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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 80| Part 2| February 2024| Pages 196-200
https://doi.org/10.1107/S2056989024000276

A triclinic polymorph of miconazole

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Hanna Kaspiaruka,b* and Lilianna Chęcińskab

aUniversity of Lodz Doctoral School of Exact and Natural Sciences, Narutowicza 68, 90-136 Łódź, Poland, and bUniversity of Lodz, Faculty of Chemistry, Pomorska 163/165, 90-236 Łódź, Poland
*Correspondence e-mail: hanna.kaspiaruk@edu.uni.lodz.pl

Edited by J. Reibenspies, Texas A & M University, USA (Received 27 November 2023; accepted 8 January 2024; online 26 January 2024)

The crystal structure of the new triclinic polymorph of miconazole {MIC; C18H14Cl4N2O; systematic name: (RS)-1-[2-(2,4-di­chloro­benz­yloxy)-2-(2,4-di­chloro­phen­yl)eth­yl]-1H-imidazole} is reported and compared with the monoclinic form of solvent-free miconazole previously reported [Kaspiaruk & Chęcińska (2022[Kaspiaruk, H. & Chęcińska, L. (2022). Acta Cryst. C78, 343-350.]). Acta Cryst. C78, 343–350]. A comparison shows a different orientation of imidazole and one di­chloro­phenyl ring between polymorphic mol­ecules. In the crystal structure of the title compound, only weak halogen bonds and C—H⋯π(arene) inter­actions are found. Hirshfeld surface analysis and energy framework calculations complement the comparison of the two polymorphic forms of the miconazole drug.

CCDC reference: 2324176

Similar articles

1. Chemical context

Miconazole {MIC; C18H14Cl4N2O; CAS No. 22916-47-8; systematic name: (RS)-1-[2-(2,4-di­chloro­benz­yloxy)-2-(2,4-di­chloro­phen­yl)eth­yl]-1H-imidazole} is a drug that belongs to the group of first-generation imidazole derivatives. It shows a broad spectrum of anti­fungal activity against dermatophytes, yeasts, and Gram-positive bacteria (Botter, 1971[Botter, A. A. (1971). Mycoses, 14, 187-191.]; Sawyer et al., 1975[Sawyer, P. R., Brogden, R. N., Pinder, R. M., Speight, T. M. & Avery, G. A. (1975). Drugs, 9, 406-423.]; Nenoff et al., 2017[Nenoff, P., Koch, D., Krüger, C., Drechsel, C. & Mayser, P. (2017). Mycoses, 60, 552-557.]). Miconazole exhibits poor aqueous solubility, therefore salts (Peeters et al., 2004[Peeters, O. M., Blaton, N. M., Aeschlimann, C. & Gal, J. (2004). Acta Cryst. E60, o365-o366.]; Patel et al., 2018[Patel, M. A., Luthra, S., Shamblin, S. L., Arora, K., Krzyzaniak, J. F. & Taylor, L. S. (2018). Mol. Pharm. 15, 40-52.]), co-crystals (Drozd et al., 2021[Drozd, K. V., Manin, A. N., Voronin, A. P., Boycov, D. E., Churakov, A. V. & Perlovich, G. L. (2021). Phys. Chem. Chem. Phys. 23, 12456-12470.], 2022[Drozd, K. V., Manin, A. N., Boycov, D. E. & Perlovich, G. L. (2022). Pharmaceutics, 14, 1107.]) and mol­ecular salts (Drozd et al., 2021[Drozd, K. V., Manin, A. N., Voronin, A. P., Boycov, D. E., Churakov, A. V. & Perlovich, G. L. (2021). Phys. Chem. Chem. Phys. 23, 12456-12470.]) with this agent have been synthesized to improve its bioavailability.

The first crystal structure of miconazole in the form of a hemihydrate was published previously (Peeters et al., 1979[Peeters, O. M., Blaton, N. M. & De Ranter, C. J. (1979). Bull. Soc. Chim. 88, 265-272.]). A monoclinic anhydrous form and solvatomorphs, namely hemi-hydrogen peroxide solvate, monohydrate, ethanol monosolvate and methanol monosolvate, have been published recently (Kersten et al., 2018[Kersten, K. M., Breen, M. E., Mapp, A. K. & Matzger, A. J. (2018). Chem. Commun. 54, 9286-9289.]; Kaspiaruk & Chęcińska, 2022[Kaspiaruk, H. & Chęcińska, L. (2022). Acta Cryst. C78, 343-350.]; Panini et al., 2022[Panini, P., Boel, E., Van Meervelt, L. & Van den Mooter, G. (2022). Cryst. Growth Des. 22, 2703-2724.]).

In this article a second polymorphic form of pure solvent-free miconazole, a triclinic form (MIC-tri), is reported, and compared with the anhydrous monoclinic form of miconazole (MIC-mono) (Kaspiaruk & Chęcińska, 2022[Kaspiaruk, H. & Chęcińska, L. (2022). Acta Cryst. C78, 343-350.]; Panini et al., 2022[Panini, P., Boel, E., Van Meervelt, L. & Van den Mooter, G. (2022). Cryst. Growth Des. 22, 2703-2724.]).

