organic compounds
Ethyl 5-(4-methylphenyl)-2,4,5,7-tetraazatricyclo[6.4.0.02,6]dodeca-1(8),3,6,9,11-pentaene-3-carboxylate
aNational Center of Energy Sciences and Nuclear Techniques, Rabat, Morocco, bLaboratory of Medicinal Chemistry, Faculty of Medicine and Pharmacy, Mohammed V University Rabat, Morocco, cLaboratoire de Chimie Organique Heterocyclique URAC 21, Av. Ibn Battouta, BP 1014, Faculté des Sciences, Université Mohammed V, Rabat, Morocco, and dDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA
*Correspondence e-mail: ahmed_moussaif@yahoo.com
In the title compound, C18H16N4O2, the dihedral angle between the fused tricyclic ring system and the pendant benzene ring is 11.03 (4)°. The C—O—C—C torsion angle in the ethyl ester is 102.97 (12)°. The molecular conformation is supported by intramolecular C—H⋯N and C—H⋯O hydrogen bonds, which close S(6) and S(7) rings, respectively. Aromatic π–π stacking is observed in the crystal [shortest centroid–centroid separation = 3.5274 (7) Å].
Keywords: crystal structure; hydrogen bond; π-stacking; crystal structure.
CCDC reference: 1850161
Structure description
As a continuation of our research into benzimidazole derivatives (Moussaif et al. 2016, El Bakri et al. 2018), the title compound (Fig. 1) was prepared and characterized by single-crystal X-ray diffraction.
The fused tricyclic unit deviates slightly from planarity as indicated by the dihedral angle of 3.87 (6)° between the planes of the C1/C6/N1/C7/N4 and the C7/N2/N3/C8/N4 rings and by the dihedral angle of 2.05 (6)° between the planes of the C1/C6/N1/C7/N4 and the C1–C6 rings. The plane of the pendant C12–C17 ring is inclined to that of the C7/N2/N3/C8/N4 ring by 7.70 (5)°, which is likely due to the combination of the intramolecular C17—H17⋯N1 hydrogen bond (Table 1 and Fig. 2) and the π-stacking interactions between C7/N2/N3/C8/N4 and C12–C17 rings in inversion-related pairs of molecules [centroid–centroid separation = 3.5274 (7) Å, interplanar angle = 7.70 (5)°]. The orientation of the carboxyl group of the ester substituent is partially determined by the intramolecular C2—H2⋯O1 hydrogen bond.
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Synthesis and crystallization
6 mmol of methylmercaptobenzimidazole was dissolved in 40 ml of THF and 8.1 mmol of diphenylnitrileimine and 8.1 mmol of TEA were added. The mixture was refluxed for 24 h using a chilled condenser and CaCl2 trap to minimize water ingress. After cooling, the salts were removed by filtration and the solvent was evaporated under reduced pressure. Light-yellow blocks were obtained by recrystallization from ethanol solution.
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 1850161
https://doi.org/10.1107/S2414314618008921/hb4241sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314618008921/hb4241Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314618008921/hb4241Isup3.cml
