Hydrogen ADPs with Cu Kα data? Invariom and Hirshfeld atom modelling of fluconazole

For the structure of fluconazole [systematic name: 2-(2,4-di­­fluoro­phen­yl)-1,3-bis­(1H-1,2,4-triazol-1-yl)pro­pan-2-ol] mono­hydrate, C₁₃H₁₂F₂N₆O·H₂O, a case study on different model refinements is reported, based on single-crystal X-ray diffraction data measured at 100 K with Cu Kα radiation to a resolution of sin θ/λ of 0.6 Å⁻¹. The structure, anisotropic dis­place­ment parameters (ADPs) and figures of merit from the independent atom model are compared to `invariom' and `Hirshfeld atom' refinements. Changing from a spherical to an aspherical atom model lowers the figures of merit and improves both the accuracy and the precision of the geometrical parameters. Differences between results from the two aspherical-atom refinements are small. However, a refinement of ADPs for H atoms is only possible with the Hirshfeld atom density model. It gives meaningful results even at a resolution of 0.6 Å⁻¹, but requires good low-order data.

S1. Introduction

Fluconazole is an anti­fungal drug consisting of two triazole units and a fluorinated phenyl ring. Different solvates and cocrystals of this drug are known (Caira et al. 2004; Karanam et al. 2012). We report a case study on the monohydrate structure as reported by Caira et al., measured with longer wavelength and at lower temperature. A detailed investigation of different polymorphs and solvates of fluconazole by Karanam et al. names this form monohydrate No. II. These authors also report structures of another monohydrate, three anhydrous forms and several other cocrystals. Fluconazole monohydrate forms crystals of good quality and its structure was therefore subjected to a comparative study of three refinement models that use different atomic scattering factors.

The invariom concept (Dittrich et al., 2004, 2013) and Hirshfeld atom refinement (HA refinement) (Jayatilaka & Dittrich, 2008) both take into account nonspherical electron density in the scattering factor formalism. For the first of the two approaches, theoretically computed electron density of model compounds is partitioned into transferable `pseudo-atom' electron-density fragments using the multipole formalism of Hansen & Coppens (Hansen & Coppens, 1978; Coppens, 1997) and then tabulated. In HA refinement, the second approach, the molecular geometry of a preliminary X-ray structure refinement is used as a starting point for a quantum mechanical single-point computation of the whole asymmetric unit of the crystal. Molecular electron density is then partitioned into HAs (Hirshfeld, 1977). Partitioning and Fourier transform give atomic scattering factors, which are used in least-squares refinement of position and anisotropic displacement parameters (ADPs). After each refinement cycle, a new single-point electron density is calculated and the procedure is repeated to convergence.

In contrast to invariom refinement relying on pseudo-atoms (Stewart, 1976), this procedure allows to include point charges as obtained from the partitioning for the surrounding molecules to approximate a crystal field (Jayatilaka & Dittrich, 2008; Dittrich et al., 2012). However, HA refinement requires a higher computational cost than the use of tabulated scattering factors due to the single-point computation, but has the potential to be closer to the real electron-density distribution present in the crystal. Especially, hydrogen-bonded systems should benefit from inclusion of the approximate crystal field.

The refined parameters in both aspherical-atom models are the same as in the conventional independent atom model (IAM): positions and ADPs of the atoms in the structure. Therefore, data of standard small-molecule structures at `normal' resolution (fullfilling Acta Crystallographica Section C requirements) should be sufficient even for adjusting hydrogen ADPs in favourable cases (for further background information, see Cooper et al., 2010), and this is further investigated. Since the hydrogen ADPs reported here are obtained from X-ray diffraction, they should also be useful in comparisons to estimated values of hydrogen ADPs, e.g. from the SHADE server (Madsen, 2006).

S2. Experimental

S2.1. Synthesis and crystallization

Crystals were obtained by recrystallization of the commercially available drug from ethanol/water.

S2.2. Refinement

Invariom refinements were carried out with a reparameterized version of XD2006 (Volkov et al., 2006), while the open source program TONTO (Jayatilaka & Grimwood, 2003) was used for HA refinements. The algorithm used in TONTO was `refine_hirshfeld_atoms' as introduced in 2008 (Jayatilaka & Dittrich, 2008). H-atom positions were refined freely in all three models. Additionaly, a typical refinement with riding H atoms and constrained U_iso values was carried out.

Figures of merit (Table 2) improve when the electron density is modelled by aspherical form factors. Both aspherical models, invariom and HA, show a considerably lower R value for the same number of refined parameters. R factors for invariom and HA refinement are almost identical for models with isotropic descriptions of H-atom displacements.

To allow comparison, refinements were performed using all reflections with weights of 1/σ², although application of a SHELXL-type weighting scheme and 4σ(F) cut-off yield a slightly better R(F). HA refinement with anisotropic hydrogen ADPs shows the best agreement between F_obs and F_calc.

Crystal data, information on data collection and details on structure refinement are summarized in Table 1 and 2.

S3. Results and discussion

Structural parameters show the expected promolecule bias in the IAM: distances to H atoms are closer to results from neutron diffraction in both aspherical-atom models, since bonding electron density is better described.

Comparing bond distances and angles from invariom and HA refinement shows no significant differences. However, since invariom refinement does not take into account inter­molecular inter­actions, this would probably be different for atoms involved in strong hydrogen bonds. The three strongest hydrogen bonds in this structure are all conventional hydrogen bonds according to Gilli & Gilli (2009). For the hydrogen bond between atom O1 and water hydrogen H1, the standard uncertainty (s.u.) of the O1—H1 bond is higher than the difference between the two aspherical-atom refinements. It can be expected that for the two water H atoms accepted by N6 and N3 the hydrogen bonds become more linear in HA refinement compared to invariom and IAM refinements, and that donor hydrogen bonds elongate while acceptor hydrogen-bond distances shorten. However, such effects could not be observed for our data set and are probably beyond the precision reachable with data of limited resolution. An improved description of hydrogen bonds by the HA model might only be dete­cta­ble at higher resolution, and this has recently been studied by Capelli et al. (2014) by comparing neutron and X-ray data.

Bond distances and angles between non-H atoms gain precision in the following order: (i) a constraint IAM, (ii) an unconstraint IAM and (iii) the aspherical density models as illustrated by the geometrical parameters selected in Tables 3–6. The s.u. for non-H bond lengths drops by 25% when the H-atom parameters are allowed to refine. Upon using the tabulated invariom form factors, the s.u. values of the bond lengths decrease by another 40%, on average.

The improvement of bond-length precision of the HA model compared to the invariom model is unexpected, and may be explained by the fact that different refinement programs and CIF creation routines were used. If both bond length are recalculated with PLATON (Spek, 2009), thereby not taking into account the information of the covariance matrix, only slightly smaller s.u. values are observed for the HA model. Nevertheless, indications remain that the s.u. values of the geometrical parameters are either underestimated by XD2006 (Volkov et al., 2006) or overestimaed by the TONTO (Jayatilaka & Grimwood, 2003) routine `refine_hirshfeld_atoms'. One such indication in XD2006 is that the geometrical parameters of different models vary more than the s.u. values would allow.

The changes of the ADPs upon introduction of asphericity are shown in a PEANUT plot (Hummel et al. 1990) in Fig. 1. It illustrates that the ADPs of the aspherical invariom model are less biased by bonding electron density than in the IAM.

In the HA model, displacement parameters of the H atoms were either refined isotropically or anisotropically. The figure of merit used in TONTO, the χ² value, suggests an improvement of the model upon including the anisotropic description of hydrogen displacements (7.91 to 6.94), although the data-to-parameter ratio then is below 10 (334 parameters and 2824 reflections). Fig. 2 shows the result of anisotropic refinement in an ORTEP plot (Burnett & Johnson, 1996). Size and shape of the ADPs look reasonable and are likely to carry physical meaning. The orientation of the hydrogen ADPs on the planar ring systems is, although no restraints were used, similar to those of neighbouring non-H atoms. The U_ij values for atoms C9, C10, C12, C13, C4, C6 and C7 display this nicely. These results for fluconazol provide a strong indication that the refinement of reasonable hydrogen ADP is indeed possible by HA refinement even at resolutions reachable with Cu Kα radiation.

As mentioned above, this work has still been carried out using the algorithm coded for the original work on HA refinement, where convergence needed to be ensured `by hand'. Considerable improvements to automatically reach convergence and a more rigurous treatment of s.u. values in an improved HA refinement routine will soon be reported in a detailed study on a dipeptide by Capelli et al. (2014).

S4. Conclusion

HA refinement can take into account the field generated by point charges and dipoles. This enables refinement of H-atom positions and their anisotropic displacements even at the relatively low resolution reachable with Cu Kα radiation. HA refinement is therefore the most advanced model available to date for modelling electron density of molecular compounds in the solid state. However, considering that a refinement using tabulated invariom scattering factors does not take much longer than a conventional IAM refinement, whereas HA refinement with the modest method/basis set combination HF/6-31G* took around 14 CPU hours, the good agreement for the two models shows that both invariom and HA refinement have complementary applications. Results are of similar quality, but only HA refinement allows adjusting ADPs of H atoms to the X-ray data.

S4.1. Acknowledgement

We thank Paolo Pabbiani for a sample of fluconazole and George Sheldrick for diffractometer access.

Related literature

For related literature, see: Caira et al. (2004); Capelli et al. (2014); Cooper et al. (2010); Coppens (1997); Dittrich et al. (2004, 2012, 2013); Gilli & Gilli (2009); Hansen & Coppens (1978); Hirshfeld (1977); Jayatilaka & Dittrich (2008); Jayatilaka & Grimwood (2003); Karanam et al. (2012); Madsen (2006); Stewart (1976); Volkov et al. (2006).

Computing details

For all compounds, data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008). Program(s) used to refine structure: XD2006 (Volkov et al., 2006) for constrained_IAM; XD2006 (Volkov et al., 2006) for IAM, Invariom; TONTO (Jayatilaka & Grimwood, 2003) for Hirshfeld, Hirshfeld-HADP. For all compounds, molecular graphics: PLATON (Spek, 2009) and ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: publCIF (Westrip, 2010).

Figures

PEANUT plot (Hummel et al. 1990) of fluconazol. U values of the invariom refinement were subtracted from those of the `spherical' IAM refinement. Blue meshes with ΔU > 0 show how ADPs of the IAM partially model bonding electron density.

ORTEPIII (Burnett & Johnson, 1996) plot of fluconazole with displacement ellipsoids at the 50% probability level for all atoms including hydrogen after HA refinement.

(constrained_IAM) 2-(2,4-Difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol monohydrate

Crystal data

C13H12F2N6O·H2O	Z = 2
Mr = 324.29	F(000) = 336
Triclinic, P1	Dx = 1.470 Mg m^−3
Hall symbol: -p 1	Cu Kα radiation, λ = 1.54178 Å
a = 5.5708 (3) Å	Cell parameters from 9877 reflections
b = 11.6873 (6) Å	θ = 3.9–74.1°
c = 12.1490 (7) Å	µ = 1.04 mm^−1
α = 70.990 (2)°	T = 100 K
β = 78.911 (2)°	Block, colourless
γ = 84.627 (2)°	0.18 × 0.10 × 0.08 mm
V = 733.47 (7) Å^3

Data collection

Bruker SMART 6000 diffractometer	2824 independent reflections
Radiation source: rotating anode	2824 reflections with I > 0σ(I)
INCOATEC optics monochromator	Rint = 0.030
ω and ϕ scans	θmax = 74.1°, θmin = 3.9°
Absorption correction: empirical (using intensity measurements) (SADABS; Sheldrick, 2012)	h = −6→6
Tmin = 0.682, Tmax = 0.754	k = −14→14
15433 measured reflections	l = −14→13

Refinement

Refinement on F	0 restraints
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.045	w1 = 1/[s^2(Fo)]
wR(F^2) = 0.069	(Δ/σ)max < 0.001
S = 7.40	Δρmax = 0.42 e Å^−3
2824 reflections	Δρmin = −0.40 e Å^−3
208 parameters

Special details

Experimental. Cooling of aqueous solution from 343 K to room temperature.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
F1	0.02432 (17)	0.36908 (8)	0.54121 (8)	0.021
F2	0.4984 (2)	0.13573 (10)	0.32706 (9)	0.036
O1	0.55145 (19)	0.29192 (9)	0.76707 (9)	0.017
O1W	0.4752 (2)	0.26866 (9)	0.99845 (10)	0.02
N1	0.2722 (2)	0.51826 (10)	0.75852 (11)	0.015
N2	0.0424 (2)	0.55734 (11)	0.79554 (11)	0.018
N3	0.3111 (3)	0.59688 (11)	0.89424 (11)	0.02
N4	0.1332 (2)	0.13561 (11)	0.83288 (11)	0.015
N5	0.0123 (3)	0.07375 (12)	0.78442 (12)	0.021
N6	0.2502 (3)	−0.05347 (12)	0.90484 (12)	0.023
C1	0.3442 (3)	0.32262 (12)	0.71149 (12)	0.014
C2	0.3892 (3)	0.27392 (12)	0.60658 (12)	0.015
C3	0.2274 (3)	0.29820 (12)	0.52722 (13)	0.017
C4	0.2597 (3)	0.25415 (13)	0.43241 (13)	0.02
C5	0.4629 (3)	0.17988 (15)	0.41877 (14)	0.024
C6	0.6286 (3)	0.14962 (15)	0.49607 (15)	0.024
C7	0.5903 (3)	0.19671 (13)	0.58924 (14)	0.018
C8	0.3187 (3)	0.46232 (13)	0.66484 (13)	0.016
C13	0.2734 (3)	0.05829 (13)	0.90304 (14)	0.02
C12	0.0885 (3)	−0.03865 (14)	0.83082 (14)	0.023
C11	0.1148 (3)	0.26731 (12)	0.79880 (12)	0.014
C10	0.4293 (3)	0.54281 (12)	0.81797 (13)	0.017
C9	0.0775 (3)	0.60388 (13)	0.87655 (14)	0.019
H1	0.5142	0.29089	0.83425	0.0243
H1W	0.51548	0.32579	1.01987	0.0315
H2W	0.5559	0.20766	1.03530	0.0306
H4	0.1467	0.27405	0.37902	0.0251
H6	0.7659	0.09731	0.48522	0.0283
H7	0.7032	0.17648	0.64269	0.0219
H8B	0.1833	0.48580	0.61884	0.0197
H8A	0.4714	0.49434	0.61067	0.0197
H13	0.3763	0.08067	0.94606	0.0246
H12	0.0340	−0.10480	0.81398	0.0279
H11B	−0.0320	0.29628	0.76145	0.0162
H11A	0.0960	0.29363	0.86973	0.0162
H10	0.6002	0.52409	0.80718	0.0201
H9	−0.0513	0.64003	0.91904	0.0232

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F1	0.0216 (5)	0.0201 (4)	0.0240 (5)	0.0025 (4)	−0.0117 (4)	−0.0069 (4)
F2	0.0480 (8)	0.0407 (6)	0.0256 (6)	−0.0004 (5)	−0.0029 (5)	−0.0213 (5)
O1	0.0108 (6)	0.0258 (5)	0.0155 (5)	0.0014 (4)	−0.0051 (4)	−0.0073 (4)
O1W	0.0262 (7)	0.0163 (5)	0.0208 (6)	0.0005 (4)	−0.0102 (5)	−0.0065 (4)
N1	0.0151 (7)	0.0125 (6)	0.0173 (6)	−0.0010 (5)	−0.0057 (5)	−0.0029 (5)
N2	0.0163 (7)	0.0165 (6)	0.0210 (7)	0.0023 (5)	−0.0060 (5)	−0.0041 (5)
N3	0.0220 (7)	0.0162 (6)	0.0217 (7)	−0.0032 (5)	−0.0069 (5)	−0.0053 (5)
N4	0.0139 (7)	0.0149 (6)	0.0147 (6)	−0.0020 (5)	−0.0027 (5)	−0.0030 (5)
N5	0.0197 (7)	0.0202 (6)	0.0266 (7)	−0.0049 (5)	−0.0059 (5)	−0.0083 (5)
N6	0.0313 (8)	0.0185 (6)	0.0178 (7)	0.0012 (5)	−0.0067 (6)	−0.0033 (5)
C1	0.0117 (8)	0.0162 (7)	0.0144 (7)	0.0010 (5)	−0.0059 (5)	−0.0042 (5)
C2	0.0142 (8)	0.0111 (6)	0.0159 (7)	−0.0044 (5)	0.0012 (5)	−0.0015 (5)
C3	0.0160 (8)	0.0118 (6)	0.0194 (7)	−0.0043 (6)	−0.0018 (6)	−0.0016 (5)
C4	0.0272 (9)	0.0207 (7)	0.0145 (7)	−0.0037 (6)	−0.0068 (6)	−0.0044 (6)
C5	0.0290 (10)	0.0239 (8)	0.0187 (8)	−0.0041 (7)	0.0007 (6)	−0.0098 (6)
C6	0.0224 (9)	0.0232 (8)	0.0249 (8)	−0.0017 (6)	0.0007 (6)	−0.0100 (6)
C7	0.0150 (8)	0.0188 (7)	0.0204 (8)	−0.0027 (6)	−0.0003 (6)	−0.0058 (6)
C8	0.0188 (8)	0.0163 (7)	0.0134 (7)	−0.0040 (6)	−0.0036 (6)	−0.0030 (5)
C13	0.0247 (9)	0.0164 (7)	0.0177 (8)	0.0006 (6)	−0.0076 (6)	−0.0009 (6)
C12	0.0298 (10)	0.0173 (7)	0.0223 (8)	−0.0017 (6)	−0.0054 (7)	−0.0063 (6)
C11	0.0118 (8)	0.0141 (7)	0.0155 (7)	0.0015 (5)	−0.0045 (5)	−0.0048 (5)
C10	0.0173 (8)	0.0129 (6)	0.0208 (8)	−0.0035 (6)	−0.0063 (6)	−0.0032 (6)
C9	0.0207 (8)	0.0173 (7)	0.0195 (8)	0.0007 (6)	−0.0050 (6)	−0.0050 (6)

Geometric parameters (Å, º)

F1—C3	1.3555 (19)	C1—C11	1.537 (2)
F2—C5	1.3480 (19)	C2—C3	1.389 (2)
O1—C1	1.4081 (16)	C2—C7	1.399 (2)
O1—H1	0.7989	C3—C4	1.383 (2)
O1W—H1W	0.8529	C4—C5	1.378 (3)
O1W—H2W	0.8485	C4—H4	0.9500
N1—N2	1.3613 (19)	C5—C6	1.384 (2)
N1—C8	1.4592 (19)	C6—C7	1.386 (2)
N1—C10	1.3399 (19)	C6—H6	0.9500
N2—C9	1.321 (2)	C7—H7	0.9500
N3—C10	1.327 (2)	C8—H8B	0.9900
N3—C9	1.350 (2)	C8—H8A	0.9900
N4—N5	1.3577 (18)	C13—H13	0.9500
N4—C13	1.333 (2)	C12—H12	0.9500
N4—C11	1.4569 (18)	C11—H11B	0.9900
N5—C12	1.315 (2)	C11—H11A	0.9900
N6—C13	1.317 (2)	C10—H10	0.9500
N6—C12	1.353 (2)	C9—H9	0.9500
C1—C2	1.528 (2)
C1—O1—H1	109.64 (14)	C4—C5—C6	122.05 (15)
H1W—O1W—H2W	103.33 (10)	C5—C6—C7	118.89 (16)
N2—N1—C8	120.73 (12)	C5—C6—H6	120.30 (10)
N2—N1—C10	109.69 (12)	C7—C6—H6	120.82 (10)
C8—N1—C10	129.56 (13)	C2—C7—C6	121.61 (15)
N1—N2—C9	102.34 (13)	C2—C7—H7	118.94 (9)
C10—N3—C9	103.01 (13)	C6—C7—H7	119.45 (10)
N5—N4—C13	109.25 (12)	N1—C8—H8B	108.93 (8)
N5—N4—C11	121.14 (12)	N1—C8—H8A	108.75 (7)
C13—N4—C11	129.40 (13)	N4—C13—N6	110.90 (14)
N4—N5—C12	102.44 (13)	N4—C13—H13	124.60 (9)
C13—N6—C12	102.35 (13)	N6—C13—H13	124.50 (9)
O1—C1—C2	107.97 (12)	N5—C12—N6	115.06 (14)
O1—C1—C11	110.29 (11)	N5—C12—H12	122.66 (9)
C2—C1—C11	110.32 (11)	N6—C12—H12	122.29 (8)
C1—C2—C3	122.21 (13)	N4—C11—C1	110.43 (12)
C1—C2—C7	121.31 (13)	N4—C11—H11B	109.11 (7)
C3—C2—C7	116.39 (14)	N4—C11—H11A	109.91 (7)
F1—C3—C2	119.48 (13)	C1—C11—H11B	109.62 (7)
F1—C3—C4	116.62 (13)	C1—C11—H11A	109.60 (8)
C2—C3—C4	123.90 (15)	N1—C10—N3	110.00 (14)
C3—C4—C5	117.13 (15)	N1—C10—H10	124.98 (9)
C3—C4—H4	121.52 (9)	N3—C10—H10	125.02 (9)
C5—C4—H4	121.35 (9)	N2—C9—N3	114.96 (14)
F2—C5—C4	118.27 (15)	N2—C9—H9	122.77 (9)
F2—C5—C6	119.68 (16)	N3—C9—H9	122.27 (9)

(IAM) 2-(2,4-Difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol monohydrate

Crystal data

C13H12F2N6O·H2O	Z = 2
Mr = 324.29	F(000) = 336
Triclinic, P1	Dx = 1.470 Mg m^−3
Hall symbol: -p 1	Cu Kα radiation, λ = 1.54178 Å
a = 5.5708 (3) Å	Cell parameters from 9877 reflections
b = 11.6873 (6) Å	θ = 3.9–74.1°
c = 12.1490 (7) Å	µ = 1.04 mm^−1
α = 70.990 (2)°	T = 100 K
β = 78.911 (2)°	Block, colourless
γ = 84.627 (2)°	0.18 × 0.10 × 0.08 mm
V = 733.47 (7) Å^3

Data collection

Bruker SMART 6000 diffractometer	2824 independent reflections
Radiation source: rotating anode	2824 reflections with I > 0σ(I)
INCOATEC optics monochromator	Rint = 0.030
ω and ϕ scans	θmax = 74.1°, θmin = 3.9°
Absorption correction: empirical (using intensity measurements) (SADABS; Sheldrick, 2012)	h = −6→6
Tmin = 0.682, Tmax = 0.754	k = −14→14
15433 measured reflections	l = −14→13

Refinement

Refinement on F	0 restraints
Least-squares matrix: full	All H-atom parameters refined
R[F^2 > 2σ(F^2)] = 0.032	w1 = 1/[s^2(Fo)]
wR(F^2) = 0.047	(Δ/σ)max < 0.001
S = 5.06	Δρmax = 0.35 e Å^−3
2824 reflections	Δρmin = −0.28 e Å^−3
264 parameters

Special details

Experimental. Cooling of aqueous solution from 343 K to room temperature.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
F1	0.02382 (12)	0.36923 (5)	0.54113 (5)	0.021
F2	0.49859 (16)	0.13572 (7)	0.32693 (6)	0.036
O1	0.55215 (13)	0.29161 (6)	0.76704 (7)	0.017
O1W	0.47526 (15)	0.26795 (7)	0.99824 (7)	0.021
N1	0.27205 (16)	0.51833 (7)	0.75845 (7)	0.015
N2	0.04189 (17)	0.55757 (8)	0.79554 (8)	0.019
N3	0.31183 (18)	0.59712 (8)	0.89426 (8)	0.02
N4	0.13279 (16)	0.13555 (7)	0.83302 (7)	0.015
N5	0.01141 (18)	0.07371 (8)	0.78435 (8)	0.022
N6	0.25063 (19)	−0.05384 (8)	0.90521 (8)	0.023
C1	0.34428 (18)	0.32284 (8)	0.71144 (8)	0.014
C2	0.38931 (19)	0.27378 (8)	0.60674 (8)	0.015
C3	0.2275 (2)	0.29817 (9)	0.52685 (9)	0.017
C4	0.2597 (2)	0.25416 (9)	0.43217 (9)	0.021
C5	0.4629 (2)	0.18000 (10)	0.41903 (10)	0.024
C6	0.6288 (2)	0.14952 (10)	0.49584 (10)	0.024
C7	0.5899 (2)	0.19693 (9)	0.58954 (9)	0.019
C8	0.3187 (2)	0.46261 (9)	0.66477 (9)	0.016
C13	0.2733 (2)	0.05854 (9)	0.90343 (9)	0.021
C12	0.0883 (2)	−0.03893 (10)	0.83100 (10)	0.024
C11	0.11422 (18)	0.26738 (8)	0.79898 (9)	0.014
C10	0.4296 (2)	0.54285 (9)	0.81787 (9)	0.017
C9	0.0770 (2)	0.60414 (9)	0.87641 (10)	0.02
H1	0.513 (3)	0.2927 (14)	0.8390 (15)	0.039 (4)
H1W	0.547 (4)	0.2037 (19)	1.0267 (17)	0.058 (5)
H2W	0.532 (3)	0.3191 (16)	1.0234 (15)	0.045 (4)
H4	0.145 (3)	0.2762 (13)	0.3790 (13)	0.033 (3)
H6	0.767 (3)	0.0954 (15)	0.4823 (13)	0.042 (4)
H7	0.705 (3)	0.1735 (12)	0.6438 (12)	0.029 (3)
H8B	0.184 (3)	0.4903 (12)	0.6195 (12)	0.027 (3)
H8A	0.475 (3)	0.4912 (12)	0.6160 (12)	0.029 (3)
H13	0.368 (3)	0.0835 (13)	0.9458 (13)	0.034 (4)
H12	0.032 (3)	−0.1076 (14)	0.8117 (13)	0.039 (4)
H11B	−0.028 (3)	0.2922 (11)	0.7651 (11)	0.021 (3)
H11A	0.094 (3)	0.2908 (11)	0.8693 (12)	0.023 (3)
H10	0.600 (3)	0.5245 (13)	0.8045 (12)	0.034 (4)
H9	−0.055 (3)	0.6424 (13)	0.9199 (13)	0.032 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F1	0.0206 (4)	0.0205 (3)	0.0250 (3)	0.0043 (2)	−0.0117 (3)	−0.0075 (2)
F2	0.0487 (5)	0.0408 (4)	0.0254 (4)	−0.0001 (4)	−0.0026 (3)	−0.0214 (3)
O1	0.0113 (4)	0.0248 (4)	0.0170 (4)	0.0004 (3)	−0.0051 (3)	−0.0068 (3)
O1W	0.0281 (5)	0.0180 (4)	0.0219 (4)	0.0012 (3)	−0.0123 (3)	−0.0072 (3)
N1	0.0145 (5)	0.0136 (4)	0.0177 (4)	−0.0011 (3)	−0.0046 (3)	−0.0037 (3)
N2	0.0152 (5)	0.0193 (4)	0.0216 (5)	0.0007 (3)	−0.0048 (3)	−0.0055 (3)
N3	0.0236 (5)	0.0166 (4)	0.0213 (5)	−0.0019 (3)	−0.0071 (4)	−0.0063 (3)
N4	0.0149 (5)	0.0145 (4)	0.0148 (4)	−0.0016 (3)	−0.0027 (3)	−0.0032 (3)
N5	0.0231 (5)	0.0193 (4)	0.0248 (5)	−0.0036 (4)	−0.0078 (4)	−0.0074 (4)
N6	0.0321 (6)	0.0166 (4)	0.0209 (5)	0.0011 (4)	−0.0073 (4)	−0.0040 (3)
C1	0.0124 (5)	0.0153 (5)	0.0152 (5)	0.0000 (4)	−0.0050 (4)	−0.0034 (4)
C2	0.0145 (5)	0.0134 (4)	0.0147 (5)	−0.0040 (4)	−0.0011 (4)	−0.0015 (4)
C3	0.0167 (5)	0.0133 (4)	0.0179 (5)	−0.0014 (4)	−0.0029 (4)	−0.0018 (4)
C4	0.0282 (7)	0.0194 (5)	0.0156 (5)	−0.0058 (4)	−0.0060 (4)	−0.0027 (4)
C5	0.0319 (7)	0.0230 (5)	0.0179 (5)	−0.0063 (5)	0.0025 (4)	−0.0096 (4)
C6	0.0223 (6)	0.0230 (5)	0.0275 (6)	−0.0004 (5)	0.0020 (4)	−0.0111 (4)
C7	0.0158 (6)	0.0194 (5)	0.0205 (5)	−0.0020 (4)	−0.0024 (4)	−0.0054 (4)
C8	0.0206 (6)	0.0151 (5)	0.0142 (5)	−0.0031 (4)	−0.0043 (4)	−0.0038 (4)
C13	0.0258 (6)	0.0168 (5)	0.0193 (5)	0.0006 (4)	−0.0096 (4)	−0.0024 (4)
C12	0.0310 (7)	0.0174 (5)	0.0236 (6)	−0.0027 (4)	−0.0056 (4)	−0.0074 (4)
C11	0.0124 (5)	0.0132 (4)	0.0160 (5)	0.0008 (4)	−0.0036 (4)	−0.0035 (4)
C10	0.0162 (6)	0.0150 (4)	0.0208 (5)	−0.0028 (4)	−0.0060 (4)	−0.0042 (4)
C9	0.0216 (6)	0.0178 (5)	0.0202 (5)	0.0009 (4)	−0.0044 (4)	−0.0060 (4)

Geometric parameters (Å, º)

F1—C3	1.3600 (13)	C1—C2	1.5281 (14)
F2—C5	1.3534 (13)	C2—C3	1.3942 (14)
O1—C1	1.4112 (11)	C2—C7	1.3939 (15)
O1—H1	0.863 (17)	C3—C4	1.3815 (16)
O1W—H1W	0.82 (2)	C4—C5	1.3767 (18)
O1W—H2W	0.86 (2)	C4—H4	0.953 (16)
N1—N2	1.3637 (13)	C5—C6	1.3799 (18)
N1—C8	1.4575 (13)	C6—C7	1.3941 (17)
N1—C10	1.3412 (13)	C6—H6	0.974 (17)
N2—C9	1.3198 (15)	C7—H7	0.968 (15)
N3—C10	1.3286 (15)	C8—H8B	0.985 (14)
N3—C9	1.3576 (15)	C8—H8A	0.972 (16)
N4—N5	1.3612 (13)	C13—H13	0.927 (16)
N4—C13	1.3337 (14)	C12—H12	0.997 (16)
N4—C11	1.4584 (12)	C11—H11B	0.941 (14)
N5—C12	1.3189 (15)	C11—H11A	0.962 (14)
N6—C13	1.3241 (14)	C10—H10	0.946 (17)
N6—C12	1.3574 (15)	C9—H9	0.980 (15)
C1—O1—H1	109.4 (11)	C5—C6—C7	118.56 (11)
H1W—O1W—H2W	104.7 (17)	C5—C6—H6	118.4 (9)
N2—N1—C8	120.82 (8)	C7—C6—H6	123.1 (9)
N2—N1—C10	109.71 (8)	C2—C7—C6	121.62 (10)
C8—N1—C10	129.44 (9)	C2—C7—H7	120.6 (8)
N1—N2—C9	102.39 (9)	C6—C7—H7	117.8 (8)
C10—N3—C9	102.81 (9)	N1—C8—H8B	106.5 (8)
N5—N4—C13	109.60 (8)	N1—C8—H8A	107.2 (8)
N5—N4—C11	121.03 (8)	H8B—C8—H8A	111.1 (11)
C13—N4—C11	129.17 (9)	N4—C13—N6	110.77 (10)
N4—N5—C12	102.18 (9)	N4—C13—H13	122.4 (9)
C13—N6—C12	102.21 (9)	N6—C13—H13	126.8 (9)
O1—C1—C2	107.70 (8)	N5—C12—N6	115.23 (10)
C1—C2—C3	122.26 (9)	N5—C12—H12	121.9 (9)
C1—C2—C7	121.33 (9)	N6—C12—H12	122.9 (9)
C3—C2—C7	116.34 (9)	N4—C11—H11B	107.3 (8)
F1—C3—C2	119.23 (9)	N4—C11—H11A	108.5 (7)
F1—C3—C4	116.72 (9)	H11B—C11—H11A	108.2 (11)
C2—C3—C4	124.05 (10)	N1—C10—N3	110.10 (10)
C3—C4—C5	116.84 (10)	N1—C10—H10	123.4 (9)
C3—C4—H4	120.2 (9)	N3—C10—H10	126.5 (9)
C5—C4—H4	123.0 (9)	N2—C9—N3	114.98 (10)
F2—C5—C4	117.97 (11)	N2—C9—H9	123.2 (9)
F2—C5—C6	119.45 (11)	N3—C9—H9	121.8 (9)
C4—C5—C6	122.57 (10)

(Invariom) 2-(2,4-Difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol monohydrate

Crystal data

C13H12F2N6O·H2O	Z = 2
Mr = 324.29	F(000) = 336
Triclinic, P1	Dx = 1.470 Mg m^−3
Hall symbol: -p 1	Cu Kα radiation, λ = 1.54178 Å
a = 5.5708 (3) Å	Cell parameters from 9877 reflections
b = 11.6873 (6) Å	θ = 3.9–74.1°
c = 12.1490 (7) Å	µ = 1.04 mm^−1
α = 70.990 (2)°	T = 100 K
β = 78.911 (2)°	Block, colourless
γ = 84.627 (2)°	0.18 × 0.10 × 0.08 mm
V = 733.47 (7) Å^3

Data collection

Bruker SMART 6000 diffractometer	2824 independent reflections
Radiation source: rotating anode	2824 reflections with I > 0σ(I)
INCOATEC optics monochromator	Rint = 0.030
ω and ϕ scans	θmax = 74.1°, θmin = 3.9°
Absorption correction: empirical (using intensity measurements) (SADABS; Sheldrick, 2012)	h = −6→6
Tmin = 0.682, Tmax = 0.754	k = −14→14
15433 measured reflections	l = −14→13

Refinement

Refinement on F	0 restraints
Least-squares matrix: full	All H-atom parameters refined
R[F^2 > 2σ(F^2)] = 0.02	w1 = 1/[s^2(Fo)]
wR(F^2) = 0.027	(Δ/σ)max < 0.001
S = 2.95	Δρmax = 0.24 e Å^−3
2824 reflections	Δρmin = −0.24 e Å^−3
264 parameters

Special details

Experimental. Cooling of aqueous solution from 343 K to room temperature.

Refinement. An invariom refinement (Dittrich; Acta Cryst. A62, 217) was performed.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
F1	0.02421 (7)	0.36911 (3)	0.54119 (3)	0.019
F2	0.49843 (9)	0.13580 (4)	0.32709 (4)	0.034
O1	0.55123 (8)	0.29169 (4)	0.76742 (4)	0.015
O1W	0.47593 (9)	0.26778 (4)	0.99855 (4)	0.02
N1	0.27216 (9)	0.51818 (4)	0.75837 (4)	0.013
N2	0.04283 (10)	0.55757 (5)	0.79544 (5)	0.017
N3	0.31197 (10)	0.59695 (4)	0.89406 (5)	0.018
N4	0.13259 (9)	0.13578 (4)	0.83288 (4)	0.013
N5	0.01194 (10)	0.07372 (5)	0.78461 (5)	0.02
N6	0.25035 (11)	−0.05357 (5)	0.90512 (5)	0.021
C1	0.34460 (10)	0.32298 (5)	0.71161 (5)	0.012
C2	0.38890 (11)	0.27390 (5)	0.60684 (5)	0.012
C3	0.22724 (11)	0.29843 (5)	0.52693 (5)	0.014
C4	0.25903 (12)	0.25432 (5)	0.43195 (5)	0.019
C5	0.46329 (14)	0.17982 (6)	0.41860 (6)	0.022
C6	0.62926 (13)	0.14934 (6)	0.49584 (6)	0.022
C7	0.59058 (11)	0.19678 (5)	0.58988 (5)	0.017
C8	0.31873 (12)	0.46266 (5)	0.66474 (5)	0.015
C13	0.27344 (12)	0.05867 (5)	0.90343 (6)	0.019
C12	0.08819 (13)	−0.03919 (6)	0.83094 (6)	0.022
C11	0.11405 (10)	0.26717 (5)	0.79888 (5)	0.012
C10	0.42945 (12)	0.54276 (5)	0.81781 (5)	0.016
C9	0.07640 (12)	0.60434 (5)	0.87671 (6)	0.018
H1	0.5076 (19)	0.2929 (9)	0.8500 (10)	0.027 (2)
H1W	0.558 (2)	0.1950 (11)	1.0312 (9)	0.041 (3)
H2W	0.5370 (19)	0.3235 (9)	1.0246 (8)	0.036 (2)
H4	0.131 (2)	0.2786 (9)	0.3724 (9)	0.033 (3)
H6	0.786 (2)	0.0880 (10)	0.4830 (9)	0.037 (3)
H7	0.7175 (19)	0.1728 (8)	0.6516 (8)	0.026 (2)
H8B	0.1731 (19)	0.4947 (8)	0.6132 (8)	0.025 (2)
H8A	0.494 (2)	0.4944 (9)	0.6093 (9)	0.027 (2)
H13	0.385 (2)	0.0866 (10)	0.9514 (10)	0.043 (3)
H12	0.024 (2)	−0.1134 (10)	0.8109 (9)	0.038 (3)
H11B	−0.0466 (19)	0.2960 (8)	0.7592 (8)	0.021 (2)
H11A	0.0964 (17)	0.2932 (8)	0.8780 (8)	0.021 (2)
H10	0.620 (2)	0.5224 (9)	0.8038 (9)	0.035 (3)
H9	−0.073 (2)	0.6448 (9)	0.9220 (9)	0.033 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F1	0.0195 (2)	0.01895 (18)	0.0225 (2)	0.00349 (14)	−0.01152 (15)	−0.00687 (14)
F2	0.0463 (3)	0.0382 (2)	0.0240 (2)	−0.0002 (2)	−0.00258 (19)	−0.01990 (18)
O1	0.0096 (2)	0.0207 (2)	0.0169 (2)	0.00029 (16)	−0.00465 (16)	−0.00593 (17)
O1W	0.0256 (3)	0.0178 (2)	0.0188 (2)	0.00062 (19)	−0.01051 (19)	−0.00661 (19)
N1	0.0130 (3)	0.0123 (2)	0.0153 (2)	−0.00141 (19)	−0.00474 (19)	−0.00380 (19)
N2	0.0134 (3)	0.0190 (2)	0.0197 (3)	0.0002 (2)	−0.0063 (2)	−0.0070 (2)
N3	0.0201 (3)	0.0167 (2)	0.0198 (3)	−0.0013 (2)	−0.0076 (2)	−0.0083 (2)
N4	0.0132 (3)	0.0120 (2)	0.0129 (2)	−0.00117 (18)	−0.00314 (18)	−0.00177 (18)
N5	0.0220 (3)	0.0154 (2)	0.0234 (3)	−0.0012 (2)	−0.0100 (2)	−0.0052 (2)
N6	0.0308 (3)	0.0121 (2)	0.0202 (3)	0.0024 (2)	−0.0091 (2)	−0.0024 (2)
C1	0.0103 (3)	0.0122 (3)	0.0120 (3)	−0.0010 (2)	−0.0032 (2)	−0.0027 (2)
C2	0.0120 (3)	0.0134 (2)	0.0121 (3)	−0.0011 (2)	−0.0028 (2)	−0.0037 (2)
C3	0.0162 (3)	0.0139 (3)	0.0132 (3)	−0.0013 (2)	−0.0051 (2)	−0.0029 (2)
C4	0.0251 (4)	0.0190 (3)	0.0141 (3)	−0.0030 (3)	−0.0057 (2)	−0.0048 (2)
C5	0.0272 (4)	0.0227 (3)	0.0170 (3)	−0.0029 (3)	−0.0003 (3)	−0.0093 (2)
C6	0.0202 (4)	0.0240 (3)	0.0240 (3)	0.0016 (3)	−0.0001 (3)	−0.0129 (3)
C7	0.0136 (3)	0.0186 (3)	0.0189 (3)	0.0006 (2)	−0.0024 (2)	−0.0078 (2)
C8	0.0185 (3)	0.0123 (3)	0.0131 (3)	−0.0030 (2)	−0.0043 (2)	−0.0026 (2)
C13	0.0254 (4)	0.0129 (3)	0.0200 (3)	0.0008 (2)	−0.0116 (2)	−0.0019 (2)
C12	0.0305 (4)	0.0138 (3)	0.0231 (3)	−0.0019 (3)	−0.0082 (3)	−0.0065 (2)
C11	0.0097 (3)	0.0122 (3)	0.0135 (3)	0.0000 (2)	−0.0022 (2)	−0.0025 (2)
C10	0.0136 (3)	0.0152 (3)	0.0198 (3)	−0.0016 (2)	−0.0058 (2)	−0.0065 (2)
C9	0.0179 (3)	0.0184 (3)	0.0199 (3)	0.0012 (2)	−0.0044 (2)	−0.0078 (2)

Geometric parameters (Å, º)

F1—C3	1.3544 (7)	C1—C2	1.5291 (8)
F2—C5	1.3450 (8)	C2—C3	1.3937 (8)
O1—C1	1.4066 (6)	C2—C7	1.3998 (9)
O1—H1	0.990 (11)	C3—C4	1.3859 (9)
O1W—H1W	0.932 (12)	C4—C5	1.3837 (10)
O1W—H2W	0.926 (12)	C4—H4	1.066 (11)
N1—N2	1.3603 (8)	C5—C6	1.3844 (10)
N1—C8	1.4555 (8)	C6—C7	1.3982 (9)
N1—C10	1.3407 (7)	C6—H6	1.096 (12)
N2—C9	1.3230 (9)	C7—H7	1.082 (11)
N3—C10	1.3263 (8)	C8—H8B	1.085 (11)
N3—C9	1.3592 (8)	C8—H8A	1.093 (11)
N4—N5	1.3571 (7)	C13—H13	1.063 (13)
N4—C13	1.3362 (8)	C12—H12	1.080 (11)
N4—C11	1.4535 (7)	C11—H11B	1.073 (10)
N5—C12	1.3198 (8)	C11—H11A	1.084 (10)
N6—C13	1.3232 (8)	C10—H10	1.062 (12)
N6—C12	1.3574 (9)	C9—H9	1.067 (11)
C1—O1—H1	110.1 (6)	C5—C6—C7	118.77 (6)
H1W—O1W—H2W	104.9 (8)	C5—C6—H6	119.8 (6)
N2—N1—C8	120.92 (5)	C7—C6—H6	121.5 (6)
N2—N1—C10	109.53 (5)	C2—C7—C6	121.34 (6)
C8—N1—C10	129.51 (5)	C2—C7—H7	119.1 (5)
N1—N2—C9	102.90 (5)	C6—C7—H7	119.6 (5)
C10—N3—C9	103.16 (5)	N1—C8—H8B	106.9 (5)
N5—N4—C13	109.41 (5)	N1—C8—H8A	107.8 (5)
N5—N4—C11	121.22 (5)	H8B—C8—H8A	109.5 (7)
C13—N4—C11	129.17 (5)	N4—C13—N6	110.63 (6)
N4—N5—C12	102.71 (5)	N4—C13—H13	123.0 (6)
C13—N6—C12	102.58 (5)	N6—C13—H13	126.4 (6)
O1—C1—C2	107.99 (5)	N5—C12—N6	114.67 (6)
C1—C2—C3	122.37 (5)	N5—C12—H12	121.9 (6)
C1—C2—C7	121.01 (5)	N6—C12—H12	123.4 (6)
C3—C2—C7	116.56 (5)	N4—C11—H11B	107.6 (5)
F1—C3—C2	119.29 (5)	N4—C11—H11A	108.2 (5)
F1—C3—C4	116.60 (5)	H11B—C11—H11A	110.1 (7)
C2—C3—C4	124.12 (6)	N1—C10—N3	110.15 (6)
C3—C4—C5	116.80 (6)	N1—C10—H10	124.1 (6)
C3—C4—H4	120.5 (6)	N3—C10—H10	125.8 (6)
C5—C4—H4	122.7 (6)	N2—C9—N3	114.25 (6)
F2—C5—C4	117.99 (6)	N2—C9—H9	120.9 (6)
F2—C5—C6	119.63 (6)	N3—C9—H9	124.9 (6)
C4—C5—C6	122.38 (6)

(Hirshfeld) 2-(2,4-Difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol monohydrate

Crystal data

C13H12F2N6O·H2O	Z = 2
Mr = 324.29	F(000) = 336
Triclinic, P1	Dx = 1.470 Mg m^−3
Hall symbol: -p 1	Cu Kα radiation, λ = 1.54178 Å
a = 5.5708 (3) Å	Cell parameters from 9877 reflections
b = 11.6873 (6) Å	θ = 3.9–74.1°
c = 12.1490 (7) Å	µ = 1.04 mm^−1
α = 70.990 (2)°	T = 100 K
β = 78.911 (2)°	Block, colourless
γ = 84.627 (2)°	0.18 × 0.10 × 0.08 mm
V = 733.47 (7) Å^3

Data collection

Bruker SMART 6000 diffractometer	2824 independent reflections
Radiation source: rotating anode	2824 reflections with I > 0σ(I)
INCOATEC optics monochromator	Rint = 0.030
ω and ϕ scans	θmax = 74.1°, θmin = 3.9°
Absorption correction: empirical (using intensity measurements) (SADABS; Sheldrick, 2012)	h = −6→6
Tmin = 0.682, Tmax = 0.754	k = −14→14
15433 measured reflections	l = −14→13

Refinement

Refinement on F	264 parameters
Least-squares matrix: full	0 restraints
R[F^2 > 2σ(F^2)] = 0.021	0 constraints
wR(F^2) = 0.027	All H-atom parameters refined
S = 2.91	w = 1/σ(F)
2824 reflections	(Δ/σ)max = 0.004

Special details

Experimental. Cooling of aqueous solution from 343 K to room temperature.

Refinement. Hirshfeld atom refinement: Uses aspherical atomic scattering factors obtained from Hirshfeld partitioning of a Gaussian quantum chemical wavefunction.. Hirshfeld weight functions obtained from spherically averaged unrestricted atomic densities.. Wavefunction type: rhf using cluster charges, radius=8.0 angstrom. Gaussian basis set: 6–31 g-star. Refinement based on |F| with weight=1/σ(|F|). Negative |F|2 were pruned from the data. Eigenvalues < 0.1E-04 removed from normal equations. Reflection used in the refinement appear below. Refined using the Tonto program:. Version: 3.2 ($Rev: 4268 $). Platform: GNU-mpif90-on-LINUX. Build-date: Thu Jun 20 13:48:46 CEST 2013

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
F1	0.02430 (7)	0.36907 (3)	0.54116 (3)	0.0181 (1)
F2	0.49847 (9)	0.13586 (4)	0.32711 (4)	0.0329 (2)
O1	0.55129 (7)	0.29168 (4)	0.76740 (4)	0.0142 (1)
O1W	0.47588 (9)	0.26771 (4)	0.99848 (4)	0.0184 (1)
N1	0.27210 (9)	0.51823 (4)	0.75842 (4)	0.0122 (1)
N2	0.0431 (1)	0.55755 (4)	0.79542 (4)	0.0156 (1)
N3	0.3120 (1)	0.59695 (4)	0.89405 (5)	0.0165 (2)
N4	0.13257 (9)	0.13581 (4)	0.83286 (4)	0.0120 (1)
N5	0.0120 (1)	0.07371 (5)	0.78470 (5)	0.0184 (2)
N6	0.2503 (1)	−0.05362 (5)	0.90515 (5)	0.0201 (2)
C1	0.3447 (1)	0.32299 (5)	0.71164 (5)	0.0110 (2)
C2	0.3888 (1)	0.27393 (5)	0.60685 (5)	0.0118 (2)
C3	0.2271 (1)	0.29852 (5)	0.52692 (5)	0.0137 (2)
C4	0.2590 (1)	0.25428 (5)	0.43203 (5)	0.0184 (2)
C5	0.4634 (1)	0.17972 (6)	0.41854 (5)	0.0211 (2)
C6	0.6290 (1)	0.14940 (6)	0.49583 (6)	0.0214 (2)
C7	0.5904 (1)	0.19683 (5)	0.58982 (5)	0.0160 (2)
C8	0.3188 (1)	0.46264 (5)	0.66483 (5)	0.0141 (2)
C13	0.2733 (1)	0.05871 (5)	0.90340 (5)	0.0186 (2)
C12	0.0884 (1)	−0.03915 (6)	0.83101 (6)	0.0211 (2)
C11	0.1143 (1)	0.26706 (5)	0.79885 (5)	0.0116 (2)
C10	0.4293 (1)	0.54277 (5)	0.81782 (5)	0.0148 (2)
C9	0.0766 (1)	0.60432 (5)	0.87669 (6)	0.0177 (2)
H1	0.511 (2)	0.291 (1)	0.850 (1)	0.0318*
H1W	0.561 (3)	0.195 (1)	1.034 (1)	0.0437*
H2W	0.538 (3)	0.325 (1)	1.023 (1)	0.0440*
H4	0.130 (2)	0.2781 (9)	0.3727 (9)	0.0385*
H6	0.781 (2)	0.0904 (9)	0.4837 (8)	0.0411*
H7	0.718 (2)	0.1731 (8)	0.6517 (8)	0.0269*
H8B	0.173 (2)	0.4927 (8)	0.6147 (8)	0.0295*
H8A	0.491 (2)	0.4949 (8)	0.6084 (8)	0.0308*
H13	0.383 (2)	0.0856 (9)	0.9511 (9)	0.0494*
H12	0.028 (2)	−0.1113 (9)	0.8119 (9)	0.0457*
H11B	−0.048 (2)	0.2958 (7)	0.7601 (7)	0.0245*
H11A	0.095 (2)	0.2924 (7)	0.8775 (7)	0.0247*
H10	0.616 (2)	0.5228 (9)	0.8037 (8)	0.0400*
H9	−0.073 (2)	0.6445 (9)	0.9215 (8)	0.0369*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F1	0.0187 (2)	0.0177 (2)	0.0208 (2)	0.0031 (1)	−0.0114 (2)	−0.0063 (1)
F2	0.0443 (3)	0.0367 (2)	0.0232 (3)	0.0000 (2)	−0.0026 (2)	−0.0191 (2)
O1	0.0081 (2)	0.0190 (2)	0.0160 (2)	0.0002 (2)	−0.0041 (2)	−0.0053 (2)
O1W	0.0241 (2)	0.0169 (2)	0.0174 (3)	0.0003 (2)	−0.0100 (2)	−0.0063 (2)
N1	0.0121 (2)	0.0110 (2)	0.0143 (3)	−0.0014 (2)	−0.0045 (2)	−0.0034 (2)
N2	0.0122 (2)	0.0179 (2)	0.0186 (3)	0.0002 (2)	−0.0063 (2)	−0.0066 (2)
N3	0.0193 (3)	0.0155 (2)	0.0184 (3)	−0.0016 (2)	−0.0076 (2)	−0.0078 (2)
N4	0.0119 (2)	0.0111 (2)	0.0118 (2)	−0.0011 (2)	−0.0027 (2)	−0.0015 (2)
N5	0.0208 (3)	0.0143 (2)	0.0220 (3)	−0.0010 (2)	−0.0099 (2)	−0.0047 (2)
N6	0.0294 (3)	0.0108 (2)	0.0191 (3)	0.0027 (2)	−0.0087 (2)	−0.0019 (2)
C1	0.0098 (3)	0.0118 (2)	0.0113 (3)	−0.0010 (2)	−0.0032 (2)	−0.0027 (2)
C2	0.0113 (3)	0.0128 (2)	0.0114 (3)	−0.0012 (2)	−0.0024 (2)	−0.0034 (2)
C3	0.0157 (3)	0.0135 (2)	0.0123 (3)	−0.0012 (2)	−0.0050 (2)	−0.0031 (2)
C4	0.0245 (3)	0.0186 (3)	0.0134 (3)	−0.0027 (2)	−0.0059 (3)	−0.0047 (2)
C5	0.0262 (4)	0.0225 (3)	0.0161 (3)	−0.0023 (3)	−0.0007 (3)	−0.0092 (2)
C6	0.0193 (3)	0.0234 (3)	0.0235 (4)	0.0020 (2)	−0.0002 (3)	−0.0130 (3)
C7	0.0128 (3)	0.0184 (3)	0.0181 (3)	0.0014 (2)	−0.0030 (2)	−0.0078 (2)
C8	0.0175 (3)	0.0119 (2)	0.0128 (3)	−0.0027 (2)	−0.0046 (2)	−0.0022 (2)
C13	0.0251 (3)	0.0119 (3)	0.0196 (3)	0.0011 (2)	−0.0126 (3)	−0.0017 (2)
C12	0.0301 (3)	0.0123 (2)	0.0233 (3)	−0.0019 (2)	−0.0084 (3)	−0.0065 (2)
C11	0.0090 (3)	0.0125 (2)	0.0124 (3)	0.0003 (2)	−0.0024 (2)	−0.0027 (2)
C10	0.0120 (3)	0.0154 (2)	0.0196 (3)	−0.0014 (2)	−0.0057 (2)	−0.0071 (2)
C9	0.0166 (3)	0.0184 (2)	0.0198 (3)	0.0014 (2)	−0.0041 (3)	−0.0083 (2)

(Hirshfeld-HADP) 2-(2,4-Difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol monohydrate

Crystal data

C13H12F2N6O·H2O	Z = 2
Mr = 324.29	F(000) = 336
Triclinic, P1	Dx = 1.470 Mg m^−3
Hall symbol: -p 1	Cu Kα radiation, λ = 1.54178 Å
a = 5.5708 (3) Å	Cell parameters from 9877 reflections
b = 11.6873 (6) Å	θ = 3.9–74.1°
c = 12.1490 (7) Å	µ = 1.04 mm^−1
α = 70.990 (2)°	T = 100 K
β = 78.911 (2)°	Block, colourless
γ = 84.627 (2)°	0.18 × 0.10 × 0.08 mm
V = 733.47 (7) Å^3

Data collection

Bruker SMART 6000 diffractometer	2824 independent reflections
Radiation source: rotating anode	2824 reflections with I > 0σ(I)
INCOATEC optics monochromator	Rint = 0.030
ω and ϕ scans	θmax = 74.1°, θmin = 3.9°
Absorption correction: empirical (using intensity measurements) (SADABS; Sheldrick, 2012)	h = −6→6
Tmin = 0.682, Tmax = 0.754	k = −13→13
15433 measured reflections	l = −14→13

Refinement

Refinement on F	334 parameters
Least-squares matrix: full	0 restraints
R[F^2 > 2σ(F^2)] = 0.019	0 constraints
wR(F^2) = 0.024	All H-atom parameters refined
S = 2.64	w = 1/σ(F)
2824 reflections	(Δ/σ)max = 0.004

Special details

Experimental. Cooling of aqueous solution from 343 K to room temperature.

Refinement. Hirshfeld atom refinement: Uses aspherical atomic scattering factors obtained from Hirshfeld partitioning of a Gaussian quantum chemical wavefunction.. Hirshfeld weight functions obtained from spherically averaged unrestricted atomic densities.. Wavefunction type: rhf using cluster charges, radius=8.0 angstrom. Gaussian basis set: 6–31 g-star. Refinement based on |F| with weight=1/σ(|F|). Negative |F|2 were pruned from the data. Eigenvalues < 0.1E-04 removed from normal equations. Reflection used in the refinement appear below. Refined using the Tonto program:. Version: 3.2 ($Rev: 4268 $). Platform: GNU-mpif90-on-LINUX. Build-date: Thu Jun 20 13:48:46 CEST 2013

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
F1	0.02430 (6)	0.36905 (3)	0.54117 (3)	0.0183 (1)
F2	0.49844 (8)	0.13584 (4)	0.32713 (3)	0.0331 (1)
O1	0.55125 (7)	0.29170 (3)	0.76741 (4)	0.0144 (1)
O1W	0.47602 (8)	0.26775 (4)	0.99853 (4)	0.0184 (1)
N1	0.27214 (8)	0.51823 (4)	0.75840 (4)	0.0124 (1)
N2	0.04306 (9)	0.55754 (4)	0.79541 (4)	0.0158 (1)
N3	0.31193 (9)	0.59694 (4)	0.89405 (4)	0.0167 (1)
N4	0.13255 (8)	0.13578 (4)	0.83287 (4)	0.0122 (1)
N5	0.01210 (9)	0.07372 (4)	0.78470 (4)	0.0186 (1)
N6	0.2504 (1)	−0.05360 (4)	0.90512 (4)	0.0203 (2)
C1	0.34472 (9)	0.32300 (4)	0.71163 (4)	0.0112 (1)
C2	0.3888 (1)	0.27391 (4)	0.60684 (4)	0.0120 (2)
C3	0.2271 (1)	0.29855 (4)	0.52696 (5)	0.0139 (2)
C4	0.2590 (1)	0.25435 (5)	0.43193 (5)	0.0187 (2)
C5	0.4634 (1)	0.17972 (5)	0.41851 (5)	0.0214 (2)
C6	0.6292 (1)	0.14936 (6)	0.49580 (5)	0.0216 (2)
C7	0.5904 (1)	0.19682 (5)	0.58985 (5)	0.0163 (2)
C8	0.3187 (1)	0.46267 (5)	0.66483 (5)	0.0142 (2)
C13	0.2733 (1)	0.05873 (5)	0.90351 (5)	0.0187 (2)
C12	0.0882 (1)	−0.03928 (5)	0.83100 (5)	0.0213 (2)
C11	0.1143 (1)	0.26708 (4)	0.79882 (5)	0.0118 (2)
C10	0.4293 (1)	0.54275 (5)	0.81781 (5)	0.0150 (2)
C9	0.0765 (1)	0.60433 (5)	0.87674 (5)	0.0178 (2)
H1	0.511 (2)	0.2908 (9)	0.8513 (9)	0.025 (3)
H2	0.561 (2)	0.1941 (9)	1.034 (1)	0.036 (4)
H3	0.539 (2)	0.3245 (9)	1.0239 (9)	0.033 (3)
H4	0.130 (2)	0.2789 (8)	0.3720 (8)	0.040 (3)
H6	0.783 (2)	0.0899 (9)	0.4836 (9)	0.047 (4)
H7	0.717 (2)	0.1732 (8)	0.6520 (8)	0.034 (3)
H8B	0.172 (2)	0.4927 (7)	0.6150 (8)	0.037 (3)
H8A	0.491 (2)	0.4944 (7)	0.6088 (7)	0.035 (3)
H13	0.384 (2)	0.0864 (8)	0.9512 (9)	0.049 (3)
H12	0.025 (2)	−0.1124 (8)	0.8117 (9)	0.050 (4)
H11B	−0.048 (2)	0.2961 (7)	0.7600 (7)	0.030 (3)
H11A	0.095 (2)	0.2926 (7)	0.8771 (7)	0.032 (3)
H10	0.618 (2)	0.5226 (8)	0.8037 (8)	0.038 (3)
H9	−0.074 (2)	0.6444 (9)	0.9219 (8)	0.041 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F1	0.0163 (6)	0.0177 (5)	0.0210 (7)	0.0011 (4)	−0.0081 (5)	0.0002 (5)
F2	0.0458 (9)	0.0302 (7)	0.0234 (8)	−0.0002 (6)	0.0003 (7)	−0.0124 (6)
O1	0.0075 (7)	0.0192 (6)	0.0164 (8)	0.0005 (5)	−0.0017 (6)	−0.0005 (6)
O1W	0.0215 (8)	0.0163 (7)	0.0174 (9)	−0.0015 (7)	−0.0072 (7)	−0.0009 (7)
N1	0.0112 (8)	0.0115 (7)	0.0145 (8)	−0.0018 (6)	−0.0021 (6)	0.0012 (6)
N2	0.0110 (8)	0.0175 (7)	0.0188 (9)	−0.0004 (6)	−0.0032 (7)	−0.0007 (7)
N3	0.0174 (9)	0.0139 (7)	0.0187 (9)	−0.0032 (6)	−0.0047 (7)	−0.0021 (7)
N4	0.0118 (8)	0.0126 (7)	0.0121 (8)	−0.0005 (6)	−0.0005 (6)	0.0024 (6)
N5	0.0182 (9)	0.0151 (7)	0.022 (1)	−0.0025 (7)	−0.0060 (7)	0.0024 (7)
N6	0.029 (1)	0.0131 (7)	0.0192 (9)	0.0018 (7)	−0.0052 (8)	0.0044 (7)
C1	0.0092 (9)	0.0127 (8)	0.012 (1)	−0.0006 (6)	−0.0012 (7)	0.0008 (7)
C2	0.0111 (9)	0.0135 (7)	0.0116 (9)	−0.0008 (7)	−0.0005 (7)	0.0002 (7)
C3	0.0147 (9)	0.0145 (8)	0.012 (1)	−0.0015 (7)	−0.0029 (8)	0.0008 (7)
C4	0.023 (1)	0.0189 (9)	0.014 (1)	−0.0033 (8)	−0.0034 (9)	−0.0005 (8)
C5	0.027 (1)	0.0206 (9)	0.016 (1)	−0.0015 (8)	0.0017 (9)	−0.0044 (8)
C6	0.021 (1)	0.0199 (9)	0.024 (1)	0.0027 (9)	0.0034 (9)	−0.0059 (9)
C7	0.013 (1)	0.0172 (8)	0.019 (1)	0.0016 (7)	0.0000 (8)	−0.0023 (8)
C8	0.017 (1)	0.0134 (8)	0.013 (1)	−0.0030 (7)	−0.0019 (9)	0.0019 (7)
C13	0.022 (1)	0.0145 (8)	0.020 (1)	−0.0008 (8)	−0.0085 (9)	0.0047 (8)
C12	0.028 (1)	0.0127 (8)	0.023 (1)	−0.0031 (8)	−0.0046 (9)	0.0011 (8)
C11	0.009 (1)	0.0133 (8)	0.013 (1)	0.0009 (7)	0.0000 (8)	0.0013 (7)
C10	0.011 (1)	0.0146 (8)	0.020 (1)	−0.0023 (7)	−0.0027 (8)	−0.0008 (8)
C9	0.017 (1)	0.0169 (8)	0.020 (1)	0.0010 (8)	−0.0012 (8)	−0.0023 (8)
H1	0.03 (2)	0.03 (2)	0.02 (2)	−0.01 (2)	−0.01 (2)	−0.01 (2)
H2	0.04 (2)	0.01 (2)	0.05 (3)	0.01 (2)	0.00 (2)	0.01 (2)
H3	0.04 (2)	0.02 (2)	0.04 (3)	−0.01 (2)	−0.01 (2)	0.00 (2)
H4	0.04 (2)	0.04 (2)	0.04 (2)	0.00 (2)	−0.02 (2)	0.01 (2)
H6	0.04 (2)	0.04 (2)	0.05 (3)	0.01 (2)	0.01 (2)	−0.01 (2)
H7	0.02 (2)	0.03 (2)	0.05 (2)	0.01 (1)	0.00 (2)	0.00 (2)
H8A	0.05 (2)	0.02 (1)	0.04 (2)	0.00 (1)	−0.02 (2)	0.00 (1)
H8B	0.04 (2)	0.03 (2)	0.03 (2)	−0.01 (2)	0.01 (2)	0.00 (1)
H13	0.05 (2)	0.03 (2)	0.07 (3)	−0.01 (2)	−0.03 (2)	0.02 (2)
H12	0.07 (3)	0.03 (2)	0.06 (3)	−0.02 (2)	−0.02 (2)	0.00 (2)
H11B	0.02 (2)	0.04 (2)	0.04 (2)	0.00 (1)	0.00 (1)	0.01 (1)
H11A	0.03 (2)	0.03 (1)	0.03 (2)	0.00 (1)	0.00 (1)	0.00 (2)
H10	0.03 (2)	0.04 (2)	0.05 (2)	−0.01 (2)	0.00 (2)	−0.01 (2)
H9	0.04 (2)	0.04 (2)	0.05 (2)	0.00 (2)	0.00 (2)	−0.02 (2)

Geometric parameters (Å, º)

F1—C3	1.3520 (7)	C1—C8	1.5461 (8)
F2—C5	1.3426 (7)	C1—C11	1.5426 (8)
O1—C1	1.4058 (7)	C2—C3	1.3931 (8)
O1—H1	1.007 (11)	C2—C7	1.3985 (8)
O1W—H2	0.958 (11)	C3—C4	1.3874 (8)
O1W—H3	0.940 (11)	C4—C5	1.3852 (8)
N1—N2	1.3588 (7)	C4—H4	1.071 (10)
N1—C8	1.4550 (8)	C5—C6	1.3839 (8)
N1—C10	1.3398 (8)	C6—C7	1.3986 (9)
N2—C9	1.3240 (8)	C6—H6	1.074 (11)
N3—C10	1.3261 (8)	C7—H7	1.077 (10)
N3—C9	1.3582 (8)	C8—H8B	1.070 (11)
N4—N5	1.3558 (7)	C8—H8A	1.080 (11)
N4—C13	1.3367 (7)	C13—H13	1.063 (11)
N4—C11	1.4524 (8)	C12—H12	1.059 (10)
N5—C12	1.3205 (8)	C11—H11B	1.069 (11)
N6—C13	1.3243 (8)	C11—H11A	1.068 (9)
N6—C12	1.3571 (8)	C10—H10	1.055 (11)
C1—C2	1.5301 (7)	C9—H9	1.066 (11)
N2—N1—C10	109.55 (5)	C2—C3—C4	124.04 (5)
N2—N1—C8	120.91 (4)	F1—C3—C2	119.37 (5)
C8—N1—C10	129.51 (5)	C3—C4—C5	116.88 (5)
N1—N2—C9	102.92 (5)	F2—C5—C4	118.01 (5)
C9—N3—C10	103.15 (5)	F2—C5—C6	119.73 (5)
C11—N4—C13	129.11 (5)	C4—C5—C6	122.26 (6)
N5—N4—C11	121.28 (4)	C5—C6—C7	118.82 (6)
N5—N4—C13	109.41 (5)	C2—C7—C6	121.38 (5)
N4—N5—C12	102.82 (5)	N1—C8—C1	113.12 (4)
C12—N6—C13	102.59 (5)	N1—C10—N3	110.17 (5)
O1—C1—C8	108.37 (4)	N4—C11—C1	110.64 (4)
O1—C1—C2	108.02 (4)	N4—C13—N6	110.60 (5)
O1—C1—C11	110.23 (4)	N5—C12—N6	114.58 (5)
F1—C3—C4	116.59 (5)	N2—C9—N3	114.20 (5)
C8—N1—N2—C9	−178.27 (5)	C11—C1—C2—C3	65.40 (6)
C10—N1—N2—C9	−0.05 (6)	C11—C1—C2—C7	−111.68 (6)
N2—N1—C8—C1	−101.66 (6)	O1—C1—C8—N1	−63.67 (6)
C10—N1—C8—C1	80.51 (7)	C2—C1—C8—N1	179.08 (4)
N2—N1—C10—N3	0.28 (7)	C11—C1—C8—N1	57.83 (6)
C8—N1—C10—N3	178.30 (5)	O1—C1—C11—N4	−65.08 (5)
N1—N2—C9—N3	−0.20 (6)	C2—C1—C11—N4	53.77 (6)
C10—N3—C9—N2	0.36 (7)	C8—C1—C11—N4	174.50 (4)
C9—N3—C10—N1	−0.37 (6)	C1—C2—C3—F1	0.53 (8)
C11—N4—N5—C12	175.70 (5)	C1—C2—C3—C4	−179.07 (5)
C13—N4—N5—C12	0.43 (6)	C7—C2—C3—F1	177.72 (5)
N5—N4—C11—C1	−101.84 (5)	C7—C2—C3—C4	−1.87 (8)
C13—N4—C11—C1	72.40 (7)	C1—C2—C7—C6	178.56 (5)
N5—N4—C13—N6	−0.40 (6)	C3—C2—C7—C6	1.33 (8)
C11—N4—C13—N6	−175.18 (5)	F1—C3—C4—C5	−178.51 (5)
N4—N5—C12—N6	−0.34 (6)	C2—C3—C4—C5	1.09 (9)
C13—N6—C12—N5	0.11 (7)	C3—C4—C5—F2	−179.95 (5)
C12—N6—C13—N4	0.18 (6)	C3—C4—C5—C6	0.28 (9)
O1—C1—C2—C3	−174.40 (5)	F2—C5—C6—C7	179.49 (5)
O1—C1—C2—C7	8.53 (6)	C4—C5—C6—C7	−0.75 (9)
C8—C1—C2—C3	−56.92 (6)	C5—C6—C7—C2	−0.09 (9)
C8—C1—C2—C7	126.00 (5)