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Volume 69 
Part 3 
Pages o378-o379  
March 2013  

Received 24 January 2013
Accepted 5 February 2013
Online 13 February 2013

Key indicators
Single-crystal X-ray study
T = 150 K
Mean [sigma](C-C) = 0.002 Å
R = 0.038
wR = 0.100
Data-to-parameter ratio = 14.6
Details
Open access

Fluconazole-malonic acid (1/1)

aKrka d.d., Smarjeska cesta 6, 8501 Novo mesto, Slovenia,bUniversity of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000 Ljubljana, Slovenia, and cUniversity of Ljubljana, Faculty of Chemistry and Chemical Technology, Askerceva 5, 1000 Ljubljana, Slovenia
Correspondence e-mail: nina.lah@fkkt.uni-lj.si

Co-crystallizaton of the antifungal drug fluconazole [2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol] with malonic acid in acetonitrile solution resulted in the formation of the title 1:1 co-crystal, C13H12F2N6O·C3H4O4. The geometry around the central fluconazole atom is distorted tetrahedral. The dihedral angles between the triazole rings and the fluorinated phenyl ring are 30.64 (7) and 61.91 (5)°. In the crystal, the basic packing motif may be envisioned as a cyclic aggregate formed of two fluconazole molecules linked by two malonic acid molecules through O-H...N and O-H...O hydrogen bonds. Such aggregates are further connected into (001) layers by further O-H...N hydrogen bonds. The structure also features weak non-classical C-H...O and C-H...N interactions.

Related literature

For general aspects of pharmaceutical co-crystals, see, for example: Brittain et al. (2012a[Brittain, H. G. (2012a). Cryst. Growth Des. 12, 1046-1054.],b[Brittain, H. G. (2012b). Cryst. Growth Des. 12, 5823-5832.]). For known fluconazole co-crystals, see: Kastelic et al. (2010[Kastelic, J., Hodnik, Z., Sket, P., Plavec, J., Lah, N., Leban, I., Pajk, M., Planinsek, O. & Kikelj, D. (2010). Cryst. Growth Des. 10, 4943-4953.], 2011[Kastelic, J., Lah, N., Kikelj, D. & Leban, I. (2011). Acta Cryst. C67, o370-o372.]). For regulatory classification of pharmaceutical co-crystals, see: US Food and Drug Administration (2011[US Food and Drug Administration (2011). Guidance for Industry; Regulatory Classification of Pharmaceutical Co-crystals. Silver Spring, MD.]).

[Scheme 1]

Experimental

Crystal data
  • C13H12F2N6O·C3H4O4

  • Mr = 410.35

  • Orthorhombic, P b c n

  • a = 14.7196 (2) Å

  • b = 8.4891 (1) Å

  • c = 28.1096 (4) Å

  • V = 3512.47 (8) Å3

  • Z = 8

  • Mo K[alpha] radiation

  • [mu] = 0.13 mm-1

  • T = 150 K

  • 0.18 × 0.18 × 0.12 mm

Data collection
  • Nonius Kappa CCD diffractometer

  • 7522 measured reflections

  • 4012 independent reflections

  • 3069 reflections with I > 2[sigma](I)

  • Rint = 0.024

Refinement
  • R[F2 > 2[sigma](F2)] = 0.038

  • wR(F2) = 0.100

  • S = 1.03

  • 4012 reflections

  • 274 parameters

  • H atoms treated by a mixture of independent and constrained refinement

  • [Delta][rho]max = 0.32 e Å-3

  • [Delta][rho]min = -0.29 e Å-3

Table 1
Hydrogen-bond geometry (Å, °)

D-H...A D-H H...A D...A D-H...A
O1-H1...O11M 0.89 (2) 1.94 (2) 2.8057 (14) 166.2 (18)
O12M-H11...N14i 0.88 (2) 1.86 (2) 2.6830 (17) 156 (2)
O21M-H12...N24ii 0.88 (3) 1.89 (3) 2.7606 (17) 171 (2)
C6-H6...N14i 0.93 2.61 3.484 (2) 156
C12M-H12B...O11Miii 0.97 2.44 3.3880 (18) 165
C13-H13...O12Miv 0.93 2.54 3.3144 (19) 141
C25-H25...O11M 0.93 2.40 3.2018 (18) 144
C25-H25...O22Miii 0.93 2.37 3.0032 (19) 125
Symmetry codes: (i) [-x+1, y, -z+{\script{3\over 2}}]; (ii) [-x+{\script{1\over 2}}, y-{\script{1\over 2}}, z]; (iii) [-x+{\script{1\over 2}}, y+{\script{1\over 2}}, z]; (iv) [x+{\script{1\over 2}}, y-{\script{1\over 2}}, -z+{\script{3\over 2}}].

Data collection: COLLECT (Nonius, 1998[Nonius (1998). COLLECT. Nonius BV, Delft, The Netherlands.]); cell refinement: DENZO and SCALEPACK (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.]); data reduction: DENZO and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).


Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: GK2552 ).


Acknowledgements

The financial support of the Slovenian Ministry of Education, Science, Culture and Sport through grant P1-175-103 is gratefully acknowledged. JK thanks ARRS for funding through the Innovative Scheme supported financially by the European Social Fund.

References

Brittain, H. G. (2012a). Cryst. Growth Des. 12, 1046-1054.  [CrossRef] [ChemPort]
Brittain, H. G. (2012b). Cryst. Growth Des. 12, 5823-5832.  [CrossRef] [ChemPort]
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.  [ISI] [CrossRef] [ChemPort] [details]
Kastelic, J., Hodnik, Z., Sket, P., Plavec, J., Lah, N., Leban, I., Pajk, M., Planinsek, O. & Kikelj, D. (2010). Cryst. Growth Des. 10, 4943-4953.  [CSD] [CrossRef] [ChemPort]
Kastelic, J., Lah, N., Kikelj, D. & Leban, I. (2011). Acta Cryst. C67, o370-o372.  [CSD] [CrossRef] [details]
Nonius (1998). COLLECT. Nonius BV, Delft, The Netherlands.
Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.  [CrossRef] [details]
Spek, A. L. (2009). Acta Cryst. D65, 148-155.  [ISI] [CrossRef] [details]
US Food and Drug Administration (2011). Guidance for Industry; Regulatory Classification of Pharmaceutical Co-crystals. Silver Spring, MD.


Acta Cryst (2013). E69, o378-o379   [ doi:10.1107/S1600536813003656 ]

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