Data collection: APEX3 (Bruker, 2016); cell
SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).C18H16N4O2 | F(000) = 672 |
Mr = 320.35 | Dx = 1.395 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
a = 9.2366 (11) Å | Cell parameters from 9939 reflections |
b = 10.2045 (12) Å | θ = 2.5–29.2° |
c = 16.1922 (18) Å | µ = 0.10 mm−1 |
β = 92.144 (2)° | T = 100 K |
V = 1525.1 (3) Å3 | Column, light yellow |
Z = 4 | 0.33 × 0.17 × 0.11 mm |
Bruker SMART APEX CCD diffractometer | 4119 independent reflections |
Radiation source: fine-focus sealed tube | 3269 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.034 |
Detector resolution: 8.3333 pixels mm-1 | θmax = 29.3°, θmin = 2.4° |
φ and ω scans | h = −12→12 |
Absorption correction: multi-scan (SADABS; Krause et al., 2015) | k = −13→14 |
Tmin = 0.88, Tmax = 0.99 | l = −22→21 |
28729 measured reflections |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.044 | Hydrogen site location: difference Fourier map |
wR(F2) = 0.126 | All H-atom parameters refined |
S = 1.10 | w = 1/[σ2(Fo2) + (0.0837P)2] where P = (Fo2 + 2Fc2)/3 |
4119 reflections | (Δ/σ)max < 0.001 |
281 parameters | Δρmax = 0.43 e Å−3 |
0 restraints | Δρmin = −0.19 e Å−3 |
Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5° in ω, colllected at φ = 0.00, 90.00 and 180.00° and 2 sets of 800 frames, each of width 0.45° in φ, collected at ω = –30.00 and 210.00°. The scan time was 20 sec/frame. |
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. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.27907 (9) | 0.03912 (8) | 0.51898 (5) | 0.0305 (2) | |
O2 | 0.22672 (9) | 0.16022 (8) | 0.40455 (5) | 0.0291 (2) | |
N1 | 0.73373 (10) | 0.31219 (9) | 0.59612 (5) | 0.0225 (2) | |
N2 | 0.59679 (9) | 0.35622 (8) | 0.46266 (5) | 0.0204 (2) | |
N3 | 0.47218 (10) | 0.30038 (8) | 0.42909 (5) | 0.0214 (2) | |
N4 | 0.53322 (10) | 0.20134 (8) | 0.54708 (5) | 0.0198 (2) | |
C1 | 0.56736 (11) | 0.14534 (10) | 0.62432 (6) | 0.0207 (2) | |
C2 | 0.50476 (12) | 0.04636 (10) | 0.66949 (6) | 0.0232 (2) | |
H2 | 0.4245 (16) | −0.0026 (14) | 0.6496 (8) | 0.033 (3)* | |
C3 | 0.56831 (12) | 0.02072 (11) | 0.74701 (7) | 0.0260 (2) | |
H3 | 0.5272 (15) | −0.0462 (12) | 0.7811 (8) | 0.029 (3)* | |
C4 | 0.68767 (12) | 0.09204 (11) | 0.77778 (7) | 0.0262 (2) | |
H4 | 0.7286 (15) | 0.0763 (13) | 0.8336 (8) | 0.031 (3)* | |
C5 | 0.75050 (12) | 0.19019 (11) | 0.73189 (7) | 0.0246 (2) | |
H5 | 0.8333 (16) | 0.2357 (12) | 0.7552 (8) | 0.035 (4)* | |
C6 | 0.69074 (11) | 0.21704 (10) | 0.65324 (6) | 0.0212 (2) | |
C7 | 0.63534 (11) | 0.29777 (10) | 0.53647 (6) | 0.0201 (2) | |
C8 | 0.43553 (12) | 0.20874 (10) | 0.48072 (6) | 0.0209 (2) | |
C9 | 0.30540 (12) | 0.12523 (10) | 0.47099 (6) | 0.0231 (2) | |
C10 | 0.09331 (13) | 0.08760 (12) | 0.38572 (8) | 0.0315 (3) | |
