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

Journal logoSTRUCTURAL
CHEMISTRY
ISSN: 2053-2296

Water-mediated inter­molecular inter­actions in 1,2-O-cyclo­hexyl­­idene-myo-inositol: a qu­anti­tative analysis1

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aDiscipline of Biological Engineering, Indian Institute of Technology Gandhinagar, Palaj Campus, Gandhinagar 382 355, Gujarat, India, bDiscipline of Chemistry, Indian Institute of Technology Gandhinagar, Palaj Campus, Gandhinagar 382 355, Gujarat, India, and cInstitute for Stem Cell Biology and Regenerative Medicine (inStem), UAS–GKVK Campus, Bellary Road, Bangalore 560 065, India
*Correspondence e-mail: vijay@iitgn.ac.in

Edited by B. D. Santarsiero, University of Illinois at Chicago, USA (Received 25 February 2016; accepted 21 November 2016; online 1 January 2017)

The syntheses of new myo-inositol derivatives have received much attention due to their important biological activities. 1,2-O-Cyclo­hexyl­idene-myo-inositol is an important inter­mediate formed during the syntheses of certain myo-inositol derivatives. We report herein the crystal structure of 1,2-O-cyclo­hexyl­idene-myo-inositol dihydrate, C12H20O6·2H2O, which is an inter­mediate formed during the syntheses of myo-inositol phosphate derivatives, to demonstrate the participation of water mol­ecules and hy­droxy groups in the formation of several inter­molecular O—H⋯O inter­actions, and to determine a low-energy conformation. The title myo-inositol derivative crystallizes with two water mol­ecules in the asymmetric unit in the space group C2/c, with Z = 8. The water mol­ecules facilitate the formation of an extensive O—H⋯O hydrogen-bonding network that assists in the formation of a dense crystal packing. Furthermore, geometrical optimization and frequency analysis was carried out using density functional theory (DFT) calculations with B3LYP hybrid functionals and 6-31G(d), 6-31G(d,p) and 6-311G(d,p) basis sets. The theoretical and experimental structures were found to be very similar, with only slight deviations. The inter­molecular inter­actions were qu­anti­tatively analysed using Hirshfeld surface analysis and 2D (two-dimensional) fingerplot plots, and the total lattice energy was calculated.

1. Introduction

In recent decades, the syntheses of new myo-inositol derivatives have received much attention due to their important biological activities. Myo-inostiol mono- and polyphosphates act as important secondary messengers in transmembrane signalling and are currently being investigated as potential chemotherapeutic agents. Inositol derivatives are important in cellular signaling via protein kinases in endocytosis and exocytosis, and in the vesicular trafficking of proteins (Berridge & Irvine, 1989[Berridge, M. J. & Irvine, R. F. (1989). Nature, 341, 197-205.]; De Camilli et al., 1996[De Camilli, P., Emr, S. D., McPherson, P. S. & Novick, P. (1996). Science, 271, 1533-1539.]; Schekman & Orci, 1996[Schekman, R. & Orci, L. (1996). Science, 271, 1526-1533.]). Different myo-inositol phosphate derivatives have been reported to possess the ability to inhibit cancer growth (Baten et al., 1989[Baten, A., Ullah, A., Tomazic, V. J. & Shamsuddin, A. M. (1989). Carcinogenesis, 10, 1595-1598.]; Shamsuddin, 1995[Shamsuddin, A. M. (1995). J. Nutr. 125, 725S-732S.]; Yang & Shamsuddin, 1995[Yang, G. Y. & Shamsuddin, A. M. (1995). Anticancer Res. 15, 2479-2487.]; Vucenik & Shamsuddin, 2003[Vucenik, I. & Shamsuddin, A. M. (2003). J. Nutr. 133, 3778S-3784S.]; Chen et al., 2015[Chen, W., Deng, Z., Chen, K., Dou, D., Song, F., Li, L. & Xi, Z. (2015). Eur J. Med. Chem. 93, 172-181.]). 1,2-O-Cyclo­hexyl­idene-myo-inositol, (1), is an important inter­mediate formed during the syntheses of certain myo-inositol derivatives. We report herein the crystal structure of the dihydrate of (1), denoted (I)·2H2O, to demonstrate the participation of water mol­ecules and hy­droxy groups in the formation of several inter­molecular O—H⋯O inter­actions, and to determine a low-energy conformation.

1,2-O-Cyclo­hexyl­idene-myo-inositol was synthesized from myo-inositol by reacting it with 1,1-di­meth­oxy­cyclo­hexane in the presence of p-toluene­sulfonic acid (see Scheme 1).

[Scheme 1]

The packing of mol­ecules in the crystal structure depends on the type of bonding present between the mol­ecules (Kaftory et al., 1994[Kaftory, M., Kapon, M. & Botoshansky, M. (1994). Chem. Mater. 6, 1245-1249.]). The most prominent bonding present is O—H⋯O hydrogen bonding and these bonds are highly directional (Desiraju, 1999[Desiraju, G. R. (1999). The Weak Hydrogen Bond in Structural Chemistry and Biology. Oxford: Oxford University Press/International Union of Crystallography.]) and are consistently present in the variety of bonding inter­actions reported for organic mol­ecules. These inter­actions play a distinct role in determining the stability and existence of an assembly of mol­ecules, and can be as important as covalent bonds (Kaftory et al., 1994[Kaftory, M., Kapon, M. & Botoshansky, M. (1994). Chem. Mater. 6, 1245-1249.]). We have determined the optimized structure parameters of (1) using density functional theory (DFT) to calculate the ground-state geometries (Parr, 1989[Parr, R. R. Y. R. G. (1989). In Density Functional Theory of Atoms and Molecules. New York: Oxford Univeristy Press.]). The geometric optimization and frequency analysis was carried out using the GAUSSIAN09 software package (Frisch et al., 2009[Frisch, M. J., et al. (2009). GAUSSIAN09. Gaussian Inc., Wallingford, CT, USA. https://www.gaussian.com.]). The calculated structures are compared with the experimental structure.

