0.5677 (2)	0.17616 (18)	0.0408 (6)
O6	0.44283 (9)	0.6368 (2)	0.49902 (17)	0.0389 (6)
O7	0.42596 (11)	0.9565 (2)	0.43874 (19)	0.0482 (6)
O8	0.42283 (9)	0.2989 (2)	0.8260 (2)	0.0440 (6)
H8B	0.4079	0.3136	0.7498	0.053*
H1C	0.5077	0.7821	0.1992	0.053*
H7A	0.4222	1.0380	0.3969	0.053*
H1B	0.4962	0.9171	0.2650	0.053*
H1A	0.4590	0.8684	0.1637	0.053*
H8A	0.4059	0.2252	0.8599	0.053*
H5	0.4389	0.5703	0.0917	0.053*
H6	0.4274	0.5623	0.4592	0.053*
N1	0.47892 (10)	0.8382 (3)	0.2369 (2)	0.0333 (6)
C1	0.36324 (13)	0.3727 (3)	0.5360 (3)	0.0339 (7)
C2	0.31629 (15)	0.2633 (4)	0.5285 (3)	0.0469 (8)
H2A	0.2801	0.3087	0.5001	0.056*
H2B	0.3254	0.1944	0.4681	0.056*
C3	0.30659 (14)	0.1871 (4)	0.6411 (3)	0.0470 (8)
H3A	0.3018	0.2554	0.7047	0.056*
H3B	0.3408	0.1309	0.6644	0.056*
C4	0.25457 (15)	0.0926 (4)	0.6304 (3)	0.0465 (8)
H4A	0.2204	0.1495	0.6080	0.056*
H4B	0.2592	0.0259	0.5656	0.056*
C5	0.24405 (15)	0.0123 (4)	0.7421 (3)	0.0502 (9)
H5A	0.2750	−0.0560	0.7580	0.060*
H5B	0.2448	0.0769	0.8099	0.060*
C6	0.18728 (15)	−0.0623 (4)	0.7312 (3)	0.0475 (9)
H6A	0.1567	0.0078	0.7184	0.057*
H6B	0.1861	−0.1212	0.6597	0.057*
C7	0.17374 (14)	−0.1507 (4)	0.8334 (3)	0.0452 (8)
H7	0.2046	−0.2222	0.8397	0.054*
C8	0.11810 (13)	−0.2336 (4)	0.8148 (3)	0.0412 (8)
C9	0.08118 (15)	−0.2237 (4)	0.7166 (4)	0.0566 (10)
H9	0.0876	−0.1562	0.6581	0.068*
C10	0.03397 (16)	−0.3118 (5)	0.7012 (5)	0.0725 (13)
H10	0.0092	−0.3051	0.6314	0.087*
C13	0.10716 (18)	−0.3320 (5)	0.8987 (4)	0.0670 (12)
H13	0.1327	−0.3426	0.9670	0.080*
C12	0.0590 (2)	−0.4157 (5)	0.8836 (5)	0.0860 (16)
H12	0.0512	−0.4800	0.9437	0.103*
C11	0.02316 (17)	−0.4075 (5)	0.7856 (5)	0.0689 (12)
H11	−0.0090	−0.4671	0.7752	0.083*
C14	0.17815 (13)	−0.0778 (3)	0.9519 (3)	0.0397 (8)
C15	0.13375 (14)	0.0248 (4)	0.9771 (3)	0.0463 (9)
C16	0.13441 (16)	0.0942 (4)	1.0924 (4)	0.0531 (9)
C19	0.22057 (13)	−0.1042 (4)	1.0361 (3)	0.0426 (8)
C18	0.21906 (15)	−0.0386 (4)	1.1559 (3)	0.0494 (9)
C17	0.17570 (17)	0.0652 (4)	1.1788 (4)	0.0555 (10)
C20	0.27017 (17)	−0.1961 (4)	1.0232 (4)	0.0655 (11)
H20A	0.2645	−0.2481	0.9491	0.098*
H20B	0.2740	−0.2607	1.0898	0.098*
H20C	0.3049	−0.1401	1.0220	0.098*
C21	0.0871 (2)	0.1955 (6)	1.1065 (5)	0.0896 (16)
H21A	0.0928	0.2408	1.1838	0.134*
H21B	0.0505	0.1466	1.1011	0.134*
H21C	0.0871	0.2653	1.0439	0.134*
C22	0.1798 (2)	0.1297 (6)	1.2988 (4)	0.0891 (17)
H22A	0.2194	0.1556	1.3207	0.134*
H22B	0.1669	0.0634	1.3565	0.134*