H10A | 0.0950 (14) | 0.0742 (12) | 0.3234 (8) | 0.029 (3)* | |
H10B | 0.1026 (15) | −0.0018 (15) | 0.4127 (8) | 0.041 (4)* | |
C11 | −0.03431 (15) | 0.16685 (15) | 0.41023 (9) | 0.0382 (3) | |
H11A | −0.0357 (17) | 0.1755 (15) | 0.4712 (10) | 0.049 (4)* | |
H11B | −0.1280 (16) | 0.1198 (14) | 0.3897 (8) | 0.041 (4)* | |
H11C | −0.0356 (17) | 0.2555 (15) | 0.3833 (9) | 0.044 (4)* | |
C12 | 0.66049 (11) | 0.46589 (9) | 0.42400 (6) | 0.0192 (2) | |
C13 | 0.58932 (11) | 0.52255 (10) | 0.35533 (6) | 0.0215 (2) | |
H13 | 0.4937 (14) | 0.4852 (12) | 0.3339 (7) | 0.027 (3)* | |
C14 | 0.65297 (12) | 0.62930 (10) | 0.31773 (6) | 0.0233 (2) | |
H14 | 0.5988 (14) | 0.6704 (13) | 0.2681 (8) | 0.034 (3)* | |
C15 | 0.78523 (12) | 0.68054 (10) | 0.34691 (6) | 0.0229 (2) | |
C16 | 0.85299 (12) | 0.62162 (11) | 0.41557 (7) | 0.0248 (2) | |
H16 | 0.9471 (16) | 0.6601 (13) | 0.4358 (9) | 0.038 (4)* | |
C17 | 0.79222 (12) | 0.51494 (11) | 0.45474 (7) | 0.0233 (2) | |
H17 | 0.8409 (14) | 0.4748 (12) | 0.5014 (8) | 0.024 (3)* | |
C18 | 0.85216 (15) | 0.79542 (12) | 0.30434 (9) | 0.0329 (3) | |
H18A | 0.881 (2) | 0.7749 (17) | 0.2454 (12) | 0.078 (6)* | |
H18B | 0.9384 (18) | 0.8226 (15) | 0.3336 (9) | 0.049 (4)* | |
H18C | 0.786 (2) | 0.870 (2) | 0.2983 (12) | 0.082 (6)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0370 (5) | 0.0272 (4) | 0.0273 (4) | −0.0104 (3) | −0.0013 (3) | 0.0036 (3) |
O2 | 0.0304 (4) | 0.0284 (4) | 0.0279 (4) | −0.0084 (3) | −0.0064 (3) | 0.0036 (3) |
N1 | 0.0221 (5) | 0.0253 (5) | 0.0199 (4) | −0.0003 (4) | −0.0001 (3) | 0.0028 (3) |
N2 | 0.0214 (4) | 0.0208 (4) | 0.0188 (4) | −0.0022 (3) | −0.0002 (3) | 0.0005 (3) |
N3 | 0.0227 (4) | 0.0208 (4) | 0.0205 (4) | −0.0029 (3) | −0.0003 (3) | −0.0018 (3) |
N4 | 0.0227 (4) | 0.0184 (4) | 0.0183 (4) | 0.0001 (3) | 0.0007 (3) | 0.0005 (3) |
C1 | 0.0231 (5) | 0.0208 (5) | 0.0185 (5) | 0.0036 (4) | 0.0016 (4) | 0.0002 (4) |
C2 | 0.0238 (5) | 0.0207 (5) | 0.0253 (5) | 0.0010 (4) | 0.0031 (4) | 0.0007 (4) |
C3 | 0.0295 (6) | 0.0242 (5) | 0.0246 (5) | 0.0033 (4) | 0.0064 (4) | 0.0051 (4) |
C4 | 0.0279 (6) | 0.0298 (6) | 0.0211 (5) | 0.0059 (4) | 0.0025 (4) | 0.0038 (4) |
C5 | 0.0225 (5) | 0.0279 (6) | 0.0233 (5) | 0.0025 (4) | 0.0010 (4) | 0.0008 (4) |
C6 | 0.0213 (5) | 0.0209 (5) | 0.0214 (5) | 0.0018 (4) | 0.0039 (4) | 0.0011 (4) |
C7 | 0.0209 (5) | 0.0205 (5) | 0.0191 (5) | 0.0003 (4) | 0.0027 (4) | −0.0001 (4) |
C8 | 0.0244 (5) | 0.0185 (5) | 0.0200 (5) | −0.0005 (4) | 0.0014 (4) | −0.0020 (4) |
C9 | 0.0263 (5) | 0.0204 (5) | 0.0226 (5) | −0.0029 (4) | 0.0010 (4) | −0.0032 (4) |
C10 | 0.0337 (6) | 0.0284 (6) | 0.0317 (6) | −0.0108 (5) | −0.0083 (5) | −0.0022 (5) |
C11 | 0.0339 (7) | 0.0448 (8) | 0.0365 (7) | −0.0162 (6) | 0.0078 (5) | −0.0090 (6) |
C12 | 0.0213 (5) | 0.0176 (5) | 0.0189 (4) | 0.0003 (4) | 0.0039 (4) | −0.0011 (4) |
C13 | 0.0226 (5) | 0.0207 (5) | 0.0211 (5) | −0.0010 (4) | 0.0018 (4) | −0.0007 (4) |