[Scheme 1]

2. Structural commentary

The mol­ecular structure of the title compound (MIC-tri) is illustrated in Fig. 1[link]. It crystallizes in the triclinic crystal system, space group P[\overline{1}]. The mol­ecule of miconazole consists of three planar groups: an imidazole ring (ring 1) and two di­chloro­phenyl groups (ring 2, atoms C6–C11; ring 3, atoms C13–C18) connected by a flexible meth­oxy­ethyl fragment. In the MIC-tri structure, the imidazole ring was found to be disordered over two orientations (ring 1A: N1A, C3A, N2A, C4A, C5A and ring 1B: N1B, C3B, N2B, C4B, C5B, respectively) with equal occupancies (0.5).

[Figure 1]
Figure 1
The mol­ecular structure of MIC-tri showing the atom-labelling scheme. The disorder components A and B have equal site-occupancies (1/2). Labels 1A, 1B, 2 and 3 refer to the best planes of the aromatic rings. Displacement ellipsoids are drawn at the 50% probability level.

To make a comparison between the triclinic and monoclinic polymorphic forms of miconazole, the superposition of the three miconazole skeletons is shown in Fig. 2[link], considering separately two disorder components A and B of MIC-tri (MIC-tri-A and MIC-tri-B). One can see the difference in the orientation of the di­chloro­phenyl ring (ring 3) in the two polymorphic forms: they are approximately perpendicular to each other. Inter­estingly, such an orientation of the arene ring (ring 3) as observed in the MIC-tri form seems to be preferable for hydrated/solvated forms of miconazole (Kaspiaruk & Chęcińska, 2022[Kaspiaruk, H. & Chęcińska, L. (2022). Acta Cryst. C78, 343-350.]). Additionally, the compared polymorphs also differ from each other with regard to the position of the N2 atom of the imidazole ring in that they are related by a rotation of about 180°. The mutual arrangement of the aromatic rings in the analysed miconazole mol­ecules can be described by the dihedral angles between their best planes, calculated by the least-squares method (Table 1[link]).

Table 1
Dihedral angles (°) between the best planes in pure solvent-free polymorphic MIC-structures

1(A/B) is the imidazole ring, 2 and 3 are the di­chloro­phenyl rings.
  1(A/B)/2 1(A/B)/3 2/3
MIC-tri-A 2.4 (1) 68.5 (1) 69.2 (3)
MIC-tri-B 1.5 (1) 68.0 (1) 69.2 (3)
MIC-mono 16.8 (2) 22.2 (2) 5.4 (2)
[Figure 2]
Figure 2
An overlay of three miconazole mol­ecules, showing the best fit for atoms C1, C2 and N1: the colour code is blue = MIC-mono, red = MIC-tri-A, green = MIC-tri-B. N2* is the position of the N2 atom in mol­ecule MIC-mono.

3. Supra­molecular features

In the crystal structure of the title miconazole polymorph (MIC-tri), there are no typical hydrogen bonds. In contrast to the monoclinic form (MIC-mono), where two C—H⋯X (X = N, Cl) inter­actions were observed, here only a weak C7—Cl1⋯Cl1(−x, −y, 1 − z) halogen inter­action is found (Fig. 3[link]); the distance of the close Cl1⋯Cl1 contact is 3.250 (3) Å and the C7—Cl1⋯Cl1 angle is 162.92 (2)°. Close inspection of the crystal packing of MIC-tri also reveals two C—H⋯π(arene) inter­actions: C12—H12B⋯Cg3(−x, 1 − y, −z) [H⋯Cg3 = 2.78 Å, C—H⋯Cg3 = 151°] and C15—H15⋯Cg1A/1B(−x, 1 − y, −z) [H⋯Cg1A/1B = 2.96 Å/2.94 Å, C—H⋯Cg1A/1B = 140°/145°] (Fig. 3[link]).

[Figure 3]
Figure 3
A part of the crystal structure of MIC-tri (only disorder component A is shown) showing the formation of C7—Cl1⋯Cl1(−x, −y, 1 − z) halogen bonds and C—H⋯π(arene) inter­actions between adjacent mol­ecules. Red balls represent the centroids of the phenyl rings (Cg1A and Cg3). Inter­actions are shown as dashed lines (blue and red), and for the sake of clarity, H atoms not involved in these inter­actions have been omitted.