The characterization and qu­anti­fication of the inter­molecular inter­actions in (1)·2H2O was carried out by Hirshfeld surface analysis and 2D (two-dimensional) fingerprint plots using the Crystal Explorer program (Spackman & Jayatilaka, 2009[Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19-32.]; Wolff et al., 2012[Wolff, S. K., Grimwood, D. J., McKinnon, J. J., Turner, M. J., Jayatilaka, D. & Spackman, M. A. (2012). Crystal Explorer. University of Western Australia.]; Spackman & McKinnon, 2002[Spackman, M. A. & McKinnon, J. J. (2002). CrystEngComm, 4, 378-392.]; McKinnon et al., 2004[McKinnon, J. J., Spackman, M. A. & Mitchell, A. S. (2004). Acta Cryst. B60, 627-668.]). The Hirshfeld surface was mapped with de, dnorm, the shape index and the curvedness, which helps to visualize the inter­molecular inter­actions and the crystal packing (González-Montiel et al., 2015[González-Montiel, S., Baca-Téllez, S., Martínez-Otero, D., Álvarez-Hernández, A. & Cruz-Borbolla, J. (2015). Mod. Chem. Appl. 3, article No. 154.]). The 2D fingerprint plots give a measurement of the different inter­molecular inter­actions (Spackman & McKinnon, 2002[Spackman, M. A. & McKinnon, J. J. (2002). CrystEngComm, 4, 378-392.]). The total lattice energy was calculated using the PIXELC program, which helps in the understanding of the crystal stability by studying the total inter­action energy as a contribution of different inter­action energies (Gavezzotti, 2011[Gavezzotti, A. (2011). New J Chem. 35, 1360-1368.]).

2. Experimental

The monoacetal derivative of myo-inositol (see Scheme 1) was synthesized by reacting myo-inositol with 1,1-di­meth­oxy­cyclo­hexane in the presence of p-toluene­sulfonic acid. All the chemicals used were purchased from Sigma–Aldrich or Alfa Aesar. The progress of the reaction was monitored using analytical thin-layer chromatography (TLC) on silica-gel plates (Silica Gel 60 F254 from Merck). Compound (1)·2H2O was characterized by an analysis of the NMR spectra, which were recorded in DMSO-d6. 1H NMR spectra were obtained on a Bruker Avance 500 (500 MHz) and 13C NMR spectra were obtained on a Bruker Avance 500 (126 MHz); chemical shifts are expressed in δ (ppm) using the solvent peak as an inter­nal standard. The multiplicity of the resonance peaks is indicated as singlet (s), doublet (d), triplet (t), quartet (q) or multiplet (m). The 13C signals were assigned with the aid of the attached proton test (APT) and the J values are in Hertz.

2.1. Synthesis and crystallization of cyclo­hexyl­idene derivatives of myo-inositol

1,2-O-Cyclo­hexyl­idene-myo-inositol, (1), was synthesized from myo-inositol by the addition of 1,1-di­meth­oxy­cyclo­hexane in the presence of p-toluene­sulfonic acid (see Scheme 1), according to a previously reported procedure with small modifications (Suzuki et al., 2002[Suzuki, T., Suzuki, S. T., Yamada, I., Koashi, Y., Yamada, K. & Chida, N. (2002). J. Org. Chem. 67, 2874-2880.]). To a solution of myo-inositol (1 g, 5.56 mmol) in di­methyl­formamide was added p-toluene­sulfonic acid (0.16 mmol). To the resulting solution, 1,1-di­meth­oxy­cyclo­hexane (2.5 ml, 16.6 mmol), prepared as described previously (Roy et al., 2009[Roy, A., Rahman, M., Das, S., Kundu, D., Kundu, S. K., Majee, A. & Hajra, A. (2009). Synth. Commun. 39, 590-595.]), was added. The reaction mixture was stirred at 373 K for 12–14 h. After completion of the reaction, as indicated by TLC analysis, the reaction mixture was cooled to room temperature and tri­ethyl­amine (772 µl, 0.54 mmol) was added. Excess 1,1-di­meth­oxy­cyclo­hexane was removed under reduced pressure. To the resultant residue, di­chloro­methane (50 ml) was added and the solution kept at 277 K for 3–4 h. The precipitate was filtered off and washed with di­chloro­methane to remove any nonpolar side products, giving 1,2-O-cyclo­hexyl­idene-myo-inositol, (1), as a white solid [yield 421 mg, 29%; m.p. 454 K, uncorrected m.p. 452–454 K (Nkambule et al., 2011[Nkambule, C. M., Kwezi, N. W., Kinfe, H. H., Nokwequ, M. G., Gammon, D. W., Oscarson, S. & Karlsson, E. (2011). Tetrahedron, 67, 618-623.]; Guthrie & Johnson, 1961[Guthrie, R. D. & Johnson, L. F. (1961). J. Chem. Soc. pp. 4166-4172.]; Jiang & Baker, 1986[Jiang, C. & Baker, D. C. (1986). J. Carbohydr. Chem. 5, 615-620.])]. 1H NMR (500 MHz, DMSO-d6): δ 5.00 (d, J = 2.7 Hz, 1H, D2O exchangeable), 4.91 (d, J = 4.9 Hz, 1H, D2O exchangeable), 4.86 (d, J = 3.1 Hz, 1H, D2O exchangeable), 4.77 (d, J = 4.1 Hz, 1H, D2O exchangeable), 4.16 (t, J = 4.7, 3.7 Hz, 2H), 3.55–3.44 (m, 2H), 3.32 (dt, J = 13.8, 8.4 Hz, 2H), 2.95–2.88 (m, 1H), 1.53–1.32 (10H); 13C NMR (126 MHz, DMSO): δ 108.99, 79.25, 76.48, 75.50, 74.64, 72.71, 70.38, 55.37, 40.48, 40.32, 40.15, 39.98, 39.82, 39.65, 39.48, 38.11, 35.40, 25.11, 24.11, 23.79.

Slow evaporation of a solution of the synthesized (1) from methanol at 277 K produced colourless block-shaped crystals suitable for single-crystal X-ray diffraction analysis.

2.2. Data collection and refinement

Single-crystal X-ray diffraction data were collected on a Bruker SMART APEXII CCD diffractometer using an Mo Kα (λ = 0.7107 Å) source at 298 K, and the intensities were measured using ω scans with a scan width of 0.3°. A total of 100 frames per set were collected in multiple settings of ϕ (ϕ = 0, 90 and 180° when the system is monoclinic, or ϕ = 0, 90, 180 and 270° when it is triclinic) and keeping a sample-to-detector distance of 6.054 cm and the detector position (2θ) fixed at −25°. Crystal data, data collection and structure refinement details are summarized in Table 1[link]. The hydroxy H atoms were fixed with O—H distances of 0.84 Å. All other H atoms were refined freely.