C14 | 0.0262 (5) | 0.0214 (5) | 0.0223 (5) | 0.0020 (4) | 0.0031 (4) | 0.0019 (4) |
C15 | 0.0238 (5) | 0.0188 (5) | 0.0265 (5) | 0.0008 (4) | 0.0071 (4) | −0.0009 (4) |
C16 | 0.0214 (5) | 0.0245 (5) | 0.0285 (5) | −0.0017 (4) | 0.0023 (4) | −0.0016 (4) |
C17 | 0.0231 (5) | 0.0234 (5) | 0.0232 (5) | 0.0000 (4) | −0.0001 (4) | 0.0010 (4) |
C18 | 0.0297 (6) | 0.0251 (6) | 0.0447 (7) | −0.0028 (5) | 0.0096 (5) | 0.0079 (5) |
O1—C9 | 1.2038 (13) | C8—C9 | 1.4770 (15) |
O2—C9 | 1.3246 (13) | C10—C11 | 1.4953 (19) |
O2—C10 | 1.4603 (13) | C10—H10A | 1.019 (13) |
N1—C7 | 1.3094 (13) | C10—H10B | 1.014 (15) |
N1—C6 | 1.4083 (13) | C11—H11A | 0.992 (16) |
N2—C7 | 1.3709 (12) | C11—H11B | 1.034 (15) |
N2—N3 | 1.3777 (12) | C11—H11C | 1.004 (15) |
N2—C12 | 1.4207 (13) | C12—C17 | 1.3905 (15) |
N3—C8 | 1.3072 (13) | C12—C13 | 1.3957 (14) |
N4—C7 | 1.3783 (14) | C13—C14 | 1.3891 (14) |
N4—C8 | 1.3791 (13) | C13—H13 | 1.011 (13) |
N4—C1 | 1.4002 (12) | C14—C15 | 1.3950 (15) |
C1—C2 | 1.3860 (14) | C14—H14 | 1.020 (13) |
C1—C6 | 1.4190 (14) | C15—C16 | 1.3918 (15) |
C2—C3 | 1.3905 (15) | C15—C18 | 1.5045 (15) |
C2—H2 | 0.941 (14) | C16—C17 | 1.3889 (15) |
C3—C4 | 1.3973 (17) | C16—H16 | 0.999 (14) |
C3—H3 | 0.965 (12) | C17—H17 | 0.956 (13) |
C4—C5 | 1.3872 (16) | C18—H18A | 1.021 (19) |
C4—H4 | 0.980 (14) | C18—H18B | 0.952 (17) |
C5—C6 | 1.3961 (14) | C18—H18C | 0.98 (2) |
C5—H5 | 0.960 (15) | ||
C9—O2—C10 | 117.77 (9) | O2—C10—C11 | 109.73 (10) |
C7—N1—C6 | 101.65 (9) | O2—C10—H10A | 103.4 (7) |
C7—N2—N3 | 110.48 (8) | C11—C10—H10A | 112.1 (7) |
C7—N2—C12 | 128.95 (8) | O2—C10—H10B | 108.0 (8) |
N3—N2—C12 | 120.37 (8) | C11—C10—H10B | 115.3 (8) |
C8—N3—N2 | 106.03 (8) | H10A—C10—H10B | 107.5 (11) |
C7—N4—C8 | 107.14 (8) | C10—C11—H11A | 110.6 (9) |
C7—N4—C1 | 105.68 (9) | C10—C11—H11B | 108.8 (8) |
C8—N4—C1 | 146.85 (9) | H11A—C11—H11B | 108.6 (12) |
C2—C1—N4 | 133.18 (10) | C10—C11—H11C | 111.6 (9) |
C2—C1—C6 | 123.18 (9) | H11A—C11—H11C | 110.6 (12) |
N4—C1—C6 | 103.63 (9) | H11B—C11—H11C | 106.4 (12) |
C1—C2—C3 | 116.31 (10) | C17—C12—C13 | 121.06 (9) |
C1—C2—H2 | 123.0 (8) | C17—C12—N2 | 119.81 (9) |
C3—C2—H2 | 120.7 (8) | C13—C12—N2 | 119.14 (9) |
C2—C3—C4 | 121.64 (10) | C14—C13—C12 | 118.66 (10) |
C2—C3—H3 | 119.2 (8) | C14—C13—H13 | 121.6 (7) |
C4—C3—H3 | 119.1 (8) | C12—C13—H13 | 119.7 (7) |
C5—C4—C3 | 121.70 (10) | C13—C14—C15 | 121.67 (10) |
C5—C4—H4 | 117.3 (8) | C13—C14—H14 | 117.6 (8) |
C3—C4—H4 | 121.0 (8) | C15—C14—H14 | 120.7 (8) |
C4—C5—C6 | 118.12 (10) | C16—C15—C14 | 118.07 (10) |
C4—C5—H5 | 118.8 (8) | C16—C15—C18 | 121.49 (10) |
C6—C5—H5 | 123.1 (8) | C14—C15—C18 | 120.43 (10) |
C5—C6—N1 | 128.52 (10) | C17—C16—C15 | 121.74 (10) |
C5—C6—C1 | 119.02 (10) | C17—C16—H16 | 121.4 (8) |
N1—C6—C1 | 112.43 (9) | C15—C16—H16 | 116.9 (8) |
N1—C7—N2 | 138.13 (10) | C16—C17—C12 | 118.80 (10) |