4. Hirshfeld surface analysis

Hirshfeld surface analysis (Spackman & Jayatilaka, 2009[Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19-32.]) complements the comparison of the two polymorphic forms of the miconazole drug. Hirshfeld surfaces and fingerprint plots (Spackman & McKinnon, 2002[Spackman, M. A. & McKinnon, J. J. (2002). CrystEngComm, 4, 378-392.]; Spackman & Jayatilaka, 2009[Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19-32.]) were generated using CrystalExplorer software (Turner et al., 2017[Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). CrystalExplorer17.5. University of Western Australia.]). Fig. 4[link] presents the 2D fingerprint plots of all close contacts characteristic of the MIC-tri and MIC-mono structures; among them, additionally, C⋯H/H⋯C inter­actions are highlighted as their contributions to the Hirshfeld surface differ the most between polymorphs. An increase in the number of such inter­actions is observed for MIC-tri. As shown in breakdown diagrams (Fig. 5[link]), in contrast to the C⋯H inter­actions, the contribution of C⋯C close contacts, mainly representing aromatic π–π inter­actions, decreased quite significantly for the triclinic form (2.0%) compared to the monoclinic one (9.8%). Other close contacts remain essentially comparable; the H⋯Cl/Cl⋯H and H⋯H contacts have the largest share of the Hirshfeld surface of both analysed polymorphs.

[Figure 4]
Figure 4
Comparison of two-dimensional fingerprint plots for the two miconazole polymorphic forms, MIC-tri (disorder component A only) and MIC-mono, showing all close contacts, and delineated into C⋯H/H⋯C inter­actions. The di and de values are the closest inter­nal and external distances (in Å) from given points on the Hirshfeld surface.
[Figure 5]
Figure 5
Diagram showing the percentage contributions of different close contacts to the Hirshfeld surface area of miconazole mol­ecules in the two polymorphic forms, MIC-tri (disorder component A only) and MIC-mono.

5. Pairwise model energies and their energy frameworks

The similarities and differences between two polymorphic forms of miconazole can also be analysed by comparison of the inter­action energies calculated between mol­ecules within a representative cluster of 3.8 Å from the crystal lattices and their visualization as energy frameworks. All inter­action energies for MIC-tri are listed in Table 2[link]. Similarly to the analysis presented previously for MIC-mono (Kaspiaruk & Chęcińska, 2022[Kaspiaruk, H. & Chęcińska, L. (2022). Acta Cryst. C78, 343-350.]), only one mol­ecular pair has a relatively high total energy value over 50 kJ mol−1 with the highest calculated contribution of dispersive and repulsive forces resulting from C—H⋯π(arene) inter­actions (Fig. 3[link]). Unfortunately, it is quite difficult to assign the remaining energies from the table to specific inter­actions in the crystal of MIC-tri because of the limited number of contacts that met the geometrical criteria of hydrogen bonds. For example, the total energy value of the mol­ecular pair connected by the Cl1⋯Cl1 halogen bond is only −6.6 kJ mol−1 while much higher total energies (45.0, 35.4, 25.5, 23.4, in kJ mol−1) seem to result from the specific mutual arrangement of mol­ecules supported by the weaker aromatic π–π inter­actions.

Table 2
Inter­action energies (kJ mol−1) for the cluster of mol­ecules with a radius of 3.8 Å for MIC-tri

N is the number of mol­ecular pairs. R is the distance (Å) between mol­ecular centroids. Etot is the total energy and Eele is the electrostatic (k = 1.057), Epol is the polarization (k = 0.740), Edis is the dispersion (k = 0.871) and Erep is the repulsion (k = 0.618) component.
N R kEele kEpol kEdis kErep Etot
1 10.41 −4.65 −0.44 −11.15 9.64 −6.6
2 9.42 −2.01 −1.26 −19.77 7.66 −15.3
1 6.73 −16.28 −3.26 −64.11 27.01 −56.6
1 7.88 −8.46 −0.67 −43.29 17.00 −35.4
2 9.49 −0.21 −0.44 −7.40 4.02 −4.1
1 10.72 −1.27 −0.15 −11.67 3.77 −9.2
1 9.90 −27.38 −5.77 −19.25 7.54 −45.0
1 8.58 3.59 −1.26 −32.49 6.86 −23.4
2 14.04 −2.85 −0.07 −4.88 4.51 −3.3
2 13.03 −2.01 −0.07 −6.62 3.58 −5.1
1 8.22 −6.76 −0.96 −26.91 9.08 −25.5
1 10.23 −3.38 −0.74 −11.93 5.99 −10.1

Generally, for MIC-tri, the contribution of dispersive forces predominates over electrostatic ones. The relationship between these two forces can be expressed by the proportions of electrostatic (ΣkEele) and dispersion (ΣkEdis) energies (both scaled), given as percentages, that contribute to their sums for all mol­ecular pairs in the cluster of mol­ecules ΣkEele/(ΣkEele+ΣkEdis); [ΣkEdis/(ΣkEdis+ΣkEele)]. The percentages showing the proportion of the electrostatic component to the dispersion component are: 20%:80% for MIC-tri, which is comparable to MIC-mono (26%:74%).

