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

IUCrJ
Volume 6| Part 4| July 2019| Pages 630-634
ISSN: 2052-2525

Plasticity in zwitterionic drugs: the bending properties of Pregabalin and Gabapentin and their hydrates

aSynthesis and Solid State Pharmaceutical Centre (SSPC), University of Limerick, Limerick, Ireland, bDepartment of Chemical Science and Bernal Institute, University of Limerick, Limerick, Ireland, and cDepartment of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick, Limerick, Ireland
*Correspondence e-mail: udaya.khandavilli@ul.ie, matteo.lusi@ul.ie

Edited by L. R. MacGillivray, University of Iowa, USA (Received 8 February 2019; accepted 8 April 2019; online 22 May 2019)

The investigation of mechanical properties in molecular crystals is emerging as a novel area of interest in crystal engineering. Indeed, good mechanical properties are required to manufacture pharmaceutical and technologically relevant substances into usable products. In such endeavour, bendable single crystals help to correlate microscopic structure to macroscopic properties for potential design. The hydrate forms of two anticonvulsant zwitterionic drugs, Pregabalin and Gabapentin, are two examples of crystalline materials that show macroscopic plasticity. The direct comparison of these structures with those of their anhydrous counterparts, which are brittle, suggests that the presence of water is critical for plasticity. In contrast, structural features such as molecular packing and anisotropic distribution of strong and weak interactions seem less important.

1. Introduction

In recent times, the classic idea of crystals as a brittle objects has been progressively abandoned (Dunitz, 1984[Dunitz, J. D. (1984). Trans. Am. Cryst. Assoc. 20, 1-13.]). Observation of phenomena such as shearing (Reddy et al., 2005a[Reddy, C. M., Basavoju, S. & Desiraju, G. R. (2005a). Chem. Commun. 44, 2439-2441.]) or bending (Reddy et al., 2005b[Reddy, C. M., Gundakaram, R. C., Basavoju, S., Kirchner, M. T., Padmanabhan, K. A. & Desiraju, G. R. (2005b). Chem. Commun. 0, 3945-3947.]) as well as martensitic (Zamir et al., 1994[Zamir, S., Bernstein, J. & Greenwood, D. J. (1994). Mol. Cryst. Liq. Cryst. 242, 193-200.]; Steiner et al., 1993[Steiner, T., Hinrichs, W., Saenger, W. & Gigg, R. (1993). Acta Cryst. B49, 708-718.]; Ding et al., 1991[Ding, J., Herbst, R., Praefcke, K., Kohne, B. & Saenger, W. (1991). Acta Cryst. B47, 739-742.]; Etter & Siedle, 1983[Etter, M. C. & Siedle, A. R. (1983). J. Am. Chem. Soc. 105, 641-643.]), super-elastic (Takamizawa & Miyamoto, 2014[Takamizawa, S. & Miyamoto, Y. (2014). Angew. Chem. Int. Ed. 53, 6970-6973.]) and super-plastic (Takamizawa et al., 2018[Takamizawa, S., Takasaki, Y., Sasaki, T. & Ozaki, N. (2018). Nat. Commun. 9, 3984.]) transformations clearly show that organic crystals share many similarities with metallic and covalent inorganic analogues. Mechanical properties of molecular crystals are investigated and discussed with increasing frequency and those studies have attracted considerable attention (Reddy et al., 2010[Reddy, C. M., Rama Krishna, G. & Ghosh, S. (2010). CrystEngComm, 12, 2296-2314.]; Naumov et al., 2015[Naumov, P., Chizhik, S., Panda, M. K., Nath, N. K. & Boldyreva, E. (2015). Chem. Rev. 115, 12440-12490.]). Aside from the understandable academic curiosity, mechanical properties are important for the manufacturing of crystalline solids into products. For example, in the pharmaceutical industry, good plasticity guarantees that microcrystalline drug substances can be readily manufactured into tablets without the addition of excipients (Thoorens et al., 2015[Thoorens, G., Krier, F., Rozet, E., Carlin, B. & Evrard, B. (2015). Int. J. Pharm. 490, 47-54.]; Chang & Sun, 2017[Chang, S.-Y. & Sun, C. C. (2017). Mol. Pharm. 14, 2047-2055.]).

A characteristic of molecular crystals is that they are held together by supramolecular interactions. It follows that crystal synthesis occurs in relatively mild conditions, whilst a supramolecular approach enables a certain degree of structure design (Desiraju, 1989[Desiraju, G. R. (1989). Crystal Engineering: The Design of Organic Solids. Amsterdam: Elsevier.]; Etter, 1990[Etter, M. C. (1990). Acc. Chem. Res. 23, 120-126.]; Moulton & Zaworotko, 2001[Moulton, B. & Zaworotko, M. J. (2001). Chem. Rev. 101, 1629-1658.]). In this view, understanding how molecular features determine a crystal structure and, in turn, material properties would enable crystal engineering and properties design.

The rapid scientific advances of the past decades allow the confident prediction of how a given set of molecules will pack in a crystal structure (Reilly et al., 2016[Reilly, A. M., Cooper, R. I., Adjiman, C. S., Bhattacharya, S., Boese, A. D., Brandenburg, J. G., Bygrave, P. J., Bylsma, R., Campbell, J. E., Car, R., Case, D. H., Chadha, R., Cole, J. C., Cosburn, K., Cuppen, H. M., Curtis, F., Day, G. M., DiStasio Jr, R. A., Dzyabchenko, A., van Eijck, B. P., Elking, D. M., van den Ende, J. A., Facelli, J. C., Ferraro, M. B., Fusti-Molnar, L., Gatsiou, C.-A., Gee, T. S., de Gelder, R., Ghiringhelli, L. M., Goto, H., Grimme, S., Guo, R., Hofmann, D. W. M., Hoja, J., Hylton, R. K., Iuzzolino, L., Jankiewicz, W., de Jong, D. T., Kendrick, J., de Klerk, N. J. J., Ko, H.-Y., Kuleshova, L. N., Li, X., Lohani, S., Leusen, F. J. J., Lund, A. M., Lv, J., Ma, Y., Marom, N., Masunov, A. E., McCabe, P., McMahon, D. P., Meekes, H., Metz, M. P., Misquitta, A. J., Mohamed, S., Monserrat, B., Needs, R. J., Neumann, M. A., Nyman, J., Obata, S., Oberhofer, H., Oganov, A. R., Orendt, A. M., Pagola, G. I., Pantelides, C. C., Pickard, C. J., Podeszwa, R., Price, L. S., Price, S. L., Pulido, A., Read, M. G., Reuter, K., Schneider, E., Schober, C., Shields, G. P., Singh, P., Sugden, I. J., Szalewicz, K., Taylor, C. R., Tkatchenko, A., Tuckerman, M. E., Vacarro, F., Vasileiadis, M., Vazquez-Mayagoitia, A., Vogt, L., Wang, Y., Watson, R. E., de Wijs, G. A., Yang, J., Zhu, Q. & Groom, C. R. (2016). Acta Cryst. B72, 439-459.]). On the other hand, a general theory is still missing to infer bulk chemical and mechanical properties from structures. Therefore, material development proceeds through the application of a series of practical rules, which often apply to specific types of materials (Lusi, 2018[Lusi, M. (2018). CrystEngComm, 20, 7042-7052.]; Corpinot & Bučar, 2019[Corpinot, M. K. & Bučar, D.-K. (2019). Cryst. Growth Des. 19, 1426-1453.]).

The first attempts to rationalize the relationship between structure and mechanical properties in molecular crystals involved small aromatic molecules (Reddy et al., 2006b[Reddy, C. M., Padmanabhan, K. A. & Desiraju, G. R. (2006b). Cryst. Growth Des. 6, 2720-2731.],a[Reddy, C. M., Kirchner, M. T., Gundakaram, R. C., Padmanabhan, K. A. & Desiraju, G. R. (2006a). Chem. Eur. J. 12, 2222-2234.]). In such materials, aromatic stacking and halogen or hydrogen interactions coexist in the same structure and extend along different crystallographic axes. Manipulation of face-indexed single crystals showed that bending occurred only perpendicular to the planes of the weaker interactions, whereas the stronger supramolecular bonds helped to preserve structural integrity in the other directions (Saha et al., 2018[Saha, S., Mishra, M. K., Reddy, C. M. & Desiraju, G. R. (2018). Acc. Chem. Res. 51, 2957-2967.]). Then, chemical anisotropy appeared as a requirement for plasticity and such features were thought to guarantee the realization of bendable single- and multi-component crystals (Krishna et al., 2016[Krishna, G. R., Devarapalli, R., Lal, G. & Reddy, C. M. (2016). J. Am. Chem. Soc. 138, 13561-13567.]; Rao Khandavilli et al., 2017[Rao Khandavilli, U. B., Bhogala, B. R., Maguire, A. R. & Lawrence, S. E. (2017). Chem. Commun. 53, 3381-3384.]; Saha & Desiraju, 2017[Saha, S. & Desiraju, G. R. (2017). Chem. Commun. 53, 6371-6374.]; Alimi et al., 2018[Alimi, L. O., Lama, P., Smith, V. J. & Barbour, L. J. (2018). Chem. Commun. 54, 2994-2997.]; Nath et al., 2018[Nath, N. K., Hazarika, M., Gupta, P., Ray, N. R., Paul, A. K. & Nauha, E. (2018). J. Mol. Struct. 1160, 20-25.]). However, the discovery of plastic bending in the (quasi)-isotropic structures of di­methyl sulfone proves that alternative mechanisms might exist (Thomas et al., 2017[Thomas, S. P., Shi, M. W., Koutsantonis, G. A., Jayatilaka, D., Edwards, A. J. & Spackman, M. A. (2017). Angew. Chem. 129, 8588-8592.]).

Due to their relevance in manufacturing and processing, many studies of mechanical properties involve APIs (active pharmaceutical ingredients), which suggest that hydrate forms might have higher plasticity than their corresponding anhydrates (Sun & Grant, 2004[Sun, C. & Grant, D. J. W. (2004). Pharm. Res. 21, 382-386.]; Liu et al., 2018[Liu, F., Hooks, D. E., Li, N., Mara, N. A. & Swift, J. A. (2018). Chem. Mater. 30, 3798-3805.]; Fucke et al., 2012[Fucke, K., McIntyre, G. J., Wilkinson, C., Henry, M., Howard, J. A. K. & Steed, J. W. (2012). Cryst. Growth Des. 12, 1395-1401.]; Chang & Sun, 2017[Chang, S.-Y. & Sun, C. C. (2017). Mol. Pharm. 14, 2047-2055.]). In these cases, the mechanical properties were only observed at the microscopic level on polycrystalline powders, making the correlation between structure and properties elusive. In p-hy­droxy­benzoic acid (Sun & Grant, 2004[Sun, C. & Grant, D. J. W. (2004). Pharm. Res. 21, 382-386.]) and uric acid (Liu et al., 2018[Liu, F., Hooks, D. E., Li, N., Mara, N. A. & Swift, J. A. (2018). Chem. Mater. 30, 3798-3805.]), despite creating a rigid 3D hydrogen-bonded network, the inclusion of water enables the separation of zigzag chains that are interdigitated in the anhydrous forms (see Figs. S10 and S11 of the supporting information). Hence, increased plasticity was explained by the removal of a mechanical (or steric) obstacle to molecular movement, which was deemed necessary for plastic bending. Anhydrous theophylline shows a different story: hydrogen bonds, π stacking and weak C=O⋯H bonds support the structure along the orthogonal crystallographic directions, and there is no mechanical interlock to prevent molecular movement (Fucke et al., 2012[Fucke, K., McIntyre, G. J., Wilkinson, C., Henry, M., Howard, J. A. K. & Steed, J. W. (2012). Cryst. Growth Des. 12, 1395-1401.]; Chang & Sun, 2017[Chang, S.-Y. & Sun, C. C. (2017). Mol. Pharm. 14, 2047-2055.]). In that view, crystals of theophylline should be highly plastic. Instead, plasticity is lower than in the hydrate form, which is characterized by 2D hydrogen-bonded networks that pack in an interdigitated zigzag fashion (see Fig. S12 of the supporting information). In the theophylline system, increased plasticity was attributed to the `lubricant' action of water molecules that allows easier slippage of the 2D sheets. Ultimately, also in the case of hydrate forms, multiple mechanisms explain plastic bending and the observation of such a phenomenon on single crystals could give new insights into the role of water. This work reports on the mechanical properties in the anhydrous and hydrate forms of Pregabalin and Gabapentin (Fig. 1[link]). Despite the similar crystal packing, the hydrate forms show superior plasticity, which results in macroscopic bending of single crystals whereas the anhydrous forms are brittle.

[Figure 1]
Figure 1
Molecular structure of Pregabalin (left) and Gabapentin (right).

2. Experimental

Pregabalin (SPG) and Gabapentin (GP) were purchased from Flourochem. Methanol was purchased from Sigma–Aldrich and Milli-Q water was used for the experiments.

Crystallization of SPG: SPG crystals were obtained from commercially available SPG dissolved in methanol to saturation and left at room temperature for 2 days.

Crystallization of SPGH I: SPG was dissolved in pure water and crystallized at 280 K for 3–5 days to obtain good-quality crystals.

Crystallization of GP and GPH: GP and its hydrate crystals are reproduced by following the same procedure mentioned in the literature (Wang et al., 2017[Wang, Y., Du, S., Wu, S., Li, L., Zhang, D., Yu, B., Zhou, L., Bekele, H. & Gong, J. (2017). J. Chem. Thermodyn. 113, 132-143.]; Reece & Levendis, 2008[Reece, H. A. & Levendis, D. C. (2008). Acta Cryst. C64, o105-o108.]).

Optical microscopy: single crystals of SPGH I and GPH were selected and bent with tweezers and a needle, the images were captured using an Olympus IX53 microscope under 4× magnification.

IR spectroscopy: IR spectra for SPG and SPGH I were collected on a PerkinElmer Spectrum 100 F T-IR Spectrometer equipped with a PerkinElmer Universal ATR Sampling Accessory.

Raman spectroscopy: Raman spectra for SPG and SPGH I were collected on a Horiba Jobin Yvon LabRam Aramis spectrometer with a 532 nm laser source. The spectrometer was coupled with an Olympus BX40 confocal microscope with a CCD camera cooled by a thermoelectric Peltier device. Raman maps were processed using the LabSPEC 5 software package.

