research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 80| Part 3| March 2024| Pages 292-295
https://doi.org/10.1107/S2056989024001403

Omadacycline dihydrate, C29H40N4O7·2H2O, from X-ray powder diffraction data

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James A. Kaduk,a* Nicholas C. Boaz,b Stacy Gates-Rector,a Amy M. Gindharta and Thomas N. Blantona

aICDD, 12 Campus Blvd., Newtown Square PA 19073-3273, USA, and bDepartment of Chemistry, North Central College, 131 S. Loomis, St., Naperville IL, 60540 , USA
*Correspondence e-mail: kaduk@polycrystallography.com

Edited by W. T. A. Harrison, University of Aberdeen, United Kingdom (Received 6 November 2023; accepted 12 February 2024; online 16 February 2024)

The crystal structure of the title compound {systematic name: (4S,4aS,5aR,12aR)-4,7-bis­(di­methyl­amino)-9-[(2,2-di­methyl­propyl­amino)­meth­yl]-1,10,11,12a-tetra­hydroxy-3,12-dioxo-4a,5,5a,6-tetra­hydro-4H-tetra­cene-2-carb­oxamide dihydrate, C29H40N4O7·2H2O} has been solved and refined using synchrotron X-ray powder diffraction data: it crystallizes in space group R3 with a = 24.34430 (7), c = 14.55212 (4) Å, V = 7468.81 (2) Å3 and Z = 9. Most of the hydrogen bonds are intra­molecular, but two classical N—H⋯O inter­molecular hydrogen bonds (along with probable weak C—H⋯O and C—H⋯N hydrogen bonds) link the mol­ecules into a three-dimensional framework. The framework contains voids, which contain disordered water mol­ecules. Keto–enol tautomerism is apparently important in this mol­ecule, and the exact mol­ecular structure is ambiguous.

CCDC reference: 2332637

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1. Chemical context

Omadacycline, sold under the brand name Nuzyra, is a broad-spectrum tetra­cycline anti­biotic. Omadacycline finds use in treating bacterial pneumonia and certain types of skin infections. The systematic name (CAS Registry No. 389139-89-3) is (4S,4aS,5aR,12aR)-4,7-bis­(di­methyl­amino)-9-[(2,2-di­methyl­propyl­amino)­meth­yl]-1,10,11,12a-tetra­hydroxy-3,12-dioxo-4a,5,5a,6-tetra­hydro-4H-tetra­cene-2-carboxamide. It is sometimes the case that the hydroxyl and carbonyl groups are misassigned in structure pictures of tetra­cycline anti­biotics, so in addition to the crystal structure it is important to consider the chemical connectivity to give insight into keto–enol tautomerism.

[Scheme 1]

This work was carried out as part of a project (Kaduk et al., 2014[Kaduk, J. A., Crowder, C. E., Zhong, K., Fawcett, T. G. & Suchomel, M. R. (2014). Powder Diffr. 29, 269-273.]) to determine the crystal structures of large-volume commercial pharmaceuticals, and include high-quality powder diffraction data for them in the Powder Diffraction File (Gates-Rector & Blanton, 2019[Gates-Rector, S. & Blanton, T. N. (2019). Powder Diffr. 34, 352-360.]).

2. Structural commentary

The powder pattern of the hydrated omadacycline studied here is not the same as that reported for crystalline omadacycline by Cvetovich & Warchol (2013[Cvetovich, R. & Warchol, T. (2013). US Patent 8,383,610 B2.]) (Fig. 1[link]). Our material was a commercial sample, but it is not clear how representative it is of the bulk pharmaceutical material.

[Figure 1]
Figure 1
Comparison of the synchrotron pattern of omadacycline dihydrate (black) to that of omadacycline (green) reported by Cvetovich & Warchol (2013[Cvetovich, R. & Warchol, T. (2013). US Patent 8,383,610 B2.]). The patent pattern, measured using Cu Kα radiation, was digitized using UN-SCAN-IT (Silk Scientific, 2013[Silk Scientific. (2013). UN-SCAN-IT 7.0. Orem, UT, USA.]), and converted to the synchrotron wavelength of 0.458133 Å using JADE Pro (MDI, 2021[MDI (2021). JADE Pro 8.1. MDI, Livermore, CA, USA.]). Image generated using JADE Pro (MDI, 2021[MDI (2021). JADE Pro 8.1. MDI, Livermore, CA, USA.]).

