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ISSN: 2056-9890

Partial charge transfer in the salt co-crystal of L-ascorbic acid and 4,4′-bi­pyridine

a730 Natural Sciences Complex, Buffalo, 14260-3000, USA, and b771 Natural Sciences Complex, Buffalo, 14260-3000, ., USA
*Correspondence e-mail: jbb6@buffalo.edu

Edited by E. V. Boldyreva, Russian Academy of Sciences, Russia (Received 14 February 2019; accepted 18 April 2019; online 3 May 2019)

In the title 1:2 co-crystal, C10H9N2+·(C6H7.75O6·C6H7.25O6), L-ascorbic acid (LAA) and 4,4′-bi­pyridine (BPy) co-crystallize in the chiral space group P21 with two mol­ecules of LAA, and one mol­ecule of bpy in the asymmetric unit. The structure was modeled in two parts due to possible proton transfer from LAA to the corresponding side of the bpy mol­ecule having an occupancy of approximately 0.25 and part 2 with an occupancy of approximately 0.75. In this structure, LAA forms hydrogen bonds with neighboring LAA mol­ecules, forming extended sheets of LAA mol­ecules which are bridged by bpy mol­ecules. A comparison to a related and previously published co-crystal of LAA and 3-bromo-4-pyridone is presented.

1. Chemical context

L-Ascorbic acid (LAA) is an anti­oxidant and integral vitamin, vitamin C, for many biological systems (Frei et al., 1989[Frei, B., England, L. & Ames, B. N. (1989). Proc. Natl Acad. Sci. USA, 86, 6377-6381.]; Yogeswaran et al., 2007[Yogeswaran, U., Thiagarajan, S. & Chen, S. M. (2007). Anal. Biochem. 365, 122-131.]). Since humans cannot synthesize LAA naturally, vitamin C is often obtained from digesting fruits and vegetables, including citrus fruits, tomatoes and potatoes (Medicine, 2000[Medicine, I. O. (2000). Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids, p 529. Washington, DC: The National Academies Press.]; Yu et al., 2016[Yu, A., Tang, L. & Czech, J. (2016). Food Sci. 34, 503-510.]). Vitamin C is also produced through the ingestion of dietary supplements composed of LAA or many other ascorbate-containing derivatives including calcium ascorbate, de­hydro­ascorbate, and calcium threonate (Johnston et al., 1994[Johnston, C. S. & Luo, B. (1994). J. Am. Diet. Assoc. 94, 779-781.]).

[Scheme 1]

Co-crystallization, a process in which two or more mol­ecules form a crystalline single phase material generally in a stoichiometric ratio (Trask, 2007[Trask, A. V. (2007). MolPharma 301-309.]), can tailor pharmaceutically important physical properties including solubility, hygroscopicity, and, active lifetime without altering the active pharmaceutical ingredient (Rodriquez-Honedo et al., 2007[Rodriquez-Honedo, N., Nehm, S. J. & Jayasanker, A. (2007). Pharmaceutical Technology, 3rd ed., pp 615-635. London: Taylor & Francis.]; Ross et al., 2016[Ross, S. A., Lamprou, D. A. & Douroumis, D. (2016). Chem. Commun. 52, 8772-8786.]; Shan & Zaworotko, 2008[Shan, N. & Zaworotko, M. J. (2008). Drug Discovery Today, 13, 440-446.]; Thipparaboina et al., 2016[Thipparaboina, R., Kumar, D., Chavan, R. B. & Shastri, N. R. (2016). Drug Discovery Today, 21, 481-490.]). Co-crystal structures are key to identifying important structure-directing inter­actions in the solid-state (Childs et al., 2007[Childs, S. L., Stahly, G. P. & Park, A. (2007). Mol. Pharm. 4, 323-338.]). In this paper, we report the synthesis and single crystal structure determination of a salt co-crystal containing LAA and a commonly used co-former, 4,4′-bi­pyridine (BPy) (Aakeröy et al., 2015[Aakeröy, C. B., Spartz, C. L., Dembowski, S., Dwyre, S. & Desper, J. (2015). IUCrJ, 2, 498-510.], Cherukuvada et al., 2016[Cherukuvada, S., Kaur, R. & Guru Row, T. N. (2016). CrystEngComm, 18, 8528-8555.]), which is known to be a secondary building component often used as a pillaring ligand to give three-dimensionality in what would normally be stacking of two-dimensional sheets in crystalline systems (Dinesh et al., 2015[Dinesh, D., Subhadip, N. & Carolina, S. E. K. B. P. (2015). Chem. Eur. J. 21, 17422-17429.]; López-Cabrelles et al., 2015[López-Cabrelles, J., Giménez-Marqués, M., Mínguez Espallargas, G. & Coronado, E. (2015). Inorg. Chem. 54, 10490-10496.]).