Powder X-ray diffraction: Powder X-ray diffraction data were collected on an Empyrean diffractometer (PANalytical, Philips) using Cu Kα1,2 radiation (λ = 0.1541 nm) at room temperature operated at 40 kV and 40 mA. The samples were scanned over the range 4–40° 2θ using a step size of 0.02° 2θ and a scan speed of 0.02° 2θ s−1.

Differential scanning calorimetry: calorimetric measurements of SPG and SPGH I were performed on a DSC 214 Polyma, NETZSCH instrument. Typically, 3–5 mg of sample was accurately weighed into a hermetically sealed aluminium pan and heated to 250 °C at a 10 °C min−1 heating rate under a nitro­gen gas flow of 40 ml min−1.

Thermogravimetric analysis: Thermograms of SPG and SPGH I were measured with a Perkin-Elmer TGA 4000 instrument at a heating rate of 10 °C min−1 under a nitro­gen stream of 20 ml min−1.

X-ray crystallography: single-crystal data for SPGH I were collected at ambient temperature using a three-circle Bruker D8 Quest diffractometer with a sealed tube Mo anode, Kα radiation = 0.71073 Å and a Photon 100 detector. Single-crystal data for SPGH II were collected at 150 K under a nitro­gen-flow (Oxford Cryosystem) using a three-circle Bruker D8 Quest with microfocus Cu anode, Kα radiation = 1.5418 Å and a Photon 100 detector.

The data were integrated and corrected for absorption with the Bruker Apex Suite. The structure solution was obtained by direct methods and refined against all F2 with the SHELX software interfaced though X-SEED (Barbour, 2001[Barbour, L. J. (2001). J. Supramol. Chem. 1, 189-191.]). Non-hydrogen atoms were refined anisotropically and hydrogen atoms were placed in calculated positions, refined using idealized geometries (riding model) and assigned fixed isotropic displacement parameters.

3. Results and discussion

Amino ­acids are an important class of biologically active molecules that exist as zwitterionic tautomers under neutral conditions. Among them, (S)-3-iso­butyl-γ-amino­butyric acid, or Pregabalin (SPG), is an anticonvulsant blockbuster drug. In the anhydrous P212121 crystal, which has the refcode CIDDEZ (Venu et al., 2007[Venu, N., Vishweshwar, P., Ram, T., Surya, D. & Apurba, B. (2007). Acta Cryst. C63, o306-o308.]) in the CSD (Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]), the zwitterion dipoles pack along the b axis generating a double layer that is coplanar to the (110) plane. The structure is supported by a 2D network of charge-assisted hydrogen bonds between the ammonium and carboxyl­ate groups [Fig. 2[link](a)]. As multiple layers stack on top of each other, the iso­butyl groups interdigitate along the [001] direction. The crystals are brittle, as expected for mechanically interlocked structures.

[Figure 2]
Figure 2
Schematic representation of the crystal packing of (a) SPG, (b) SPGH form I and (c) SPGH form II. Hydrogen bonding interactions are in green, selected hydrogen atoms have been omitted for clarity.

Recrystallization of SPG in water at 280 K results in the monohydrate form SPGH I. Single-crystal analysis reveals a monoclinic C2 polar structure (Table 1[link]). The zwitterions are arranged along the [010] axis and are intercalated by water molecules so that the double molecular layers separate into parallel planes. At the same time, the molecules in each layer come closer together preventing interdigitation [Fig. 2[link](b)].

Table 1
Crystallographic data for SPGH I and SPGH II

Crystal form SPGH I SPGH II
Formula C8H17NO2, H2O C8H17NO2, H2O
CCDC code 1879470 1879471
Temperature (K) 298 150
Space group C2 P21
a (Å) 9.566 (7) 9.6559 (2)
b (Å) 7.440 (6) 29.8416 (6)
c (Å) 15.911 (12) 30.1248 (7)
β (°) 101.54 (3) 98.540 (1)
V3) 1109.5 (15) 8584.1 (3)
Z, Z 4, 1 32, 16
ρ (g cm−3) 1.061 1.097
μ (mm−1) 0.080 0.677
R[F2 > 2σ(F2)] (No. of reflections) 0.0586 (1721) 0.0482 (28820)

SPGH I is unstable at room temperature, reverting to the anhydrous SPG phase in air (Fig. S6). As expected from the different crystal packing, the dehydration is associated with a loss of macroscopic crystallinity. SPGH I undergoes a polymorphic transition upon cooling below 150 K. The phase transition is reversible (enantiotropic) and occurs in a single-crystal-to-single-crystal fashion, as demonstrated by variable-temperature single-crystal diffraction experiments. The packing of the low-temperature SPGH II phase is virtually identical to the high-temperature phase. The differences are limited to a reduced symmetry (Z′ = 16) and a different arrangement of the hydrogen-bonded bridges with water [Fig. 2[link](c)].

In molecular materials, the single-crystal-to-single-crystal reduction of symmetry on cooling is known. Often, such transformations assume the aspect of an order–disorder transition, whereby a certain thermal energy is required for a molecule to rotate or vibrate between symmetry-related crystallographic positions (Lusi & Barbour, 2013[Lusi, M. & Barbour, L. J. (2013). Chem. Commun. 49, 2634-2636.]; Braga et al., 2018[Braga, D., Grepioni, F., Maini, L. & d'Agostino, S. (2018). Eur. J. Inorg. Chem. 2018, 3597-3605.]). Here, the change occurs between two fully ordered structures instead. In that view, the preserved crystallinity is evidence of the high plasticity of these phases, and suggests that the supramolecular bonds with water can be easily broken and reformed without affecting the rest of the structure.

Indeed, crystals of SPGH I exhibit plastic bending on the application of a moment perpendicular to the c axis (Fig. 3[link]). Hence, the bending mechanism involves the sliding of successive layers along the crystallographic b direction (Fig. 2[link]). In order for this to happens, either the hydrogen bond between water and zwitterions or the dispersion forces between the non-polar-layer intermolecular bonds need to quickly break and reform; crystallographic studies cannot determine which are responsible for the bending.

[Figure 3]
Figure 3
Single crystals of SPGH I and GPH II before and after the mechanical deformation. The larger crystal faces are indexed.

GP is a molecular and pharmaceutical analogue of SPG. In GP, cyclo­pentane substitutes the iso­butyl group but the supramolecular feature of the two molecules are essentially equivalent. Due to extensive polymorph screening, multiple anhydrous and hydrate forms of GP are reported (Braga et al., 2008[Braga, D., Grepioni, F., Maini, L., Rubini, K., Polito, M., Brescello, R., Cotarca, L., Duarte, M. T., André, V. & Piedade, M. F. M. (2008). New J. Chem. 32, 1788-1795.]; Reece & Levendis, 2008[Reece, H. A. & Levendis, D. C. (2008). Acta Cryst. C64, o105-o108.]; Wang et al., 2017[Wang, Y., Du, S., Wu, S., Li, L., Zhang, D., Yu, B., Zhou, L., Bekele, H. & Gong, J. (2017). J. Chem. Thermodyn. 113, 132-143.]).

Like SPG, the structure of GP form α (CCDC refcode QIMKIG) is dominated by 2D networks of charge-assisted hydrogen bonds. In the latter, the bulkier cyclo­pentane group prevents interdigitation of successive layers (Fig. 4[link]). GPβ (CCDC refcode QIMKIG02) forms 1D chains (Reece & Levendis, 2008[Reece, H. A. & Levendis, D. C. (2008). Acta Cryst. C64, o105-o108.]; Wang et al., 2017[Wang, Y., Du, S., Wu, S., Li, L., Zhang, D., Yu, B., Zhou, L., Bekele, H. & Gong, J. (2017). J. Chem. Thermodyn. 113, 132-143.]; Ibers, 2001[Ibers, J. A. (2001). Acta Cryst. C57, 641-643.]; Vasudev et al., 2009[Vasudev, P. G., Aravinda, S., Ananda, K., Veena, S. D., Nagarajan, K., Shamala, N. & Balaram, P. (2009). Chem. Biol. Drug Des. 73, 83-96.]), whereas the packing in the anhydrous γ form (CCDC refcode QIMKIG03) resembles those of the hydrate forms, GPH I and II (CCDC refcodes QIMKOM and QIMKOM02), and SPGH I and II, the zwitterionic groups being separated into two planes. Remarkably, despite structural similarities, only the hydrates undergo plastic bending, whereas all the anhydrous forms are brittle. This observation suggests that the intercalated water molecules, rather than the weak dispersion forces, are responsible for the observed plastic bending.

[Figure 4]
Figure 4
Schematic representation of the crystal packing of the (a) GP form α, (b) GP form β, (c) GP form γ, (d) GPH form I and (e) GPH form II. Hydrogen-bonding interactions are in green, selected hydrogen atoms have been omitted for clarity.

4. Conclusions

High plasticity is a desirable property that guarantees processability in crystalline drug materials. To date, different sets of factors have been identified as responsible for plastic crystals, but a universal supramolecular strategy to improve such a property is not recognized yet. For example, it was suggested that bending requires the anisotropic hierarchical distribution of strong and weak supramolecular interactions along perpendicular directions. On the other hand, interdigitation and cross-linked hydrogen bonds (mechanical and chemical interlocks, respectively) have been seen as detrimental for macroscopic plastic bending. At the same time, an increasing number of studies report that, at the microscopic level, hydrated forms exhibit higher plasticity than the anhydrous equivalents. In such phases, increased plasticity does not seem to correlate to a particular structural feature. This is also true for the two zwitterionic drugs SPG and GP. Here, plasticity occurs also at a macroscopic level, on large single crystals, allowing a rationalization for such a phenomenon.

Limited to the investigated systems, the alternation of 2D hydrogen-bonded networks and weak dispersive forces does not guarantee plastic deformation in the anhydrous crystals. In contrast, plasticity occurs in the hydrate forms even when mechanical and chemical interlocks are present. Therefore, in these instances the presence of water appears crucial. Many studies highlight the structural diversity possible for water molecules (Mascal et al., 2006[Mascal, M., Infantes, L. & Chisholm, J. (2006). Angew. Chem. Int. Ed. 45, 32-36.]; Infantes & Motherwell, 2002[Infantes, L. & Motherwell, S. (2002). CrystEngComm, 4, 454-461.]; Bajpai et al., 2016[Bajpai, A., Scott, H. S., Pham, T., Chen, K.-J., Space, B., Lusi, M., Perry, M. L. & Zaworotko, M. J. (2016). IUCrJ, 3, 430-439.]). We speculate that such promiscuity, together with the high mobility of these molecules, enables the quick rearrangement of the supramolecular interactions that are broken by mechanical stress.

Finally we note that SPG and GP are two examples of a wide class of amino acids with biological activity. As sustained by strong and directional charge-assisted hydrogen bonds, the molecular packing of SPG and GP is common to other zwitterionic β-amino­propionic and γ-amino­butyric acids. Therefore, it would be of little surprise if those systems showed the same properties, and the reported observations could be valid for a wide class of drug substances.