The refined structure of the omadacycline mol­ecule is different in chemical connectivity and conformation from that archived in PubChem (Kim et al., 2019[Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky, L., Zhang, J. & Bolton, E. E. (2019). Nucleic Acids Res. 47, D1102-D1109.]; Figs. 2[link] and 3[link]). In particular, C20—O3 (our numbering scheme) is a double bond, while C30—O7, C21—O5, and C18—O2 are single bonds. C21—C24 is a double bond, C20—C24 is a single bond, and several other C—C bonds in the ring system differ in order. It is unclear whether the differences represent differences between solution and the solid state, or merely the limited information content of the powder diffraction pattern of a very complex material. The bond-distance and bond-angle restraints were deliberately given low weight to gain insight into what information the diffraction data can give regarding the chemical connectivity.

[Figure 2]
Figure 2
The omadacycline mol­ecule in omadacycline dihydrate, with the atom numbering. The atoms are represented by 50% probability spheres.
[Figure 3]
Figure 3
Comparison of the structure of the omadacycline mol­ecule from this Rietveld refinement (green) to that archived in PubChem (purple). The root-mean-square Cartesian displacement of the non-H atoms is 1.08 Å.

It was clear from both the structure solution and refinement and a DFT calculation that the C30—O7—N10 group is oriented to form a strong intra­molecular O7—H55⋯O3 hydrogen bond, and that N10 participates in inter­molecular hydrogen bonds (Table 1[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O7—H55⋯O3 0.98 1.84 2.614 (15) 134
O2—H57⋯O4 0.74 1.78 2.506 (15) 169
O6—H60⋯O4 1.28 1.26 2.485 (15) 155
O1—H48⋯O2 0.82 2.42 2.721 (13) 103
N10—H61⋯O5 1.11 1.79 2.686 (12) 135
N10—H62⋯O2i 1.11 2.04 2.935 (13) 135
N11—H69⋯O84ii 1.11 2.15 3.18 (2) 153
C33—H58⋯N10iii 1.14 2.51 3.63 (2) 165
C34—H64⋯O1iv 1.14 2.35 3.46 (2) 165
C35—H68⋯O1iv 1.14 2.58 3.642 (15) 154
C39—H76⋯O85v 1.18 2.41 3.32 (2) 132
Symmetry codes: (i) [-y+{\script{4\over 3}}, x-y-{\script{1\over 3}}, z-{\script{1\over 3}}]; (ii) [-y+1, x-y, z]; (iii) [-y+{\script{2\over 3}}, x-y-{\script{2\over 3}}, z+{\script{1\over 3}}]; (iv) [-y+{\script{2\over 3}}, x-y-{\script{2\over 3}}, z-{\script{2\over 3}}]; (v) [x+{\script{2\over 3}}, y+{\script{1\over 3}}, z-{\script{2\over 3}}].

There are many unusual bond distances, bond angles, and torsion angles indicated by a Mercury Mogul Geometry check (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]). Although there are some large Z-scores among the bond distances, the largest ones tend to be on the periphery of the mol­ecule, where the chemical connectivity is not in doubt. In the ring system, the distinctions between single and double bonds seem to be clear. It is hard to make conclusions about the Z-scores of the bond angles, but some of the large Z-scores result from very small standard uncertainties on the average bond angles. Both for bond distances and bond angles, greater- and less-than-normal values tend to be correlated, probably reflecting errors in atom positions, which were restrained only modestly. Some torsion angles involving rotation about the C16—N8, C26—N9, C24—C30, C37—C36, and C31—C33 bonds are flagged as unusual. All of these reflect the orientations of peripheral groups, which do seem to be unusual in this crystal structure.

3. Supra­molecular features

We obtained guidance on whether potential inter­atomic contacts were real hydrogen bonds from a DFT optimization of the anhydrous structure (without the disordered water mol­ecules). This structure is close to that of the disordered anhydrate. A DFT optimization of an ordered dihydrate yielded a different mol­ecular connectivity, and it is unclear how relevant such a calculation is to the disordered structure. The differences point out that the mol­ecular connectivity may vary depending on the state of hydration, and also in solution versus the solid state.