Table 1
Experimental details

Crystal data
Chemical formula C12H20O6·2H2O
Mr 296.31
Crystal system, space group Monoclinic, C2/c
Temperature (K) 298
a, b, c (Å) 38.459 (3), 8.6208 (7), 8.2420 (7)
β (°) 95.371 (2)
V3) 2720.6 (4)
Z 8
Radiation type Mo Kα
μ (mm−1) 0.12
Crystal size (mm) 0.45 × 0.35 × 0.35
 
Data collection
Diffractometer Bruker APEXII CCD
Absorption correction Multi-scan (SADABS; Bruker, 2008[Bruker (2008). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.935, 0.972
No. of measured, independent and observed [I > 2σ(I)] reflections 38263, 3391, 2347
Rint 0.129
(sin θ/λ)max−1) 0.668
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.055, 0.140, 1.24
No. of reflections 3391
No. of parameters 261
No. of restraints 1
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.20, −0.21
Computer programs: APEX2 (Bruker, 2009[Bruker (2009). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.]), SAINT-Plus (Bruker, 2012[Bruker (2012). SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]) in WinGX (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]), ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]), CAMERON (Watkin & Prout, 1993[Watkin, D. M. P. L. & Prout, C. K. (1993). CAMERON. Chemical Crystallography Laboratory, University of Oxford, England.]), Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]) and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

2.3. Geometry optimization and frequency analysis of (1)

To obtain the optimized structure of (1), quantum-chemical calculations were performed using Becke's three-parameter exchange function (B3) with the Lee–Yang–Parr correlation function (LYP) and three different basis sets, i.e. 6-31G(d), 6-31G(d,p) and 6-311G(d,p) (Becke, 1993[Becke, A. D. (1993). J. Chem. Phys. 98, 5648-5652.]). Geometry optimizations of (1) were carried out in the gas phase at the DFT level of theory using B3LYP without any symmetry restrictions, and all of the optimized geometries were confirmed by frequency analyses at the same level of theory as explained by Tokay et al. (2008[Tokay, N., Seferoğl, Z., Öğretir, C. & Ertan, N. (2008). ARKIVOK, 2008, 9-20.]). Geometry optimization and frequency calculations were carried out using the GAUSSIAN09 package (Frisch et al., 2009[Frisch, M. J., et al. (2009). GAUSSIAN09. Gaussian Inc., Wallingford, CT, USA. https://www.gaussian.com.]). The overlay and r.m.s. deviation calculations using the experimental and calculated structures of (1) were performed using CHEMCRAFT (https://www.chemcraftprog.com).

2.4. Inter­molecular inter­actions by Hirshfeld surface analysis and 2D fingerprint plots

The inter­molecular inter­actions in (1) were qu­anti­fied by Hirshfeld surface (HS) and fingerprint plot analysis using the Crystal Explorer software package (Wolff et al., 2012[Wolff, S. K., Grimwood, D. J., McKinnon, J. J., Turner, M. J., Jayatilaka, D. & Spackman, M. A. (2012). Crystal Explorer. University of Western Australia.]) using the CIF file directly. The Hirshfeld surfaces were mapped with dnorm, shape index and curvedness, and the distribution of electron densities and the inter­molecular inter­actions in the crystal packing were explored (Spackman & Jayatilaka, 2009[Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19-32.]). The overall inter­molecular inter­actions contributed by individual inter­actions (i.e. H⋯H, O⋯H, O⋯O and H⋯H) were estimated using 2D fingerplot plots (Spackman & McKinnon, 2002[Spackman, M. A. & McKinnon, J. J. (2002). CrystEngComm, 4, 378-392.]). Also, in order to visualize the electrostatic complementarities in the crystal packing, the electrostatic potentials were mapped onto the HS surface using the STO-3G basis set for the DFT calculations and the crystal coordinates as the input into the TONTO package (Jayatilaka et al., 2005[Jayatilaka, D., Grimwood, D. J., Lee, A., Lemay, A., Russel, A. J., Taylor, C., Wolff, S. K., Cassam-Chenai, P. & Whitton, A. (2005). TONTO. University of Western Australia.]) integrated with Crystal Explorer.

2.5. Lattice energy calculations for (1)

The lattice energy of (1) was calculated using the PIXELC module in the CLP (Coulomb–London–Pauli) package (Version 3.0 of November 2015; Gavezzotti, 2011[Gavezzotti, A. (2011). New J Chem. 35, 1360-1368.]; Elahi & Kant, 2014[Elahi, A. & Kant, R. (2014). Eur Chem Bull. 3, 619-623.]) using the atomic coordinates from the CIF file.

3. Results and discussion

3.1. Synthesis and crystal structure of cyclo­hexyl­idene derivatives of myo-inositol

The title compound, (1)·2H2O, was synthesized from myo-inositol using 1,1-di­meth­oxy­cyclo­hexane in the presence of p-toluene­sulfonic acid. 1,2-O-Cyclo­hexyl­idene-myo-inositol was formed as the major product in 29% yield. 1,2;4,5-Di-O-cyclo­hexyl­idene-myo-inositol, (2), was recovered in a very low yield of 5.5%. This may be due to the trans configuration of the hy­droxy groups present at positions 4 and 5 of the myo-inositol skeleton and difficulties in the formation of the acetal inter­mediate.

The crystal structure of (1)·2H2O shows the presence of trans hy­droxy groups at positions 4 and 5 of the myo-inositol skeleton (Fig. 1[link]), and gives complete details of the conformation of the mol­ecule. It is clearly identifiable that the hy­droxy groups (3,4,5,6-OH) of the inositol unit are in equatorial positions and atom O1 attached to the cyclo­hexyl­idene ring is in an axial position. The C4—C3—C2—O2 torsion angle of −161.70 (14)° demonstrates that the atoms are very nearly planar, whereas the C5—C6—C1—O1 torsion angle of 68.50 (18)° demonstrates that the atoms are nonplanar. Tables 1[link] and 2[link] list the relevant crystallographic data and inter­molecular inter­actions of (1) and Table 3[link] lists the torsion angles for the assignment of equatorial and axial configurations. The network of O—H⋯O inter­actions can be seen in the packing diagram (Fig. 2[link]). Here, the two water mol­ecules are involved in bifurcated inter­molecular O—H⋯O hydro­gen bonding, as shown in Fig. 3[link], which stabilizes the extended crystal packing.