Fig. 6[link] shows the representative energy frameworks for the analysed structure of MIC-tri. Energies between two mol­ecules are represented as cylinders connecting these mol­ecular pairs, with the radius of the cylinder proportional to the contribution of the corresponding energy. Red individual cylinders correspond to electrostatic energy (Eele), green to dispersive energy (Edis), and blue to total energy (Etot). Views along all crystallographic axes demonstrate that the MIC-tri structure exhibits a tri-periodic energy pattern; the total energy framework reflects the framework of its dominant dispersion component. Pairwise model energies (Turner et al., 2014[Turner, M. J., Grabowsky, S., Jayatilaka, D. & Spackman, M. A. (2014). J. Phys. Chem. Lett. 5, 4249-4255.]) were estimated and visualized (Turner et al., 2015[Turner, M. J., Thomas, S. P., Shi, M. W., Jayatilaka, D. & Spackman, M. A. (2015). Chem. Commun. 51, 3735-3738.]; Mackenzie et al., 2017[Mackenzie, C. F., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). IUCrJ, 4, 575-587.]) between mol­ecules within a cluster with a radius of 3.8 Å, using CrystalExplorer software (Turner et al., 2017[Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). CrystalExplorer17.5. University of Western Australia.]). The computational approach uses a B3LYP/6-31G(d,p) mol­ecular wave function calculated for the respective mol­ecular arrangement in the crystal. The total inter­action energy between any nearest-neighbour mol­ecular pairs was estimated in terms of four components: electrostatic, polarization, dispersion and exchange-repulsion, with scale factors (k) of 1.057, 0.740, 0.871 and 0.618, respectively.

[Figure 6]
Figure 6
Representative energy framework diagrams for separate electrostatic (red) and dispersion (green) components, and the total inter­action energy (blue) for MIC-tri (disorder component A only). All diagrams use the same energy tube scale factor of 80 and an energy threshold of 20 kJ mol−1 to be compatible with Fig. 6[link] (Kaspiaruk & Chęcińska, 2022[Kaspiaruk, H. & Chęcińska, L. (2022). Acta Cryst. C78, 343-350.]).

6. Database survey

A search of the Cambridge Structural Database (CSD version 5.44, September 2023, Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) revealed only one solvent-free miconazole form in the monoclinic system (PAVPIP; Panini et al., 2022[Panini, P., Boel, E., Van Meervelt, L. & Van den Mooter, G. (2022). Cryst. Growth Des. 22, 2703-2724.]; PAVPIP01; Kaspiaruk & Chęcińska, 2022[Kaspiaruk, H. & Chęcińska, L. (2022). Acta Cryst. C78, 343-350.]).

7. Synthesis and crystallization

A second polymorphic form of solvent-free miconazole (MIC-tri) was found after a couple of months, probably as an effect of decomposition of miconazole co-crystals with small aromatic carb­oxy­lic acids or any other hydrated/solvated forms of miconazole. The MIC-tri crystals are dull and yellow in colour; they are distinctly different from the co-crystals (Fig. S1 in the supporting information).

8. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3[link]. During the refinement of the title compound MIC-tri, the imidazole ring was found to be disordered over two orientations (ring 1A: N1A, C3A, N2A, C4A, C5A and ring 1B: N1B, C3B, N2B, C4B, C5B); site occupancies of two components were fixed at 0.5. Component B of the disordered imidazole ring was restrained using RIGU and SADI commands in SHELXL. Furthermore, the C2 methyl­ene atom was also split; constraints (EXYZ and EADP) were used to fix the overlapping atoms C2A and C2B. It was difficult to determine the position of the nitro­gen N2 atom in the disordered imidazole ring, mainly due to the poor quality of the crystals for which the single-crystal diffraction pattern was disturbed by powder diffraction effects.

Table 3
Experimental details

Crystal data
Chemical formula C18H14Cl4N2O
Mr 416.11
Crystal system, space group Triclinic, P[\overline{1}]
Temperature (K) 295
a, b, c (Å) 8.8691 (8), 9.4161 (9), 13.0347 (11)
α, β, γ (°) 75.502 (8), 85.013 (8), 62.478 (10)
V (Å3) 934.11 (17)
Z 2
Radiation type Cu Kα
μ (mm−1) 5.83
Crystal size (mm) 0.26 × 0.09 × 0.05
 
Data collection
Diffractometer XtaLAB Synergy, Dualflex, HyPix
Absorption correction Gaussian (CrysAlis PRO; Rigaku OD, 2023[Rigaku OD (2023). CrysAlis PRO. Rigaku Corporation, Wroclaw, Poland.])
Tmin, Tmax 0.521, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections 8698, 3412, 2548
Rint 0.051
(sin θ/λ)max (Å−1) 0.610
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.085, 0.224, 1.10
No. of reflections 3412
No. of parameters 271
No. of restraints 35
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.47, −0.34
Computer programs: CrysAlis PRO (Rigaku OD, 2023[Rigaku OD (2023). CrysAlis PRO. Rigaku Corporation, Wroclaw, Poland.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2019/2 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]), PLATON (Spek, 2020[Spek, A. L. (2020). Acta Cryst. E76, 1-11.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

All hydrogen atoms bonded to carbon atoms were placed geometrically and refined as riding, with Uiso(H) = 1.2Ueq(C) for the methyl­ene, methine and aromatic groups.

Supporting information

CCDC reference: 2324176

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2056989024000276/jy2040sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989024000276/jy2040Isup2.hkl

The MIC-tri crystals. DOI: https://doi.org/10.1107/S2056989024000276/jy2040sup3.tif

Supporting information file. DOI: https://doi.org/10.1107/S2056989024000276/jy2040Isup4.cml

checkCIF report


Computing details top

(RS)-1-[2-(2,4-Dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole top
Crystal data top
C18H14Cl4N2OZ = 2
Mr = 416.11F(000) = 424
Triclinic, P1Dx = 1.479 Mg m−3
a = 8.8691 (8) ÅCu Kα radiation, λ = 1.54184 Å
b = 9.4161 (9) ÅCell parameters from 3917 reflections
c = 13.0347 (11) Åθ = 5.4–69.1°
α = 75.502 (8)°µ = 5.83 mm−1
β = 85.013 (8)°T = 295 K
γ = 62.478 (10)°Prism, pale yellow
V = 934.11 (17) Å30.26 × 0.09 × 0.05 mm
Data collection top
XtaLAB Synergy, Dualflex, HyPix
diffractometer		3412 independent reflections
Radiation source: micro-focus sealed X-ray tube, PhotonJet (Cu) X-ray Source2548 reflections with I > 2σ(I)
Mirror monochromatorRint = 0.051
Detector resolution: 10.0000 pixels mm-1θmax = 70.0°, θmin = 3.5°
ω scansh = −10→8
Absorption correction: gaussian
(CrysAlisPro; Rigaku OD, 2023)		k = −11→10
Tmin = 0.521, Tmax = 1.000l = −15→15
8698 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.085H-atom parameters constrained
wR(F2) = 0.224 w = 1/[σ2(Fo2) + (0.0932P)2 + 1.192P]
where P = (Fo2 + 2Fc2)/3
S = 1.10(Δ/σ)max < 0.001
3412 reflectionsΔρmax = 0.47 e Å−3
271 parametersΔρmin = −0.34 e Å−3
35 restraints
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*/UeqOcc. (<1)
Cl10.0819 (3)0.1162 (2)0.51579 (13)0.1083 (7)
Cl20.2681 (2)0.4980 (3)0.65792 (14)0.1076 (6)
Cl3−0.1424 (2)0.80046 (19)0.10302 (13)0.1010 (6)
Cl40.2330 (2)0.8416 (2)−0.23760 (12)0.0995 (6)
O10.2576 (4)0.2922 (4)0.2041 (2)0.0625 (8)
C10.2397 (6)0.1992 (6)0.3050 (4)0.0607 (11)
H10.1315050.1944210.3058880.073*
C2A0.3861 (7)0.0273 (7)0.3190 (4)0.0746 (14)0.5
H2A10.4916110.0345820.3036570.090*0.5
H2A20.393547−0.0329850.3921600.090*0.5
N1A0.365 (2)−0.0616 (18)0.2502 (11)0.065 (6)0.5
C3A0.431 (3)−0.047 (3)0.1510 (13)0.073 (5)0.5
H3A0.4861080.0155260.1215290.087*0.5
N2A0.399 (3)−0.140 (2)0.1066 (17)0.108 (5)0.5
C4A0.303 (2)−0.206 (2)0.178 (2)0.098 (9)0.5
H4A0.260498−0.2725930.1637090.117*0.5
C5A0.285 (4)−0.159 (4)0.268 (3)0.116 (14)0.5
H5A0.230134−0.1852130.3288050.140*0.5
C2B0.3861 (7)0.0273 (7)0.3190 (4)0.0746 (14)0.5
H2B10.4911110.0355280.3035310.090*0.5
H2B20.393827−0.0316880.3925170.090*0.5
N1B0.370 (3)−0.067 (2)0.2518 (15)0.091 (8)0.5
C3B0.405 (3)−0.083 (3)0.1500 (17)0.075 (5)0.5
H3B0.459801−0.0304320.1036720.091*0.5
N2B0.353 (2)−0.1802 (18)0.1247 (12)0.075 (4)0.5
C4B0.281 (3)−0.243 (2)0.2120 (15)0.072 (4)0.5
H4B0.240982−0.3206280.2198840.087*0.5
C5B0.286 (4)−0.162 (4)0.281 (2)0.089 (9)0.5
H5B0.234048−0.1688140.3462790.106*0.5
C60.2468 (6)0.2745 (6)0.3939 (3)0.0579 (11)
C70.1771 (7)0.2453 (6)0.4925 (4)0.0666 (13)
C80.1827 (7)0.3111 (7)0.5737 (4)0.0726 (14)
H80.1352730.2887070.6384790.087*
C90.2605 (7)0.4110 (7)0.5565 (4)0.0724 (14)
C100.3307 (7)0.4456 (7)0.4610 (4)0.0771 (15)
H100.3820230.5145340.4506590.093*
C110.3238 (7)0.3763 (7)0.3805 (4)0.0688 (13)
H110.3719340.3986430.3160690.083*
C120.1108 (6)0.4420 (6)0.1695 (4)0.0614 (11)
H12A0.0782200.5042460.2236560.074*
H12B0.0178170.4201310.1576450.074*
C130.1438 (6)0.5415 (5)0.0680 (3)0.0528 (10)
C140.0343 (6)0.7054 (6)0.0308 (4)0.0624 (12)
C150.0596 (7)0.8006 (6)−0.0624 (4)0.0680 (13)
H15−0.0160940.911639−0.0860780.082*
C160.2007 (7)0.7245 (6)−0.1184 (4)0.0657 (12)
C170.3117 (7)0.5628 (7)−0.0858 (4)0.0661 (12)
H170.4058960.514221−0.1254710.079*
C180.2828 (6)0.4704 (6)0.0077 (4)0.0626 (12)
H180.3580390.3590340.0302810.075*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.1649 (17)0.1257 (13)0.0818 (10)−0.1152 (14)0.0240 (10)−0.0122 (9)
Cl20.1128 (13)0.1450 (16)0.0939 (11)−0.0657 (12)0.0058 (9)−0.0633 (11)
Cl30.0908 (11)0.0796 (9)0.0871 (10)−0.0107 (8)0.0275 (8)−0.0090 (7)
Cl40.1312 (14)0.0926 (11)0.0754 (9)−0.0619 (10)0.0262 (9)−0.0070 (8)
O10.069 (2)0.0617 (18)0.0508 (16)−0.0262 (16)0.0056 (14)−0.0107 (14)
C10.068 (3)0.063 (3)0.054 (2)−0.035 (2)0.001 (2)−0.007 (2)
C2A0.080 (4)0.067 (3)0.070 (3)−0.031 (3)−0.006 (3)−0.009 (3)
N1A0.049 (8)0.047 (8)0.062 (7)0.006 (5)0.000 (5)−0.009 (6)
C3A0.099 (12)0.053 (9)0.079 (8)−0.040 (7)0.008 (7)−0.029 (6)
N2A0.142 (14)0.064 (10)0.140 (13)−0.062 (8)−0.015 (10)−0.026 (8)
C4A0.093 (13)0.046 (10)0.16 (3)−0.052 (8)0.012 (14)0.001 (12)
C5A0.098 (19)0.09 (2)0.127 (19)−0.023 (15)0.039 (16)−0.028 (15)
C2B0.080 (4)0.067 (3)0.070 (3)−0.031 (3)−0.006 (3)−0.009 (3)
N1B0.127 (16)0.085 (13)0.098 (10)−0.075 (12)0.009 (9)−0.035 (8)
C3B0.105 (10)0.055 (10)0.095 (8)−0.056 (8)0.005 (7)−0.027 (6)
N2B0.091 (10)0.044 (7)0.101 (8)−0.040 (6)−0.013 (6)−0.013 (6)
C4B0.102 (9)0.047 (8)0.095 (8)−0.054 (7)0.002 (7)−0.021 (7)
C5B0.12 (2)0.070 (15)0.109 (9)−0.069 (16)0.006 (9)−0.033 (9)
C60.066 (3)0.060 (3)0.053 (2)−0.036 (2)0.001 (2)−0.007 (2)
C70.083 (3)0.068 (3)0.057 (3)−0.047 (3)0.003 (2)−0.004 (2)
C80.079 (4)0.087 (4)0.055 (3)−0.045 (3)0.008 (2)−0.012 (2)
C90.072 (3)0.088 (4)0.063 (3)−0.037 (3)0.000 (2)−0.027 (3)
C100.088 (4)0.092 (4)0.077 (3)−0.063 (3)0.001 (3)−0.019 (3)
C110.078 (3)0.086 (3)0.058 (3)−0.052 (3)0.012 (2)−0.017 (2)
C120.059 (3)0.066 (3)0.056 (2)−0.027 (2)0.002 (2)−0.010 (2)
C130.052 (3)0.056 (2)0.054 (2)−0.026 (2)0.0002 (19)−0.0151 (19)
C140.065 (3)0.062 (3)0.059 (3)−0.028 (2)0.006 (2)−0.017 (2)
C150.074 (3)0.053 (3)0.069 (3)−0.024 (2)0.002 (2)−0.010 (2)
C160.081 (3)0.067 (3)0.057 (3)−0.041 (3)0.005 (2)−0.013 (2)
C170.065 (3)0.076 (3)0.059 (3)−0.034 (3)0.010 (2)−0.018 (2)
C180.064 (3)0.058 (3)0.061 (3)−0.023 (2)0.001 (2)−0.014 (2)
Geometric parameters (Å, º) top
Cl1—C71.733 (5)C3B—H3B0.9300
Cl2—C91.741 (5)N2B—C4B1.391 (17)
Cl3—C141.736 (5)C4B—C5B1.335 (15)
Cl4—C161.752 (5)C4B—H4B0.9300
O1—C121.405 (6)C5B—H5B0.9300
O1—C11.428 (5)C6—C111.383 (7)
C1—C2B1.514 (7)C6—C71.397 (7)
C1—C2A1.514 (7)C7—C81.368 (7)
C1—C61.522 (6)C8—C91.370 (8)
C1—H10.9800C8—H80.9300
C2A—N1A1.444 (12)C9—C101.376 (8)
C2A—H2A10.9700C10—C111.387 (7)
C2A—H2A20.9700C10—H100.9300
N1A—C5A1.367 (16)C11—H110.9300
N1A—C3A1.372 (13)C12—C131.511 (6)
C3A—N2A1.30 (2)C12—H12A0.9700
C3A—H3A0.9300C12—H12B0.9700
N2A—C4A1.421 (18)C13—C141.372 (6)
C4A—C5A1.331 (17)C13—C181.384 (6)
C4A—H4A0.9300C14—C151.387 (7)
C5A—H5A0.9300C15—C161.374 (7)
C2B—N1B1.453 (12)C15—H150.9300
C2B—H2B10.9700C16—C171.353 (7)
C2B—H2B20.9700C17—C181.389 (7)
N1B—C3B1.364 (15)C17—H170.9300
N1B—C5B1.376 (14)C18—H180.9300
C3B—N2B1.32 (2)
C12—O1—C1112.8 (3)C4B—C5B—H5B121.6
O1—C1—C2B106.6 (4)N1B—C5B—H5B121.6
O1—C1—C2A106.6 (4)C11—C6—C7116.6 (4)
O1—C1—C6111.2 (4)C11—C6—C1121.1 (4)
C2B—C1—C6109.8 (4)C7—C6—C1122.4 (4)
C2A—C1—C6109.8 (4)C8—C7—C6123.3 (5)
O1—C1—H1109.7C8—C7—Cl1117.5 (4)
C2A—C1—H1109.7C6—C7—Cl1119.1 (4)
C6—C1—H1109.7C7—C8—C9117.9 (5)
N1A—C2A—C1111.7 (7)C7—C8—H8121.1
N1A—C2A—H2A1109.3C9—C8—H8121.1
C1—C2A—H2A1109.3C8—C9—C10121.7 (5)
N1A—C2A—H2A2109.3C8—C9—Cl2119.0 (4)
C1—C2A—H2A2109.3C10—C9—Cl2119.3 (4)
H2A1—C2A—H2A2107.9C9—C10—C11119.0 (5)
C5A—N1A—C3A113.0 (16)C9—C10—H10120.5
C5A—N1A—C2A129.2 (15)C11—C10—H10120.5
C3A—N1A—C2A117.8 (15)C6—C11—C10121.5 (5)
N2A—C3A—N1A105.7 (16)C6—C11—H11119.3
N2A—C3A—H3A127.1C10—C11—H11119.3
N1A—C3A—H3A127.1O1—C12—C13110.1 (4)
C3A—N2A—C4A108.0 (16)O1—C12—H12A109.6
C5A—C4A—N2A110.3 (18)C13—C12—H12A109.6
C5A—C4A—H4A124.9O1—C12—H12B109.6
N2A—C4A—H4A124.9C13—C12—H12B109.6
C4A—C5A—N1A103 (2)H12A—C12—H12B108.2
C4A—C5A—H5A128.5C14—C13—C18117.6 (4)
N1A—C5A—H5A128.5C14—C13—C12120.9 (4)
N1B—C2B—C1113.7 (10)C18—C13—C12121.5 (4)
N1B—C2B—H2B1108.8C13—C14—C15122.6 (5)
C1—C2B—H2B1108.8C13—C14—Cl3119.4 (4)
N1B—C2B—H2B2108.8C15—C14—Cl3117.9 (4)
C1—C2B—H2B2108.8C16—C15—C14117.4 (4)
H2B1—C2B—H2B2107.7C16—C15—H15121.3
C3B—N1B—C5B99.6 (14)C14—C15—H15121.3
C3B—N1B—C2B136.9 (16)C17—C16—C15122.3 (5)
C5B—N1B—C2B123.1 (14)C17—C16—Cl4119.6 (4)
N2B—C3B—N1B112.5 (14)C15—C16—Cl4118.2 (4)
N2B—C3B—H3B123.8C16—C17—C18119.0 (5)
N1B—C3B—H3B123.8C16—C17—H17120.5
C3B—N2B—C4B109.8 (13)C18—C17—H17120.5
C5B—C4B—N2B100.9 (14)C13—C18—C17121.1 (4)
C5B—C4B—H4B129.6C13—C18—H18119.5
N2B—C4B—H4B129.6C17—C18—H18119.5
C4B—C5B—N1B116.9 (17)
C12—O1—C1—C2B166.2 (4)C2A—C1—C6—C7−84.5 (6)
C12—O1—C1—C2A166.2 (4)C11—C6—C7—C8−0.2 (8)
C12—O1—C1—C6−74.1 (5)C1—C6—C7—C8179.7 (5)
O1—C1—C2A—N1A−71.4 (9)C11—C6—C7—Cl1−178.9 (4)
C6—C1—C2A—N1A168.0 (9)C1—C6—C7—Cl11.0 (7)
C1—C2A—N1A—C5A−89 (3)C6—C7—C8—C90.2 (8)
C1—C2A—N1A—C3A89.4 (16)Cl1—C7—C8—C9178.9 (4)
C5A—N1A—C3A—N2A−3 (3)C7—C8—C9—C100.2 (8)
C2A—N1A—C3A—N2A178.8 (14)C7—C8—C9—Cl2179.5 (4)
N1A—C3A—N2A—C4A3 (2)C8—C9—C10—C11−0.6 (9)
C3A—N2A—C4A—C5A−3 (3)Cl2—C9—C10—C11−179.8 (4)
N2A—C4A—C5A—N1A1 (3)C7—C6—C11—C10−0.1 (8)
C3A—N1A—C5A—C4A1 (3)C1—C6—C11—C10179.9 (5)
C2A—N1A—C5A—C4A179.2 (15)C9—C10—C11—C60.5 (9)
O1—C1—C2B—N1B−71.8 (10)C1—O1—C12—C13174.5 (4)
C6—C1—C2B—N1B167.6 (9)O1—C12—C13—C14−165.8 (4)
C1—C2B—N1B—C3B84 (3)O1—C12—C13—C1815.8 (6)
C1—C2B—N1B—C5B−88 (3)C18—C13—C14—C15−1.1 (7)
C5B—N1B—C3B—N2B−2 (3)C12—C13—C14—C15−179.5 (5)
C2B—N1B—C3B—N2B−175 (2)C18—C13—C14—Cl3179.8 (4)
N1B—C3B—N2B—C4B−2 (3)C12—C13—C14—Cl31.3 (6)
C3B—N2B—C4B—C5B5 (3)C13—C14—C15—C160.2 (8)
N2B—C4B—C5B—N1B−7 (4)Cl3—C14—C15—C16179.4 (4)
C3B—N1B—C5B—C4B6 (4)C14—C15—C16—C170.5 (8)
C2B—N1B—C5B—C4B−180 (2)C14—C15—C16—Cl4178.9 (4)
O1—C1—C6—C11−22.3 (6)C15—C16—C17—C18−0.4 (8)
C2B—C1—C6—C1195.4 (5)Cl4—C16—C17—C18−178.7 (4)
C2A—C1—C6—C1195.4 (5)C14—C13—C18—C171.2 (7)
O1—C1—C6—C7157.7 (4)C12—C13—C18—C17179.7 (4)
C2B—C1—C6—C7−84.5 (6)C16—C17—C18—C13−0.5 (8)
Dihedral angles (°) between the best planes in pure solvent-free polymorphic MIC-structures top
1(A/B) is the imidazole ring, 2 and 3 are the dichlorophenyl rings.
1(A/B)/21(A/B)/32/3
MIC-tri-A2.4 (1)68.5 (1)69.2 (3)
MIC-tri-B1.5 (1)68.0 (1)69.2 (3)
MIC-mono16.8 (2)22.2 (2)5.4 (2)
Interaction energies (kJ mol-1) for the cluster of molecules with a radius of 3.8Å for MIC-tri top
N is the number of molecular pairs. R is the distance (Å) between molecular centroids. Etot is the total energy and Eele is the electrostatic (k = 1.057), Epol is the polarization (k = 0.740), Edis is the dispersion (k = 0.871) and Erep is the repulsion (k = 0.618) component.
NRkEelekEpolkEdiskErepEtot
110.41-4.65-0.44-11.159.64-6.6
29.42-2.01-1.26-19.777.66-15.3
16.73-16.28-3.26-64.1127.01-56.6
17.88-8.46-0.67-43.2917.00-35.4
29.49-0.21-0.44-7.404.02-4.1
110.72-1.27-0.15-11.673.77-9.2
19.90-27.38-5.77-19.257.54-45.0
18.583.59-1.26-32.496.86-23.4
214.04-2.85-0.07-4.884.51-3.3
213.03-2.01-0.07-6.623.58-5.1
18.22-6.76-0.96-26.919.08-25.5
110.23-3.38-0.74-11.935.99-10.1
 

Acknowledgements

Financial support from the University of Lodz Doctoral School of Exact and Natural Sciences is gratefully acknowledged.

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ISSN: 2056-9890
Volume 80| Part 2| February 2024| Pages 196-200
https://doi.org/10.1107/S2056989024000276
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