2. Structural commentary

LAA and BPy co-crystallize in the chiral space group P21 with two mol­ecules of LAA, and one mol­ecule of BPy in the asymmetric unit (Fig. 1[link]). While the lattice is composed of mol­ecules in a variety of charge states (vide infra), the neutral mol­ecule abbreviations (LAA and BPy) provide a convenient method for describing the structure in terms of these fragments.

[Figure 1]
Figure 1
Asymmetric unit of the title compound, showing the numbering scheme.

The overall three-dimensional structure is formed by inter­locking sheets of LAA bridged by BPy mol­ecules. Initial attempts to refine the structure as neutral mol­ecules were not satisfactory and suggested the presence of disorder in the positions of the protons involved in inter­molecular hydrogen bonding between LAA and Bpy (H4 and H10). Fourier difference maps produced following a refinement using all atoms except the suspected disorders protons (H4, H10) revealed the presence of two peaks of electron density between the two pairs of heavy atoms involved in the hydrogen bonding (N1 and O4; N2 and O10, Fig. 2[link]). The positions of the two protons were initially modeled independently (model 1) in two parts to account for the disorder arising from proton transfer from LAA to Bpy. In this model, the occupancy of H10 and its disorder partner atom H2 refined to 0.22736 and 0.70972, respectively. The occupancy of H4 and its disorder partner atom H1 refined to 0.70972 and 0.23932, respectively. The similarity of the occupancies for the two pairs indicated that the disorder was likely correlated.

[Figure 2]
Figure 2
Fourier difference map of the LAA–BPy salt co-crystal showing two peaks of electron density between N1⋯O4 (upper) and N2⋯O10 (lower).

An additional refinement was performed in which the occupancies were constrained to be identical for the pairs of atoms (single part command for both pairs, model 2). The occupancies for model 2 were determined to be 0.73718 and 0.26282 for the pairs, similar to what was observed in model 1. The R1 values for both model 1 and model 2 were found to be 3.94%. Given the same values for R1 for both models, the model with the fewer parameters, model 2, will be reported. There has been an active debate in the community whether an organic salt due to proton transfer is considered a co-crystal (Aakeröy et al., 2007[Aakeröy, C. B., Fasulo, M. E. & Desper, J. (2007). Mol. Pharm. 4, 317-322.]; Cruz-Cabeza, 2012[Cruz-Cabeza, A. J. (2012). CrystEngComm, 14, 6362-6365.]; Wang et al., 2018[Wang, T., Stevens, J. S., Vetter, T., Whitehead, G. F. S., Vitorica-Yrezabal, I. J., Hao, H. & Cruz-Cabeza, A. J. (2018). Cryst. Growth Des. 18, 6973-6983.]). However, as we cannot rule out the presence of a non-ionized species within the lattice, we will refer to the obtained product as a salt co-crystal (Cherukuvada et al., 2016[Cherukuvada, S., Kaur, R. & Guru Row, T. N. (2016). CrystEngComm, 18, 8528-8555.]).