Table 2
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O3—H3A⋯O8i 0.84 1.89 2.724 (2) 170
O4—H4A⋯O3i 0.84 1.91 2.754 (2) 177
O5—H5⋯O4 0.84 2.46 2.853 (2) 109
O5—H5⋯O7ii 0.84 1.98 2.776 (2) 158
O6—H6A⋯O8iii 0.84 2.30 2.914 (2) 130
O7—H7A⋯O4iv 0.843 (18) 1.944 (18) 2.779 (2) 171 (3)
O8—H8C⋯O6v 0.76 (3) 2.31 (3) 2.914 (2) 137 (3)
O8—H8D⋯O2 0.91 (3) 2.08 (3) 2.950 (3) 161 (3)
Symmetry codes: (i) [x, -y+1, z+{\script{1\over 2}}]; (ii) [-x, y, -z+{\script{3\over 2}}]; (iii) [x, -y, z+{\script{1\over 2}}]; (iv) [x, -y+1, z-{\script{1\over 2}}]; (v) [x, -y, z-{\script{1\over 2}}].

Table 3
Selected torsion angles (°)

C7—O1—C1—C2 −43.11 (16) C2—C3—C4—C5 55.05 (18)
C7—O1—C1—C6 −166.48 (14) C2—C3—C4—O4 177.68 (14)
C1—O1—C7—C12 −91.05 (17) O3—C3—C4—O4 −60.68 (17)
C1—O1—C7—O2 26.96 (16) O3—C3—C4—C5 176.70 (13)
C1—O1—C7—C8 144.73 (16) O4—C4—C5—O5 60.37 (18)
C2—O2—C7—C12 120.33 (16) C3—C4—C5—C6 −56.44 (19)
C7—O2—C2—C1 −26.72 (16) O4—C4—C5—C6 179.93 (15)
C7—O2—C2—C3 93.59 (15) C3—C4—C5—O5 −176.00 (13)
C2—O2—C7—O1 0.95 (17) C4—C5—C6—C1 51.3 (2)
C2—O2—C7—C8 −116.94 (16) O5—C5—C6—O6 −65.51 (18)
C6—C1—C2—C3 44.6 (2) O5—C5—C6—C1 173.16 (14)
C6—C1—C2—O2 162.97 (14) C4—C5—C6—O6 172.60 (15)
C2—C1—C6—O6 −169.97 (14) O1—C7—C8—C9 178.85 (17)
O1—C1—C6—O6 −55.56 (18) O2—C7—C8—C9 −65.9 (2)
O1—C1—C6—C5 68.50 (18) C12—C7—C8—C9 55.1 (2)
O1—C1—C2—O2 42.40 (15) O1—C7—C12—C11 −177.88 (17)
C2—C1—C6—C5 −45.9 (2) O2—C7—C12—C11 66.3 (2)
O1—C1—C2—C3 −75.94 (18) C8—C7—C12—C11 −54.9 (2)
O2—C2—C3—O3 77.97 (18) C7—C8—C9—C10 −55.7 (3)
C1—C2—C3—O3 −169.16 (15) C8—C9—C10—C11 56.1 (3)
C1—C2—C3—C4 −48.8 (2) C9—C10—C11—C12 −55.1 (3)
O2—C2—C3—C4 −161.70 (14) C10—C11—C12—C7 54.5 (3)
[Figure 1]
Figure 1
A view of the title compound, (1)·2H2O, showing the atom-numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 50% probability level. Note that the second H atom on water atom O7 was not located and has not been included in the picture or the refinement model.
[Figure 2]
Figure 2
The network of inter­molecular hydrogen bonding in myo-inositol derivative (1)·2H2O.
[Figure 3]
Figure 3
Inter­actions driven specifically by the water mol­ecules with myo-inositol derivative (1)·2H2O. Generic atom labels without symmetry codes have been used.

The structure determination of (1) allows for the analysis of conformational features of both the equatorial and axial configurations in the hydrated form of (1). This provides useful insights into the design aspects of anti­cancer agents.

3.2. Cambridge Structural Database (CSD) analysis

A CSD (Version 5.36, update of November 2014, and Web CSD Version 5.36, update of February 2015; Groom & Allen, 2014[Groom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. Engl. 53, 662-671.]; Allen, 2002[Allen, F. H. (2002). Acta Cryst. B58, 380-388.]; Allen & Motherwell, 2002[Allen, F. H. & Motherwell, W. D. S. (2002). Acta Cryst. B58, 407-422.]) search for the myo-inositol framework yielded ten substructures highlighting the inositol moiety. It is very inter­esting to see that most substructures, i.e. nine, are found in the anhydrous form; the remaining structure is myo-inositol-1,2-camphor acetal trihydrate (Gainsford et al., 2007[Gainsford, G. J., Baars, S. M. & Falshaw, A. (2007). Acta Cryst. C63, o169-o172.]). The CSD similar-structure search for (1) gave 1320 hits with a minimum similarity coefficient (MSC) cut-off of 0.7. These included 47 structures having the inositol scaffold with an MSC cut-off of 0.974 to 0.900, and 893 similar structures with an MSC cut-off of 0.897 to 0.80, followed by 378 structures with an MSC cut-off of 0.798 to 0.70. The MSC lies between 0 and 1, and a value near 1 suggests a similar structure based on the structural features, e.g. bond lengths, bond angles, torsion angles, atom types and crystallographic information.

3.3. Comparison of the single-crystal X-ray diffraction (XRD) and GAUSSIAN09-optimized structures

To compare the experimental structure of (1) with the minimized structure, we performed a geometry optimization and frequency analysis with B3LYP functionals and three different basis sets, namely 6-31G(d), 6-31G(d,p) and 6-311G(d,p), using GAUSSIAN09 (Frisch et al., 2009[Frisch, M. J., et al. (2009). GAUSSIAN09. Gaussian Inc., Wallingford, CT, USA. https://www.gaussian.com.]). A visual comparison of the experimental structure with the calculated structure of (1) is shown in Fig. 4[link]. All three calculations gave minimized structures with low r.m.s. deviations in the range 0.280–0.285, suggesting high similarities between the experimental and calculated structures of (1). The slight variation between the experimental and calculated structures could be due to hydrogen-bonding inter­actions, which are present in the crystal structure, as well as to the difference in the form of the mol­ecule (experimental structure: crystalline state; theoretical structure: gas phase). A qu­anti­tative comparison between the experimental and calculated optimized geometrical parameters for selected bond lengths, bond angles and torsion angles is given in Tables 4[link], 5[link] and 6[link]. This also indicates the close agreement between the combinations of B3LYP functionals with 6-31G(d), 6-31G(d,p) and 6-311G(d,p) basis-set calculations and the X-ray crystallographic structure.

