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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

Crystal structure of the tri­ethyl­ammonium salt of 3-[(4-hy­dr­oxy-3-meth­­oxy­phen­yl)(4-hy­dr­oxy-2-oxo-2H-chromen-3-yl)meth­yl]-2-oxo-2H-chromen-4-olate

CROSSMARK_Color_square_no_text.svg

aDepartment of Chemistry, Abdul Wali Khan University Mardan, Pakistan, bDepartment of Microbiology, Abbotabad University of Science and Technology, Abbotabad, Pakistan, and cInstitut für Biochemie, Ernst-Moritz-Arndt Universität Greifswald, Felix-Hausdorff-Strasse 4, D-17487 Greifswald, Germany
*Correspondence e-mail: ikram@awkum.edu.pk, carola.schulzke@uni-greifswald.de

Edited by A. J. Lough, University of Toronto, Canada (Received 14 January 2018; accepted 23 January 2018; online 2 February 2018)

The reaction between 3,3′-[(3-meth­oxy-4-hy­droxy­phen­yl)methanedi­yl]bis­(4-hy­droxy-2H-chromen-2-one) and tri­ethyl­amine in methanol yielded the title compound tri­ethyl­ammonium 3-[(4-hy­droxy-3-meth­oxy­phen­yl)(4-hy­droxy-2-oxo-2H-chromen-3-yl)meth­yl]-2-oxo-2H-chromen-4-olate, C6H16N+·C26H17O8 or (NHEt3)+(C26H17O8), which crystallized directly from its methano­lic mother liquor. The non-deprotonated coumarol substituent shares its H atom with the deprotonated coumarolate substituent in a short negative charge-assisted hydrogen bond in which the freely refined H atom is moved from its parent O atom towards the acceptor O atom, elongating the covalent O—H bond to 1.18 (3) Å. The respective H atom can therefore be described as being shared by two alcohol O atoms, culminating in the formation of an eight-membered ring.

1. Chemical context

Requisite chemotherapeutical treatments of cancer and inhibition of bacterial activities encourage the design of drugs that can effectively target the affected cells or respective pathogens (Nolan et al., 2007[Nolan, K. A., Zhao, H., Faulder, P. F., Frenkel, A. D., Timson, D. J., Siegel, D., Ross, D., Burke, T. R. Jr, Stratford, I. J. & Bryce, R. A. (2007). J. Med. Chem. 50, 6316-6325.]; Jung & Park, 2009[Jung, J.-C. & Park, O.-S. (2009). Molecules, 14, 4790-4803.]).

4-Hy­droxy coumarine and its derivatives have been developed and exploited by various researchers in this context (Nolan et al., 2007[Nolan, K. A., Zhao, H., Faulder, P. F., Frenkel, A. D., Timson, D. J., Siegel, D., Ross, D., Burke, T. R. Jr, Stratford, I. J. & Bryce, R. A. (2007). J. Med. Chem. 50, 6316-6325.]; Tavolari et al., 2008[Tavolari, S., Bonafè, M., Marini, M., Ferreri, C., Bartolini, G., Brighenti, E., Manara, S., Tomasi, V., Laufer, S. & Guarnieri, T. (2008). Carcinogenesis, 29, 371-380.]; Jung & Park, 2009[Jung, J.-C. & Park, O.-S. (2009). Molecules, 14, 4790-4803.]; Li et al., 2015[Li, J., Sui, Y. P., Xin, J. J., Du, X. L., Li, J. T., Huo, H. R., Ma, H., Wang, W. H., Zhou, H. Y., Zhan, H. D., Wang, Z. J., Li, C., Sui, F. & Li, X. (2015). Bioorg. Med. Chem. Lett. 25, 5520-5523.]; David, 2017[David, J. T. (2017). Curr. Drug Targets, 18, 500-510.]). In biological tests with 3,3′-[(3-meth­oxy-4-hy­droxy­phen­yl)methanedi­yl]bis­(4-hy­droxy-2H-chromen-2-one), much lower than expected cytotoxic activity was found (Rehman et al., 2013[Rehman, S., Ikram, M., Baker, R. J., Zubair, M., Azad, E., Min, S., Riaz, K., Mok, K. H., Kh, & Rehman, S. U. (2013). Chem. Cent. J. 7, 68.]), which may be attributed to insufficient solubility. The hydro­phobic nature of this compound is most likely due to strong intra­molecular hydrogen bonding between the two coumarol moieties via two O—H⋯O=C inter­actions, which was confirmed for the solid state by X-ray structural analysis of this compound (Bandyopadhyay, 2015[Bandyopadhyay, D. (2015). CCDC communication, doi: 10.5517/cc1j9kq3]) and close relatives (Manolov et al., 2006[Manolov, I., Maichle-Moessmer, C. & Danchev, N. (2006). Eur. J. Med. Chem. 41, 882-890.]; Stanchev et al., 2007[Stanchev, S., Maichle-Mössmer, C. & Manolov, I. (2007). Z. Naturforsch. Teil B, 62, 737-741.]).

Hydro­phobic mol­ecules are not only ineffective inside biological fluids but they may also accumulate inside an organism. Increasing the solubility by increasing the hydro­philicity of potentially bioactive mol­ecules may be achieved by converting them into salts (Smith et al., 2009[Smith, S. M. & Gums, J. G. (2009). Expert Opin. Drug Metab. Toxicol. 5, 813-822.]). Therefore, the synthesis of readily soluble ammonium salts of dicoumarol derivatives is of considerable importance. Herein, a crystallographically characterized example (being only the fourth of its kind) is discussed with a focus on its structural aspects.