There are many hydrogen bonds in the structure, but (perhaps surprisingly) almost all of them are intra­molecular. Only the N10—H62⋯O2 and N11—H69⋯O84 hydrogen bonds (as well as probable weak C—H⋯O and C—H⋯N hydrogen bonds) link different mol­ecules. The inter­molecular hydrogen bonds link the mol­ecules into a three-dimensional network (Fig. 4[link]). There are three very strong intra­molecular O—H⋯O hydrogen bonds between hydroxyl and carbonyl groups. There are also short intra­molecular meth­yl⋯methyl contacts between H49 and H52 and H66 and H63. The shortest (and only) O⋯O distances between water mol­ecules and omadacycline mol­ecules are 2.727 (17) and 3.119 (16) Å between O84 and two symmetry-equivalent O7; the water mol­ecules only loosely inter­act with the framework and it was not possible to unambiguously locate the water H atoms.

[Figure 4]
Figure 4
The crystal structure of omadacycline dihydrate, viewed down the c-axis direction showing the voids occupied by disordered water mol­ecules.

We may state that we have established the crystal structure of omadacyclic dihydrate, but the exact mol­ecular structure is ambiguous.

4. Database survey

Polymorphs of crystalline omadacycline tosyl­ate are claimed in US Patent 8,383,610 B2 (Cvetovich & Warchol, 2013[Cvetovich, R. & Warchol, T. (2013). US Patent 8,383,610 B2.]; Paratek Pharmaceuticals). A powder pattern of the parent compound is also provided. A reduced cell search in the Cambridge Structural Database (CSD, version 5.45 November 2023; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) combined with C, H, N, and O only, yielded two hits, but no structures of omadacycline derivatives.

5. Synthesis and crystallization

Omadacycline was a commercial reagent, purchased from TargetMol (Batch #132019), and was used as received.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link].

Table 2
Experimental details

Crystal data
Chemical formula C29H40N4O7·2H2O
Mr 588.03
Crystal system, space group Trigonal, R3
Temperature (K) 295
a, c (Å) 24.34430 (7), 14.55212 (4)
V (Å3) 7468.81 (2)
Z 9
Radiation type Synchrotron, λ = 0.45813 Å
μ (mm−1) 0.01
Specimen shape, size (mm) Cylinder, 3 × 1.5
 
Data collection
Diffractometer 11-BM, APS
Specimen mounting Kapton capillary
Data collection mode Transmission
Scan method Step
2θ values (°) 2θmin = 0.500, 2θmax = 49.997, 2θstep = 0.001
 
Refinement
R factors and goodness of fit Rp = 0.048, Rwp = 0.061, Rexp = 0.043, R(F2) = 0.06407, χ2 = 2.161
No. of parameters 148
No. of restraints 112
H-atom treatment Only H-atom displacement parameters refined
(Δ/σ)max 4.723
Computer programs: GSAS-II (Toby & Von Dreele, 2013[Toby, B. H. & Von Dreele, R. B. (2013). J. Appl. Cryst. 46, 544-549.]), Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]), and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

The pattern was first indexed using JADE Pro 8.1 (MDI, 2021[MDI (2021). JADE Pro 8.1. MDI, Livermore, CA, USA.]) as a primitive monoclinic unit cell with a = 11.98344, b = 12.17479, c = 8.54255 Å, β = 91.30°, V = 1246.0 Å3, and Z = 2. Indexing using N-TREOR (Altomare et al., 2013[Altomare, A., Cuocci, C., Giacovazzo, C., Moliterni, A., Rizzi, R., Corriero, N. & Falcicchio, A. (2013). J. Appl. Cryst. 46, 1231-1235.]) yielded a hexa­gonal unit cell with a = 24.34510, c = 14.55468 Å, and V = 7470.6 Å3. Re-indexing with JADE, allowing for higher-symmetry cells, yielded the same hexa­gonal cell. The space group suggested by both programs was R3.