H22C	0.1556	0.2125	1.2979	0.134*
C23	0.47623 (12)	0.6918 (3)	0.4125 (2)	0.0319 (6)
H23A	0.4992	0.6168	0.3801	0.038*
H23B	0.5029	0.7612	0.4494	0.038*
C24	0.40803 (12)	0.6541 (3)	0.2309 (3)	0.0346 (7)
H24A	0.3833	0.5965	0.2781	0.042*
H24B	0.3834	0.7023	0.1693	0.042*
C25	0.39738 (13)	0.8612 (3)	0.3592 (3)	0.0392 (7)
H25A	0.3773	0.9124	0.2930	0.047*
H25B	0.3686	0.8093	0.4008	0.047*
C26	0.43939 (11)	0.7603 (3)	0.3108 (2)	0.0296 (6)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0627 (15)	0.0412 (12)	0.0308 (13)	−0.0161 (10)	0.0075 (10)	0.0027 (10)
O2	0.0810 (18)	0.0487 (14)	0.0311 (13)	−0.0191 (12)	0.0032 (12)	−0.0005 (11)
O3	0.0648 (18)	0.090 (2)	0.067 (2)	0.0198 (16)	−0.0195 (15)	0.0060 (17)
O4	0.0712 (19)	0.099 (3)	0.062 (2)	−0.0058 (17)	−0.0235 (15)	0.0159 (18)
O5	0.0564 (13)	0.0365 (11)	0.0280 (12)	0.0050 (10)	−0.0064 (10)	−0.0036 (9)
O6	0.0626 (14)	0.0380 (12)	0.0156 (10)	−0.0120 (10)	−0.0012 (9)	0.0025 (9)
O7	0.0854 (18)	0.0351 (12)	0.0226 (12)	0.0038 (11)	−0.0057 (11)	0.0000 (9)
O8	0.0505 (13)	0.0447 (13)	0.0368 (13)	−0.0080 (10)	0.0037 (10)	−0.0006 (10)
N1	0.0433 (14)	0.0333 (12)	0.0227 (13)	−0.0094 (10)	−0.0014 (10)	0.0024 (10)
C1	0.0450 (17)	0.0294 (14)	0.0279 (17)	0.0010 (12)	0.0072 (13)	0.0024 (12)
C2	0.052 (2)	0.053 (2)	0.0360 (19)	−0.0131 (16)	0.0066 (15)	0.0017 (16)
C3	0.0459 (18)	0.052 (2)	0.044 (2)	−0.0116 (15)	0.0043 (15)	0.0099 (16)
C4	0.0498 (19)	0.052 (2)	0.038 (2)	−0.0124 (15)	0.0065 (15)	0.0046 (16)
C5	0.053 (2)	0.057 (2)	0.040 (2)	−0.0163 (16)	0.0010 (16)	0.0065 (17)
C6	0.052 (2)	0.056 (2)	0.0357 (19)	−0.0158 (16)	0.0109 (15)	−0.0008 (16)
C7	0.0446 (18)	0.053 (2)	0.0377 (19)	−0.0103 (15)	0.0033 (14)	−0.0009 (16)
C8	0.0364 (16)	0.0511 (19)	0.0372 (18)	−0.0077 (14)	0.0110 (13)	−0.0085 (15)
C9	0.045 (2)	0.066 (2)	0.059 (2)	−0.0098 (17)	0.0019 (17)	−0.006 (2)
C10	0.043 (2)	0.083 (3)	0.089 (3)	−0.010 (2)	−0.015 (2)	−0.017 (3)
C13	0.061 (2)	0.081 (3)	0.059 (3)	−0.031 (2)	0.0041 (19)	0.004 (2)
C12	0.067 (3)	0.073 (3)	0.119 (5)	−0.032 (2)	0.011 (3)	0.008 (3)
C11	0.044 (2)	0.064 (3)	0.099 (4)	−0.0171 (19)	0.003 (2)	−0.012 (3)
C14	0.0358 (16)	0.0472 (18)	0.0365 (18)	−0.0106 (13)	0.0043 (13)	0.0026 (15)
C15	0.0420 (18)	0.053 (2)	0.043 (2)	−0.0035 (15)	−0.0028 (15)	0.0080 (16)
C16	0.056 (2)	0.048 (2)	0.057 (2)	−0.0016 (16)	0.0137 (18)	−0.0014 (18)
C19	0.0399 (17)	0.0440 (17)	0.044 (2)	−0.0069 (13)	0.0005 (14)	0.0041 (15)