Table 4
Comparison of selected experimental and calculated bond lengths (Å) for (1)

Functional/Basis set O4—C4 C4—C3 O3—C3 C3—C2 C2—O2 O2—C7 C7—C8 C8—C9
B3LYP 6–31G(d) 1.4297 1.5217 1.4246 1.5296 1.4433 1.4621 1.5157 1.5267
B3LYP 6–31G(d,p) 1.4297 1.5217 1.4246 1.5296 1.4433 1.4621 1.5157 1.5267
B3LYP 6–311G(d,p) 1.4297 1.5217 1.4246 1.5296 1.4433 1.4621 1.5157 1.5267
SCXRD 1.425 1.523 1.426 1.529 1.442 1.463 1.517 1.529

Table 5
Comparison of selected experimental and calculated bond angles (°) for (1)

Functional/Basis set C5—O4—C4 O4—C4—C3 C4—C3—O3 O3—C3—C2 C3—C2—O2 C2—O2—C7 O2—C7—C8 C7—C8—C9
B3LYP 6–31G(d) 109.5531 111.326 108.0938 110.2346 110.5034 107.1887 109.5274 110.6744
B3LYP 6–31G(d,p) 109.5531 111.326 108.0938 110.2346 110.5034 107.1887 109.5274 110.6744
B3LYP 6–311G(d,p) 109.5531 111.326 108.0938 110.2346 110.5034 107.1887 109.5274 110.6744
SCXRD 109.63 111.39 108.00 110.2 110.49 107.27 109.48 110.60

Table 6
Comparison of selected experimental and calculated torsion angles (°) for (1)

Functional/Basis set O5—C5—C4—O4 O4—C4—C3—O3 O3—C3—C2—O2 C2—O2—C7—C8 O2—C7—C8—C9 C7—C8—C9—C10
B3LYP 6–31G(d) 60.40 −60.7377 78.0022 −117.1225 −65.6377 −55.7909
B3LYP 6–31G(d,p) 60.40 −60.7377 78.0022 −117.1225 −65.6377 −55.7909
B3LYP 6–311G(d,p) 60.40 −60.7377 78.0022 −117.1225 −65.6377 −55.7909
SCXRD 60.37 −60.68 77.97 −116.94 −65.9 −55.7
[Figure 4]
Figure 4
Structures of (1) overlayed using CHEMCRAFT (https://www.chemcraftprog.com): (a) B3LYP/6-31G(d) (r.m.s. deviation 0.2847); (b) B3LYP/6-31G(d,p) (r.m.s. deviation 0.2839); (c) B3LYP/6-311G(d,p) (r.m.s. deviation 0.2804).

3.4. Hirshfeld surface analysis

To visualize the inter­molecular inter­actions in (1), the Hirshfeld surface (HS) was mapped with dnorm, curvedness and shape index (Fig. 5[link]). In the HS with the dform (Fig. 5[link]a), the white surface indicates contacts with distances equal to the sum of the van der Waals (vdW) radii, and the red and blue colours indicate distances shorter (in close contact) or longer (distant contact) than the vdW radii, respectively (Venkatesan et al., 2016[Venkatesan, P., Thamotharan, S., Ilangovan, A., Liang, H. & Sundius, T. (2016). Spectrochim. Acta Part A, 153, 625-636.]). Fig. 5[link](b) demonstrates the curvature of the surface, with flat surfaces in green and curved regions in blue, and is useful for depicting favourable stacking of the mol­ecule in the crystal (Soman et al., 2014[Soman, R., Sujatha, S. & Arunkumar, C. (2014). J. Fluorine Chem. 163, 16-22.]). The shape index on the HS is a tool to visualize the ππ stacking by the presence of adjacent red and blue triangles; Fig. 5[link](c) clearly suggests that there are no ππ stacking inter­actions in (1), since there are no adjacent red and blue triangles (Seth et al., 2011[Seth, S. K., Maity, G. C. & Kar, T. (2011). J. Mol. Struct. 1000, 120-126.]).

[Figure 5]
Figure 5
The Hirshfeld surfaces of (1) mapped with (a) dnorm, (b) curvature and (c) shape index.

Most of the inter­molecular inter­actions (Figs. 6[link]–8[link][link]) are of the H⋯H (57.6%) and O⋯H (39.6%) types, with a few of the O⋯O type (2.8%). The large number of H⋯H and O⋯H inter­actions suggests that vdW inter­actions and hydrogen bonding play the major roles in the crystal packing (Hathwar et al., 2015[Hathwar, V. R., Sist, M., Jørgensen, M. R. V., Mamakhel, A. H., Wang, X., Hoffmann, C. M., Sugimoto, K., Overgaard, J. & Iversen, B. B. (2015). IUCrJ, 2, 563-574.]). The electrostatic complementarity of (1) is shown in Fig. 9[link]. The blue region indicates the positive electrostatic potential (hydrogen-bond donor), while the red region indicates the negative electrostatic potential (hydrogen-bond acceptors) (Spackman et al., 2008[Spackman, M. A., McKinnon, J. J. & Jayatilaka, D. (2008). CrystEngComm, 10, 377-388.]).

[Figure 6]
Figure 6
The contribution of different kinds of inter­molecular inter­actions contributing to the total inter­action energy in (1). 2D fingerprint plots of (1), with di and de ranging from 1.0 to 2.8 Å are shown for (a) H⋯H, (b) O⋯H and (c) O⋯O, and Hirshfeld surface representations with the function dnorm plotted onto the surface are shown for (d) H⋯H, (e) O⋯H and (f) O⋯O.
[Figure 7]
Figure 7
The percentages of the various types of inter­molecular inter­actions in (1).
[Figure 8]
Figure 8
The important inter­molecular O—H⋯O inter­actions in (1) via Hirshfeld surfaces.
[Figure 9]
Figure 9
The electrostatic potentials mapped on Hirshfeld surfaces for mol­ecules in (1). The blue region corresponds to positive electrostatic potential and the red region corresponds to negative electrostatic potential.

3.5. Lattice-energy calculations using the PIXELC module

Using the PIXELC software package, the total lattice energy has been calculated for (1) and denotes the different types of energy inter­actions, such as Coulombic, polarization, dispersion or repulsion components, as shown in Table 7[link]. Dispersion plays a major role in the crystal packing, with a substantial contribution from polarization.