Supporting information


Computing details top

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

(I) top
Crystal data top
C8H19NO3F(000) = 3136
Mr = 177.24Dx = 1.097 Mg m3
Monoclinic, P21Cu Kα radiation, λ = 1.54178 Å
a = 9.6559 (2) ÅCell parameters from 1234 reflections
b = 29.8416 (6) Åθ = 4–40°
c = 30.1248 (7) ŵ = 0.68 mm1
β = 98.540 (1)°T = 150 K
V = 8584.1 (3) Å3Prism, colourless
Z = 320.33 × 0.21 × 0.10 mm
Data collection top
Bruker D8 Quest
diffractometer
Rint = 0.041
Absorption correction: multi-scan
sadabs
θmax = 80.2°, θmin = 3.0°
Tmin = 0.648, Tmax = 0.754h = 1211
123474 measured reflectionsk = 3737
35695 independent reflectionsl = 3737
28820 reflections with I > 2σ(I)
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.048 w = 1/[σ2(Fo2) + (0.0511P)2 + 2.5076P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.134(Δ/σ)max = 0.001
S = 1.01Δρmax = 0.36 e Å3
35695 reflectionsΔρmin = 0.21 e Å3
1834 parametersAbsolute structure: Flack x determined using 11798 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
1 restraintAbsolute structure parameter: 0.00 (4)
Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O830.90280 (18)0.14068 (5)0.08707 (7)0.0311 (4)
O1630.10703 (19)1.01615 (5)0.41722 (7)0.0333 (4)
O1430.40687 (18)0.26416 (5)0.10036 (7)0.0320 (4)
O4020.87056 (19)0.85734 (6)0.47760 (7)0.0328 (4)
H40A0.88040.82960.46990.049*
H40B0.79180.86570.46200.049*
O4110.12176 (19)0.72935 (6)0.01096 (7)0.0318 (4)
H41A0.121 (3)0.7015 (12)0.0187 (11)0.048*
H41B0.199 (4)0.7373 (11)0.0241 (11)0.048*
O230.88745 (19)0.88989 (5)0.06970 (8)0.0342 (4)
O4160.65273 (19)0.10625 (6)0.04600 (7)0.0329 (4)
H41C0.73480.11500.05890.049*
H41D0.64660.07860.05460.049*
O2230.59712 (19)0.14039 (5)0.40558 (8)0.0346 (4)
O4040.87133 (19)0.60385 (6)0.48839 (7)0.0328 (4)
H40C0.87850.57640.47940.049*
H40D0.79770.61430.47140.049*
O30.39496 (19)1.01507 (5)0.07857 (8)0.0350 (4)
O4090.1491 (2)0.98066 (6)0.03367 (7)0.0350 (4)
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H48B1.01940.60850.13490.056*
C3110.1197 (4)0.21482 (14)0.25775 (12)0.0654 (10)
H31G0.18990.19090.25400.098*
H31H0.07500.21690.23070.098*
H31I0.16530.24340.26260.098*
C1280.4977 (4)0.45307 (10)0.15944 (13)0.0522 (9)
H12H0.59010.43940.17000.063*
H12I0.51380.48510.15350.063*
C701.1135 (5)0.34920 (15)0.23472 (13)0.0717 (11)
H70A1.18650.32620.23950.108*
H70B1.06870.35190.26170.108*
H70C1.15550.37800.22850.108*
C3090.0085 (4)0.20442 (11)0.29834 (11)0.0478 (8)
H3090.04080.17610.29230.057*
C2240.4694 (3)0.07228 (8)0.40947 (12)0.0420 (7)
H22H0.37010.06350.40090.050*
H22I0.49880.06250.44090.050*
C2310.7464 (4)0.05153 (16)0.30619 (13)0.0689 (11)
H23A0.79660.04020.28250.103*
H23B0.78680.03840.33500.103*
H23C0.75490.08420.30790.103*
C710.8920 (5)0.37318 (15)0.18667 (14)0.0743 (12)
H71A0.93540.40100.17830.111*
H71B0.85090.37810.21410.111*
H71C0.81850.36400.16240.111*
C1290.4098 (4)0.45004 (13)0.19705 (12)0.0621 (10)
H1290.38720.41770.20070.075*
C910.8795 (5)0.10406 (15)0.19919 (14)0.0777 (13)
H91A0.83850.10640.22700.117*
H91B0.80540.09810.17400.117*
H91C0.92660.13220.19400.117*
C2910.7498 (4)0.33411 (15)0.30314 (13)0.0676 (11)
H29D0.80810.32880.27970.101*
H29E0.79580.32140.33150.101*
H29F0.73700.36640.30670.101*
C691.0041 (4)0.33605 (12)0.19494 (12)0.0549 (9)
H690.95770.30770.20270.066*
C2300.5327 (5)0.05326 (13)0.24834 (13)0.0751 (13)
H23D0.53530.08600.24630.113*
H23E0.43550.04290.24140.113*
H23F0.58820.04020.22690.113*
C890.9852 (4)0.06601 (12)0.20337 (11)0.0492 (8)
H890.93440.03710.20540.059*
C2490.5182 (5)0.79663 (15)0.32064 (13)0.0750 (13)
H2490.51580.76310.32140.090*
C1710.0008 (5)0.94376 (14)0.26009 (13)0.0701 (11)
H17A0.09590.93140.25540.105*
H17B0.04880.93410.23560.105*
H17C0.00550.97660.26060.105*
C2690.5558 (5)0.57305 (13)0.31600 (13)0.0677 (11)
H2690.56400.54020.31040.081*
C100.5619 (6)0.92358 (15)0.23154 (14)0.0925 (17)
H10A0.56020.95620.23470.139*
H10B0.65840.91360.23120.139*
H10C0.52510.90970.25680.139*
C901.0905 (5)0.07203 (15)0.24589 (12)0.0718 (12)
H90A1.14200.10010.24400.108*
H90B1.15640.04690.24900.108*
H90C1.04090.07300.27200.108*
C310.7763 (5)0.81818 (19)0.17852 (16)0.0915 (16)
H31A0.73330.81200.20540.137*
H31B0.72220.80330.15250.137*
H31C0.77700.85060.17330.137*
C1890.0505 (5)0.68307 (13)0.31820 (12)0.0727 (13)
H1890.05320.64970.31600.087*
C1090.4607 (5)0.68558 (15)0.17638 (13)0.0740 (12)
H1090.46210.65230.18000.089*
C1700.2253 (5)0.94606 (19)0.31354 (14)0.0887 (16)
H17D0.22080.97850.31820.133*
H17E0.27370.93990.28780.133*
H17F0.27660.93200.34050.133*
C490.9539 (5)0.56665 (15)0.18199 (12)0.0692 (11)
H490.95430.53350.18670.083*
C110.3192 (6)0.92032 (19)0.18840 (16)0.0937 (16)
H11A0.28960.90730.21530.141*
H11B0.26300.90750.16160.141*
H11C0.30570.95290.18860.141*
C2090.0117 (5)0.45508 (16)0.31403 (14)0.0741 (12)
H2090.03510.42350.30700.089*
C2110.0904 (6)0.47253 (17)0.27507 (15)0.0944 (16)
H21A0.11670.50340.28130.142*
H21B0.17420.45360.27090.142*
H21C0.04650.47200.24780.142*
C1310.2718 (6)0.4748 (2)0.18615 (16)0.121 (2)
H13A0.21980.47260.21160.181*
H13B0.21650.46140.15950.181*
H13C0.28990.50640.18020.181*
C1300.4910 (6)0.46589 (18)0.24137 (17)0.109 (2)
H13D0.57860.44890.24790.164*
H13E0.43460.46110.26540.164*
H13F0.51220.49790.23930.164*
C2710.7008 (6)0.5924 (2)0.32133 (17)0.119 (2)
H27D0.73700.59050.29270.179*
H27E0.76210.57540.34420.179*
H27F0.69790.62380.33060.179*
C301.0068 (7)0.81765 (16)0.22895 (15)0.1010 (19)
H30A1.01350.85040.22790.151*
H30B1.10100.80470.23310.151*
H30C0.95870.80890.25400.151*
C2500.4151 (7)0.81197 (19)0.27977 (16)0.108 (2)
H25A0.40790.84470.27990.162*
H25B0.32280.79880.28110.162*
H25C0.44880.80220.25220.162*
C1900.1982 (7)0.6998 (2)0.32109 (17)0.117 (2)
H19A0.23310.69360.29280.176*
H19B0.25760.68450.34570.176*
H19C0.20040.73210.32670.176*
C2700.4608 (7)0.59281 (18)0.27582 (17)0.108 (2)
H27G0.45130.62520.28010.162*
H27H0.36830.57870.27310.162*
H27I0.50170.58730.24840.162*
C1110.3126 (7)0.7004 (3)0.17543 (18)0.130 (3)
H11D0.28140.69270.20400.194*
H11E0.25280.68520.15080.194*
H11F0.30640.73290.17080.194*
C501.0458 (7)0.58740 (17)0.22215 (15)0.1004 (19)
H50A1.04810.62000.21840.151*
H50B1.14110.57540.22420.151*
H50C1.00750.58020.24960.151*
C510.8045 (7)0.5823 (3)0.17819 (18)0.140 (3)
H51A0.76900.57630.20640.210*
H51B0.74720.56620.15370.210*
H51C0.80010.61450.17200.210*
C2510.6648 (7)0.8104 (2)0.31677 (17)0.118 (2)
H25D0.67360.84300.32010.178*
H25E0.68700.80150.28730.178*
H25F0.72990.79570.34040.178*
C1100.5580 (7)0.70490 (18)0.21631 (15)0.109 (2)
H11G0.65260.69290.21660.163*
H11H0.52370.69660.24420.163*
H11I0.56020.73760.21380.163*
C1910.0443 (8)0.70031 (17)0.27693 (16)0.122 (3)
H19D0.05790.73270.27980.184*
H19E0.13510.68510.27430.184*
H19F0.00100.69430.25010.184*
C2100.1448 (8)0.4818 (4)0.3188 (2)0.243 (7)
H21D0.13850.50680.33950.364*
H21E0.15880.49350.28940.364*
H21F0.22390.46250.33070.364*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O830.0246 (9)0.0151 (8)0.0537 (12)0.0009 (7)0.0066 (8)0.0002 (7)
O1630.0254 (9)0.0146 (8)0.0612 (13)0.0013 (7)0.0105 (8)0.0031 (8)
O1430.0263 (9)0.0168 (8)0.0533 (12)0.0006 (7)0.0072 (8)0.0018 (8)
O4020.0263 (10)0.0188 (8)0.0524 (12)0.0024 (7)0.0033 (8)0.0039 (8)
O4110.0264 (9)0.0212 (8)0.0462 (11)0.0022 (7)0.0001 (8)0.0029 (8)
O230.0274 (10)0.0159 (8)0.0606 (13)0.0011 (7)0.0104 (9)0.0044 (8)
O4160.0264 (10)0.0248 (9)0.0464 (12)0.0026 (7)0.0016 (8)0.0029 (8)
O2230.0253 (9)0.0159 (8)0.0632 (13)0.0013 (7)0.0081 (9)0.0031 (8)
O4040.0303 (10)0.0211 (8)0.0454 (11)0.0050 (7)0.0002 (8)0.0037 (8)
O30.0257 (9)0.0169 (8)0.0632 (13)0.0010 (7)0.0088 (9)0.0056 (8)
O4090.0329 (10)0.0236 (9)0.0469 (12)0.0046 (7)0.0010 (8)0.0027 (8)
O1610.0241 (9)0.0171 (8)0.0640 (13)0.0037 (7)0.0060 (8)0.0027 (8)
O430.0268 (9)0.0171 (8)0.0562 (12)0.0012 (7)0.0071 (8)0.0021 (8)
O4120.0326 (11)0.0297 (10)0.0510 (12)0.0069 (8)0.0037 (9)0.0069 (9)
O4070.0249 (9)0.0301 (9)0.0437 (11)0.0029 (8)0.0020 (8)0.0051 (9)
O630.0265 (10)0.0174 (8)0.0713 (14)0.0007 (7)0.0070 (9)0.0059 (9)
O410.0277 (10)0.0186 (8)0.0667 (14)0.0026 (7)0.0067 (9)0.0065 (8)
O1030.0252 (9)0.0170 (8)0.0601 (13)0.0010 (7)0.0057 (8)0.0042 (8)
O4140.0263 (10)0.0301 (9)0.0492 (12)0.0037 (7)0.0033 (8)0.0076 (8)
O2030.0271 (10)0.0154 (8)0.0640 (13)0.0001 (7)0.0074 (9)0.0025 (8)
O810.0253 (9)0.0178 (8)0.0630 (13)0.0028 (7)0.0053 (9)0.0053 (8)
O2430.0258 (10)0.0147 (8)0.0701 (14)0.0001 (7)0.0090 (9)0.0030 (8)
O210.0262 (10)0.0190 (8)0.0691 (14)0.0036 (7)0.0102 (9)0.0012 (8)
O1830.0260 (9)0.0144 (8)0.0580 (12)0.0018 (7)0.0074 (8)0.0025 (8)
O4010.0266 (10)0.0237 (9)0.0572 (13)0.0054 (7)0.0003 (8)0.0055 (8)
O1410.0283 (10)0.0176 (8)0.0782 (15)0.0034 (7)0.0141 (10)0.0070 (9)
O4030.0322 (10)0.0312 (9)0.0418 (11)0.0095 (8)0.0016 (8)0.0083 (9)
O2630.0268 (10)0.0157 (8)0.0676 (14)0.0016 (7)0.0059 (9)0.0013 (8)
O3030.0251 (9)0.0145 (8)0.0691 (14)0.0003 (7)0.0065 (9)0.0031 (8)