3. Supra­molecular features

In the structure, LAA forms hydrogen bonds with neighboring LAA mol­ecules, giving rise to extended sheets of LAA mol­ecules which are bridged by BPy mol­ecules (Table 1[link], Fig. 3[link]). The LAA–LAA inter­actions consist of O—H⋯O—H hydrogen bonds where each LAA forms a total of three hydrogen bonds with three different LAA mol­ecules, O—H⋯O=hydrogen bond where each LAA forms a hydrogen bond with one different LAA, and O—H⋯Oether where each LAA forms a hydrogen bond with one different LAA. The LAA–BPy inter­action consists of O—H⋯Npyrid­yl hydrogen bonds such that each BPy forms a hydrogen bond with two neighboring LAA mol­ecules (Fig. 4[link]). C—H⋯O inter­actions also occur.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N2—H2⋯O10i 0.86 (3) 1.74 (3) 2.5862 (14) 169 (2)
O3—H3⋯O5ii 0.817 (19) 2.531 (19) 2.8832 (13) 107.5 (15)
O3—H3⋯O6ii 0.817 (19) 1.903 (19) 2.7117 (14) 170.0 (19)
O4—H4⋯N1ii 0.93 (3) 1.64 (3) 2.5428 (14) 163 (3)
O5—H5⋯O1iii 0.85 (2) 2.00 (2) 2.8510 (13) 173 (2)
O6—H6⋯O2iv 0.83 (2) 1.84 (2) 2.6616 (14) 173 (2)
O9—H9⋯O12v 0.79 (2) 1.91 (2) 2.6902 (14) 175 (2)
O11—H11⋯O10iii 0.79 (2) 1.91 (2) 2.6663 (13) 162 (2)
O12—H12⋯O8vi 0.87 (2) 1.81 (2) 2.6683 (14) 169 (2)
C5—H5A⋯O11 1.00 (1) 2.44 (1) 3.2950 (14) 143 (1)
C12—H12B⋯O4 0.99 (1) 2.50 (1) 3.3249 (16) 141 (1)
C14—H14⋯O8vii 0.95 (1) 2.40 (1) 3.3311 (15) 166 (1)
C16—H16⋯O2 0.95 (1) 2.51 (1) 3.4513 (16) 170 (1)
C17—H17⋯O5 0.95 (1) 2.55 (1) 3.4651 (14) 163 (1)
C19—H19⋯O7vii 0.95 (1) 2.56 (1) 3.2181 (14) 127 (1)
C19—H19⋯O8vii 0.95 (1) 2.48 (1) 3.4267 (15) 174 (1)
C21—H21⋯O2 0.95 (1) 2.40 (1) 3.3418 (17) 173 (1)
C22—H22⋯O6viii 0.95 (1) 2.44 (1) 3.1860 (16) 136 (1)
Symmetry codes: (i) [-x, y+{\script{1\over 2}}, -z+1]; (ii) [-x+2, y+{\script{1\over 2}}, -z+1]; (iii) x+1, y, z; (iv) [-x+1, y-{\script{1\over 2}}, -z+1]; (v) [-x+1, y-{\script{1\over 2}}, -z]; (vi) [-x+2, y+{\script{1\over 2}}, -z]; (vii) x-1, y, z+1; (viii) [-x+1, y+{\script{1\over 2}}, -z+1].
[Figure 3]
Figure 3
Diagram illustrating the hydrogen-bonding inter­actions (dashed lines, see Table 1[link]) present in the two-dimensional sheets of LAA mol­ecules, looking down [001]; BPy inter­actions were omitted for clarity.
[Figure 4]
Figure 4
View down [100] showing the packing of the title compound.

4. Database survey

Recently the co-crystal structure of LAA and 3-bromo-4-pyridone (BrPyd) was reported (Wang et al., 2016[Wang, J.-R., Fan, X., Ding, Q. & Mei, X. (2016). J. Mol. Struct. 1119, 269-275.]). While the LAA mol­ecules in each structure contain similar inter­actions, LAA–BPy and LAA–BrPyd demonstrate important differences with regard to the three-dimensional structure because of the different binding synthons of BrPyd compared to BPy (Fig. 5[link]). In the structure of LAA–BrPyd, the carbonyl on the BrPyd hydrogen bonds with both hydroxyl groups located on the five-membered ring of LAA, whereas the carbonyl located on the five-membered ring of LAA hydrogen bonds with the pyridinium group of BrPyd. The corresponding hydrogen-bond network results in two-dimensional sheets. The three-dimensional aspect of LAA–BrPyd arises from stacking of the sheets, which are held together by hydrogen bonding of the terminal hydroxyl group of the aliphatic carbon chain with the hydroxyl group on the five-membered ring on the LAA in the adjacent sheet.

[Figure 5]
Figure 5
Diagram illustrating the hydrogen-bonding network of the previously reported structure of LAA–BPyBr (Wang et al., 2016[Wang, J.-R., Fan, X., Ding, Q. & Mei, X. (2016). J. Mol. Struct. 1119, 269-275.]).

5. Synthesis and crystallization

All chemicals were obtained commercially and used as received. Solid L-ascorbic acid (0.0450 g, 0.256 mmol) and 4,4′-bi­pyridine (0.0200 g, 0.128 mmol) were added to a 25 ml scintillation vial. To this were added approximately 12 ml of 200 proof ethanol followed by gentle heating. The loosely capped vial was then placed into a dark cabinet. Plate crystals of the title compound suitable for single crystal X-ray diffraction measurements were obtained.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. All H atoms were located in a difference-Fourier map and freely refined. As the Flack parameter is 0.4, the absolute configuration of LAA cannot be determined by the crystal structure; however, the co-crystal was synthesized using an enanti­omerically pure starting material.