[Scheme 1]

2. Structural commentary

The mol­ecular structure of the title compound is shown in Fig. 1[link]. The deprotonation of one hy­droxy-coumarin substit­uent but not the other leads to a short intra­molecular negative charge-assisted hydrogen bond between the two hy­droxy-coumarin substituents. The formation of such intra­molecular hydrogen bonds between hy­droxy-coumarin substituents is rare though not unprecedented (Kolos et al., 2007[Kolos, N. N., Gozalishvili, L. L., Yaremenko, F. G., Shishkin, O. V., Shishkina, S. V. & Konovalova, I. S. (2007). Russ. Chem. Bull. 56, 2277-2283.]; Vijayalakshmi et al., 2001[Vijayalakshmi, L., Parthasarathi, V., Vora, V., Desai, B. & Shah, A. (2001). Acta Cryst. C57, 817-818.]; Waheed & Ahmed, 2016[Waheed, M. & Ahmed, N. (2016). Tetrahedron Lett. 57, 3785-3789.]). Recently, Bengiat and coworkers surveyed the occurrence of negative charge-assisted hydrogen bonds (–CAHB) in the Cambridge Structural Database (Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) in general (Bengiat et al., 2016a[Bengiat, R., Gil, M., Klein, A., Bogoslavsky, B., Cohen, S. & Almog, J. (2016a). Acta Cryst. E72, 399-402.]), covering 19 such compounds although excluding the report by Waheed & Ahmed (2016[Waheed, M. & Ahmed, N. (2016). Tetrahedron Lett. 57, 3785-3789.]), which was published later that year. Bengiat et al. (2016b[Bengiat, R., Gil, M., Klein, A., Bogoslavsky, B., Cohen, S., Dubnikova, F., Yardeni, G., Zilbermann, I. & Almog, J. (2016b). Dalton Trans. 45, 8734-8739.]) also discovered the shortest distance between donor and acceptor oxygen atoms of such inter­molecular inter­actions to be 2.404 (3) Å, whereas in all other examples the distance was given as at least 2.430 Å (Bengiat et al., 2016a[Bengiat, R., Gil, M., Klein, A., Bogoslavsky, B., Cohen, S. & Almog, J. (2016a). Acta Cryst. E72, 399-402.]). The metrical parameters of the intra­molecular –CAHB in the title compound are D⋯A 2.4139 (15) Å and D—H⋯A 169 (2)°. The distance of the freely refined hydrogen atom to its parent atom O3 is elong­ated to 1.18 (3) Å, while the H⋯A hydrogen-bond length to O6 is rather short at only 1.24 (3) Å. This inter­action is therefore the second shortest such –CAHB overall and the shortest intra­molecular one. In the three related deprotonated dicoumarols, the DA distances range from 2.423 Å (Waheed & Ahmed, 2016[Waheed, M. & Ahmed, N. (2016). Tetrahedron Lett. 57, 3785-3789.]) to 2.491 Å (Kolos et al., 2007[Kolos, N. N., Gozalishvili, L. L., Yaremenko, F. G., Shishkin, O. V., Shishkina, S. V. & Konovalova, I. S. (2007). Russ. Chem. Bull. 56, 2277-2283.]). Based on the short, and hence strong, intra­molecular hydrogen bond, an eight membered ring is formed (C1/C2/C10/O3/H3O/O6/C19/C11). The distances between the alcohol oxygen atoms and bound carbon atoms are 1.3005 (16) Å (O3—C10) and 1.2939 (17) Å (O6—C19); i.e. both very similar and both significantly shorter than those reported for non-deprotonated derivatives, which range from 1.331 to 1.338 Å (Stanchev et al., 2007[Stanchev, S., Maichle-Mössmer, C. & Manolov, I. (2007). Z. Naturforsch. Teil B, 62, 737-741.]). This is in accordance with both alcohol functions being deprotonated and proton­ated to a certain extent at the same time, as was also found in one related structure of a salt (Vijayalakshmi et al., 2001[Vijayalakshmi, L., Parthasarathi, V., Vora, V., Desai, B. & Shah, A. (2001). Acta Cryst. C57, 817-818.]) but not in the other two analogous structures (Kolos et al., 2007[Kolos, N. N., Gozalishvili, L. L., Yaremenko, F. G., Shishkin, O. V., Shishkina, S. V. & Konovalova, I. S. (2007). Russ. Chem. Bull. 56, 2277-2283.]; Waheed & Ahmed, 2016[Waheed, M. & Ahmed, N. (2016). Tetrahedron Lett. 57, 3785-3789.]).

[Figure 1]
Figure 1
The mol­ecular structure of tri­ethyl­ammonium 3-[(4-hy­droxy-3-meth­oxy­phen­yl)(4-hy­droxy-2-oxo-2H-chro­men-3-yl)meth­yl]-2-oxo-2H-chromen-4-olate. Displacement ellipsoids are shown at the 50% probability level.

The ammonium hydrogen atom, which was refined freely, exhibits a hydrogen bond to the carbonyl oxygen atom of the deprotonated coumarol substituent (N1—H1N⋯O4) with D⋯A = 2.7727 (19) Å and D-–H⋯A = 164.5 (18)°.