O1010.0264 (10)0.0180 (8)0.0664 (14)0.0030 (7)0.0064 (9)0.0007 (8)
O2010.0269 (10)0.0190 (8)0.0696 (14)0.0026 (7)0.0057 (9)0.0103 (9)
O610.0275 (10)0.0196 (8)0.0736 (15)0.0024 (7)0.0056 (9)0.0111 (9)
O4130.0401 (12)0.0264 (9)0.0517 (13)0.0059 (8)0.0001 (9)0.0078 (9)
O2830.0284 (10)0.0154 (8)0.0712 (14)0.0011 (7)0.0111 (9)0.0018 (8)
O4100.0322 (10)0.0297 (10)0.0463 (12)0.0079 (8)0.0008 (8)0.0060 (8)
O1230.0273 (10)0.0174 (8)0.0825 (16)0.0010 (7)0.0096 (10)0.0016 (9)
O4050.0280 (10)0.0301 (10)0.0626 (14)0.0031 (8)0.0019 (9)0.0082 (9)
O1810.0258 (9)0.0165 (8)0.0694 (14)0.0022 (7)0.0081 (9)0.0039 (8)
O10.0265 (10)0.0170 (8)0.0787 (15)0.0024 (7)0.0076 (9)0.0001 (9)
O4080.0443 (12)0.0291 (10)0.0470 (12)0.0133 (9)0.0069 (9)0.0104 (9)
O2610.0258 (10)0.0184 (8)0.0730 (15)0.0016 (7)0.0078 (9)0.0063 (9)
O2410.0252 (10)0.0163 (8)0.0809 (15)0.0021 (7)0.0086 (9)0.0005 (9)
O2210.0269 (10)0.0162 (8)0.0779 (15)0.0053 (7)0.0112 (9)0.0000 (9)
O3010.0249 (9)0.0184 (8)0.0773 (15)0.0040 (7)0.0036 (9)0.0098 (9)
O4150.0524 (13)0.0334 (11)0.0536 (13)0.0145 (10)0.0129 (10)0.0144 (10)
O4060.0528 (14)0.0315 (11)0.0553 (14)0.0132 (10)0.0048 (11)0.0117 (10)
N2470.0252 (10)0.0132 (8)0.0376 (11)0.0010 (8)0.0056 (8)0.0000 (8)
N1870.0259 (11)0.0133 (9)0.0417 (12)0.0017 (8)0.0049 (9)0.0001 (8)
O1210.0286 (10)0.0214 (9)0.0961 (18)0.0021 (8)0.0129 (11)0.0149 (10)
N270.0258 (10)0.0135 (9)0.0435 (12)0.0017 (8)0.0054 (9)0.0024 (8)
N470.0277 (11)0.0141 (9)0.0429 (13)0.0029 (8)0.0046 (9)0.0033 (8)
N1670.0243 (11)0.0134 (9)0.0488 (14)0.0014 (8)0.0071 (9)0.0018 (9)
N1070.0279 (11)0.0135 (9)0.0467 (13)0.0005 (8)0.0059 (9)0.0011 (9)
N1470.0265 (11)0.0149 (9)0.0419 (13)0.0007 (8)0.0064 (9)0.0013 (8)
N2870.0222 (10)0.0146 (8)0.0367 (11)0.0020 (8)0.0048 (8)0.0008 (8)
N70.0265 (11)0.0154 (9)0.0421 (13)0.0025 (8)0.0069 (9)0.0015 (8)
O2810.0302 (11)0.0194 (9)0.1002 (18)0.0023 (8)0.0178 (11)0.0128 (10)
N2670.0278 (11)0.0136 (9)0.0530 (14)0.0010 (8)0.0090 (10)0.0006 (9)
N1270.0277 (11)0.0140 (9)0.0413 (13)0.0019 (8)0.0074 (9)0.0020 (8)
N3070.0244 (11)0.0129 (8)0.0422 (12)0.0007 (8)0.0066 (9)0.0017 (8)
N2070.0272 (11)0.0123 (9)0.0506 (14)0.0014 (8)0.0080 (9)0.0051 (9)
N670.0297 (11)0.0127 (8)0.0426 (12)0.0003 (8)0.0084 (9)0.0037 (8)
N870.0272 (11)0.0138 (9)0.0462 (13)0.0003 (8)0.0074 (9)0.0007 (8)
N2270.0238 (11)0.0142 (9)0.0549 (14)0.0017 (8)0.0092 (10)0.0004 (9)
C820.0249 (12)0.0148 (10)0.0370 (14)0.0015 (9)0.0022 (10)0.0012 (9)
C420.0278 (13)0.0147 (10)0.0411 (15)0.0027 (9)0.0037 (10)0.0009 (10)
C220.0266 (13)0.0145 (10)0.0450 (15)0.0011 (9)0.0048 (11)0.0010 (10)
C1420.0282 (13)0.0156 (10)0.0412 (15)0.0009 (9)0.0053 (11)0.0018 (10)
C1620.0256 (13)0.0159 (10)0.0403 (15)0.0021 (9)0.0039 (10)0.0000 (10)
C2020.0291 (13)0.0158 (11)0.0425 (15)0.0021 (9)0.0026 (11)0.0016 (10)
C1020.0272 (13)0.0154 (11)0.0419 (15)0.0020 (9)0.0054 (11)0.0009 (10)
C1460.0315 (13)0.0156 (11)0.0410 (15)0.0026 (9)0.0022 (11)0.0020 (10)
C620.0282 (13)0.0157 (11)0.0446 (15)0.0015 (9)0.0014 (11)0.0038 (10)
C860.0332 (14)0.0157 (11)0.0428 (15)0.0009 (10)0.0052 (11)0.0045 (10)
C2620.0276 (13)0.0150 (11)0.0494 (16)0.0020 (9)0.0043 (11)0.0005 (10)
C1820.0265 (13)0.0164 (11)0.0437 (15)0.0017 (9)0.0044 (11)0.0002 (10)
C1650.0294 (13)0.0138 (10)0.0448 (15)0.0007 (9)0.0059 (11)0.0001 (10)
C3020.0253 (13)0.0155 (11)0.0470 (16)0.0016 (9)0.0027 (11)0.0041 (10)
C1490.0489 (17)0.0291 (13)0.0350 (15)0.0025 (12)0.0003 (12)0.0018 (11)
C450.0322 (14)0.0192 (11)0.0372 (14)0.0004 (10)0.0014 (11)0.0016 (10)
C1450.0287 (13)0.0136 (10)0.0411 (15)0.0023 (9)0.0048 (10)0.0009 (9)
C2220.0272 (13)0.0146 (11)0.0527 (17)0.0029 (9)0.0081 (12)0.0034 (11)
C1660.0338 (14)0.0157 (11)0.0446 (16)0.0005 (10)0.0046 (11)0.0008 (10)
C3060.0317 (14)0.0176 (11)0.0399 (15)0.0008 (10)0.0024 (11)0.0045 (10)
C2860.0283 (13)0.0173 (11)0.0363 (14)0.0017 (9)0.0016 (10)0.0004 (10)
C2820.0295 (14)0.0169 (11)0.0564 (18)0.0016 (10)0.0098 (12)0.0037 (11)
C1850.0307 (13)0.0152 (11)0.0417 (15)0.0003 (9)0.0020 (11)0.0005 (10)
C20.0284 (13)0.0145 (11)0.0524 (17)0.0021 (9)0.0068 (12)0.0012 (10)
C250.0278 (13)0.0144 (10)0.0436 (15)0.0027 (9)0.0018 (11)0.0022 (10)
C2260.0285 (14)0.0185 (12)0.0529 (17)0.0004 (10)0.0001 (12)0.0009 (11)
C1050.0310 (13)0.0173 (11)0.0408 (15)0.0017 (10)0.0016 (11)0.0017 (10)
C2650.0314 (14)0.0159 (11)0.0494 (17)0.0010 (10)0.0007 (12)0.0002 (11)
C460.0355 (14)0.0200 (11)0.0385 (15)0.0012 (10)0.0006 (11)0.0030 (10)
C660.0326 (14)0.0209 (12)0.0412 (15)0.0002 (10)0.0021 (11)0.0036 (10)
C850.0289 (13)0.0149 (10)0.0392 (14)0.0001 (9)0.0045 (11)0.0008 (10)
C260.0309 (14)0.0167 (11)0.0437 (15)0.0042 (10)0.0019 (11)0.0004 (10)
C50.0302 (13)0.0154 (11)0.0467 (16)0.0006 (9)0.0035 (11)0.0022 (10)
C1220.0294 (14)0.0146 (11)0.067 (2)0.0015 (10)0.0074 (13)0.0039 (12)
C1060.0340 (14)0.0193 (11)0.0438 (16)0.0034 (10)0.0014 (12)0.0023 (11)
C2460.0344 (14)0.0164 (11)0.0382 (14)0.0006 (10)0.0001 (11)0.0002 (10)
C2450.0297 (13)0.0151 (11)0.0398 (15)0.0011 (9)0.0015 (11)0.0023 (10)
C2250.0234 (13)0.0158 (11)0.0557 (17)0.0001 (9)0.0022 (11)0.0004 (11)
C1860.0346 (14)0.0170 (11)0.0407 (15)0.0004 (10)0.0009 (11)0.0019 (10)
C2060.0338 (14)0.0175 (11)0.0457 (16)0.0005 (10)0.0040 (12)0.0030 (10)
C3050.0289 (13)0.0163 (11)0.0394 (14)0.0005 (9)0.0017 (10)0.0002 (10)
C650.0307 (14)0.0175 (11)0.0440 (16)0.0017 (10)0.0020 (11)0.0004 (10)
C2050.0333 (14)0.0154 (11)0.0450 (16)0.0007 (10)0.0068 (11)0.0007 (10)
C2420.0266 (13)0.0162 (11)0.0510 (17)0.0025 (9)0.0053 (11)0.0021 (10)
C60.0322 (14)0.0172 (11)0.0429 (15)0.0015 (10)0.0015 (11)0.0008 (10)
C2850.0266 (13)0.0173 (11)0.0427 (15)0.0003 (9)0.0054 (11)0.0004 (10)
C440.0340 (15)0.0174 (11)0.0549 (18)0.0005 (10)0.0133 (12)0.0003 (11)
C1260.0319 (14)0.0186 (11)0.0449 (16)0.0018 (10)0.0015 (11)0.0012 (10)
C2040.0308 (14)0.0160 (11)0.0487 (16)0.0008 (10)0.0089 (11)0.0014 (10)
C840.0305 (13)0.0173 (11)0.0421 (15)0.0013 (10)0.0087 (11)0.0008 (10)
C1250.0311 (14)0.0171 (11)0.0513 (17)0.0025 (10)0.0016 (12)0.0003 (11)
C1040.0321 (14)0.0171 (11)0.0505 (17)0.0015 (10)0.0095 (12)0.0025 (11)
C2290.082 (3)0.0291 (14)0.0441 (18)0.0122 (15)0.0088 (17)0.0017 (13)
C640.0313 (14)0.0179 (12)0.0485 (17)0.0020 (10)0.0067 (12)0.0021 (11)
C680.0371 (16)0.0281 (13)0.0506 (18)0.0032 (11)0.0005 (13)0.0020 (12)
C3080.0355 (15)0.0310 (14)0.0451 (16)0.0044 (11)0.0001 (12)0.0022 (12)
C2660.0340 (14)0.0189 (12)0.0537 (18)0.0003 (10)0.0001 (12)0.0042 (11)
C2640.0353 (15)0.0153 (11)0.0626 (19)0.0009 (10)0.0135 (13)0.0007 (12)
C2440.0300 (14)0.0163 (11)0.0542 (18)0.0016 (10)0.0108 (12)0.0017 (11)
C1510.0479 (18)0.0524 (18)0.0419 (17)0.0035 (15)0.0129 (13)0.0022 (14)
C880.0421 (16)0.0249 (13)0.0429 (16)0.0003 (11)0.0019 (12)0.0007 (11)
C3040.0286 (13)0.0161 (11)0.0525 (17)0.0008 (10)0.0092 (11)0.0016 (11)
C1480.0346 (14)0.0214 (12)0.0429 (16)0.0013 (10)0.0052 (11)0.0016 (11)
C2890.0501 (19)0.0432 (16)0.0422 (17)0.0056 (14)0.0018 (14)0.0100 (13)
C1840.0333 (14)0.0159 (11)0.0571 (18)0.0003 (10)0.0158 (12)0.0006 (11)
C2080.0564 (19)0.0248 (13)0.0485 (18)0.0011 (13)0.0008 (14)0.0016 (12)
C240.0340 (15)0.0179 (12)0.0616 (19)0.0024 (10)0.0173 (13)0.0046 (11)
C1440.0314 (14)0.0169 (11)0.0556 (18)0.0010 (10)0.0123 (12)0.0007 (11)
C40.0295 (14)0.0185 (11)0.0586 (18)0.0021 (10)0.0146 (12)0.0054 (11)
C1500.071 (2)0.0471 (18)0.0411 (18)0.0006 (16)0.0044 (16)0.0021 (14)
C1690.065 (2)0.0404 (16)0.0409 (17)0.0059 (15)0.0019 (15)0.0065 (13)
C1680.0441 (17)0.0228 (13)0.0500 (18)0.0011 (11)0.0006 (13)0.0014 (12)
C1240.0366 (16)0.0189 (12)0.078 (2)0.0003 (11)0.0193 (15)0.0076 (13)
C90.087 (3)0.0449 (18)0.0402 (18)0.0042 (18)0.0086 (18)0.0070 (15)
C1640.0322 (14)0.0158 (11)0.0547 (18)0.0021 (10)0.0141 (12)0.0022 (11)
C2280.0359 (15)0.0242 (13)0.061 (2)0.0012 (11)0.0130 (13)0.0028 (13)
C2680.056 (2)0.0253 (14)0.061 (2)0.0006 (13)0.0117 (16)0.0036 (13)
C2880.0373 (16)0.0263 (13)0.0522 (18)0.0028 (11)0.0024 (13)0.0076 (12)
C1080.057 (2)0.0315 (14)0.0455 (17)0.0078 (14)0.0098 (14)0.0017 (13)
C2900.084 (3)0.071 (3)0.051 (2)0.001 (2)0.006 (2)0.0191 (19)
C2840.0352 (15)0.0175 (12)0.069 (2)0.0002 (10)0.0216 (14)0.0041 (12)
C80.0515 (18)0.0256 (13)0.0528 (19)0.0019 (12)0.0115 (14)0.0071 (12)
C3100.067 (2)0.065 (2)0.057 (2)0.0055 (18)0.0227 (18)0.0160 (17)
C280.0494 (18)0.0249 (13)0.0531 (19)0.0013 (12)0.0138 (15)0.0068 (13)
C290.094 (3)0.0349 (16)0.0405 (19)0.0002 (17)0.0084 (18)0.0002 (14)
C1880.058 (2)0.0246 (13)0.0529 (19)0.0013 (13)0.0151 (15)0.0052 (13)
C2480.0525 (19)0.0293 (14)0.0489 (18)0.0000 (13)0.0091 (14)0.0095 (13)
C480.059 (2)0.0262 (14)0.0487 (18)0.0021 (13)0.0112 (15)0.0028 (12)
C3110.073 (3)0.079 (3)0.0419 (19)0.017 (2)0.0002 (17)0.0067 (18)
C1280.053 (2)0.0255 (14)0.072 (2)0.0003 (13)0.0137 (17)0.0116 (14)
C700.087 (3)0.074 (3)0.051 (2)0.018 (2)0.000 (2)0.012 (2)
C3090.0523 (19)0.0446 (17)0.0469 (18)0.0087 (14)0.0083 (14)0.0010 (14)