Table 2
Experimental details

Crystal data
Chemical formula C10H9N2+·(C6H7.75O6·C6H7.25O6)
Mr 508.44
Crystal system, space group Monoclinic, P21
Temperature (K) 90
a, b, c (Å) 4.7724 (6), 14.4069 (17), 15.6857 (19)
β (°) 98.393 (2)
V3) 1066.9 (2)
Z 2
Radiation type Mo Kα
μ (mm−1) 0.13
Crystal size (mm) 0.2 × 0.1 × 0.02
 
Data collection
Diffractometer Bruker SMART APEXII area detector
Absorption correction Multi-scan (SADABS; Bruker, 2013[Bruker (2013). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.683, 0.747
No. of measured, independent and observed [I ≥ 2u(I)] reflections 31611, 9452, 8448
Rint 0.039
(sin θ/λ)max−1) 0.809
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.040, 0.099, 1.06
No. of reflections 9452
No. of parameters 357
No. of restraints 1
H-atom treatment All H-atom parameters refined
Δρmax, Δρmin (e Å−3) 0.47, −0.29
Absolute structure Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.])
Absolute structure parameter 0.4 (6)
Computer programs: APEX2 and SAINT (Bruker, 2013[Bruker (2013). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), olex2.refine (Bourhis et al., 2015[Bourhis, L. J., Dolomanov, O. V., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2015). Acta Cryst. A71, 59-75.]) and OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]).

Supporting information


Computing details top

Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXS (Sheldrick, 2008); program(s) used to refine structure: olex2.refine (Bourhis et al., 2015); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

L-Ascorbic acid–4,4'-bipyridine (1/1) top
Crystal data top
C10H9N2+·C6H7.75O60.25·C6H7.25O60.75F(000) = 532.3832
Mr = 508.44Dx = 1.583 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
a = 4.7724 (6) ÅCell parameters from 8756 reflections
b = 14.4069 (17) Åθ = 2.6–36.2°
c = 15.6857 (19) ŵ = 0.13 mm1
β = 98.393 (2)°T = 90 K
V = 1066.9 (2) Å3Plate, yellow
Z = 20.2 × 0.1 × 0.02 mm
Data collection top
Bruker SMART APEXII area detector
diffractometer
9452 independent reflections
Radiation source: microfocus rotating anode, Incoatec Iµs8448 reflections with I 2u(I)
Mirror optics monochromatorRint = 0.039
Detector resolution: 7.9 pixels mm-1θmax = 35.1°, θmin = 1.9°
ω and φ scansh = 77
Absorption correction: multi-scan
(SADABS; Bruker, 2013)
k = 2323
Tmin = 0.683, Tmax = 0.747l = 2525
31611 measured reflections
Refinement top
Refinement on F237 constraints
Least-squares matrix: fullAll H-atom parameters refined
R[F2 > 2σ(F2)] = 0.040 w = 1/[σ2(Fo2) + (0.0536P)2 + 0.0945P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.099(Δ/σ)max < 0.001
S = 1.06Δρmax = 0.47 e Å3
9452 reflectionsΔρmin = 0.29 e Å3
357 parametersAbsolute structure: Flack (1983)
1 restraintAbsolute structure parameter: 0.4 (6)
Special details top