Table 7
Lattice energy from CLP (in kcal mol−1) for (1)

Compound Ecol EPol EDisp ERep ETot
(1) −28.9 −59.6 −106.3 46.7 −151.6

4. Conclusion

In the present study, we have reported on the synthesis of 1,2-O-cyclo­hexyl­idene-myo-inositol, (1), with two water mol­ecules in the crystal structure. It is confirmed that the hy­droxy groups at positions 4 and 5 are in a trans configuration, and a rationale is suggested for the difficulties in synthesizing 1,2;4,5-di-O-cyclo­hexyl­idene-myo-inositol. The structure determination of (1) revealed the conformational features (equatorial and axial configuration) in the hydrated form of the compound. We also carried out geometry optimizations and frequency analysis of (1) using the GAUSSIAN09 package with B3LYP functionals and three different basis sets. These calculated structures were found to be very similar to that of the experimental structure. To study the inter­molecular inter­actions in the crystal packing, we calculated the Hirshfeld surface analysis with fingerprint plots, and demonstrated that the O—H⋯O inter­actions are the major inter­molecular inter­actions. Lattice-energy calculations suggested that dispersion is the major contributor to the crystal packing. These insights into the details of the inter­molecular inter­actions and crystal packing will aid in the design and synthesis of new potential anti­cancer derivatives of myo-inositol.

Supporting information


Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: APEX2 (Bruker, 2009); data reduction: SAINT-Plus (Bruker, 2012); program(s) used to solve structure: SHELXL97 (Sheldrick, 2008) in WinGX (Farrugia, 2012); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008) in WinGX (Farrugia, 2012); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012), CAMERON (Watkin & Prout, 1993) and Mercury (Macrae et al., 2008); software used to prepare material for publication: PLATON (Spek, 2009).

1,2-O-Cyclohexylidene-myo-inositol dihydrate top
Crystal data top
C12H20O6·2H2OF(000) = 1272
Mr = 296.31Dx = 1.447 Mg m3
Monoclinic, C2/cMelting point: 454 K
Hall symbol: -C 2ycMo Kα radiation, λ = 0.71073 Å
a = 38.459 (3) ÅCell parameters from 8730 reflections
b = 8.6208 (7) Åθ = 2.4–26.1°
c = 8.2420 (7) ŵ = 0.12 mm1
β = 95.371 (2)°T = 298 K
V = 2720.6 (4) Å3Block, white
Z = 80.45 × 0.35 × 0.35 mm
Data collection top
Bruker APEXII CCD
diffractometer
2347 reflections with I > 2σ(I)
Radiation source: fine-focus sealed X-ray tubeRint = 0.129
φ and ω scansθmax = 28.3°, θmin = 2.1°
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
h = 5151
Tmin = 0.935, Tmax = 0.972k = 1111
38263 measured reflectionsl = 1110
3391 independent reflections
Refinement top
Refinement on F21 restraint
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.055H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.140 w = 1/[σ2(Fo2) + (0.0598P)2 + 0.8204P]
where P = (Fo2 + 2Fc2)/3
S = 1.24(Δ/σ)max < 0.001
3391 reflectionsΔρmax = 0.20 e Å3
261 parametersΔρmin = 0.21 e Å3
Special details top

Experimental. The data was collected with the Bruker cryosystem a low-temperature attachment.

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell esds are taken into account in the estimation of distances, angles and torsion angles

Refinement. Reflections were merged by SHELXL according to the crystal class for the calculation of statistics and refinement.

_reflns_Friedel_fraction is defined as the number of unique Friedel pairs measured divided by the number that would be possible theoretically, ignoring centric projections and systematic absences.