All of the C—C1—C angles around the central methine carbon atom [C11—C1—C2 = 116.48 (12), C11—C1—C20 = 114.44 (12), C2—C1—C20 = 110.79 (11)°] are slightly widened compared to the ideal tetra­hedral value. As this is most pronounced for the angle involving the two coumarin substit­uents, it is most likely based on steric strain. The bond lengths involving the two pyran oxygen atoms [O2—C3 = 1.3773 (18), O2—C4 =1.3692 (17), O5—C12 = 1.3789 (18) and O5—C13 = 1.365 (2) Å] are similar as observed previously, indicating conjugation between the six-membered rings in the two benzo­pyran systems (Alcock & Hough, 1972[Alcock, N. W. & Hough, E. (1972). Acta Cryst. B28, 1957-1960.]; Vijayalakshmi et al., 2001[Vijayalakshmi, L., Parthasarathi, V., Vora, V., Desai, B. & Shah, A. (2001). Acta Cryst. C57, 817-818.]). The planarity of the two benzo­pyran moieties (C2/C3/O2/C4–C10, and C11/C12/O5/C13–C19) support this conclusion, with the largest deviations from the planes found for C2 [0.089 (1) Å; carbon atom binding the central methine carbon C1] and for C18 [0.020 (1) Å]. The dihedral angle between these planes is 50.84 (4)° and they form angles with the phenyl ring plane of 76.24 (5) and 59.40 (5)°, respectively.

Notable differences to the neutral parent mol­ecule (Bandyopadhyay, 2015[Bandyopadhyay, D. (2015). CCDC communication, doi: 10.5517/cc1j9kq3]) comprise (i) the orientation of the hy­droxy coumarin substituents (in the neutral structure one is flipped so that the lactone and alcohol moieties face each other, whereas in the present case alcohol faces alcohol and lactone faces lactone), (ii) a contraction [1.516 (2) Å, C1—C11] and elongation [1.5277 (19) Å, C1—C2] of the methine-to-benzo­pyran-carbon-atom distances of the deprotonated and non-deprotonated substituents compared to the neutral structure (1.520 and 1.521 Å) and (iii) a higher mol­ecular symmetry including the orientation of the 4-hy­droxy-3-meth­oxy­phenyl substituent of the neutral mol­ecule compared to the anion of the title compound, emphasized by the torsion angles between the phenyl moiety and the two benzo­pyrane moieties, which are much more distinct in the anion [C2—C1—C20—C25 = 124.22 (15) and C11—C1—C20—C21 = 169.11 (13)° vs 153.28 and 163.81° in the neutral mol­ecule].

3. Supra­molecular features

The crystal packing appears to be dominated by inter­molecular hydrogen-bonding inter­actions. No parallel alignments of the aromatic systems (phenyl, benzo­pyran) in a stacking fashion are observed, i.e. ππ inter­actions are not present.

The alcohol oxygen atom of the 4-hy­droxy-3-meth­oxy­phenyl substituent (O8) bridges the adjacent cation and anion by hydrogen bonding as a classical donor [O8—H8O⋯O1(−x + [{3\over 2}], y + [{1\over 2}], −z + [{3\over 2}]); DA = 2.4139 (15) Å] and as acceptor [O8⋯H27B—C27(−x + [{3\over 2}], y + [{1\over 2}], −z + [{3\over 2}]); DA = 3.257 (2) Å] in a non-classical hydrogen bond from an amine methyl group (Table 1[link]; Fig. 2[link], top). The ammonium cations bridge adjacent anions by the intra-formula classical hydrogen bond (N1—H1N⋯O4; see above) and the non-classical donation towards O8 [C27—H27B⋯O8(−x + [{3\over 2}], y − [{1\over 2}], −z + [{3\over 2}]; D⋯A = 3.257 (2) (19) Å]. Supported by the hydrogen bond with the carbonyl oxygen atom O1 as acceptor [O1⋯H8O—O8(−x + [{3\over 2}], y − [{1\over 2}], −z + [{3\over 2}]); DA = 2.6488 (16) Å], these inter­actions form infinite flat chains with `up and down'-pointing benzo­pyrane moieties protruding along b (Fig. 2[link], bottom left). The packing diagram exhibits a zigzag pattern along b in which adjacent chains are aligned in a zipper-like fashion (Fig. 2[link], bottom right).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O3—H3O⋯O6 1.18 (3) 1.24 (3) 2.4139 (15) 169 (2)
O8—H8O⋯O1i 0.869 (19) 1.789 (19) 2.6488 (16) 170.0 (18)
C27—H27B⋯O8ii 0.99 2.31 3.257 (2) 161
N1—H1N⋯O4 0.98 (2) 1.82 (2) 2.7727 (19) 164.5 (18)
Symmetry codes: (i) [-x+{\script{3\over 2}}, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]; (ii) [-x+{\script{3\over 2}}, y-{\script{1\over 2}}, -z+{\script{3\over 2}}].
[Figure 2]
Figure 2
Hydrogen-bonding inter­actions forming infinite flat chains protruding along b viewed along c (top) and along b (bottom, left; showing the benzo­pyran moieties sticking out up and down). The crystal packing exhibiting a zigzag pattern viewed along b (bottom, right).