N1—C7—N4 | 116.59 (9) | C16—C17—H17 | 120.7 (8) |
N2—C7—N4 | 105.22 (9) | C12—C17—H17 | 120.5 (8) |
N3—C8—N4 | 111.10 (9) | C15—C18—H18A | 113.1 (10) |
N3—C8—C9 | 125.01 (9) | C15—C18—H18B | 110.4 (9) |
N4—C8—C9 | 123.88 (9) | H18A—C18—H18B | 106.6 (14) |
O1—C9—O2 | 127.09 (10) | C15—C18—H18C | 112.8 (12) |
O1—C9—C8 | 122.38 (10) | H18A—C18—H18C | 104.3 (15) |
O2—C9—C8 | 110.53 (9) | H18B—C18—H18C | 109.3 (14) |
C7—N2—N3—C8 | −0.56 (11) | C1—N4—C7—N2 | −177.11 (8) |
C12—N2—N3—C8 | −175.94 (8) | N2—N3—C8—N4 | −0.66 (12) |
C7—N4—C1—C2 | 179.09 (11) | N2—N3—C8—C9 | 178.15 (9) |
C8—N4—C1—C2 | 7.4 (2) | C7—N4—C8—N3 | 1.62 (12) |
C7—N4—C1—C6 | 0.22 (10) | C1—N4—C8—N3 | 173.26 (13) |
C8—N4—C1—C6 | −171.48 (14) | C7—N4—C8—C9 | −177.21 (9) |
N4—C1—C2—C3 | −177.77 (10) | C1—N4—C8—C9 | −5.6 (2) |
C6—C1—C2—C3 | 0.92 (15) | C10—O2—C9—O1 | −0.36 (17) |
C1—C2—C3—C4 | 0.69 (16) | C10—O2—C9—C8 | −179.86 (9) |
C2—C3—C4—C5 | −1.30 (17) | N3—C8—C9—O1 | 177.45 (10) |
C3—C4—C5—C6 | 0.26 (16) | N4—C8—C9—O1 | −3.88 (17) |
C4—C5—C6—N1 | 179.03 (10) | N3—C8—C9—O2 | −3.03 (15) |
C4—C5—C6—C1 | 1.28 (15) | N4—C8—C9—O2 | 175.64 (10) |
C7—N1—C6—C5 | −176.48 (11) | C9—O2—C10—C11 | 102.97 (12) |
C7—N1—C6—C1 | 1.39 (11) | C7—N2—C12—C17 | 10.61 (16) |
C2—C1—C6—C5 | −1.94 (16) | N3—N2—C12—C17 | −174.96 (9) |
N4—C1—C6—C5 | 177.08 (9) | C7—N2—C12—C13 | −169.52 (9) |
C2—C1—C6—N1 | 179.97 (9) | N3—N2—C12—C13 | 4.91 (14) |
N4—C1—C6—N1 | −1.02 (11) | C17—C12—C13—C14 | 0.22 (15) |
C6—N1—C7—N2 | 175.57 (12) | N2—C12—C13—C14 | −179.65 (9) |
C6—N1—C7—N4 | −1.28 (12) | C12—C13—C14—C15 | −0.02 (16) |
N3—N2—C7—N1 | −175.57 (12) | C13—C14—C15—C16 | −0.06 (16) |
C12—N2—C7—N1 | −0.7 (2) | C13—C14—C15—C18 | 179.39 (10) |
N3—N2—C7—N4 | 1.52 (11) | C14—C15—C16—C17 | −0.07 (16) |
C12—N2—C7—N4 | 176.39 (9) | C18—C15—C16—C17 | −179.52 (11) |
C8—N4—C7—N1 | 175.98 (9) | C15—C16—C17—C12 | 0.28 (16) |
C1—N4—C7—N1 | 0.72 (12) | C13—C12—C17—C16 | −0.35 (16) |
C8—N4—C7—N2 | −1.85 (11) | N2—C12—C17—C16 | 179.52 (9) |
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2···O1 | 0.941 (14) | 2.498 (13) | 3.1480 (14) | 126.3 (11) |
C17—H17···N1 | 0.956 (13) | 2.490 (12) | 3.1473 (14) | 125.8 (10) |
Funding information
JTM thanks Tulane University for support of the Tulane Crystallography Laboratory.
References
Brandenburg, K. & Putz, H. (2012). DIAMOND, Crystal Impact GbR, Bonn, Germany. Google Scholar
Bruker (2016). APEX3 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
El Bakri, Y., Anouar, E. H., Ramli, Y., Essassi, E. M. & Mague, J. T. (2018). J. Mol. Struct. 1152, 154–162. Web of Science CrossRef Google Scholar
Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Moussaif, A., Ramli, Y., Sebbar, N. K., Essassi, E. M. & Mague, J. T. (2016). IUCrData, 1, x161948. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
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