An omadacycline mol­ecule was downloaded from PubChem (Kim et al., 2019[Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky, L., Zhang, J. & Bolton, E. E. (2019). Nucleic Acids Res. 47, D1102-D1109.]) as Conformer3D_CID_5469735.sdf. It was converted into a *.mol2 file using Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]), and into a Fenske-Hall Z-matrix file using OpenBabel (O'Boyle et al., 2011[O'Boyle, N. M., Banck, M., James, C. A., Morley, C., Vandermeersch, T. & Hutchison, G. R. (2011). J. Chem. Informatics, 3, 33.]). The structure was solved using FOX (Favre-Nicolin & Černý, 2002[Favre-Nicolin, V. & Černý, R. (2002). J. Appl. Cryst. 35, 734-743.]) using (sin θ/λ)max = 0.4 Å−1. Visualization of the structure revealed the presence of several voids. By placing oxygen atoms (possibly water mol­ecules) into the voids and refining their positions and occupancies (some refined to less than 0, and were removed from the model), four potential sites, corresponding to 18.1 H2O/cell, or 2.0 H2O/omadacycline (i.e., a dihydrate) were identified.

NMR analysis of the omadacycline sample was performed using a 400 MHz Bruker Avance spectrometer equipped with a multinuclear probe. The 1H NMR of the pharmaceutical sample was performed in d6 DMSO, which was stored over flame-dried 3 Å mol­ecular sieves. The 1H NMR analysis of the sample indicated the presence of water in addition to omadacycline (Gottlieb et al., 1997[Gottlieb, H. E., Kotlyar, V. & Nudelman, A. (1997). J. Org. Chem. 62, 7512-7515.]). By comparing the water signal at 3.33 ppm to the signal at 7.41 ppm, which belongs to the arene C—H group of the pharmaceutical moleucle, the water content was estimated to be approximately 1.5 water mol­ecules to 1 omadacycline. Moreover, the 1H NMR spectrum of the omadacycline sample indicated that there was no observable trace of residual organic solvent or tosyl­ate counter-ion. The NMR data therefore indicate that the species in the pores in the crystal structure is water. After evaporation of the DMSO solvent, the solid was discolored.

Rietveld refinement (Fig. 5[link]) was carried out using GSAS-II (Toby & Von Dreele, 2013[Toby, B. H. & Von Dreele, R. B. (2013). J. Appl. Cryst. 46, 544-549.]). Only the 2.0–25.0° portion of the pattern was included in the refinement (dmin = 1.058 Å). The z-coordinate of O1 was fixed to define the origin. All non-H bond distances and angles were subjected to restraints, based on a Mercury Mogul Geometry Check (Sykes et al., 2011[Sykes, R. A., McCabe, P., Allen, F. H., Battle, G. M., Bruno, I. J. & Wood, P. A. (2011). J. Appl. Cryst. 44, 882-886.]; Bruno et al., 2004[Bruno, I. J., Cole, J. C., Kessler, M., Luo, J., Motherwell, W. D. S., Purkis, L. H., Smith, B. R., Taylor, R., Cooper, R. I., Harris, S. E. & Orpen, A. G. (2004). J. Chem. Inf. Comput. Sci. 44, 2133-2144.]). The Mogul average and standard deviation for each qu­antity were used as the restraint parameters. The weight of the restraints was gradually decreased during the refinement. The restraints contributed 3.8% to the final χ2. The hydrogen atoms were included in calculated positions, which were recalculated during the refinement using Materials Studio (Dassault, 2021[Dassault (2021). Materials Studio. Dassault Systèmes, San Diego, CA, USA.]). The Uiso values were grouped by chemical similarity. The Uiso for the H atoms were fixed at 1.3 × the Uiso of the heavy atoms to which they are attached. A second-order spherical harmonic model was included in the refinement to account for preferred orientation and the refined texture index is 1.001 (0). The peak profiles were described using the generalized microstrain model. The background was modeled using a six-term shifted Chebyshev polynomial, plus a peak at 5.63° 2θ to model the scattering from the Kapton capillary and any amorphous component.

[Figure 5]
Figure 5
The Rietveld plot for the refinement of omadacycline dihydrate. The blue crosses represent the observed data points, and the green line is the calculated pattern. The cyan curve is the normalized difference plot. The vertical scale has been multiplied by a factor of 20× for 2θ > 8.0°.