Refinement. X-ray diffraction data was collected on a Bruker SMART APEX2 CCD diffractometer installed at a rotating anode source (MoKα radiation, λ=0.71073 Å), and equipped with an Oxford Cryosystems (Cryostream700) nitrogen gas-flow apparatus. The data were collected by the rotation method with a 0.5° frame-width (ω scan) and a 15 second exposure per frame. Three sets of data (360 frames in each set) were collected, nominally covering complete reciprocal space. The structure was solved in the Olex2 (Dolomanov, O. V. B. et al., 2009) crystallography program using the XS structure solution program (Sheldrick,G. M, 2008) using the Charge Flipping method and refined using the olex2.refine refinement package(Bourhis, L. J., et al., 2015) using least-squares minimization.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
O10.49355 (18)0.45455 (6)0.44984 (6)0.01210 (15)
O20.4742 (2)0.55289 (7)0.55860 (6)0.01868 (18)
O30.8313 (2)0.67789 (6)0.46065 (6)0.01575 (17)
H30.921 (4)0.6856 (13)0.5086 (12)0.014 (4)*
O40.9691 (2)0.55149 (6)0.31883 (6)0.01423 (16)
H41.069 (6)0.607 (2)0.3253 (17)0.0213 (2)*0.75 (2)
O50.98812 (19)0.35794 (6)0.47231 (5)0.01216 (15)
H51.142 (5)0.3877 (16)0.4705 (14)0.031 (6)*
O60.8176 (2)0.19330 (6)0.38768 (6)0.01444 (16)
H60.716 (5)0.1509 (15)0.4013 (13)0.026 (5)*
C10.5661 (2)0.53643 (8)0.49141 (8)0.01170 (19)
C20.7521 (2)0.58827 (7)0.44491 (7)0.01084 (18)
C30.8080 (2)0.53592 (7)0.37784 (7)0.00969 (18)
C40.6454 (2)0.44679 (7)0.37658 (7)0.00959 (17)
H4a0.5081 (2)0.44220 (7)0.32212 (7)0.0115 (2)*
C50.8294 (2)0.35942 (8)0.38832 (7)0.00976 (17)
H5a0.9613 (2)0.35849 (8)0.34430 (7)0.0117 (2)*
C60.6423 (2)0.27408 (8)0.37799 (8)0.01268 (19)
H6a0.5258 (2)0.27417 (8)0.32035 (8)0.0152 (2)*
H6b0.5135 (2)0.27418 (8)0.42206 (8)0.0152 (2)*
O70.86622 (18)0.29619 (5)0.00750 (5)0.00983 (14)
O81.02947 (19)0.17939 (6)0.06529 (6)0.01324 (16)
O90.6792 (2)0.05632 (6)0.03244 (6)0.01390 (16)
H90.558 (5)0.0416 (17)0.0046 (16)0.032 (6)*
O100.39236 (18)0.19546 (6)0.13751 (6)0.01330 (15)
H100.353 (13)0.1386 (9)0.137 (4)0.0199 (2)*0.25 (2)
O111.0111 (2)0.30023 (6)0.20099 (5)0.01293 (15)
H111.115 (4)0.2763 (15)0.1732 (13)0.026 (5)*
O120.7556 (2)0.51222 (7)0.09005 (7)0.01958 (19)
H120.845 (5)0.5638 (16)0.0855 (14)0.033 (6)*
C70.8780 (2)0.20343 (7)0.01219 (7)0.00978 (18)
C80.6981 (2)0.15146 (7)0.03486 (7)0.00985 (18)
C90.5682 (2)0.21089 (7)0.08490 (7)0.00962 (18)
C100.6682 (2)0.30805 (7)0.06851 (7)0.00877 (17)
H10a0.5036 (2)0.34608 (7)0.04143 (7)0.0105 (2)*
C110.8137 (2)0.35734 (8)0.14937 (7)0.00942 (17)
H11a0.6630 (2)0.37406 (8)0.18475 (7)0.0113 (2)*