4. Synthesis and crystallization

3,3′-[(3-Meth­oxy-4-hy­droxy­phen­yl)methanedi­yl]bis­(4-hy­droxy-2H-chromen-2-one) was synthesized following essentially the reported procedure (Rehman et al., 2013[Rehman, S., Ikram, M., Baker, R. J., Zubair, M., Azad, E., Min, S., Riaz, K., Mok, K. H., Kh, & Rehman, S. U. (2013). Chem. Cent. J. 7, 68.]). 20 mmol of 3-meth­oxy-4-hy­droxy­benzaldehyde dissolved in anyhydrous ethanol was added to 50 mmol of an ethano­lic solution of 4-hy­droxy­coumarin. The resulting mixture was refluxed at 393 K for 3 h. Upon cooling, a solid white powder was obtained, which was washed with 10% copious ethano­lic/n-hexane solution. The subsequent deprotonation of 3,3′-[(3-meth­oxy-4-hy­droxy­phen­yl)methanedi­yl]bis­(4-hy­droxy-2H-chromen-2-one) was carried out by adding 1 mL of tri­ethyl­amine to its methano­lic solution. The resulting transparent yellowish solution was left standing overnight to grow transparent crystals of tri­ethyl­ammonium 3-[(4-hy­droxy-3-meth­oxy­phen­yl)(4-hy­droxy-2-oxo-2H-chromen-3-yl)meth­yl]-2-oxo-2H-chromen-4-olate.

5. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. The three hydrogen atoms bound to heteroatoms (N1, O3, O8) were freely refined. Carbon-bound hydrogen atoms were placed in calculated positions, and refined with a riding-model approximation: C—H = 0.95–1.00 Å with Uiso(H) = 1.5Ueq(C-methyl) and 1.2Ueq(C) for other H atoms.

Table 2
Experimental details

Crystal data
Chemical formula C6H16N+·C26H17O8
Mr 559.59
Crystal system, space group Monoclinic, C2/c
Temperature (K) 170
a, b, c (Å) 19.408 (4), 13.518 (3), 21.714 (4)
β (°) 100.16 (3)
V3) 5607 (2)
Z 8
Radiation type Mo Kα
μ (mm−1) 0.10
Crystal size (mm) 0.44 × 0.39 × 0.37
 
Data collection
Diffractometer Stoe IPDS2T
Absorption correction Numerical (X-RED32 and X-SHAPE; Stoe & Cie, 2010[Stoe & Cie (2010). X-AREA. Stoe & Cie, Darmstadt, Germany.])
Tmin, Tmax 0.784, 0.927
No. of measured, independent and observed [I > 2σ(I)] reflections 31033, 7726, 4433
Rint 0.054
(sin θ/λ)max−1) 0.695
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.044, 0.122, 0.90
No. of reflections 7726
No. of parameters 386
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.44, −0.27
Computer programs: X-AREA (Stoe & Cie, 2010[Stoe & Cie (2010). X-AREA. Stoe & Cie, Darmstadt, Germany.]), SHELXT2016 (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2016 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), XP in SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), CIFTAB (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]) and Mercury (Macrae et al., 2006[Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453-457.]).

Hydrogen-bonding inter­actions were identified and analysed using PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]) and finally calculated using the HTAB instruction in SHELXL (together with EQIV) (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]).

Supporting information


Computing details top

Data collection: X-AREA (Stoe & Cie, 2010); cell refinement: X-AREA (Stoe & Cie, 2010); data reduction: X-AREA (Stoe & Cie, 2010); program(s) used to solve structure: SHELXT2016 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2016 (Sheldrick, 2015b); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: CIFTAB (Sheldrick, 2008) and Mercury (Macrae et al., 2006).