Various restraints, for example riding model, were used on the hydrogen atoms. All hydrogen atom evident from the difference maps. There appears to be disorder among the hydrogen atoms on atoms O5, O6, and the two water molecules O7 and O8. Successive trials with placement and refinement of hydrogen atoms resulted in the model deposited, with only one short H···H contact distance.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.13181 (3)0.11890 (16)0.82458 (16)0.0139 (4)
O20.14165 (3)0.32282 (16)0.65515 (16)0.0138 (4)
O30.08365 (4)0.55158 (15)0.70889 (16)0.0160 (4)
O40.03829 (4)0.43349 (16)0.93025 (16)0.0144 (4)
O50.02128 (3)0.11220 (16)0.89709 (17)0.0170 (4)
O60.07640 (4)0.08649 (15)0.81162 (17)0.0157 (4)
C10.10407 (5)0.1245 (2)0.6947 (2)0.0120 (6)
C20.10464 (5)0.2942 (2)0.6505 (2)0.0121 (6)
C30.08820 (5)0.3984 (2)0.7725 (2)0.0117 (6)
C40.05265 (5)0.3387 (2)0.8116 (2)0.0116 (6)
C50.05495 (5)0.1712 (2)0.8713 (2)0.0117 (6)
C60.07008 (5)0.0650 (2)0.7490 (2)0.0117 (6)
C70.15910 (5)0.2109 (2)0.7687 (2)0.0146 (6)
O70.02069 (4)0.25520 (17)0.39098 (17)0.0170 (5)
C80.17810 (6)0.2966 (3)0.9113 (3)0.0191 (7)
C90.20799 (6)0.3936 (3)0.8548 (3)0.0254 (7)
C100.23303 (6)0.2941 (3)0.7669 (3)0.0292 (8)
C110.21388 (6)0.2082 (3)0.6237 (3)0.0233 (7)
C120.18374 (6)0.1127 (3)0.6789 (3)0.0185 (6)
O80.14014 (5)0.2676 (2)0.3013 (2)0.0245 (6)
H10.1103 (6)0.058 (2)0.609 (3)0.015 (6)*
H20.0948 (6)0.321 (3)0.541 (3)0.019 (6)*
H30.1049 (6)0.400 (3)0.878 (3)0.022 (6)*
H3A0.102290.601780.728550.0240*
H40.0361 (6)0.343 (3)0.711 (3)0.015 (5)*
H4A0.051880.434351.016200.0216*
H50.010590.177410.949580.0254*
H5A0.0696 (5)0.172 (2)0.976 (3)0.014 (5)*
H60.0517 (5)0.058 (2)0.648 (2)0.007 (5)*
H6A0.088220.136560.748750.0235*
H8A0.1883 (6)0.210 (3)0.989 (3)0.021 (6)*
H8B0.1612 (6)0.365 (3)0.963 (3)0.016 (6)*
H9A0.2201 (7)0.445 (3)0.951 (3)0.030 (7)*
H9B0.1967 (6)0.477 (3)0.790 (3)0.027 (7)*
H10A0.2438 (7)0.212 (3)0.846 (3)0.034 (7)*
H10B0.2503 (7)0.351 (3)0.732 (3)0.032 (7)*
H11A0.2294 (7)0.141 (3)0.569 (3)0.033 (7)*
H11B0.2042 (7)0.284 (3)0.538 (3)0.042 (8)*
H12A0.1929 (5)0.025 (3)0.754 (2)0.011 (5)*
H12B0.1706 (6)0.064 (3)0.596 (3)0.026 (7)*
H7A0.0239 (7)0.351 (2)0.406 (3)0.033 (7)*
H8C0.1319 (8)0.188 (4)0.306 (4)0.056 (12)*
H8D0.1447 (8)0.300 (4)0.406 (4)0.061 (10)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0107 (7)0.0172 (8)0.0137 (7)0.0012 (6)0.0001 (5)0.0041 (6)
O20.0114 (7)0.0164 (7)0.0138 (7)0.0001 (6)0.0023 (5)0.0032 (6)
O30.0185 (8)0.0104 (7)0.0186 (7)0.0026 (6)0.0007 (6)0.0038 (6)
O40.0183 (8)0.0138 (7)0.0115 (7)0.0020 (6)0.0031 (6)0.0028 (5)
O50.0145 (8)0.0138 (7)0.0242 (8)0.0004 (6)0.0104 (6)0.0027 (6)
O60.0175 (8)0.0093 (7)0.0208 (8)0.0036 (6)0.0048 (6)0.0004 (6)
C10.0113 (10)0.0143 (10)0.0102 (9)0.0022 (8)0.0006 (8)0.0001 (8)
C20.0112 (10)0.0143 (10)0.0111 (10)0.0012 (8)0.0021 (8)0.0005 (8)
C30.0145 (10)0.0089 (10)0.0116 (9)0.0006 (8)0.0001 (8)0.0019 (8)
C40.0137 (10)0.0120 (10)0.0091 (9)0.0007 (8)0.0019 (8)0.0020 (8)
C50.0112 (10)0.0132 (10)0.0106 (9)0.0024 (8)0.0013 (8)0.0000 (8)
C60.0136 (10)0.0091 (10)0.0123 (9)0.0000 (8)0.0006 (8)0.0012 (8)
C70.0123 (10)0.0169 (11)0.0146 (10)0.0006 (8)0.0009 (8)0.0044 (8)
O70.0210 (8)0.0113 (8)0.0189 (8)0.0008 (6)0.0028 (6)0.0007 (6)
C80.0157 (11)0.0223 (12)0.0192 (11)0.0014 (9)0.0008 (9)0.0008 (9)
C90.0203 (12)0.0272 (13)0.0278 (12)0.0076 (11)0.0020 (10)0.0001 (11)
C100.0148 (12)0.0387 (16)0.0343 (14)0.0084 (11)0.0028 (10)0.0033 (12)
C110.0168 (12)0.0270 (13)0.0271 (12)0.0012 (10)0.0073 (10)0.0016 (10)
C120.0162 (11)0.0177 (11)0.0217 (11)0.0002 (9)0.0029 (9)0.0010 (9)
O80.0274 (10)0.0224 (10)0.0242 (9)0.0018 (8)0.0056 (7)0.0020 (8)
Geometric parameters (Å, º) top
O1—C11.440 (2)C10—C111.524 (3)
O1—C71.426 (2)C11—C121.526 (3)
O2—C21.442 (2)C1—H10.96 (2)
O2—C71.463 (2)C2—H20.97 (2)
O3—C31.426 (2)C3—H31.03 (2)
O4—C41.425 (2)C4—H41.00 (2)
O5—C51.426 (2)C5—H5A0.99 (2)
O6—C61.417 (2)C6—H61.042 (17)
O3—H3A0.8400O7—H7A0.843 (18)
O4—H4A0.8400C8—H8B1.00 (2)
O5—H50.8400C8—H8A1.04 (3)
O6—H6A0.8400C9—H9A0.99 (3)
C1—C61.511 (3)C9—H9B0.97 (3)
C1—C21.508 (2)C10—H10B0.90 (3)
C2—C31.529 (2)C10—H10A1.02 (3)
C3—C41.523 (3)C11—H11A0.97 (3)
C4—C51.525 (2)C11—H11B1.01 (3)
C5—C61.517 (2)C12—H12A1.02 (2)
C7—C81.517 (3)C12—H12B0.91 (2)
C7—C121.515 (3)O8—H8C0.76 (3)
C8—C91.529 (3)O8—H8D0.91 (3)
C9—C101.523 (3)
C1—O1—C7104.94 (13)C3—C2—H2108.8 (15)
C2—O2—C7107.27 (13)O3—C3—H3110.1 (14)
C3—O3—H3A109.00C2—C3—H3107.4 (14)
C4—O4—H4A109.00C4—C3—H3109.1 (13)
C5—O5—H5109.00O4—C4—H4106.9 (14)
C6—O6—H6A109.00C3—C4—H4109.1 (14)