C18	0.0477 (19)	0.055 (2)	0.044 (2)	−0.0183 (16)	−0.0044 (16)	0.0112 (17)
C17	0.064 (2)	0.054 (2)	0.049 (2)	−0.0185 (18)	0.0087 (18)	−0.0054 (18)
C20	0.053 (2)	0.060 (2)	0.082 (3)	0.0060 (18)	−0.003 (2)	0.009 (2)
C21	0.087 (3)	0.082 (4)	0.101 (4)	0.029 (3)	0.021 (3)	−0.009 (3)
C22	0.120 (4)	0.092 (4)	0.058 (3)	−0.029 (3)	0.025 (3)	−0.026 (3)
C23	0.0401 (15)	0.0323 (14)	0.0224 (15)	−0.0022 (12)	−0.0033 (12)	0.0006 (12)
C24	0.0361 (15)	0.0371 (15)	0.0297 (16)	−0.0072 (12)	−0.0043 (12)	0.0038 (13)
C25	0.0427 (17)	0.0362 (16)	0.0385 (18)	0.0011 (13)	0.0009 (13)	0.0006 (14)
C26	0.0362 (15)	0.0316 (14)	0.0210 (14)	−0.0061 (11)	0.0009 (11)	0.0043 (12)

Geometric parameters (Å, º)

O1—C1	1.258 (4)	C9—C10	1.400 (5)
O2—C1	1.232 (4)	C9—H9	0.9500
O3—C15	1.226 (4)	C10—C11	1.369 (7)
O4—C18	1.209 (4)	C10—H10	0.9500
O5—C24	1.428 (4)	C13—C12	1.392 (5)
O5—H5	0.9657	C13—H13	0.9500
O6—C23	1.406 (4)	C12—C11	1.347 (7)
O6—H6	0.9109	C12—H12	0.9500
O7—C25	1.423 (4)	C11—H11	0.9500
O7—H7A	0.9202	C14—C19	1.353 (4)
O8—H8B	0.9191	C14—C15	1.483 (5)
O8—H8A	0.9142	C15—C16	1.469 (5)
N1—C26	1.499 (4)	C16—C17	1.357 (6)
N1—H1C	0.9892	C16—C21	1.499 (6)
N1—H1B	0.9100	C19—C20	1.482 (5)
N1—H1A	0.9682	C19—C18	1.502 (5)
C1—C2	1.526 (4)	C18—C17	1.467 (6)
C2—C3	1.507 (5)	C17—C22	1.493 (6)
C2—H2A	0.9900	C20—H20A	0.9800
C2—H2B	0.9900	C20—H20B	0.9800
C3—C4	1.523 (4)	C20—H20C	0.9800
C3—H3A	0.9900	C21—H21A	0.9800
C3—H3B	0.9900	C21—H21B	0.9800
C4—C5	1.522 (5)	C21—H21C	0.9800
C4—H4A	0.9900	C22—H22A	0.9800
C4—H4B	0.9900	C22—H22B	0.9800
C5—C6	1.514 (5)	C22—H22C	0.9800
C5—H5A	0.9900	C23—C26	1.540 (4)
C5—H5B	0.9900	C23—H23A	0.9900
C6—C7	1.493 (5)	C23—H23B	0.9900
C6—H6A	0.9900	C24—C26	1.524 (4)
C6—H6B	0.9900	C24—H24A	0.9900
C7—C14	1.515 (5)	C24—H24B	0.9900
C7—C8	1.535 (4)	C25—C26	1.519 (4)
C7—H7	1.0000	C25—H25A	0.9900
C8—C9	1.364 (5)	C25—H25B	0.9900
C8—C13	1.383 (5)
C24—O5—H5	108.4	C12—C11—C10	118.7 (4)
C23—O6—H6	100.0	C12—C11—H11	120.6
C25—O7—H7A	101.8	C10—C11—H11	120.6
H8B—O8—H8A	111.6	C19—C14—C15	118.8 (3)
C26—N1—H1C	116.1	C19—C14—C7	122.5 (3)
C26—N1—H1B	120.2	C15—C14—C7	118.7 (3)
H1C—N1—H1B	108.0	O3—C15—C16	120.2 (4)
C26—N1—H1A	110.6	O3—C15—C14	118.7 (3)
H1C—N1—H1A	95.6	C16—C15—C14	121.1 (3)
H1B—N1—H1A	102.8	C17—C16—C15	120.6 (4)
O2—C1—O1	123.3 (3)	C17—C16—C21	123.7 (4)
O2—C1—C2	119.9 (3)	C15—C16—C21	115.7 (4)
O1—C1—C2	116.7 (3)	C14—C19—C20	126.0 (3)