Triethylammonium 3-[(4-hydroxy-3-methoxyphenyl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-2-oxo-2H-chromen-4-olate top
Crystal data top
C6H16N+·C26H17O8F(000) = 2368
Mr = 559.59Dx = 1.326 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.71073 Å
a = 19.408 (4) ÅCell parameters from 31667 reflections
b = 13.518 (3) Åθ = 6.3–59.2°
c = 21.714 (4) ŵ = 0.10 mm1
β = 100.16 (3)°T = 170 K
V = 5607 (2) Å3Prism, colourless
Z = 80.44 × 0.39 × 0.37 mm
Data collection top
Stoe IPDS2T
diffractometer
7726 independent reflections
Radiation source: fine-focus sealed tube4433 reflections with I > 2σ(I)
Detector resolution: 6.67 pixels mm-1Rint = 0.054
ω scansθmax = 29.6°, θmin = 3.2°
Absorption correction: numerical
(X-RED32 and X-SHAPE; Stoe & Cie, 2010)
h = 2626
Tmin = 0.784, Tmax = 0.927k = 1818
31033 measured reflectionsl = 2930
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.044H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.122 w = 1/[σ2(Fo2) + (0.0718P)2]
where P = (Fo2 + 2Fc2)/3
S = 0.90(Δ/σ)max < 0.001
7726 reflectionsΔρmax = 0.44 e Å3
386 parametersΔρmin = 0.26 e Å3
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
O10.65404 (7)0.33340 (8)0.59806 (5)0.0450 (3)
O20.71609 (6)0.37291 (7)0.52747 (5)0.0351 (2)
O30.72176 (6)0.66489 (7)0.57698 (5)0.0349 (2)
O40.54117 (6)0.42562 (8)0.68855 (5)0.0392 (3)
O50.46745 (5)0.54780 (8)0.66496 (5)0.0413 (3)
O60.61390 (6)0.72322 (8)0.60507 (5)0.0380 (3)
O70.89787 (6)0.52052 (8)0.78148 (5)0.0432 (3)
O80.88267 (5)0.69683 (8)0.82643 (5)0.0382 (3)
C10.65911 (7)0.52333 (10)0.65646 (6)0.0283 (3)
H10.6532260.4565180.6746160.034*
C20.68601 (7)0.50216 (10)0.59576 (6)0.0274 (3)
C30.68308 (8)0.40112 (10)0.57585 (6)0.0307 (3)
C40.75438 (8)0.43890 (10)0.49954 (7)0.0304 (3)
C50.79254 (9)0.40104 (12)0.45636 (7)0.0380 (3)
H50.7914020.3323820.4468890.046*
C60.83190 (9)0.46504 (12)0.42771 (7)0.0397 (4)
H60.8592560.4403270.3988850.048*
C70.83193 (9)0.56603 (12)0.44068 (7)0.0391 (4)
H70.8582780.6099930.4197850.047*
C80.79410 (8)0.60231 (11)0.48347 (7)0.0340 (3)
H80.7942090.6712880.4918810.041*
C90.75550 (7)0.53842 (10)0.51466 (6)0.0282 (3)
C100.71880 (7)0.57089 (10)0.56401 (6)0.0280 (3)
C110.58739 (7)0.57065 (11)0.64990 (6)0.0306 (3)
C120.53443 (8)0.51111 (11)0.66936 (7)0.0334 (3)
C130.45011 (8)0.64011 (12)0.64179 (7)0.0384 (4)
C140.38105 (9)0.66885 (15)0.63775 (9)0.0515 (4)
H140.3478690.6261440.6513620.062*
C150.36156 (10)0.76085 (16)0.61355 (10)0.0577 (5)
H150.3143190.7816720.6104230.069*
C160.40959 (9)0.82347 (15)0.59370 (9)0.0517 (5)
H160.3953110.8867580.5771640.062*
C170.47810 (9)0.79387 (12)0.59795 (8)0.0420 (4)
H170.5110840.8369230.5843440.050*
C180.49943 (8)0.70091 (11)0.62216 (7)0.0352 (3)
C190.57071 (7)0.66420 (11)0.62576 (7)0.0313 (3)
C200.71563 (7)0.57348 (10)0.70423 (6)0.0282 (3)
C210.77965 (8)0.52424 (10)0.72074 (7)0.0315 (3)
H210.7857840.4615180.7027250.038*
C220.83384 (7)0.56465 (11)0.76247 (6)0.0313 (3)
C230.82595 (7)0.65759 (11)0.78824 (6)0.0303 (3)
C240.76243 (8)0.70469 (11)0.77388 (7)0.0338 (3)
H240.7560160.7668840.7924460.041*
C250.70744 (8)0.66260 (11)0.73256 (7)0.0331 (3)
H250.6636620.6957910.7237760.040*
C260.90262 (10)0.41779 (13)0.76835 (9)0.0543 (5)
H26A0.8651340.3821100.7837830.081*
H26B0.9481230.3924670.7891700.081*
H26C0.8978900.4080940.7230740.081*
H3O0.6704 (13)0.6889 (17)0.5951 (11)0.085 (7)*
H8O0.8688 (10)0.7456 (14)0.8472 (9)0.047 (5)*
N10.43844 (8)0.30039 (12)0.62696 (7)0.0470 (4)
C270.44835 (9)0.20824 (14)0.66564 (9)0.0509 (5)
H27A0.4311360.2202870.7052720.061*
H27B0.4990390.1936400.6763150.061*
C280.41125 (13)0.11883 (15)0.63391 (11)0.0694 (6)
H28A0.3606060.1303540.6262760.104*
H28B0.4221800.0607440.6608760.104*