Supporting information

CCDC reference: 2332637

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989024001403/hb8082sup1.cif

Supporting information file. DOI: https://doi.org/10.1107/S2056989024001403/hb8082Isup2.cml

checkCIF report


Computing details top

(4S,4aS,5aR,12aR)-4,7-Bis(dimethylamino)-9-[(2,2-dimethylpropylamino)methyl]-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide dihydrate top
Crystal data top
C29H40N4O7·2H2OZ = 9
Mr = 588.03Dx = 1.177 Mg m−3
Trigonal, R3Synchrotron radiation, λ = 0.45813 Å
Hall symbol: R 3µ = 0.01 mm−1
a = 24.34430 (7) ÅT = 295 K
c = 14.55212 (4) Åwhite
V = 7468.81 (2) Å3cylinder, 3 × 1.5 mm
Data collection top
11-BM, APS
diffractometer		Data collection mode: transmission
Radiation source: synchrotronScan method: step
Double Si(111) sngle crystal monochromator2θmin = 0.500°, 2θmax = 49.997°, 2θstep = 0.001°
Specimen mounting: Kapton capillary
Refinement top
Least-squares matrix: full148 parameters
Rp = 0.048112 restraints
Rwp = 0.0617 constraints
Rexp = 0.043Only H-atom displacement parameters refined
R(F2) = 0.06407Weighting scheme based on measured s.u.'s
49575 data points(Δ/σ)max = 4.723
Excluded region(s): Th regions 0.5-2.0 and 25.0-50.0° contained no peaks.Background function: Background function: "chebyschev-1" function with 6 terms: 242.80(28), -5.7(4), -17.4(4), 6.6(4), 19.4(3), -39.10(30), Background peak parameters: pos, int, sig, gam: 5.635, 59368.501, 16287.514, 0.100,
Profile function: Finger-Cox-Jephcoat function parameters U, V, W, X, Y, SH/L: peak variance(Gauss) = Utan(Th)2+Vtan(Th)+W: peak HW(Lorentz) = X/cos(Th)+Ytan(Th); SH/L = S/L+H/L U, V, W in (centideg)2, X & Y in centideg 1.163, -0.126, 0.063, 0.000, 0.000, 0.002,Preferred orientation correction: Simple spherical harmonic correction Order = 2 Coefficients: 0:0:C(2,0) = 0.081(5)
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
O10.8514 (3)0.1354 (3)0.511100.0497 (10)*
O20.7746 (4)0.1858 (4)0.4890 (7)0.0497 (10)*
O30.8837 (4)0.2363 (4)0.3587 (8)0.0497 (10)*
O40.6658 (4)0.1617 (4)0.4417 (7)0.0497 (10)*
O50.9444 (4)0.0918 (4)0.2428 (7)0.0497 (10)*
O60.5495 (4)0.1148 (4)0.4214 (7)0.0497 (10)*
O70.9888 (4)0.2785 (4)0.2650 (7)0.031 (2)*
N80.8862 (7)0.0578 (6)0.4539 (9)0.092 (4)*
N90.5642 (5)0.0056 (5)0.1009 (9)0.057 (3)*
N101.0152 (5)0.2154 (4)0.2006 (9)0.031 (2)*
N110.4343 (6)0.0952 (7)0.2570 (10)0.107 (3)*
C120.8049 (5)0.0645 (5)0.3856 (9)0.0336 (9)*
C130.8248 (4)0.1300 (5)0.4225 (7)0.0336 (9)*
C140.7724 (5)0.0573 (5)0.2953 (9)0.0336 (9)*
C150.7089 (5)0.0561 (6)0.3079 (9)0.0336 (9)*
C160.8606 (5)0.0550 (6)0.3636 (10)0.0336 (9)*
C170.7161 (5)0.1108 (5)0.3646 (9)0.0336 (9)*
C180.7652 (5)0.1424 (5)0.4282 (9)0.0336 (9)*