C2240.0336 (15)0.0172 (12)0.080 (2)0.0029 (11)0.0237 (15)0.0041 (13)
C2310.067 (3)0.093 (3)0.048 (2)0.034 (2)0.0129 (18)0.005 (2)
C710.074 (3)0.086 (3)0.067 (3)0.012 (2)0.025 (2)0.018 (2)
C1290.077 (3)0.053 (2)0.049 (2)0.0218 (19)0.0147 (18)0.0155 (16)
C910.102 (3)0.079 (3)0.057 (2)0.031 (3)0.029 (2)0.006 (2)
C2910.059 (2)0.088 (3)0.058 (2)0.026 (2)0.0155 (18)0.003 (2)
C690.065 (2)0.0472 (19)0.052 (2)0.0167 (16)0.0086 (17)0.0030 (15)
C2300.114 (4)0.048 (2)0.053 (2)0.008 (2)0.021 (2)0.0025 (17)
C890.064 (2)0.0444 (17)0.0392 (17)0.0002 (15)0.0064 (15)0.0036 (14)
C2490.115 (4)0.065 (2)0.040 (2)0.014 (2)0.003 (2)0.0085 (18)
C1710.099 (3)0.059 (2)0.049 (2)0.002 (2)0.001 (2)0.0037 (18)
C2690.103 (3)0.048 (2)0.044 (2)0.007 (2)0.014 (2)0.0003 (16)
C100.156 (5)0.060 (2)0.049 (2)0.001 (3)0.026 (3)0.006 (2)
C900.096 (3)0.073 (3)0.044 (2)0.024 (2)0.002 (2)0.0040 (18)
C310.100 (4)0.124 (4)0.057 (3)0.023 (3)0.032 (3)0.006 (3)
C1890.131 (4)0.0424 (19)0.0385 (19)0.004 (2)0.008 (2)0.0015 (15)
C1090.115 (4)0.061 (2)0.041 (2)0.015 (2)0.004 (2)0.0011 (18)
C1700.072 (3)0.146 (5)0.053 (2)0.034 (3)0.024 (2)0.018 (3)
C490.100 (3)0.065 (2)0.0390 (19)0.010 (2)0.0034 (19)0.0077 (17)
C110.113 (4)0.116 (4)0.057 (3)0.019 (3)0.029 (3)0.000 (3)
C2090.090 (3)0.085 (3)0.047 (2)0.001 (2)0.009 (2)0.006 (2)
C2110.145 (5)0.081 (3)0.050 (2)0.003 (3)0.008 (3)0.010 (2)
C1310.126 (5)0.177 (6)0.058 (3)0.100 (5)0.008 (3)0.002 (3)
C1300.145 (5)0.093 (4)0.074 (3)0.013 (4)0.036 (3)0.038 (3)
C2710.120 (5)0.184 (7)0.059 (3)0.046 (5)0.028 (3)0.004 (4)
C300.170 (6)0.069 (3)0.051 (3)0.020 (3)0.029 (3)0.005 (2)
C2500.164 (6)0.096 (4)0.052 (3)0.000 (4)0.029 (3)0.021 (3)
C1900.133 (5)0.162 (6)0.067 (3)0.018 (5)0.048 (3)0.008 (3)
C2700.164 (6)0.080 (3)0.065 (3)0.010 (3)0.031 (3)0.015 (3)
C1110.122 (5)0.212 (8)0.064 (3)0.002 (5)0.045 (3)0.020 (4)
C500.161 (5)0.076 (3)0.052 (3)0.008 (3)0.023 (3)0.019 (2)
C510.123 (5)0.247 (9)0.057 (3)0.056 (5)0.033 (3)0.017 (4)
C2510.123 (5)0.179 (6)0.063 (3)0.023 (4)0.043 (3)0.032 (4)
C1100.175 (6)0.088 (3)0.050 (3)0.026 (4)0.025 (3)0.006 (2)
C1910.232 (7)0.066 (3)0.052 (3)0.004 (4)0.037 (4)0.011 (2)
C2100.134 (6)0.515 (18)0.076 (4)0.166 (9)0.004 (4)0.092 (7)
Geometric parameters (Å, º) top
O83—C821.259 (3)C6—H6B0.9900
O163—C1621.258 (3)C285—C2841.526 (4)
O143—C1421.254 (3)C285—C2881.529 (4)
O402—H40A0.8701C285—H2851.0000
O402—H40B0.8699C44—H44A0.9900
O411—H41A0.86 (4)C44—H44B0.9900
O411—H41B0.83 (4)C126—C1251.537 (3)
O23—C221.259 (3)C126—H12D0.9900
O416—H41C0.8701C126—H12E0.9900
O416—H41D0.8695C204—H20F0.9900
O223—C2221.256 (3)C204—H20G0.9900
O404—H40C0.8699C84—H84A0.9900
O404—H40D0.8700C84—H84B0.9900
O3—C21.259 (3)C125—C1281.527 (4)
O409—H40E0.8702C125—C1241.537 (4)
O409—H40F0.8699C125—H1251.0000
O161—C1621.255 (3)C104—H10I0.9900
O43—C421.260 (3)C104—H10J0.9900
O412—H41E0.8701C229—C2311.516 (5)
O412—H41F0.8698C229—C2301.520 (5)
O407—H40G0.82 (4)C229—C2281.529 (5)
O407—H40H0.86 (4)C229—H2291.0000
O63—C621.258 (3)C64—H64A0.9900
O41—C421.254 (3)C64—H64B0.9900
O103—C1021.263 (3)C68—C691.514 (5)
O414—H41G0.8699C68—H68A0.9900
O414—H41H0.8701C68—H68B0.9900
O203—C2021.259 (3)C308—C3091.510 (4)
O81—C821.251 (3)C308—H30I0.9900
O243—C2421.259 (3)C308—H30J0.9900
O21—C221.253 (3)C266—H26F0.9900
O183—C1821.257 (3)C266—H26G0.9900
O401—H40I0.8699C264—H26H0.9900
O401—H40J0.8698C264—H26I0.9900
O141—C1421.256 (3)C244—H24H0.9900
O403—H40K0.8701C244—H24I0.9900
O403—H40L0.8699C151—H15A0.9800
O263—C2621.259 (3)C151—H15B0.9800
O303—C3021.262 (3)C151—H15C0.9800
O101—C1021.248 (3)C88—C891.533 (4)
O201—C2021.258 (3)C88—H88A0.9900
O61—C621.254 (3)C88—H88B0.9900
O413—H41I0.8700C304—H30K0.9900
O413—H41J0.8701C304—H30L0.9900
O283—C2821.255 (3)C148—H14F0.9900
O410—H41K0.8697C148—H14G0.9900
O410—H41L0.8699C289—C2901.512 (5)
O123—C1221.259 (3)C289—C2911.526 (5)
O405—H40M0.8702C289—C2881.528 (4)
O405—H40N0.8701C289—H2891.0000
O181—C1821.258 (3)C184—H18F0.9900
O1—C21.254 (3)C184—H18G0.9900
O408—H40O0.8701C208—C2091.501 (5)
O408—H40P0.8702C208—H20H0.9900
O261—C2621.252 (3)C208—H20I0.9900
O241—C2421.255 (3)C24—H24A0.9900
O221—C2221.257 (3)C24—H24B0.9900
O301—C3021.251 (3)C144—H14H0.9900
O415—H41M0.8699C144—H14I0.9900
O415—H41N0.8699C4—H4A0.9900
O406—H40Q0.80 (4)C4—H4B0.9900
O406—H40R0.82 (4)C150—H15D0.9800
N247—C2461.475 (3)C150—H15E0.9800
N247—H24C0.9100C150—H15F0.9800
N247—H24D0.9100C169—C1711.519 (5)
N247—H24E0.9100C169—C1701.526 (5)
N187—C1861.477 (3)C169—C1681.530 (4)
N187—H18A0.9100C169—H1691.0000
N187—H18B0.9100C168—H16F0.9900
N187—H18C0.9100C168—H16G0.9900
O121—C1221.249 (3)C124—H12F0.9900
N27—C261.483 (3)C124—H12G0.9900
N27—H27A0.9100C9—C111.508 (6)
N27—H27B0.9100C9—C101.522 (5)
N27—H27C0.9100C9—C81.530 (5)
N47—C461.473 (3)C9—H91.0000
N47—H47A0.9100C164—H16H0.9900
N47—H47B0.9100C164—H16I0.9900
N47—H47C0.9100C228—H22F0.9900
N167—C1661.479 (3)C228—H22G0.9900
N167—H16A0.9100C268—C2691.532 (5)
N167—H16B0.9100C268—H26J0.9900
N167—H16C0.9100C268—H26K0.9900
N107—C1061.478 (3)C288—H28H0.9900
N107—H10D0.9100C288—H28I0.9900
N107—H10E0.9100C108—C1091.527 (5)
N107—H10F0.9100C108—H10K0.9900
N147—C1461.476 (3)C108—H10L0.9900
N147—H14A0.9100C290—H29A0.9800
N147—H14B0.9100C290—H29B0.9800
N147—H14C0.9100C290—H29C0.9800
N287—C2861.483 (3)C284—H28J0.9900
N287—H28C0.9100C284—H28K0.9900
N287—H28D0.9100C8—H8A0.9900
N287—H28E0.9100C8—H8B0.9900
N7—C61.481 (3)C310—C3091.535 (5)
N7—H7A0.9100C310—H31D0.9800
N7—H7B0.9100C310—H31E0.9800
N7—H7C0.9100C310—H31F0.9800
O281—C2821.257 (3)C28—C291.540 (5)
N267—C2661.481 (4)C28—H28A0.9900
N267—H26C0.9100C28—H28B0.9900
N267—H26D0.9100C29—C311.512 (6)
N267—H26E0.9100C29—C301.519 (5)
N127—C1261.480 (3)C29—H291.0000
N127—H12A0.9100C188—C1891.534 (5)
N127—H12B0.9100C188—H18H0.9900
N127—H12C0.9100C188—H18I0.9900
N307—C3061.481 (3)C248—C2491.514 (5)
N307—H30D0.9100C248—H24J0.9900
N307—H30E0.9100C248—H24K0.9900
N307—H30F0.9100C48—C491.525 (5)
N207—C2061.477 (3)C48—H48A0.9900
N207—H20A0.9100C48—H48B0.9900
N207—H20B0.9100C311—C3091.534 (5)
N207—H20C0.9100C311—H31G0.9800
N67—C661.487 (3)C311—H31H0.9800
N67—H67A0.9100C311—H31I0.9800
N67—H67B0.9100C128—C1291.516 (6)
N67—H67C0.9100C128—H12H0.9900
N87—C861.479 (3)C128—H12I0.9900
N87—H87A0.9100C70—C691.526 (5)
N87—H87B0.9100C70—H70A0.9800
N87—H87C0.9100C70—H70B0.9800
N227—C2261.479 (4)C70—H70C0.9800
N227—H22A0.9100C309—H3091.0000
N227—H22B0.9100C224—H22H0.9900
N227—H22C0.9100C224—H22I0.9900
C82—C841.525 (3)C231—H23A0.9800
C42—C441.522 (3)C231—H23B0.9800
C22—C241.518 (3)C231—H23C0.9800
C142—C1441.528 (3)C71—C691.543 (6)
C162—C1641.525 (3)C71—H71A0.9800
C202—C2041.515 (3)C71—H71B0.9800
C102—C1041.527 (3)C71—H71C0.9800
C146—C1451.539 (3)C129—C1311.517 (5)
C146—H14D0.9900C129—C1301.520 (5)
C146—H14E0.9900C129—H1291.0000
C62—C641.521 (3)C91—C891.519 (5)
C86—C851.534 (3)C91—H91A0.9800
C86—H86A0.9900C91—H91B0.9800
C86—H86B0.9900C91—H91C0.9800
C262—C2641.525 (3)C291—H29D0.9800
C182—C1841.521 (3)C291—H29E0.9800
C165—C1681.524 (4)C291—H29F0.9800
C165—C1641.528 (4)C69—H691.0000
C165—C1661.531 (3)C230—H23D0.9800
C165—H1651.0000C230—H23E0.9800
C302—C3041.519 (3)C230—H23F0.9800
C149—C1501.521 (4)C89—C901.523 (5)
C149—C1511.523 (4)C89—H891.0000
C149—C1481.530 (4)C249—C2511.494 (7)
C149—H1491.0000C249—C2501.534 (6)
C45—C481.528 (4)C249—H2491.0000
C45—C461.531 (3)C171—H17A0.9800
C45—C441.532 (4)C171—H17B0.9800
C45—H451.0000C171—H17C0.9800
C145—C1441.527 (3)C269—C2711.500 (7)
C145—C1481.532 (4)C269—C2701.525 (6)
C145—H1451.0000C269—H2691.0000
C222—C2241.523 (3)C10—H10A0.9800
C166—H16D0.9900C10—H10B0.9800
C166—H16E0.9900C10—H10C0.9800
C306—C3051.535 (3)C90—H90A0.9800
C306—H30G0.9900C90—H90B0.9800
C306—H30H0.9900C90—H90C0.9800
C286—C2851.536 (3)C31—H31A0.9800
C286—H28F0.9900C31—H31B0.9800
C286—H28G0.9900C31—H31C0.9800
C282—C2841.526 (3)C189—C1901.501 (7)
C185—C1881.519 (4)C189—C1911.520 (6)
C185—C1841.530 (4)C189—H1891.0000
C185—C1861.530 (3)C109—C1111.492 (7)
C185—H1851.0000C109—C1101.525 (6)
C2—C41.524 (3)C109—H1091.0000
C25—C281.523 (4)C170—H17D0.9800
C25—C241.525 (4)C170—H17E0.9800
C25—C261.530 (3)C170—H17F0.9800
C25—H251.0000C49—C511.504 (7)
C226—C2251.531 (3)C49—C501.522 (6)
C226—H22D0.9900C49—H491.0000
C226—H22E0.9900C11—H11A0.9800
C105—C1081.530 (4)C11—H11B0.9800
C105—C1041.532 (4)C11—H11C0.9800
C105—C1061.534 (3)C209—C2101.501 (8)
C105—H1051.0000C209—C2111.509 (6)
C265—C2681.523 (4)C209—H2091.0000
C265—C2661.533 (3)C211—H21A0.9800
C265—C2641.533 (4)C211—H21B0.9800
C265—H2651.0000C211—H21C0.9800
C46—H46A0.9900C131—H13A0.9800
C46—H46B0.9900C131—H13B0.9800
C66—C651.533 (3)C131—H13C0.9800
C66—H66A0.9900C130—H13D0.9800
C66—H66B0.9900C130—H13E0.9800
C85—C881.534 (4)C130—H13F0.9800
C85—C841.535 (3)C271—H27D0.9800
C85—H851.0000C271—H27E0.9800
C26—H26A0.9900C271—H27F0.9800
C26—H26B0.9900C30—H30A0.9800
C5—C81.525 (4)C30—H30B0.9800
C5—C61.532 (3)C30—H30C0.9800
C5—C41.536 (4)C250—H25A0.9800
C5—H51.0000C250—H25B0.9800
C122—C1241.528 (3)C250—H25C0.9800