C3—C2—C1	116.4 (3)	C14—C19—C18	119.6 (3)
C3—C2—H2A	108.2	C20—C19—C18	114.4 (3)
C1—C2—H2A	108.2	O4—C18—C17	119.8 (4)
C3—C2—H2B	108.2	O4—C18—C19	119.4 (4)
C1—C2—H2B	108.2	C17—C18—C19	120.8 (3)
H2A—C2—H2B	107.3	C16—C17—C18	118.8 (4)
C2—C3—C4	113.3 (3)	C16—C17—C22	124.5 (4)
C2—C3—H3A	108.9	C18—C17—C22	116.7 (4)
C4—C3—H3A	108.9	C19—C20—H20A	109.5
C2—C3—H3B	108.9	C19—C20—H20B	109.5
C4—C3—H3B	108.9	H20A—C20—H20B	109.5
H3A—C3—H3B	107.7	C19—C20—H20C	109.5
C5—C4—C3	114.7 (3)	H20A—C20—H20C	109.5
C5—C4—H4A	108.6	H20B—C20—H20C	109.5
C3—C4—H4A	108.6	C16—C21—H21A	109.5
C5—C4—H4B	108.6	C16—C21—H21B	109.5
C3—C4—H4B	108.6	H21A—C21—H21B	109.5
H4A—C4—H4B	107.6	C16—C21—H21C	109.5
C6—C5—C4	111.8 (3)	H21A—C21—H21C	109.5
C6—C5—H5A	109.3	H21B—C21—H21C	109.5
C4—C5—H5A	109.3	C17—C22—H22A	109.5
C6—C5—H5B	109.3	C17—C22—H22B	109.5
C4—C5—H5B	109.3	H22A—C22—H22B	109.5
H5A—C5—H5B	107.9	C17—C22—H22C	109.5
C7—C6—C5	116.5 (3)	H22A—C22—H22C	109.5
C7—C6—H6A	108.2	H22B—C22—H22C	109.5
C5—C6—H6A	108.2	O6—C23—C26	111.9 (2)
C7—C6—H6B	108.2	O6—C23—H23A	109.2
C5—C6—H6B	108.2	C26—C23—H23A	109.2
H6A—C6—H6B	107.3	O6—C23—H23B	109.2
C6—C7—C14	114.7 (3)	C26—C23—H23B	109.2
C6—C7—C8	114.9 (3)	H23A—C23—H23B	107.9
C14—C7—C8	111.5 (3)	O5—C24—C26	110.5 (2)
C6—C7—H7	104.8	O5—C24—H24A	109.6
C14—C7—H7	104.8	C26—C24—H24A	109.6
C8—C7—H7	104.8	O5—C24—H24B	109.6
C9—C8—C13	118.1 (3)	C26—C24—H24B	109.6
C9—C8—C7	124.0 (3)	H24A—C24—H24B	108.1
C13—C8—C7	117.7 (3)	O7—C25—C26	110.8 (2)
C8—C9—C10	120.7 (4)	O7—C25—H25A	109.5
C8—C9—H9	119.7	C26—C25—H25A	109.5
C10—C9—H9	119.7	O7—C25—H25B	109.5
C11—C10—C9	120.7 (4)	C26—C25—H25B	109.5
C13—C10—H10	119.7	H25A—C25—H25B	108.1
C9—C10—H10	119.7	N1—C26—C25	109.1 (2)
C8—C13—C12	120.4 (4)	N1—C26—C24	107.3 (2)
C8—C13—H13	119.8	C25—C26—C24	110.4 (2)
C12—C13—H13	119.8	N1—C26—C23	107.3 (2)
C11—C12—C13	121.4 (5)	C25—C26—C23	110.5 (2)
C11—C12—H12	119.3	C24—C26—C23	112.1 (2)
C13—C12—H12	119.3

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1C···O8^i	0.99	1.85	2.800 (4)	160
N1—H1B···O5^ii	0.91	2.04	2.935 (3)	166
N1—H1A···O6^iii	0.97	1.88	2.779 (3)	153
O5—H5···O7^iii	0.97	1.76	2.714 (3)	170
O6—H6···O1	0.91	1.81	2.662 (3)	154
O7—H7A···O8^iii	0.92	1.77	2.686 (3)	173
O8—H8B···O2	0.92	1.76	2.617 (3)	1523
O8—H8A···O1^iv	0.91	1.76	2.667 (3)	173
C24—H24A···O1	0.99	2.55	3.410 (4)	146
C25—H25A···O2^iii	0.99	2.44	3.326 (4)	149

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