C190.6766 (5)0.0564 (6)0.2273 (9)0.0336 (9)*
C200.8734 (5)0.1842 (5)0.3436 (9)0.0336 (9)*
C210.9163 (6)0.1090 (5)0.3060 (8)0.0336 (9)*
C220.6082 (4)0.0559 (6)0.2353 (10)0.0336 (9)*
C230.6654 (5)0.1270 (5)0.3751 (8)0.0336 (9)*
C240.9206 (5)0.1664 (5)0.3003 (9)0.0336 (9)*
C250.6071 (4)0.0848 (5)0.3199 (9)0.0336 (9)*
C260.5612 (5)0.0287 (5)0.1824 (9)0.0336 (9)*
C270.5555 (6)0.0851 (6)0.3527 (8)0.0336 (9)*
C280.8490 (8)0.0023 (8)0.5002 (10)0.092 (4)*
C290.9504 (7)0.0844 (7)0.4781 (12)0.092 (4)*
C300.9828 (5)0.2244 (5)0.2738 (10)0.031 (2)*
C310.4989 (6)0.0548 (6)0.2996 (9)0.0336 (9)*
C320.5042 (6)0.0304 (6)0.2106 (9)0.0336 (9)*
C330.4478 (7)0.0581 (7)0.3171 (11)0.107 (3)*
C340.6218 (7)0.0548 (7)0.0311 (13)0.107 (3)*
C350.5180 (7)−0.0357 (7)0.0567 (9)0.057 (3)*
C360.4804 (6)0.1595 (6)0.2292 (10)0.057 (3)*
C370.4713 (8)0.1946 (8)0.1400 (11)0.107 (3)*
C380.4917 (7)0.1708 (7)0.0725 (13)0.107 (3)*
C390.5218 (8)0.2717 (8)0.1705 (10)0.107 (3)*
C400.4133 (8)0.1868 (7)0.1118 (13)0.107 (3)*
H410.771340.026660.435920.0437 (11)*
H420.763060.011190.261410.0437 (11)*
H430.804230.098820.248660.0437 (11)*
H440.693530.016030.328950.0437 (11)*
H450.843610.006600.330800.0437 (11)*
H460.708210.100880.185600.0437 (11)*
H470.667870.013690.184150.0437 (11)*
H480.855430.164350.544610.0646 (13)*
H490.80861−0.031980.453740.120 (5)*
H500.87885−0.019740.521550.120 (5)*
H510.828560.012440.564230.120 (5)*
H520.959920.045200.501300.120 (5)*
H530.981380.109850.416090.120 (5)*
H540.961980.119720.536530.120 (5)*
H560.487090.021130.142400.0437 (11)*
H570.744020.183070.477000.0646 (13)*
H580.454300.077850.389800.139 (4)*
H590.405390.007840.317160.139 (4)*
H600.609440.150050.434020.0646 (13)*
H611.007080.166310.202870.040 (3)*
H621.066750.249700.206700.040 (3)*
H630.649740.103320.065100.139 (4)*
H640.600370.05953−0.036020.139 (4)*
H650.654850.035340.016260.139 (4)*
H660.47237−0.039540.084250.074 (4)*
H670.51579−0.083350.064500.074 (4)*
H680.52365−0.02191−0.019020.074 (4)*
H690.418640.070820.189630.139 (4)*
H700.531330.180840.246630.139 (4)*
H710.463090.186670.270360.139 (4)*
H720.472120.175510.003620.139 (4)*
H730.474390.118620.086860.139 (4)*
H740.545740.198230.070200.139 (4)*
H750.496330.285120.212280.139 (4)*
H760.559180.262840.209820.139 (4)*
H770.543250.297050.105630.139 (4)*
H780.400540.217380.156210.139 (4)*
H790.375090.134850.119200.139 (4)*
H800.416660.201760.036830.139 (4)*
H550.965190.283440.315790.0646 (13)*
O820.000000.000001.127 (2)0.1000*0.640 (28)
O830.000000.000001.031 (2)0.1000*1.087 (25)
O840.6271 (4)0.6381 (4)0.1054 (10)0.1000*1.077 (10)
O850.000000.000000.9249 (17)0.1000*0.925 (24)
Geometric parameters (Å, º) top
O1—C131.420 (10)C24—C201.550 (12)
O1—H480.823C24—C211.349 (9)