C106—H10G0.9900C190—H19A0.9800
C106—H10H0.9900C190—H19B0.9800
C246—C2451.528 (3)C190—H19C0.9800
C246—H24F0.9900C270—H27G0.9800
C246—H24G0.9900C270—H27H0.9800
C245—C2481.528 (4)C270—H27I0.9800
C245—C2441.534 (4)C111—H11D0.9800
C245—H2451.0000C111—H11E0.9800
C225—C2241.530 (4)C111—H11F0.9800
C225—C2281.530 (4)C50—H50A0.9800
C225—H2251.0000C50—H50B0.9800
C186—H18D0.9900C50—H50C0.9800
C186—H18E0.9900C51—H51A0.9800
C206—C2051.531 (3)C51—H51B0.9800
C206—H20D0.9900C51—H51C0.9800
C206—H20E0.9900C251—H25D0.9800
C305—C3081.529 (4)C251—H25E0.9800
C305—C3041.536 (4)C251—H25F0.9800
C305—H3051.0000C110—H11G0.9800
C65—C641.528 (4)C110—H11H0.9800
C65—C681.533 (4)C110—H11I0.9800
C65—H651.0000C191—H19D0.9800
C205—C2041.531 (4)C191—H19E0.9800
C205—C2081.531 (4)C191—H19F0.9800
C205—H2051.0000C210—H21D0.9800
C242—C2441.530 (3)C210—H21E0.9800
C6—H6A0.9900C210—H21F0.9800
H40A—O402—H40B104.5C245—C244—H24I109.3
H41A—O411—H41B101 (3)H24H—C244—H24I108.0
H41C—O416—H41D104.5C149—C151—H15A109.5
H40C—O404—H40D104.5C149—C151—H15B109.5
H40E—O409—H40F104.5H15A—C151—H15B109.5
H41E—O412—H41F104.5C149—C151—H15C109.5
H40G—O407—H40H102 (3)H15A—C151—H15C109.5
H41G—O414—H41H104.5H15B—C151—H15C109.5
H40I—O401—H40J104.5C89—C88—C85115.5 (2)
H40K—O403—H40L104.5C89—C88—H88A108.4
H41I—O413—H41J104.5C85—C88—H88A108.4
H41K—O410—H41L104.5C89—C88—H88B108.4
H40M—O405—H40N104.5C85—C88—H88B108.4
H40O—O408—H40P104.5H88A—C88—H88B107.5
H41M—O415—H41N104.5C302—C304—C305111.1 (2)
H40Q—O406—H40R108 (4)C302—C304—H30K109.4
C246—N247—H24C109.5C305—C304—H30K109.4
C246—N247—H24D109.5C302—C304—H30L109.4
H24C—N247—H24D109.5C305—C304—H30L109.4
C246—N247—H24E109.5H30K—C304—H30L108.0
H24C—N247—H24E109.5C149—C148—C145116.4 (2)
H24D—N247—H24E109.5C149—C148—H14F108.2
C186—N187—H18A109.5C145—C148—H14F108.2
C186—N187—H18B109.5C149—C148—H14G108.2
H18A—N187—H18B109.5C145—C148—H14G108.2
C186—N187—H18C109.5H14F—C148—H14G107.3
H18A—N187—H18C109.5C290—C289—C291111.6 (3)
H18B—N187—H18C109.5C290—C289—C288111.7 (3)
C26—N27—H27A109.5C291—C289—C288112.0 (3)
C26—N27—H27B109.5C290—C289—H289107.0
H27A—N27—H27B109.5C291—C289—H289107.0
C26—N27—H27C109.5C288—C289—H289107.0
H27A—N27—H27C109.5C182—C184—C185112.7 (2)
H27B—N27—H27C109.5C182—C184—H18F109.1
C46—N47—H47A109.5C185—C184—H18F109.1
C46—N47—H47B109.5C182—C184—H18G109.1
H47A—N47—H47B109.5C185—C184—H18G109.1
C46—N47—H47C109.5H18F—C184—H18G107.8
H47A—N47—H47C109.5C209—C208—C205115.7 (3)
H47B—N47—H47C109.5C209—C208—H20H108.3
C166—N167—H16A109.5C205—C208—H20H108.3
C166—N167—H16B109.5C209—C208—H20I108.3
H16A—N167—H16B109.5C205—C208—H20I108.3
C166—N167—H16C109.5H20H—C208—H20I107.4
H16A—N167—H16C109.5C22—C24—C25113.4 (2)
H16B—N167—H16C109.5C22—C24—H24A108.9
C106—N107—H10D109.5C25—C24—H24A108.9
C106—N107—H10E109.5C22—C24—H24B108.9
H10D—N107—H10E109.5C25—C24—H24B108.9
C106—N107—H10F109.5H24A—C24—H24B107.7
H10D—N107—H10F109.5C145—C144—C142115.1 (2)
H10E—N107—H10F109.5C145—C144—H14H108.5
C146—N147—H14A109.5C142—C144—H14H108.5
C146—N147—H14B109.5C145—C144—H14I108.5
H14A—N147—H14B109.5C142—C144—H14I108.5
C146—N147—H14C109.5H14H—C144—H14I107.5
H14A—N147—H14C109.5C2—C4—C5112.3 (2)
H14B—N147—H14C109.5C2—C4—H4A109.1
C286—N287—H28C109.5C5—C4—H4A109.1
C286—N287—H28D109.5C2—C4—H4B109.1
H28C—N287—H28D109.5C5—C4—H4B109.1
C286—N287—H28E109.5H4A—C4—H4B107.9
H28C—N287—H28E109.5C149—C150—H15D109.5
H28D—N287—H28E109.5C149—C150—H15E109.5
C6—N7—H7A109.5H15D—C150—H15E109.5
C6—N7—H7B109.5C149—C150—H15F109.5
H7A—N7—H7B109.5H15D—C150—H15F109.5
C6—N7—H7C109.5H15E—C150—H15F109.5
H7A—N7—H7C109.5C171—C169—C170111.3 (3)
H7B—N7—H7C109.5C171—C169—C168110.3 (3)
C266—N267—H26C109.5C170—C169—C168111.3 (3)
C266—N267—H26D109.5C171—C169—H169107.9
H26C—N267—H26D109.5C170—C169—H169107.9
C266—N267—H26E109.5C168—C169—H169107.9
H26C—N267—H26E109.5C165—C168—C169117.0 (2)
H26D—N267—H26E109.5C165—C168—H16F108.0
C126—N127—H12A109.5C169—C168—H16F108.0
C126—N127—H12B109.5C165—C168—H16G108.0
H12A—N127—H12B109.5C169—C168—H16G108.0
C126—N127—H12C109.5H16F—C168—H16G107.3
H12A—N127—H12C109.5C122—C124—C125113.6 (2)
H12B—N127—H12C109.5C122—C124—H12F108.9
C306—N307—H30D109.5C125—C124—H12F108.9
C306—N307—H30E109.5C122—C124—H12G108.9
H30D—N307—H30E109.5C125—C124—H12G108.9
C306—N307—H30F109.5H12F—C124—H12G107.7
H30D—N307—H30F109.5C11—C9—C10111.7 (4)
H30E—N307—H30F109.5C11—C9—C8113.2 (3)
C206—N207—H20A109.5C10—C9—C8109.8 (3)
C206—N207—H20B109.5C11—C9—H9107.3
H20A—N207—H20B109.5C10—C9—H9107.3
C206—N207—H20C109.5C8—C9—H9107.3
H20A—N207—H20C109.5C162—C164—C165113.6 (2)
H20B—N207—H20C109.5C162—C164—H16H108.9
C66—N67—H67A109.5C165—C164—H16H108.9
C66—N67—H67B109.5C162—C164—H16I108.9
H67A—N67—H67B109.5C165—C164—H16I108.9
C66—N67—H67C109.5H16H—C164—H16I107.7
H67A—N67—H67C109.5C229—C228—C225116.8 (2)
H67B—N67—H67C109.5C229—C228—H22F108.1
C86—N87—H87A109.5C225—C228—H22F108.1
C86—N87—H87B109.5C229—C228—H22G108.1
H87A—N87—H87B109.5C225—C228—H22G108.1
C86—N87—H87C109.5H22F—C228—H22G107.3
H87A—N87—H87C109.5C265—C268—C269116.6 (3)
H87B—N87—H87C109.5C265—C268—H26J108.2
C226—N227—H22A109.5C269—C268—H26J108.2
C226—N227—H22B109.5C265—C268—H26K108.2
H22A—N227—H22B109.5C269—C268—H26K108.2
C226—N227—H22C109.5H26J—C268—H26K107.3
H22A—N227—H22C109.5C289—C288—C285116.2 (2)
H22B—N227—H22C109.5C289—C288—H28H108.2
O81—C82—O83124.3 (2)C285—C288—H28H108.2
O81—C82—C84118.3 (2)C289—C288—H28I108.2
O83—C82—C84117.4 (2)C285—C288—H28I108.2
O41—C42—O43124.4 (2)H28H—C288—H28I107.4
O41—C42—C44118.3 (2)C109—C108—C105117.0 (3)
O43—C42—C44117.3 (2)C109—C108—H10K108.1
O21—C22—O23124.4 (2)C105—C108—H10K108.1
O21—C22—C24117.9 (2)C109—C108—H10L108.1
O23—C22—C24117.6 (2)C105—C108—H10L108.1
O143—C142—O141124.5 (2)H10K—C108—H10L107.3
O143—C142—C144118.9 (2)C289—C290—H29A109.5
O141—C142—C144116.6 (2)C289—C290—H29B109.5
O161—C162—O163124.4 (2)H29A—C290—H29B109.5
O161—C162—C164117.9 (2)C289—C290—H29C109.5
O163—C162—C164117.7 (2)H29A—C290—H29C109.5
O201—C202—O203124.1 (2)H29B—C290—H29C109.5
O201—C202—C204118.7 (2)C282—C284—C285115.5 (2)
O203—C202—C204117.1 (2)C282—C284—H28J108.4
O101—C102—O103124.0 (2)C285—C284—H28J108.4
O101—C102—C104118.9 (2)C282—C284—H28K108.4
O103—C102—C104117.1 (2)C285—C284—H28K108.4
N147—C146—C145112.7 (2)H28J—C284—H28K107.5
N147—C146—H14D109.0C5—C8—C9116.0 (3)
C145—C146—H14D109.0C5—C8—H8A108.3
N147—C146—H14E109.0C9—C8—H8A108.3
C145—C146—H14E109.0C5—C8—H8B108.3
H14D—C146—H14E107.8C9—C8—H8B108.3
O61—C62—O63124.2 (2)H8A—C8—H8B107.4
O61—C62—C64118.5 (2)C309—C310—H31D109.5
O63—C62—C64117.3 (2)C309—C310—H31E109.5
N87—C86—C85112.9 (2)H31D—C310—H31E109.5
N87—C86—H86A109.0C309—C310—H31F109.5
C85—C86—H86A109.0H31D—C310—H31F109.5
N87—C86—H86B109.0H31E—C310—H31F109.5
C85—C86—H86B109.0C25—C28—C29117.1 (3)
H86A—C86—H86B107.8C25—C28—H28A108.0
O261—C262—O263124.0 (2)C29—C28—H28A108.0
O261—C262—C264118.6 (2)C25—C28—H28B108.0
O263—C262—C264117.3 (2)C29—C28—H28B108.0
O183—C182—O181124.3 (2)H28A—C28—H28B107.3
O183—C182—C184117.3 (2)C31—C29—C30111.3 (4)
O181—C182—C184118.4 (2)C31—C29—C28112.0 (3)
C168—C165—C164110.8 (2)C30—C29—C28109.6 (4)
C168—C165—C166110.1 (2)C31—C29—H29108.0
C164—C165—C166111.2 (2)C30—C29—H29108.0
C168—C165—H165108.2C28—C29—H29108.0
C164—C165—H165108.2C185—C188—C189116.8 (3)
C166—C165—H165108.2C185—C188—H18H108.1
O301—C302—O303124.0 (2)C189—C188—H18H108.1
O301—C302—C304118.6 (2)C185—C188—H18I108.1
O303—C302—C304117.3 (2)C189—C188—H18I108.1
C150—C149—C151110.7 (3)H18H—C188—H18I107.3
C150—C149—C148110.6 (3)C249—C248—C245117.0 (3)
C151—C149—C148111.7 (2)C249—C248—H24J108.1
C150—C149—H149107.9C245—C248—H24J108.1
C151—C149—H149107.9C249—C248—H24K108.1
C148—C149—H149107.9C245—C248—H24K108.1
C48—C45—C46110.3 (2)H24J—C248—H24K107.3
C48—C45—C44111.2 (2)C49—C48—C45116.6 (3)
C46—C45—C44110.5 (2)C49—C48—H48A108.1
C48—C45—H45108.3C45—C48—H48A108.1
C46—C45—H45108.3C49—C48—H48B108.1
C44—C45—H45108.3C45—C48—H48B108.1
C144—C145—C148110.8 (2)H48A—C48—H48B107.3
C144—C145—C146110.6 (2)C309—C311—H31G109.5
C148—C145—C146110.2 (2)C309—C311—H31H109.5
C144—C145—H145108.4H31G—C311—H31H109.5
C148—C145—H145108.4C309—C311—H31I109.5
C146—C145—H145108.4H31G—C311—H31I109.5
O223—C222—O221124.2 (2)H31H—C311—H31I109.5
O223—C222—C224118.3 (2)C129—C128—C125116.0 (3)
O221—C222—C224117.5 (2)C129—C128—H12H108.3
N167—C166—C165112.7 (2)C125—C128—H12H108.3
N167—C166—H16D109.1C129—C128—H12I108.3
C165—C166—H16D109.1C125—C128—H12I108.3
N167—C166—H16E109.1H12H—C128—H12I107.4
C165—C166—H16E109.1C69—C70—H70A109.5
H16D—C166—H16E107.8C69—C70—H70B109.5
N307—C306—C305112.7 (2)H70A—C70—H70B109.5
N307—C306—H30G109.0C69—C70—H70C109.5
C305—C306—H30G109.0H70A—C70—H70C109.5
N307—C306—H30H109.0H70B—C70—H70C109.5
C305—C306—H30H109.0C308—C309—C311110.4 (3)
H30G—C306—H30H107.8C308—C309—C310111.2 (3)
N287—C286—C285112.6 (2)C311—C309—C310109.0 (3)
N287—C286—H28F109.1C308—C309—H309108.7
C285—C286—H28F109.1C311—C309—H309108.7
N287—C286—H28G109.1C310—C309—H309108.7
C285—C286—H28G109.1C222—C224—C225114.8 (2)
H28F—C286—H28G107.8C222—C224—H22H108.6
O283—C282—O281124.2 (2)C225—C224—H22H108.6
O283—C282—C284118.6 (2)C222—C224—H22I108.6
O281—C282—C284117.2 (2)C225—C224—H22I108.6
C188—C185—C184111.0 (2)H22H—C224—H22I107.6
C188—C185—C186110.1 (2)C229—C231—H23A109.5
C184—C185—C186110.5 (2)C229—C231—H23B109.5
C188—C185—H185108.4H23A—C231—H23B109.5
C184—C185—H185108.4C229—C231—H23C109.5
C186—C185—H185108.4H23A—C231—H23C109.5
O1—C2—O3124.3 (2)H23B—C231—H23C109.5
O1—C2—C4118.5 (2)C69—C71—H71A109.5
O3—C2—C4117.2 (2)C69—C71—H71B109.5
C28—C25—C24110.7 (2)H71A—C71—H71B109.5
C28—C25—C26110.1 (2)C69—C71—H71C109.5
C24—C25—C26111.3 (2)H71A—C71—H71C109.5
C28—C25—H25108.2H71B—C71—H71C109.5
C24—C25—H25108.2C128—C129—C131112.4 (3)
C26—C25—H25108.2C128—C129—C130111.4 (4)
N227—C226—C225113.0 (2)C131—C129—C130111.1 (4)
N227—C226—H22D109.0C128—C129—H129107.2
C225—C226—H22D109.0C131—C129—H129107.2
N227—C226—H22E109.0C130—C129—H129107.2
C225—C226—H22E109.0C89—C91—H91A109.5
H22D—C226—H22E107.8C89—C91—H91B109.5
C108—C105—C104110.9 (2)H91A—C91—H91B109.5
C108—C105—C106109.2 (2)C89—C91—H91C109.5
C104—C105—C106111.4 (2)H91A—C91—H91C109.5
C108—C105—H105108.4H91B—C91—H91C109.5
C104—C105—H105108.4C289—C291—H29D109.5
C106—C105—H105108.4C289—C291—H29E109.5
C268—C265—C266109.2 (2)H29D—C291—H29E109.5
C268—C265—C264111.0 (2)C289—C291—H29F109.5
C266—C265—C264111.1 (2)H29D—C291—H29F109.5
C268—C265—H265108.5H29E—C291—H29F109.5
C266—C265—H265108.5C68—C69—C70111.2 (3)
C264—C265—H265108.5C68—C69—C71111.0 (3)
N47—C46—C45112.3 (2)C70—C69—C71109.2 (3)
N47—C46—H46A109.1C68—C69—H69108.5
C45—C46—H46A109.1C70—C69—H69108.5
N47—C46—H46B109.1C71—C69—H69108.5
C45—C46—H46B109.1C229—C230—H23D109.5
H46A—C46—H46B107.9C229—C230—H23E109.5
N67—C66—C65112.3 (2)H23D—C230—H23E109.5
N67—C66—H66A109.2C229—C230—H23F109.5
C65—C66—H66A109.2H23D—C230—H23F109.5
N67—C66—H66B109.2H23E—C230—H23F109.5
C65—C66—H66B109.2C91—C89—C90109.7 (3)
H66A—C66—H66B107.9C91—C89—C88110.2 (3)
C88—C85—C86109.2 (2)C90—C89—C88110.5 (3)
C88—C85—C84111.1 (2)C91—C89—H89108.8
C86—C85—C84111.6 (2)C90—C89—H89108.8
C88—C85—H85108.3C88—C89—H89108.8
C86—C85—H85108.3C251—C249—C248113.0 (4)
C84—C85—H85108.3C251—C249—C250111.4 (4)
N27—C26—C25112.5 (2)C248—C249—C250109.5 (4)
N27—C26—H26A109.1C251—C249—H249107.6
C25—C26—H26A109.1C248—C249—H249107.6
N27—C26—H26B109.1C250—C249—H249107.6
C25—C26—H26B109.1C169—C171—H17A109.5
H26A—C26—H26B107.8C169—C171—H17B109.5
C8—C5—C6109.5 (2)H17A—C171—H17B109.5
C8—C5—C4110.4 (2)C169—C171—H17C109.5
C6—C5—C4111.7 (2)H17A—C171—H17C109.5
C8—C5—H5108.4H17B—C171—H17C109.5
C6—C5—H5108.4C271—C269—C270112.2 (4)
C4—C5—H5108.4C271—C269—C268112.5 (3)
O121—C122—O123124.2 (2)C270—C269—C268109.7 (4)
O121—C122—C124117.8 (2)C271—C269—H269107.4
O123—C122—C124118.0 (2)C270—C269—H269107.4
N107—C106—C105112.8 (2)C268—C269—H269107.4
N107—C106—H10G109.0C9—C10—H10A109.5
C105—C106—H10G109.0C9—C10—H10B109.5
N107—C106—H10H109.0H10A—C10—H10B109.5
C105—C106—H10H109.0C9—C10—H10C109.5
H10G—C106—H10H107.8H10A—C10—H10C109.5
N247—C246—C245113.5 (2)H10B—C10—H10C109.5
N247—C246—H24F108.9C89—C90—H90A109.5
C245—C246—H24F108.9C89—C90—H90B109.5
N247—C246—H24G108.9H90A—C90—H90B109.5
C245—C246—H24G108.9C89—C90—H90C109.5
H24F—C246—H24G107.7H90A—C90—H90C109.5
C248—C245—C246109.4 (2)H90B—C90—H90C109.5
C248—C245—C244110.7 (2)C29—C31—H31A109.5
C246—C245—C244111.4 (2)C29—C31—H31B109.5
C248—C245—H245108.4H31A—C31—H31B109.5
C246—C245—H245108.4C29—C31—H31C109.5
C244—C245—H245108.4H31A—C31—H31C109.5
C224—C225—C228110.6 (2)H31B—C31—H31C109.5
C224—C225—C226111.0 (2)C190—C189—C191112.7 (4)
C228—C225—C226110.6 (2)C190—C189—C188112.2 (3)
C224—C225—H225108.2C191—C189—C188109.0 (4)
C228—C225—H225108.2C190—C189—H189107.5
C226—C225—H225108.2C191—C189—H189107.5
N187—C186—C185112.7 (2)C188—C189—H189107.5
N187—C186—H18D109.1C111—C109—C110112.3 (4)
C185—C186—H18D109.1C111—C109—C108113.2 (4)
N187—C186—H18E109.1C110—C109—C108109.7 (4)
C185—C186—H18E109.1C111—C109—H109107.1
H18D—C186—H18E107.8C110—C109—H109107.1
N207—C206—C205112.2 (2)C108—C109—H109107.1
N207—C206—H20D109.2C169—C170—H17D109.5
C205—C206—H20D109.2C169—C170—H17E109.5
N207—C206—H20E109.2H17D—C170—H17E109.5
C205—C206—H20E109.2C169—C170—H17F109.5
H20D—C206—H20E107.9H17D—C170—H17F109.5
C308—C305—C306109.5 (2)H17E—C170—H17F109.5
C308—C305—C304110.7 (2)C51—C49—C50112.0 (4)
C306—C305—C304111.0 (2)C51—C49—C48112.1 (4)
C308—C305—H305108.5C50—C49—C48110.0 (4)
C306—C305—H305108.5C51—C49—H49107.5
C304—C305—H305108.5C50—C49—H49107.5
C64—C65—C66110.8 (2)C48—C49—H49107.5
C64—C65—C68111.8 (2)C9—C11—H11A109.5
C66—C65—C68109.1 (2)C9—C11—H11B109.5
C64—C65—H65108.4H11A—C11—H11B109.5
C66—C65—H65108.4C9—C11—H11C109.5
C68—C65—H65108.4H11A—C11—H11C109.5
C204—C205—C208111.1 (2)H11B—C11—H11C109.5
C204—C205—C206110.9 (2)C208—C209—C210111.9 (4)
C208—C205—C206109.3 (2)C208—C209—C211111.5 (4)
C204—C205—H205108.5C210—C209—C211110.0 (5)
C208—C205—H205108.5C208—C209—H209107.7
C206—C205—H205108.5C210—C209—H209107.7
O241—C242—O243124.2 (2)C211—C209—H209107.7
O241—C242—C244118.8 (2)C209—C211—H21A109.5
O243—C242—C244117.0 (2)C209—C211—H21B109.5
N7—C6—C5113.3 (2)H21A—C211—H21B109.5
N7—C6—H6A108.9C209—C211—H21C109.5
C5—C6—H6A108.9H21A—C211—H21C109.5
N7—C6—H6B108.9H21B—C211—H21C109.5
C5—C6—H6B108.9C129—C131—H13A109.5
H6A—C6—H6B107.7C129—C131—H13B109.5
C284—C285—C288111.5 (2)H13A—C131—H13B109.5
C284—C285—C286110.9 (2)C129—C131—H13C109.5
C288—C285—C286109.3 (2)H13A—C131—H13C109.5
C284—C285—H285108.3H13B—C131—H13C109.5
C288—C285—H285108.3C129—C130—H13D109.5
C286—C285—H285108.3C129—C130—H13E109.5
C42—C44—C45112.5 (2)H13D—C130—H13E109.5
C42—C44—H44A109.1C129—C130—H13F109.5
C45—C44—H44A109.1H13D—C130—H13F109.5
C42—C44—H44B109.1H13E—C130—H13F109.5
C45—C44—H44B109.1C269—C271—H27D109.5
H44A—C44—H44B107.8C269—C271—H27E109.5
N127—C126—C125112.6 (2)H27D—C271—H27E109.5
N127—C126—H12D109.1C269—C271—H27F109.5
C125—C126—H12D109.1H27D—C271—H27F109.5
N127—C126—H12E109.1H27E—C271—H27F109.5
C125—C126—H12E109.1C29—C30—H30A109.5
H12D—C126—H12E107.8C29—C30—H30B109.5
C202—C204—C205111.6 (2)H30A—C30—H30B109.5
C202—C204—H20F109.3C29—C30—H30C109.5
C205—C204—H20F109.3H30A—C30—H30C109.5
C202—C204—H20G109.3H30B—C30—H30C109.5
C205—C204—H20G109.3C249—C250—H25A109.5
H20F—C204—H20G108.0C249—C250—H25B109.5
C82—C84—C85111.7 (2)H25A—C250—H25B109.5
C82—C84—H84A109.3C249—C250—H25C109.5
C85—C84—H84A109.3H25A—C250—H25C109.5
C82—C84—H84B109.3H25B—C250—H25C109.5
C85—C84—H84B109.3C189—C190—H19A109.5
H84A—C84—H84B107.9C189—C190—H19B109.5
C128—C125—C126109.0 (2)H19A—C190—H19B109.5
C128—C125—C124111.5 (2)C189—C190—H19C109.5
C126—C125—C124110.8 (2)H19A—C190—H19C109.5
C128—C125—H125108.5H19B—C190—H19C109.5
C126—C125—H125108.5C269—C270—H27G109.5
C124—C125—H125108.5C269—C270—H27H109.5
C102—C104—C105111.4 (2)H27G—C270—H27H109.5
C102—C104—H10I109.3C269—C270—H27I109.5
C105—C104—H10I109.3H27G—C270—H27I109.5
C102—C104—H10J109.3H27H—C270—H27I109.5
C105—C104—H10J109.3C109—C111—H11D109.5
H10I—C104—H10J108.0C109—C111—H11E109.5
C231—C229—C230110.6 (3)H11D—C111—H11E109.5
C231—C229—C228112.0 (3)C109—C111—H11F109.5
C230—C229—C228110.7 (3)H11D—C111—H11F109.5
C231—C229—H229107.8H11E—C111—H11F109.5
C230—C229—H229107.8C49—C50—H50A109.5
C228—C229—H229107.8C49—C50—H50B109.5
C62—C64—C65111.1 (2)H50A—C50—H50B109.5
C62—C64—H64A109.4C49—C50—H50C109.5
C65—C64—H64A109.4H50A—C50—H50C109.5
C62—C64—H64B109.4H50B—C50—H50C109.5
C65—C64—H64B109.4C49—C51—H51A109.5
H64A—C64—H64B108.0C49—C51—H51B109.5
C69—C68—C65115.4 (3)H51A—C51—H51B109.5
C69—C68—H68A108.4C49—C51—H51C109.5
C65—C68—H68A108.4H51A—C51—H51C109.5
C69—C68—H68B108.4H51B—C51—H51C109.5
C65—C68—H68B108.4C249—C251—H25D109.5
H68A—C68—H68B107.5C249—C251—H25E109.5
C309—C308—C305114.8 (2)H25D—C251—H25E109.5
C309—C308—H30I108.6C249—C251—H25F109.5
C305—C308—H30I108.6H25D—C251—H25F109.5
C309—C308—H30J108.6H25E—C251—H25F109.5
C305—C308—H30J108.6C109—C110—H11G109.5
H30I—C308—H30J107.5C109—C110—H11H109.5
N267—C266—C265113.0 (2)H11G—C110—H11H109.5
N267—C266—H26F109.0C109—C110—H11I109.5
C265—C266—H26F109.0H11G—C110—H11I109.5
N267—C266—H26G109.0H11H—C110—H11I109.5
C265—C266—H26G109.0C189—C191—H19D109.5
H26F—C266—H26G107.8C189—C191—H19E109.5
C262—C264—C265112.1 (2)H19D—C191—H19E109.5
C262—C264—H26H109.2C189—C191—H19F109.5
C265—C264—H26H109.2H19D—C191—H19F109.5
C262—C264—H26I109.2H19E—C191—H19F109.5
C265—C264—H26I109.2C209—C210—H21D109.5
H26H—C264—H26I107.9C209—C210—H21E109.5
C242—C244—C245111.7 (2)H21D—C210—H21E109.5
C242—C244—H24H109.3C209—C210—H21F109.5
C245—C244—H24H109.3H21D—C210—H21F109.5
C242—C244—H24I109.3H21E—C210—H21F109.5
N147—C146—C145—C14467.4 (3)O21—C22—C24—C25137.1 (3)
N147—C146—C145—C148169.8 (2)O23—C22—C24—C2542.8 (4)
C168—C165—C166—N167174.7 (2)C28—C25—C24—C2260.3 (3)
C164—C165—C166—N16762.1 (3)C26—C25—C24—C22176.9 (2)
C48—C45—C46—N47174.5 (2)C148—C145—C144—C14268.0 (3)
C44—C45—C46—N4762.2 (3)C146—C145—C144—C142169.5 (2)
N87—C86—C85—C88178.5 (2)O143—C142—C144—C14532.0 (4)