H28C0.4268850.1073450.5939940.104*
C290.46749 (11)0.28595 (16)0.56641 (9)0.0583 (5)
H29A0.5122400.2492570.5761270.070*
H29B0.4342450.2449310.5372700.070*
C300.47967 (13)0.38019 (16)0.53470 (9)0.0651 (6)
H30A0.4348590.4138190.5209660.098*
H30B0.5015850.3660450.4983110.098*
H30C0.5105890.4228270.5639150.098*
C310.36666 (10)0.34013 (16)0.61423 (10)0.0604 (5)
H31A0.3349310.2894390.5918060.072*
H31B0.3654070.3984520.5864720.072*
C320.34037 (11)0.3698 (2)0.67264 (10)0.0723 (7)
H32A0.3314480.3104480.6959040.108*
H32B0.2968770.4076090.6613280.108*
H32C0.3756350.4108130.6987840.108*
H1N0.4677 (11)0.3515 (15)0.6501 (10)0.064 (6)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0646 (8)0.0275 (5)0.0459 (6)0.0090 (5)0.0180 (6)0.0021 (5)
O20.0467 (6)0.0250 (5)0.0350 (5)0.0026 (4)0.0105 (5)0.0019 (4)
O30.0372 (6)0.0243 (5)0.0460 (6)0.0043 (4)0.0146 (5)0.0036 (4)
O40.0366 (6)0.0435 (6)0.0367 (5)0.0117 (5)0.0039 (4)0.0044 (5)
O50.0263 (5)0.0525 (7)0.0458 (6)0.0047 (5)0.0080 (5)0.0017 (5)
O60.0306 (6)0.0333 (5)0.0511 (6)0.0003 (4)0.0094 (5)0.0053 (5)
O70.0334 (6)0.0446 (6)0.0470 (6)0.0127 (5)0.0056 (5)0.0110 (5)
O80.0284 (6)0.0417 (6)0.0427 (6)0.0011 (5)0.0011 (5)0.0143 (5)
C10.0270 (7)0.0281 (7)0.0295 (7)0.0029 (5)0.0042 (5)0.0015 (5)
C20.0250 (7)0.0277 (6)0.0282 (6)0.0012 (5)0.0012 (5)0.0000 (5)
C30.0330 (8)0.0278 (7)0.0300 (7)0.0009 (6)0.0023 (6)0.0018 (5)
C40.0316 (7)0.0284 (7)0.0299 (7)0.0019 (6)0.0021 (6)0.0012 (5)
C50.0440 (9)0.0333 (8)0.0368 (8)0.0032 (7)0.0074 (7)0.0039 (6)
C60.0410 (9)0.0470 (9)0.0326 (8)0.0028 (7)0.0104 (7)0.0022 (6)
C70.0401 (9)0.0413 (9)0.0373 (8)0.0039 (7)0.0105 (7)0.0012 (6)
C80.0344 (8)0.0315 (7)0.0362 (7)0.0028 (6)0.0068 (6)0.0004 (6)
C90.0266 (7)0.0275 (6)0.0289 (7)0.0003 (5)0.0002 (5)0.0008 (5)
C100.0255 (7)0.0258 (6)0.0311 (7)0.0009 (5)0.0008 (5)0.0003 (5)
C110.0256 (7)0.0362 (7)0.0292 (7)0.0039 (6)0.0031 (5)0.0028 (6)
C120.0283 (7)0.0427 (8)0.0284 (7)0.0058 (6)0.0031 (6)0.0041 (6)
C130.0278 (8)0.0513 (9)0.0352 (8)0.0002 (7)0.0032 (6)0.0065 (7)
C140.0292 (8)0.0706 (12)0.0546 (10)0.0016 (8)0.0072 (7)0.0067 (9)
C150.0303 (9)0.0755 (13)0.0647 (12)0.0120 (9)0.0010 (8)0.0129 (10)
C160.0396 (10)0.0584 (11)0.0526 (10)0.0135 (9)0.0045 (8)0.0088 (8)
C170.0366 (9)0.0457 (9)0.0414 (8)0.0059 (7)0.0003 (7)0.0054 (7)
C180.0285 (8)0.0433 (8)0.0318 (7)0.0017 (6)0.0001 (6)0.0067 (6)
C190.0271 (7)0.0347 (7)0.0313 (7)0.0037 (6)0.0032 (6)0.0034 (6)
C200.0268 (7)0.0301 (7)0.0280 (6)0.0018 (6)0.0055 (5)0.0003 (5)
C210.0345 (8)0.0289 (7)0.0302 (7)0.0038 (6)0.0028 (6)0.0027 (5)
C220.0266 (7)0.0355 (7)0.0307 (7)0.0043 (6)0.0023 (5)0.0012 (6)
C230.0260 (7)0.0351 (7)0.0288 (7)0.0037 (6)0.0025 (5)0.0033 (6)
C240.0315 (8)0.0311 (7)0.0385 (8)0.0007 (6)0.0056 (6)0.0081 (6)
C250.0261 (7)0.0340 (7)0.0384 (8)0.0030 (6)0.0037 (6)0.0033 (6)
C260.0536 (11)0.0461 (10)0.0575 (11)0.0231 (9)0.0055 (9)0.0063 (8)
N10.0418 (8)0.0546 (8)0.0391 (7)0.0160 (7)0.0081 (6)0.0083 (6)
C270.0362 (9)0.0638 (12)0.0495 (10)0.0042 (8)0.0010 (8)0.0164 (9)
C280.0777 (15)0.0541 (12)0.0745 (14)0.0127 (11)0.0082 (12)0.0119 (10)
C290.0603 (12)0.0710 (13)0.0402 (9)0.0151 (10)0.0002 (8)0.0013 (9)
C300.0820 (15)0.0759 (14)0.0356 (9)0.0231 (12)0.0051 (9)0.0010 (9)
C310.0511 (11)0.0590 (12)0.0622 (12)0.0008 (9)0.0145 (9)0.0007 (10)
C320.0476 (12)0.1114 (19)0.0579 (12)0.0237 (12)0.0092 (10)0.0128 (12)
Geometric parameters (Å, º) top
O1—C31.2183 (17)C16—C171.376 (2)
O2—C41.3692 (17)C16—H160.9500
O2—C31.3773 (18)C17—C181.396 (2)
O3—C101.3005 (16)C17—H170.9500
O3—H3O1.18 (3)C18—C191.459 (2)
O4—C121.2275 (18)C20—C251.375 (2)
O5—C131.365 (2)C20—C211.399 (2)
O5—C121.3789 (18)C21—C221.375 (2)
O6—C191.2939 (17)C21—H210.9500
O6—H3O1.24 (3)C22—C231.395 (2)