O2—C181.308 (9)C24—C301.516 (11)
O2—H570.735C25—C221.425 (13)
O3—C201.183 (10)C25—C231.502 (11)
O4—C231.281 (7)C25—C271.348 (12)
O4—H601.261C26—N91.329 (12)
O5—C211.334 (11)C26—C221.259 (12)
O6—C271.284 (7)C26—C321.469 (13)
O6—H601.283C27—O61.284 (7)
O7—C301.256 (12)C27—C251.348 (12)
O7—H550.979C27—C311.421 (11)
N8—C161.441 (14)C28—N81.369 (16)
N8—C281.369 (16)C28—H491.141
N8—C291.404 (15)C28—H501.140
N9—C261.329 (12)C28—H511.140
N9—C341.660 (15)C29—N81.404 (15)
N9—C351.250 (14)C29—H521.141
N10—C301.408 (12)C29—H531.140
N10—H611.110C29—H541.139
N10—H621.109C30—O71.256 (12)
N11—C331.409 (15)C30—N101.408 (12)
N11—C361.456 (13)C30—C241.516 (11)
N11—H691.110C31—C271.421 (11)
C12—C131.515 (9)C31—C321.456 (12)
C12—C141.498 (13)C31—C331.313 (10)
C12—C161.520 (10)C32—C261.469 (13)
C12—H411.139 (12)C32—C311.456 (12)
C13—O11.420 (10)C32—H561.056 (13)
C13—C121.515 (9)C33—N111.409 (15)
C13—C181.625 (9)C33—C311.313 (10)
C13—C201.703 (11)C33—H581.139
C14—C121.498 (13)C33—H591.139
C14—C151.544 (11)C34—N91.660 (15)
C14—H421.139C34—H631.139
C14—H431.140C34—H641.140
C15—C141.544 (11)C34—H651.140
C15—C171.501 (10)C35—N91.250 (14)
C15—C191.413 (12)C35—H661.140
C15—H440.906C35—H671.139
C16—N81.441 (14)C35—H681.140
C16—C121.520 (10)C36—N111.456 (13)
C16—C211.577 (13)C36—C371.631 (17)
C16—H451.140C36—H701.107
C17—C151.501 (10)C36—H711.120
C17—C181.398 (11)C37—C361.631 (17)
C17—C231.480 (11)C37—C381.356 (17)
C18—O21.308 (9)C37—C391.709 (16)
C18—C131.625 (9)C37—C401.388 (17)
C18—C171.398 (11)C38—C371.356 (17)
C19—C151.413 (12)C38—H721.140
C19—C221.663 (10)C38—H731.140
C19—H461.140C38—H741.139
C19—H471.139C39—C371.709 (16)
C20—O31.183 (10)C39—H751.031
C20—C131.703 (11)C39—H761.182
C20—C241.550 (12)C39—H771.106
C21—O51.334 (11)C40—C371.388 (17)
C21—C161.577 (13)C40—H781.141
C21—C241.349 (9)C40—H791.139
C22—C191.663 (10)C40—H801.140
C22—C251.425 (13)O82—O831.39 (3)
C22—C261.259 (12)O83—O821.39 (3)
C23—O41.281 (7)O83—O851.55 (3)
C23—C171.480 (11)O85—O831.55 (3)
C23—C251.502 (11)
C13—O1—H48118.0O6—C27—C25130.3 (11)
C18—O2—H5790.3O6—C27—C31111.3 (11)
C23—O4—H6097.8C25—C27—C31118.0 (8)
C27—O6—H6094.4N8—C28—H49109.4
C30—O7—H55106.5N8—C28—H50109.6
C16—N8—C28110.2 (13)H49—C28—H50109.7
C16—N8—C29127.3 (14)N8—C28—H51109.5
C28—N8—C29111.5 (15)H49—C28—H51109.4
C26—N9—C35125.6 (10)H50—C28—H51109.2
C30—N10—H61109.5N8—C29—H52109.4
C30—N10—H62109.5N8—C29—H53109.5
H61—N10—H62109.5H52—C29—H53109.4
C33—N11—C36124.0 (12)N8—C29—H54109.6
C33—N11—H69109.5H52—C29—H54109.4
C36—N11—H69101.7H53—C29—H54109.5
C13—C12—C14107.9 (8)O7—C30—N10107.8 (9)
C13—C12—C16113.3 (8)O7—C30—C24122.8 (11)
C14—C12—C16104.8 (9)N10—C30—C24115.1 (11)
C13—C12—H41110.2C27—C31—C32115.8 (10)
C14—C12—H41110.2C27—C31—C33124.4 (12)
C16—C12—H41110.2C32—C31—C33118.4 (11)
O1—C13—C12108.0 (9)C26—C32—C31122.5 (10)
C12—C14—C15111.3 (9)C26—C32—H5690.4
C12—C14—H42109.3C31—C32—H56144.9 (11)
C15—C14—H42109.1N11—C33—C31116.8 (13)
C12—C14—H43109.5N11—C33—H58109.5
C15—C14—H43108.4C31—C33—H58105.6
H42—C14—H43109.2N11—C33—H59108.2
C14—C15—C17112.1 (8)C31—C33—H59108.2
C14—C15—C19117.1 (10)H58—C33—H59108.3
C17—C15—C19105.7 (9)H63—C34—H64109.5
C14—C15—H4486.0H63—C34—H65109.5
C17—C15—H44124.9H64—C34—H65109.5
C19—C15—H44110.8N9—C35—H66109.4
N8—C16—C12101.5 (10)N9—C35—H67109.4
N8—C16—H45110.8H66—C35—H67109.5
C12—C16—H45110.8N9—C35—H68109.4
C15—C17—C18122.7 (4)H66—C35—H68109.5
C15—C17—C23123.4 (9)H67—C35—H68109.5
C18—C17—C23112.5 (8)N11—C36—H70121.5
O2—C18—C17130.4 (8)N11—C36—H7199.8
C15—C19—H46109.5H70—C36—H71105.3
C15—C19—H47107.7C38—C37—C40107.0 (16)
H46—C19—H47107.6C37—C38—H72109.4
O3—C20—C24126.0 (10)C37—C38—H73109.4
O5—C21—C24119.7 (8)H72—C38—H73109.4
C25—C22—C26123.5 (7)C37—C38—H74109.5
O4—C23—C17121.4 (9)H72—C38—H74109.5
O4—C23—C25123.3 (9)H73—C38—H74109.6
C17—C23—C25113.0 (8)H75—C39—H76114.4
C20—C24—C21125.5 (8)H75—C39—H77121.1
C20—C24—C30112.1 (9)H76—C39—H77108.8
C21—C24—C30120.3 (9)C37—C40—H78109.4
C22—C25—C23123.7 (9)C37—C40—H79109.5
C22—C25—C27123.8 (7)H78—C40—H79109.5
C23—C25—C27111.8 (10)C37—C40—H80109.5
N9—C26—C22122.7 (10)H78—C40—H80109.4
N9—C26—C32121.0 (10)H79—C40—H80109.5
C22—C26—C32115.9 (8)O4—H60—O6155.4 (5)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O7—H55···O30.981.842.614 (15)134
O2—H57···O40.741.782.506 (15)169
O6—H60···O41.281.262.485 (15)155
O1—H48···O20.822.422.721 (13)103
N10—H61···O51.111.792.686 (12)135
N10—H62···O2i1.112.042.935 (13)135
N11—H69···O84ii1.112.153.18 (2)153
C33—H58···N10iii1.142.513.63 (2)165
C34—H64···O1iv1.142.353.46 (2)165
C35—H68···O1iv1.142.583.642 (15)154
C39—H76···O85v1.182.413.32 (2)132
Symmetry codes: (i) −y+4/3, x−y−1/3, z−1/3; (ii) −y+1, x−y, z; (iii) −y+2/3, x−y−2/3, z+1/3; (iv) −y+2/3, x−y−2/3, z−2/3; (v) x+2/3, y+1/3, z−2/3.
 

Acknowledgements

Use of the Advanced Photon Source at Argonne National Laboratory was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02–06CH11357. This work was partially supported by the Inter­national Centre for Diffraction Data. We thank Lynn Ribaud and Saul Lapidus for their assistance in the data collection.

Funding information

Funding for this research was provided by: International Centre for Diffraction Data (grant No. 09-03 to Poly Crystallography Inc.).

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ISSN: 2056-9890
Volume 80| Part 3| March 2024| Pages 292-295
https://doi.org/10.1107/S2056989024001403
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