C120.9591 (2)0.44733 (8)0.12926 (8)0.01143 (18)
H12a1.0989 (2)0.43428 (8)0.08998 (8)0.0137 (2)*
H12b1.0615 (2)0.47396 (8)0.18315 (8)0.0137 (2)*
N10.7273 (2)0.19521 (7)0.69016 (6)0.01118 (16)
H10.8437 (2)0.15248 (7)0.67582 (6)0.0134 (2)*0.25 (2)
N20.1522 (2)0.54416 (7)0.82171 (6)0.01059 (16)
H20.249 (5)0.5896 (18)0.8370 (15)0.01271 (19)*0.75 (2)
C130.5899 (2)0.18296 (8)0.75790 (8)0.01196 (19)
H130.6182 (2)0.12658 (8)0.78939 (8)0.0144 (2)*
C140.4091 (2)0.24834 (8)0.78414 (8)0.01189 (19)
H140.3166 (2)0.23705 (8)0.83281 (8)0.0143 (2)*
C150.3638 (2)0.33182 (7)0.73790 (7)0.00892 (17)
C160.5031 (2)0.34329 (8)0.66607 (7)0.01098 (19)
H160.4744 (2)0.39804 (8)0.63217 (7)0.0132 (2)*
C170.6837 (2)0.27425 (8)0.64452 (7)0.01128 (18)
H170.7792 (2)0.28315 (8)0.59609 (7)0.0135 (2)*
C180.1299 (2)0.46219 (8)0.86276 (7)0.01123 (19)
H180.2282 (2)0.45253 (8)0.91050 (7)0.0135 (2)*
C190.0339 (3)0.39174 (8)0.83650 (7)0.01045 (18)
H190.0474 (3)0.33395 (8)0.86598 (7)0.0125 (2)*
C200.1802 (2)0.40554 (7)0.76632 (7)0.00874 (17)
C210.1521 (3)0.49220 (8)0.72563 (8)0.0149 (2)
H210.2475 (3)0.50417 (8)0.67768 (8)0.0179 (3)*
C220.0134 (3)0.56029 (8)0.75481 (8)0.0146 (2)
H220.0293 (3)0.61916 (8)0.72725 (8)0.0176 (3)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0126 (4)0.0088 (3)0.0165 (4)0.0019 (3)0.0075 (3)0.0001 (3)
O20.0275 (5)0.0128 (4)0.0190 (4)0.0043 (3)0.0144 (4)0.0019 (3)
O30.0253 (4)0.0062 (3)0.0153 (4)0.0035 (3)0.0013 (3)0.0006 (3)
O40.0203 (4)0.0101 (4)0.0142 (4)0.0039 (3)0.0089 (3)0.0005 (3)
O50.0126 (3)0.0114 (3)0.0122 (3)0.0020 (3)0.0007 (3)0.0016 (3)
O60.0203 (4)0.0068 (3)0.0170 (4)0.0012 (3)0.0053 (3)0.0003 (3)
C10.0138 (5)0.0078 (4)0.0143 (5)0.0021 (4)0.0050 (4)0.0008 (4)
C20.0145 (5)0.0064 (4)0.0121 (5)0.0009 (3)0.0036 (4)0.0011 (3)
C30.0114 (4)0.0073 (4)0.0106 (4)0.0012 (3)0.0022 (3)0.0015 (3)
C40.0103 (4)0.0079 (4)0.0109 (4)0.0006 (3)0.0028 (3)0.0006 (3)
C50.0125 (4)0.0073 (4)0.0098 (4)0.0011 (3)0.0027 (3)0.0002 (3)
C60.0152 (5)0.0073 (4)0.0155 (5)0.0021 (4)0.0021 (4)0.0004 (4)
O70.0139 (3)0.0068 (3)0.0100 (3)0.0000 (3)0.0060 (3)0.0005 (3)
O80.0184 (4)0.0109 (4)0.0118 (4)0.0030 (3)0.0067 (3)0.0004 (3)
O90.0167 (4)0.0056 (3)0.0182 (4)0.0009 (3)0.0016 (3)0.0008 (3)
O100.0126 (3)0.0093 (3)0.0198 (4)0.0007 (3)0.0086 (3)0.0026 (3)
O110.0173 (4)0.0122 (3)0.0095 (3)0.0056 (3)0.0029 (3)0.0017 (3)
O120.0169 (4)0.0100 (4)0.0295 (5)0.0025 (3)0.0044 (4)0.0079 (4)
C70.0125 (4)0.0077 (4)0.0089 (4)0.0009 (3)0.0006 (3)0.0000 (3)
C80.0115 (4)0.0061 (4)0.0120 (5)0.0003 (3)0.0019 (4)0.0001 (3)
C90.0088 (4)0.0078 (4)0.0122 (4)0.0004 (3)0.0015 (3)0.0015 (3)
C100.0106 (4)0.0063 (4)0.0103 (4)0.0008 (3)0.0047 (3)0.0010 (3)
C110.0123 (4)0.0073 (4)0.0093 (4)0.0015 (3)0.0037 (3)0.0007 (3)
C120.0134 (5)0.0081 (4)0.0127 (4)0.0013 (4)0.0016 (4)0.0000 (4)
N10.0116 (4)0.0101 (4)0.0121 (4)0.0017 (3)0.0027 (3)0.0020 (3)
N20.0117 (4)0.0083 (4)0.0125 (4)0.0025 (3)0.0039 (3)0.0013 (3)
C130.0147 (5)0.0086 (4)0.0132 (5)0.0026 (4)0.0039 (4)0.0005 (4)
C140.0144 (5)0.0094 (4)0.0130 (5)0.0022 (4)0.0059 (4)0.0013 (4)
C150.0095 (4)0.0073 (4)0.0104 (4)0.0006 (3)0.0027 (3)0.0012 (3)
C160.0135 (5)0.0097 (4)0.0104 (4)0.0014 (3)0.0038 (4)0.0006 (3)
C170.0135 (4)0.0106 (4)0.0104 (4)0.0015 (4)0.0040 (3)0.0014 (4)
C180.0135 (5)0.0102 (4)0.0110 (5)0.0003 (3)0.0052 (4)0.0009 (3)
C190.0144 (5)0.0083 (4)0.0096 (4)0.0008 (3)0.0046 (4)0.0000 (3)
C200.0100 (4)0.0069 (4)0.0098 (4)0.0006 (3)0.0034 (3)0.0014 (3)
C210.0204 (5)0.0099 (5)0.0171 (5)0.0055 (4)0.0118 (4)0.0041 (4)
C220.0204 (5)0.0093 (5)0.0162 (5)0.0051 (4)0.0092 (4)0.0038 (4)
Geometric parameters (Å, º) top
O1—C11.3677 (14)C8—C91.3694 (16)
O1—C41.4494 (13)C9—C101.5130 (15)
O2—C11.2223 (15)C10—H10a1.0000
O3—H30.816 (19)C10—C111.5290 (16)
O3—C21.3579 (14)C11—H11a1.0000
O4—H40.93 (3)C11—C121.5251 (16)
O4—C31.3062 (14)C12—H12a0.9900
O5—H50.86 (2)C12—H12b0.9900
O5—C51.4207 (14)N1—H10.8800
O6—H60.83 (2)N1—C131.3394 (15)
O6—C61.4283 (15)N1—C171.3449 (15)
C1—C21.4376 (16)N2—H20.85 (3)
C2—C31.3523 (16)N2—C181.3419 (15)
C3—C41.4991 (15)N2—C221.3403 (15)
C4—H4a1.0000C13—H130.9500
C4—C51.5306 (16)C13—C141.3802 (16)
C5—H5a1.0000C14—H140.9500
C5—C61.5142 (16)C14—C151.4049 (16)
C6—H6a0.9900C15—C161.3992 (15)
C6—H6b0.9900C15—C201.4858 (14)
O7—C71.3746 (13)C16—H160.9500
O7—C101.4499 (13)C16—C171.3897 (15)
O8—C71.2296 (14)C17—H170.9500
O9—H90.79 (3)C18—H180.9500
O9—C81.3739 (13)C18—C191.3803 (16)
O10—H100.8400C19—H190.9500
O10—C91.2794 (14)C19—C201.4012 (15)
O11—H110.79 (2)C20—C211.3998 (15)
O11—C111.4134 (14)C21—H210.9500
O12—H120.86 (2)C21—C221.3789 (16)
O12—C121.4217 (15)C22—H220.9500
C7—C81.4240 (16)
C4—O1—C1108.88 (8)C11—C10—O7109.96 (9)
C2—O3—H3113.0 (13)C11—C10—C9113.89 (9)
C5—O5—H5107.8 (15)C11—C10—H10a109.35 (6)
C6—O6—H6105.8 (15)C10—C11—O11112.89 (9)
O2—C1—O1118.74 (10)H11a—C11—O11107.21 (5)
C2—C1—O1109.77 (10)H11a—C11—C10107.21 (6)
C2—C1—O2131.48 (11)C12—C11—O11109.14 (9)
C1—C2—O3125.30 (11)C12—C11—C10112.86 (9)
C3—C2—O3126.19 (10)C12—C11—H11a107.21 (6)
C3—C2—C1108.15 (10)C11—C12—O12110.23 (9)
C2—C3—O4131.22 (10)H12a—C12—O12109.61 (7)
C4—C3—O4119.67 (10)H12a—C12—C11109.61 (6)
C4—C3—C2109.11 (10)H12b—C12—O12109.61 (6)
C3—C4—O1103.96 (9)H12b—C12—C11109.61 (6)
H4a—C4—O1109.96 (6)H12b—C12—H12a108.1
H4a—C4—C3109.96 (6)C17—N1—C13118.57 (10)
C5—C4—O1108.21 (9)C22—N2—C18120.98 (10)
C5—C4—C3114.57 (9)H13—C13—N1118.44 (6)
C5—C4—H4a109.96 (6)C14—C13—N1123.12 (11)
C4—C5—O5110.05 (9)C14—C13—H13118.44 (7)
H5a—C5—O5109.63 (6)H14—C14—C13120.45 (7)
H5a—C5—C4109.63 (6)C15—C14—C13119.10 (10)
C6—C5—O5108.26 (9)C15—C14—H14120.45 (6)
C6—C5—C4109.62 (9)C16—C15—C14117.47 (10)
C6—C5—H5a109.63 (6)C20—C15—C14120.67 (9)
C5—C6—O6108.86 (9)C20—C15—C16121.84 (9)
H6a—C6—O6109.91 (6)H16—C16—C15120.14 (6)
H6a—C6—C5109.91 (6)C17—C16—C15119.73 (10)
H6b—C6—O6109.91 (6)C17—C16—H16120.14 (7)
H6b—C6—C5109.91 (6)C16—C17—N1122.00 (10)
H6b—C6—H6a108.3H17—C17—N1119.00 (6)
C10—O7—C7108.36 (8)H17—C17—C16119.00 (7)
C8—O9—H9109.1 (18)H18—C18—N2119.58 (6)
C11—O11—H11111.1 (15)C19—C18—N2120.83 (10)
C12—O12—H12106.7 (15)C19—C18—H18119.58 (7)
O8—C7—O7118.26 (10)H19—C19—C18120.03 (7)
C8—C7—O7110.31 (9)C20—C19—C18119.94 (10)
C8—C7—O8131.42 (10)C20—C19—H19120.03 (6)
C7—C8—O9123.53 (10)C19—C20—C15121.17 (9)
C9—C8—O9127.32 (10)C21—C20—C15121.48 (9)
C9—C8—C7109.03 (10)C21—C20—C19117.33 (10)
C8—C9—O10130.96 (10)H21—C21—C20119.85 (6)
C10—C9—O10121.55 (10)C22—C21—C20120.30 (11)
C10—C9—C8107.50 (9)C22—C21—H21119.85 (7)
C9—C10—O7104.79 (8)C21—C22—N2120.61 (11)
H10a—C10—O7109.35 (5)H22—C22—N2119.70 (6)
H10a—C10—C9109.35 (6)H22—C22—C21119.70 (7)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2···O10i0.86 (3)1.74 (3)2.5862 (14)169 (2)
O3—H3···O5ii0.817 (19)2.531 (19)2.8832 (13)107.5 (15)
O3—H3···O6ii0.817 (19)1.903 (19)2.7117 (14)170.0 (19)
O4—H4···N1ii0.93 (3)1.64 (3)2.5428 (14)163 (3)
O5—H5···O1iii0.85 (2)2.00 (2)2.8510 (13)173 (2)
O6—H6···O2iv0.83 (2)1.84 (2)2.6616 (14)173 (2)
O9—H9···O12v0.79 (2)1.91 (2)2.6902 (14)175 (2)
O11—H11···O10iii0.79 (2)1.91 (2)2.6663 (13)162 (2)
O12—H12···O8vi0.87 (2)1.81 (2)2.6683 (14)169 (2)
C5—H5A···O111.00 (1)2.44 (1)3.2950 (14)143 (1)
C12—H12B···O40.99 (1)2.50 (1)3.3249 (16)141 (1)
C14—H14···O8vii0.95 (1)2.40 (1)3.3311 (15)166 (1)
C16—H16···O20.95 (1)2.51 (1)3.4513 (16)170 (1)
C17—H17···O50.95 (1)2.55 (1)3.4651 (14)163 (1)
C19—H19···O7vii0.95 (1)2.56 (1)3.2181 (14)127 (1)
C19—H19···O8vii0.95 (1)2.48 (1)3.4267 (15)174 (1)
C21—H21···O20.95 (1)2.40 (1)3.3418 (17)173 (1)
C22—H22···O6viii0.95 (1)2.44 (1)3.1860 (16)136 (1)
Symmetry codes: (i) x, y+1/2, z+1; (ii) x+2, y+1/2, z+1; (iii) x+1, y, z; (iv) x+1, y1/2, z+1; (v) x+1, y1/2, z; (vi) x+2, y+1/2, z; (vii) x1, y, z+1; (viii) x+1, y+1/2, z+1.
 

Funding information

Funding for this research was provided by: National Science Foundation, Directorate for Mathematical and Physical Sciences (award No. DMR-1455039).

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