O7—C221.3745 (17)C23—C241.374 (2)
O7—C261.424 (2)C24—C251.389 (2)
O8—C231.3634 (17)C24—H240.9500
O8—H8O0.869 (19)C25—H250.9500
C1—C111.516 (2)C26—H26A0.9800
C1—C21.5277 (19)C26—H26B0.9800
C1—C201.5287 (19)C26—H26C0.9800
C1—H11.0000N1—C311.473 (2)
C2—C101.3779 (19)N1—C271.496 (2)
C2—C31.4307 (19)N1—C291.532 (3)
C4—C91.384 (2)N1—H1N0.98 (2)
C4—C51.391 (2)C27—C281.510 (3)
C5—C61.374 (2)C27—H27A0.9900
C5—H50.9500C27—H27B0.9900
C6—C71.394 (2)C28—H28A0.9800
C6—H60.9500C28—H28B0.9800
C7—C81.372 (2)C28—H28C0.9800
C7—H70.9500C29—C301.487 (3)
C8—C91.395 (2)C29—H29A0.9900
C8—H80.9500C29—H29B0.9900
C9—C101.455 (2)C30—H30A0.9800
C11—C191.385 (2)C30—H30B0.9800
C11—C121.427 (2)C30—H30C0.9800
C13—C141.383 (2)C31—C321.503 (3)
C13—C181.385 (2)C31—H31A0.9900
C14—C151.377 (3)C31—H31B0.9900
C14—H140.9500C32—H32A0.9800
C15—C161.383 (3)C32—H32B0.9800
C15—H150.9500C32—H32C0.9800
C4—O2—C3121.30 (11)C25—C20—C21118.02 (13)
C10—O3—H3O109.5 (11)C25—C20—C1124.51 (13)
C13—O5—C12121.49 (12)C21—C20—C1117.47 (12)
C19—O6—H3O118.4 (11)C22—C21—C20121.43 (13)
C22—O7—C26116.76 (13)C22—C21—H21119.3
C23—O8—H8O108.6 (12)C20—C21—H21119.3
C11—C1—C2116.48 (12)O7—C22—C21124.85 (13)
C11—C1—C20114.44 (12)O7—C22—C23115.34 (12)
C2—C1—C20110.79 (11)C21—C22—C23119.80 (13)
C11—C1—H1104.5O8—C23—C24123.63 (13)
C2—C1—H1104.5O8—C23—C22117.41 (13)
C20—C1—H1104.5C24—C23—C22118.96 (13)
C10—C2—C3119.32 (13)C23—C24—C25120.88 (13)
C10—C2—C1124.31 (12)C23—C24—H24119.6
C3—C2—C1115.99 (12)C25—C24—H24119.6
O1—C3—O2113.83 (12)C20—C25—C24120.78 (13)
O1—C3—C2126.45 (14)C20—C25—H25119.6
O2—C3—C2119.72 (12)C24—C25—H25119.6
O2—C4—C9121.00 (13)O7—C26—H26A109.5
O2—C4—C5117.01 (12)O7—C26—H26B109.5
C9—C4—C5121.98 (14)H26A—C26—H26B109.5
C6—C5—C4118.58 (14)O7—C26—H26C109.5
C6—C5—H5120.7H26A—C26—H26C109.5
C4—C5—H5120.7H26B—C26—H26C109.5
C5—C6—C7120.38 (15)C31—N1—C27115.64 (15)
C5—C6—H6119.8C31—N1—C29111.38 (15)
C7—C6—H6119.8C27—N1—C29110.21 (15)
C8—C7—C6120.37 (15)C31—N1—H1N106.5 (12)
C8—C7—H7119.8C27—N1—H1N107.2 (12)
C6—C7—H7119.8C29—N1—H1N105.2 (12)
C7—C8—C9120.32 (14)N1—C27—C28114.01 (15)
C7—C8—H8119.8N1—C27—H27A108.8
C9—C8—H8119.8C28—C27—H27A108.8
C4—C9—C8118.30 (14)N1—C27—H27B108.8
C4—C9—C10118.59 (13)C28—C27—H27B108.8
C8—C9—C10123.06 (13)H27A—C27—H27B107.6
O3—C10—C2123.86 (13)C27—C28—H28A109.5
O3—C10—C9116.45 (12)C27—C28—H28B109.5
C2—C10—C9119.63 (12)H28A—C28—H28B109.5
C19—C11—C12119.64 (13)C27—C28—H28C109.5
C19—C11—C1124.77 (13)H28A—C28—H28C109.5
C12—C11—C1115.57 (13)H28B—C28—H28C109.5
O4—C12—O5113.87 (13)C30—C29—N1113.64 (17)
O4—C12—C11126.33 (14)C30—C29—H29A108.8
O5—C12—C11119.74 (13)N1—C29—H29A108.8
O5—C13—C14116.94 (15)C30—C29—H29B108.8
O5—C13—C18121.14 (14)N1—C29—H29B108.8
C14—C13—C18121.90 (16)H29A—C29—H29B107.7
C15—C14—C13118.40 (18)C29—C30—H30A109.5
C15—C14—H14120.8C29—C30—H30B109.5
C13—C14—H14120.8H30A—C30—H30B109.5
C14—C15—C16121.12 (17)C29—C30—H30C109.5
C14—C15—H15119.4H30A—C30—H30C109.5
C16—C15—H15119.4H30B—C30—H30C109.5
C17—C16—C15119.84 (18)N1—C31—C32112.94 (17)
C17—C16—H16120.1N1—C31—H31A109.0
C15—C16—H16120.1C32—C31—H31A109.0
C16—C17—C18120.38 (18)N1—C31—H31B109.0
C16—C17—H17119.8C32—C31—H31B109.0
C18—C17—H17119.8H31A—C31—H31B107.8
C13—C18—C17118.36 (15)C31—C32—H32A109.5
C13—C18—C19118.82 (14)C31—C32—H32B109.5
C17—C18—C19122.80 (15)H32A—C32—H32B109.5
O6—C19—C11124.88 (13)C31—C32—H32C109.5
O6—C19—C18115.97 (13)H32A—C32—H32C109.5
C11—C19—C18119.14 (13)H32B—C32—H32C109.5
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3O···O61.18 (3)1.24 (3)2.4139 (15)169 (2)
O8—H8O···O1i0.869 (19)1.789 (19)2.6488 (16)170.0 (18)
C27—H27B···O8ii0.992.313.257 (2)161
N1—H1N···O40.98 (2)1.82 (2)2.7727 (19)164.5 (18)
Symmetry codes: (i) x+3/2, y+1/2, z+3/2; (ii) x+3/2, y1/2, z+3/2.
 