N87—C86—C85—C8458.3 (3)O141—C142—C144—C145149.9 (3)
C28—C25—C26—N27174.9 (2)O1—C2—C4—C5126.0 (3)
C24—C25—C26—N2762.0 (3)O3—C2—C4—C553.2 (4)
C108—C105—C106—N107177.9 (2)C8—C5—C4—C257.8 (3)
C104—C105—C106—N10759.3 (3)C6—C5—C4—C2180.0 (2)
N247—C246—C245—C248179.2 (2)C164—C165—C168—C169166.0 (2)
N247—C246—C245—C24458.1 (3)C166—C165—C168—C16970.6 (3)
N227—C226—C225—C22465.4 (3)C171—C169—C168—C165178.6 (3)
N227—C226—C225—C228171.5 (2)C170—C169—C168—C16554.6 (4)
C188—C185—C186—N187176.5 (2)O121—C122—C124—C125137.9 (3)
C184—C185—C186—N18760.5 (3)O123—C122—C124—C12542.9 (4)
N307—C306—C305—C308177.4 (2)C128—C125—C124—C12261.2 (3)
N307—C306—C305—C30460.0 (3)C126—C125—C124—C122177.3 (2)
N67—C66—C65—C6461.1 (3)O161—C162—C164—C165139.0 (3)
N67—C66—C65—C68175.5 (2)O163—C162—C164—C16540.9 (4)
N207—C206—C205—C20461.9 (3)C168—C165—C164—C16260.3 (3)
N207—C206—C205—C208175.3 (2)C166—C165—C164—C162177.0 (2)
C8—C5—C6—N7177.4 (2)C231—C229—C228—C22554.5 (4)
C4—C5—C6—N759.9 (3)C230—C229—C228—C225178.4 (3)
N287—C286—C285—C28465.5 (3)C224—C225—C228—C229174.8 (2)
N287—C286—C285—C288171.2 (2)C226—C225—C228—C22961.8 (3)
O41—C42—C44—C45129.8 (3)C266—C265—C268—C26969.2 (3)
O43—C42—C44—C4550.2 (3)C264—C265—C268—C269168.1 (3)
C48—C45—C44—C4257.4 (3)C290—C289—C288—C285171.8 (3)
C46—C45—C44—C42179.9 (2)C291—C289—C288—C28562.1 (4)
O201—C202—C204—C205121.9 (3)C284—C285—C288—C289167.3 (2)
O203—C202—C204—C20556.7 (3)C286—C285—C288—C28969.7 (3)
C208—C205—C204—C20257.0 (3)C104—C105—C108—C109170.6 (3)
C206—C205—C204—C202178.7 (2)C106—C105—C108—C10966.3 (4)
O81—C82—C84—C85126.1 (3)O283—C282—C284—C28534.3 (4)
O83—C82—C84—C8552.1 (3)O281—C282—C284—C285147.2 (3)
C88—C85—C84—C8258.7 (3)C288—C285—C284—C28266.6 (3)
C86—C85—C84—C82179.2 (2)C286—C285—C284—C282171.3 (2)
N127—C126—C125—C128175.8 (2)C6—C5—C8—C961.1 (3)
N127—C126—C125—C12461.2 (3)C4—C5—C8—C9175.6 (3)
O101—C102—C104—C105122.1 (3)C11—C9—C8—C554.1 (4)
O103—C102—C104—C10557.0 (3)C10—C9—C8—C5179.7 (3)
C108—C105—C104—C10256.6 (3)C24—C25—C28—C29169.0 (2)
C106—C105—C104—C102178.4 (2)C26—C25—C28—C2967.6 (3)
O61—C62—C64—C65117.5 (3)C25—C28—C29—C3155.8 (4)
O63—C62—C64—C6561.2 (3)C25—C28—C29—C30179.8 (3)
C66—C65—C64—C62178.5 (2)C184—C185—C188—C189171.2 (3)
C68—C65—C64—C6256.6 (3)C186—C185—C188—C18966.1 (3)
C64—C65—C68—C69148.4 (3)C246—C245—C248—C24963.3 (4)
C66—C65—C68—C6988.7 (3)C244—C245—C248—C249173.6 (3)
C306—C305—C308—C30989.7 (3)C46—C45—C48—C4965.8 (4)
C304—C305—C308—C309147.6 (2)C44—C45—C48—C49171.4 (3)
C268—C265—C266—N267178.8 (2)C126—C125—C128—C12973.2 (3)
C264—C265—C266—N26758.6 (3)C124—C125—C128—C129164.3 (3)
O261—C262—C264—C265126.1 (3)C305—C308—C309—C311170.0 (3)
O263—C262—C264—C26553.0 (4)C305—C308—C309—C31068.9 (3)
C268—C265—C264—C26257.6 (3)O223—C222—C224—C22539.8 (4)
C266—C265—C264—C262179.2 (2)O221—C222—C224—C225141.3 (3)
O241—C242—C244—C245122.5 (3)C228—C225—C224—C22263.5 (3)
O243—C242—C244—C24556.8 (3)C226—C225—C224—C222173.3 (2)
C248—C245—C244—C24256.7 (3)C125—C128—C129—C13164.6 (5)
C246—C245—C244—C242178.7 (2)C125—C128—C129—C130170.0 (3)
C86—C85—C88—C8986.7 (3)C65—C68—C69—C70169.4 (3)
C84—C85—C88—C89149.8 (2)C65—C68—C69—C7168.8 (4)
O301—C302—C304—C305119.9 (3)C85—C88—C89—C9169.6 (4)
O303—C302—C304—C30558.2 (3)C85—C88—C89—C90168.9 (3)
C308—C305—C304—C30258.0 (3)C245—C248—C249—C25157.7 (5)
C306—C305—C304—C302179.9 (2)C245—C248—C249—C250177.5 (3)
C150—C149—C148—C145177.5 (2)C265—C268—C269—C27160.0 (5)
C151—C149—C148—C14558.7 (3)C265—C268—C269—C270174.4 (3)
C144—C145—C148—C149169.3 (2)C185—C188—C189—C19058.1 (5)
C146—C145—C148—C14968.0 (3)C185—C188—C189—C191176.3 (3)
O183—C182—C184—C18548.1 (4)C105—C108—C109—C11156.1 (5)
O181—C182—C184—C185132.1 (3)C105—C108—C109—C110177.5 (3)
C188—C185—C184—C18258.8 (3)C45—C48—C49—C5158.2 (5)
C186—C185—C184—C182178.7 (2)C45—C48—C49—C50176.6 (3)
C204—C205—C208—C209159.7 (3)C205—C208—C209—C21062.8 (6)
C206—C205—C208—C20977.7 (3)C205—C208—C209—C211173.5 (3)
(SPGHI) top
Crystal data top
C8H19NO3F(000) = 392
Mr = 177.24Dx = 1.061 Mg m3
Monoclinic, C2Mo Kα radiation, λ = 0.71073 Å
a = 9.566 (7) ÅCell parameters from 465 reflections
b = 7.440 (6) Åθ = 3–30°
c = 15.911 (12) ŵ = 0.08 mm1
β = 101.54 (3)°T = 298 K
V = 1109.5 (15) Å3Prism, colourless
Z = 40.20 × 0.05 × 0.05 mm
Data collection top
Bruker D8 Quest
diffractometer
Rint = 0.040
Absorption correction: multi-scan
sadabs
θmax = 26.6°, θmin = 2.6°
Tmin = 0.641, Tmax = 0.745h = 1111
6482 measured reflectionsk = 99
2286 independent reflectionsl = 1919
1721 reflections with I > 2σ(I)
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.059 w = 1/[σ2(Fo2) + (0.0579P)2 + 0.5616P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.141(Δ/σ)max < 0.001
S = 1.06Δρmax = 0.19 e Å3
2286 reflectionsΔρmin = 0.13 e Å3
131 parametersAbsolute structure: Flack x determined using 588 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
1 restraintAbsolute structure parameter: 0.1 (8)
Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
H12A0.811 (6)0.310 (8)0.575 (3)0.080 (16)*
H12B0.887 (6)0.449 (9)0.566 (4)0.09 (2)*
H1A0.695 (4)0.946 (7)0.636 (3)0.061 (13)*
H1B0.634 (5)0.800 (6)0.584 (3)0.052 (14)*
H1C0.782 (5)0.784 (6)0.622 (3)0.061 (13)*
O60.6844 (2)0.1902 (3)0.6378 (2)0.0577 (9)
O120.8769 (3)0.3435 (4)0.5506 (2)0.0624 (9)
O70.4526 (2)0.1752 (3)0.6269 (2)0.0669 (10)
N10.6889 (3)0.8253 (4)0.6301 (3)0.0422 (8)
C50.5647 (4)0.2604 (4)0.6324 (3)0.0455 (10)
C30.6591 (4)0.5455 (4)0.7099 (3)0.0450 (10)
H30.75640.50900.70700.054*
C20.6522 (4)0.7499 (5)0.7072 (3)0.0511 (11)
H2A0.55640.78780.71060.061*
H2B0.71700.79750.75700.061*
C40.5585 (4)0.4649 (4)0.6341 (3)0.0553 (12)
H4A0.58190.51150.58160.066*
H4B0.46180.50200.63560.066*
C80.6262 (7)0.4767 (7)0.7935 (4)0.0811 (16)
H8A0.53870.53320.80190.097*
H8B0.60800.34860.78750.097*
C90.7372 (12)0.5060 (13)0.8725 (5)0.140 (3)
H90.75160.63590.87960.169*
C100.6759 (17)0.4364 (16)0.9499 (5)0.232 (7)
H10A0.73460.47801.00240.348*
H10B0.67460.30740.94950.348*
H10C0.58050.48080.94570.348*
C110.8741 (15)0.426 (3)0.8677 (7)0.300 (14)
H11A0.86100.30140.85290.450*
H11B0.93780.43730.92230.450*
H11C0.91380.48720.82480.450*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O60.0425 (14)0.0205 (11)0.117 (3)0.0022 (11)0.0314 (15)0.0037 (14)
O120.0625 (18)0.0464 (18)0.089 (2)0.0165 (16)0.0412 (17)0.0116 (18)
O70.0427 (14)0.0233 (12)0.142 (3)0.0071 (12)0.0365 (16)0.0085 (17)
N10.0358 (15)0.0183 (13)0.074 (3)0.0036 (12)0.0145 (17)0.0022 (15)
C50.040 (2)0.0199 (15)0.080 (3)0.0059 (14)0.020 (2)0.0009 (17)
C30.049 (2)0.0212 (17)0.070 (3)0.0011 (15)0.025 (2)0.0021 (16)
C20.057 (2)0.0258 (16)0.077 (3)0.0025 (16)0.029 (2)0.0067 (18)
C40.041 (2)0.0216 (18)0.104 (4)0.0008 (14)0.016 (2)0.0047 (19)
C80.124 (4)0.045 (3)0.090 (4)0.002 (3)0.059 (4)0.004 (3)
C90.235 (10)0.123 (6)0.075 (4)0.001 (8)0.061 (6)0.011 (5)
C100.42 (2)0.200 (15)0.096 (6)0.019 (11)0.112 (10)0.039 (6)
C110.215 (12)0.56 (4)0.107 (7)0.196 (19)0.014 (8)0.009 (11)
Geometric parameters (Å, º) top
O6—C51.245 (4)C4—H4A0.9700
O12—H12A0.84 (6)C4—H4B0.9700
O12—H12B0.82 (6)C8—C91.490 (11)
O7—C51.234 (4)C8—H8A0.9700
N1—C21.455 (5)C8—H8B0.9700
N1—H1A0.90 (5)C9—C111.453 (13)
N1—H1B0.84 (5)C9—C101.556 (11)
N1—H1C0.97 (5)C9—H90.9800
C5—C41.523 (5)C10—H10A0.9600
C3—C41.509 (6)C10—H10B0.9600
C3—C81.516 (6)C10—H10C0.9600
C3—C21.522 (5)C11—H11A0.9600
C3—H30.9800C11—H11B0.9600
C2—H2A0.9700C11—H11C0.9600
C2—H2B0.9700
H12A—O12—H12B101 (5)C5—C4—H4B109.0
C2—N1—H1A109 (3)H4A—C4—H4B107.8
C2—N1—H1B116 (3)C9—C8—C3116.9 (5)
H1A—N1—H1B109 (4)C9—C8—H8A108.1
C2—N1—H1C112 (2)C3—C8—H8A108.1
H1A—N1—H1C106 (4)C9—C8—H8B108.1
H1B—N1—H1C104 (4)C3—C8—H8B108.1
O7—C5—O6124.3 (3)H8A—C8—H8B107.3
O7—C5—C4118.6 (3)C11—C9—C8113.2 (8)
O6—C5—C4117.1 (3)C11—C9—C10113.1 (10)
C4—C3—C8110.9 (4)C8—C9—C10107.5 (9)
C4—C3—C2111.0 (3)C11—C9—H9107.6
C8—C3—C2110.3 (3)C8—C9—H9107.6
C4—C3—H3108.2C10—C9—H9107.6
C8—C3—H3108.2C9—C10—H10A109.5
C2—C3—H3108.2C9—C10—H10B109.5
N1—C2—C3113.1 (3)H10A—C10—H10B109.5
N1—C2—H2A109.0C9—C10—H10C109.5
C3—C2—H2A109.0H10A—C10—H10C109.5
N1—C2—H2B109.0H10B—C10—H10C109.5
C3—C2—H2B109.0C9—C11—H11A109.5
H2A—C2—H2B107.8C9—C11—H11B109.5
C3—C4—C5113.0 (4)H11A—C11—H11B109.5
C3—C4—H4A109.0C9—C11—H11C109.5
C5—C4—H4A109.0H11A—C11—H11C109.5
C3—C4—H4B109.0H11B—C11—H11C109.5
C4—C3—C2—N159.3 (5)O6—C5—C4—C352.6 (6)
C8—C3—C2—N1177.4 (4)C4—C3—C8—C9164.8 (5)
C8—C3—C4—C558.8 (5)C2—C3—C8—C971.9 (7)
C2—C3—C4—C5178.3 (3)C3—C8—C9—C1158.1 (12)
O7—C5—C4—C3126.5 (4)C3—C8—C9—C10176.3 (7)
 

Funding information

This work was conducted within the Synthesis and Solid State Pharmaceutical Centre (SSPC) and the Bernal Institute at the University of Limerick. The following funding is acknowledged: Science Foundation Ireland (grant No. 12/RC/2275; grant No. 15/SIRG/3577).

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IUCrJ
Volume 6| Part 4| July 2019| Pages 630-634
ISSN: 2052-2525