O1—C1—C6111.71 (13)C5—C4—H4108.5 (15)
C2—C1—C6115.69 (15)O5—C5—H5A109.0 (12)
O1—C1—C2100.70 (14)C4—C5—H5A106.7 (10)
O2—C2—C3110.49 (14)C6—C5—H5A111.3 (11)
C1—C2—C3113.26 (14)O6—C6—H6108.5 (10)
O2—C2—C1101.32 (14)C1—C6—H6108.9 (10)
O3—C3—C2110.28 (14)C5—C6—H6107.0 (10)
O3—C3—C4108.00 (15)C7—C8—H8A104.8 (14)
C2—C3—C4112.04 (14)C7—C8—H8B109.4 (14)
O4—C4—C3111.39 (14)C9—C8—H8A109.3 (13)
C3—C4—C5111.22 (15)C9—C8—H8B110.1 (14)
O4—C4—C5109.63 (14)H8A—C8—H8B113 (2)
O5—C5—C4111.09 (15)C8—C9—H9A108.2 (15)
O5—C5—C6107.09 (14)C8—C9—H9B105.2 (14)
C4—C5—C6111.79 (14)C10—C9—H9A111.3 (15)
C1—C6—C5112.84 (15)C10—C9—H9B115.1 (15)
O6—C6—C1107.29 (15)H9A—C9—H9B105 (2)
O6—C6—C5112.18 (14)C9—C10—H10A108.8 (14)
O1—C7—C8109.66 (15)C9—C10—H10B111.5 (17)
O1—C7—C12111.11 (16)C11—C10—H10A107.2 (14)
O2—C7—C8109.48 (15)C11—C10—H10B109.7 (16)
O1—C7—O2105.43 (14)H10A—C10—H10B108 (2)
O2—C7—C12109.06 (15)C10—C11—H11A112.1 (15)
C8—C7—C12111.89 (18)C10—C11—H11B110.4 (15)
C7—C8—C9110.60 (19)C12—C11—H11A109.5 (16)
C8—C9—C10111.3 (2)C12—C11—H11B108.5 (15)
C9—C10—C11111.16 (19)H11A—C11—H11B105 (2)
C10—C11—C12110.9 (2)C7—C12—H12A108.3 (11)
C7—C12—C11111.8 (2)C7—C12—H12B107.2 (15)
O1—C1—H1108.0 (14)C11—C12—H12A110.6 (11)
C2—C1—H1113.1 (12)C11—C12—H12B114.1 (16)
C6—C1—H1107.4 (13)H12A—C12—H12B104 (2)
O2—C2—H2106.3 (14)H8C—O8—H8D106 (3)
C1—C2—H2116.2 (15)
C7—O1—C1—C243.11 (16)C2—C3—C4—C555.05 (18)
C7—O1—C1—C6166.48 (14)C2—C3—C4—O4177.68 (14)
C1—O1—C7—C1291.05 (17)O3—C3—C4—O460.68 (17)
C1—O1—C7—O226.96 (16)O3—C3—C4—C5176.70 (13)
C1—O1—C7—C8144.73 (16)O4—C4—C5—O560.37 (18)
C2—O2—C7—C12120.33 (16)C3—C4—C5—C656.44 (19)
C7—O2—C2—C126.72 (16)O4—C4—C5—C6179.93 (15)
C7—O2—C2—C393.59 (15)C3—C4—C5—O5176.00 (13)
C2—O2—C7—O10.95 (17)C4—C5—C6—C151.3 (2)
C2—O2—C7—C8116.94 (16)O5—C5—C6—O665.51 (18)
C6—C1—C2—C344.6 (2)O5—C5—C6—C1173.16 (14)
C6—C1—C2—O2162.97 (14)C4—C5—C6—O6172.60 (15)
C2—C1—C6—O6169.97 (14)O1—C7—C8—C9178.85 (17)
O1—C1—C6—O655.56 (18)O2—C7—C8—C965.9 (2)
O1—C1—C6—C568.50 (18)C12—C7—C8—C955.1 (2)
O1—C1—C2—O242.40 (15)O1—C7—C12—C11177.88 (17)
C2—C1—C6—C545.9 (2)O2—C7—C12—C1166.3 (2)
O1—C1—C2—C375.94 (18)C8—C7—C12—C1154.9 (2)
O2—C2—C3—O377.97 (18)C7—C8—C9—C1055.7 (3)
C1—C2—C3—O3169.16 (15)C8—C9—C10—C1156.1 (3)
C1—C2—C3—C448.8 (2)C9—C10—C11—C1255.1 (3)
O2—C2—C3—C4161.70 (14)C10—C11—C12—C754.5 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3A···O8i0.841.892.724 (2)170
O4—H4A···O3i0.841.912.754 (2)177
O5—H5···O40.842.462.853 (2)109
O5—H5···O7ii0.841.982.776 (2)158
O6—H6A···O8iii0.842.302.914 (2)130
O7—H7A···O4iv0.843 (18)1.944 (18)2.779 (2)171 (3)
O8—H8C···O6v0.76 (3)2.31 (3)2.914 (2)137 (3)
O8—H8D···O20.91 (3)2.08 (3)2.950 (3)161 (3)
Symmetry codes: (i) x, y+1, z+1/2; (ii) x, y, z+3/2; (iii) x, y, z+1/2; (iv) x, y+1, z1/2; (v) x, y, z1/2.
Comparison of selected experimental and calculated bond lengths (Å) of (1) top
Functional/Basis setO4—C4C4—C3O3—C3C3—C2C2—O2O2—C7C7—C8C8—C9
B3LYP 6-31G(d)1.42971.52171.42461.52961.44331.46211.51571.5267
B3LYP 6-31G(d,p)1.42971.52171.42461.52961.44331.46211.51571.5267
B3LYP 6-311G(d,p)1.42971.52171.42461.52961.44331.46211.51571.5267
SCXRD1.4251.5231.4261.5291.4421.4631.5171.529
Comparison of selected experimental and calculated bond angles (°) of (1) top
Functional/Basis setC5—O4—C4O4—C4—C3C4—C3—O3O3—C3—C2C3—C2—O2C2—O2—C7O2—C7—C8C7—C8—C9
B3LYP 6-31G(d)109.5531111.326108.0938110.2346110.5034107.1887109.5274110.6744
B3LYP 6-31G(d,p)109.5531111.326108.0938110.2346110.5034107.1887109.5274110.6744
B3LYP 6-311G(d,p)109.5531111.326108.0938110.2346110.5034107.1887109.5274110.6744
SCXRD109.63111.39108.00110.2110.49107.27109.48110.60
Comparison of selected experimental and calculated torsion angles (°) of (1) top
Functional/Basis setO5—C5—C4—O4O4—C4—C3—O3O3—C3—C2—O2C2—O2—C7—C8O2—C7—C8—C9C7—C8—C9—C10
B3LYP 6-31G(d)60.40-60.737778.0022-117.1225-65.6377-55.7909
B3LYP 6-31G(d,p)60.40-60.737778.0022-117.1225-65.6377-55.7909
B3LYP 6-311G(d,p)60.40-60.737778.0022-117.1225-65.6377-55.7909
SCXRD60.37-60.6877.97-116.94-65.9-55.7
Lattice energy from CLP (in kcal mol-1) for (1) top
CompoundEcolEPolEDispERepETot
(1)-28.9-59.6-106.346.7-151.6
 

Footnotes

1This paper is dedicated to Professor S. Chandrasekaran.

Acknowledgements

The authors would like to thank the X-Ray facility at IISER Pune for allowing us to collect the data. GP, KJ and VT thank IITGN for funding. SK is grateful for a Ramanujan Fellowship, DST. PKV thanks the Department of Biotechnology, Government of India, for a Ramalingaswami Re-Entry Fellowship.

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