Acknowledgements

CS gratefully acknowledges general financial support from the ERC (project MocoModels).

Funding information

Funding for this research was provided by: FP7 Ideas: European Research Council (grant No. 281257 to Carola Schulzke).

References

First citationAlcock, N. W. & Hough, E. (1972). Acta Cryst. B28, 1957–1960.  CSD CrossRef IUCr Journals Web of Science Google Scholar
First citationBandyopadhyay, D. (2015). CCDC communication, doi: 10.5517/cc1j9kq3  Google Scholar
First citationBengiat, R., Gil, M., Klein, A., Bogoslavsky, B., Cohen, S. & Almog, J. (2016a). Acta Cryst. E72, 399–402.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationBengiat, R., Gil, M., Klein, A., Bogoslavsky, B., Cohen, S., Dubnikova, F., Yardeni, G., Zilbermann, I. & Almog, J. (2016b). Dalton Trans. 45, 8734–8739.  Web of Science CSD CrossRef CAS PubMed Google Scholar
First citationDavid, J. T. (2017). Curr. Drug Targets, 18, 500–510.  Web of Science PubMed Google Scholar
First citationGroom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationJung, J.-C. & Park, O.-S. (2009). Molecules, 14, 4790–4803.  Web of Science CrossRef CAS Google Scholar
First citationKolos, N. N., Gozalishvili, L. L., Yaremenko, F. G., Shishkin, O. V., Shishkina, S. V. & Konovalova, I. S. (2007). Russ. Chem. Bull. 56, 2277–2283.  Web of Science CrossRef CAS Google Scholar
First citationLi, J., Sui, Y. P., Xin, J. J., Du, X. L., Li, J. T., Huo, H. R., Ma, H., Wang, W. H., Zhou, H. Y., Zhan, H. D., Wang, Z. J., Li, C., Sui, F. & Li, X. (2015). Bioorg. Med. Chem. Lett. 25, 5520–5523.  Web of Science CSD CrossRef CAS PubMed Google Scholar
First citationMacrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
First citationManolov, I., Maichle-Moessmer, C. & Danchev, N. (2006). Eur. J. Med. Chem. 41, 882–890.  Web of Science CSD CrossRef PubMed CAS Google Scholar
First citationNolan, K. A., Zhao, H., Faulder, P. F., Frenkel, A. D., Timson, D. J., Siegel, D., Ross, D., Burke, T. R. Jr, Stratford, I. J. & Bryce, R. A. (2007). J. Med. Chem. 50, 6316–6325.  Web of Science CrossRef PubMed CAS Google Scholar
First citationRehman, S., Ikram, M., Baker, R. J., Zubair, M., Azad, E., Min, S., Riaz, K., Mok, K. H., Kh, & Rehman, S. U. (2013). Chem. Cent. J. 7, 68.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSmith, S. M. & Gums, J. G. (2009). Expert Opin. Drug Metab. Toxicol. 5, 813–822.  Web of Science CrossRef PubMed CAS Google Scholar
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationStanchev, S., Maichle-Mössmer, C. & Manolov, I. (2007). Z. Naturforsch. Teil B, 62, 737–741.  CAS Google Scholar
First citationStoe & Cie (2010). X-AREA. Stoe & Cie, Darmstadt, Germany.  Google Scholar
First citationTavolari, S., Bonafè, M., Marini, M., Ferreri, C., Bartolini, G., Brighenti, E., Manara, S., Tomasi, V., Laufer, S. & Guarnieri, T. (2008). Carcinogenesis, 29, 371–380.  Web of Science CrossRef PubMed CAS Google Scholar
First citationVijayalakshmi, L., Parthasarathi, V., Vora, V., Desai, B. & Shah, A. (2001). Acta Cryst. C57, 817–818.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
First citationWaheed, M. & Ahmed, N. (2016). Tetrahedron Lett. 57, 3785–3789.  Web of Science CSD CrossRef CAS Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds