Ketoconazole - p-aminobenzoic acid cocrystal: revival of an old drug by crystal engineering.
Martin, Flavia; Pop, Mihaela; Kacso, Irina; Grosu, Ioana Georgeta; Miclaus, Maria; Vodnar, Dan; Lung, Ildiko; Filip, Gabriela Adriana; Olteanu, Elena Diana; Moldovan, Remus; Nagy, Andras; Filip, Xenia; Baldea, Ioana; Molecular pharmaceutics  (2020) –; doi:10.1021/acs.molpharmaceut.9b01178

data_1557269
_publ_section_title
;
 Ketoconazole - p-aminobenzoic acid cocrystal: revival of an old drug by
 crystal engineering.
;
_journal_name_full               'Molecular pharmaceutics'
_journal_paper_doi               10.1021/acs.molpharmaceut.9b01178
_journal_year                    2020
_chemical_formula_moiety         'C26 H23 Cl2 N4 O4, C7 H7 N O2'
_chemical_formula_sum            'C33 H30 Cl2 N5 O6'
_chemical_formula_weight         663.52
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_date             2013-03-29
_audit_creation_method
;
  Olex2 1.1
  (compiled 2011.11.01 svn.r2039, GUI svn.r3906)
;
_cell_angle_alpha                65.035(5)
_cell_angle_beta                 72.196(4)
_cell_angle_gamma                84.857(4)
_cell_formula_units_Z            2
_cell_length_a                   9.7532(4)
_cell_length_b                   13.0997(6)
_cell_length_c                   14.7094(7)
_cell_measurement_reflns_used    6615
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      70.4960
_cell_measurement_theta_min      3.8820
_cell_volume                     1620.45(15)
_computing_cell_refinement
;
CrysAlisPro, Agilent Technologies,
Version 1.171.36.24 (release 03-12-2012 CrysAlis171 .NET)
(compiled Dec  3 2012,18:21:49)
;
_computing_data_collection
;
CrysAlisPro, Agilent Technologies,
Version 1.171.36.24 (release 03-12-2012 CrysAlis171 .NET)
(compiled Dec  3 2012,18:21:49)
;
_computing_data_reduction
;
CrysAlisPro, Agilent Technologies,
Version 1.171.36.24 (release 03-12-2012 CrysAlis171 .NET)
(compiled Dec  3 2012,18:21:49)
;
_computing_molecular_graphics
;
O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and H. Puschmann,
OLEX2: a complete structure solution, refinement and analysis program.
J. Appl. Cryst. (2009). 42, 339-341.
;
_computing_publication_material
;
O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and H. Puschmann,
OLEX2: a complete structure solution, refinement and analysis program.
J. Appl. Cryst. (2009). 42, 339-341.
;
_computing_structure_refinement
;
SHELXL, G.M. Sheldrick, Acta Cryst.
2008). A64, 112-122
;
_computing_structure_solution
;
SHELXS, G.M. Sheldrick, Acta Cryst.
(2008). A64, 112-122
;
_diffrn_ambient_temperature      293(2)
_diffrn_detector_area_resol_mean 16.4335
_diffrn_measured_fraction_theta_full 0.9945
_diffrn_measured_fraction_theta_max 0.9945
_diffrn_measurement_details
;
  1 omega  -24.00    8.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -        0.0000   57.0000 -180.0000 32

  2 omega  -80.00  -40.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -        0.0000  178.0000    0.0000 40

  3 omega   27.00   71.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -        0.0000   57.0000 -180.0000 44

  4 omega    7.00   56.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -        0.0000   57.0000  -90.0000 49

  5 omega -128.00  -78.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -56.3168 -126.0000  -60.0000 50

  6 omega -113.00  -87.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -56.3168  -95.0000   30.0000 26

  7 omega -130.00  -87.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -56.3168  -95.0000   90.0000 43

  8 omega   12.00   99.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       56.3168  -95.0000    0.0000 87

  9 omega   23.00  118.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       56.3168   77.0000  -60.0000 95

 10 omega   46.00  105.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       56.3168 -126.0000 -120.0000 59

 11 omega  -57.00    6.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -64.5000   50.0000 -150.0000 63

 12 omega -132.00  -79.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -64.5000  -92.0000 -120.0000 53

 13 omega  -55.00  -21.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -64.5000   50.0000  -60.0000 34

 14 omega -133.00  -35.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -64.5000  -77.0000  120.0000 98

 15 omega   79.00  116.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336 -112.0000 -180.0000 37

 16 omega   49.00   76.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336 -112.0000 -180.0000 27

 17 omega   61.00  100.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336 -112.0000  -60.0000 39

 18 omega   75.00  126.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336  178.0000  -60.0000 51

 19 omega   40.00   79.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336  -38.0000  -60.0000 39

 20 omega   42.00   79.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336  -25.0000   60.0000 37

 21 omega   39.00   88.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336  -25.0000  -30.0000 49

 22 omega   59.00  101.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336 -112.0000    0.0000 42

 23 omega   41.00  130.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336  -77.0000   81.0000 89

 24 omega   59.00   85.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336  -38.0000 -180.0000 26

 25 omega   79.00  112.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336 -112.0000   60.0000 33

 26 omega   40.00   93.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336  -38.0000   90.0000 53

 27 omega   48.00  175.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336   12.0000    0.0000 127

 28 omega   49.00  106.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336  -64.0000  -30.0000 57

 29 omega   96.00  177.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336   50.0000 -120.0000 81

 30 omega   56.00   82.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336  -38.0000    0.0000 26

 31 omega  102.00  177.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336  112.0000    0.0000 75

 32 omega   41.00  104.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336  -50.0000 -120.0000 63

 33 omega  -72.00   33.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -        0.0000  -77.0000  -27.0000 105

 34 omega  -82.00  -34.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -        0.0000  178.0000   60.0000 48

 35 omega  -82.00  -34.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -        0.0000  178.0000  -60.0000 48

 36 omega -129.00  -23.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -56.3168  -77.0000 -180.0000 106

 37 omega -126.00  -31.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -56.3168  -61.0000   30.0000 95

 38 omega -129.00  -72.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -56.3168 -126.0000    0.0000 57

 39 omega  -55.00   16.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -56.3168   45.0000  -30.0000 71

 40 omega   29.00  129.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       56.3168   45.0000  -90.0000 100

 41 omega   23.00  129.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       56.3168   77.0000    0.0000 106

 42 omega   80.00  178.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336   77.0000  -30.0000 98

 43 omega   80.00  178.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336   77.0000 -120.0000 98

 44 omega   86.00  178.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336   64.0000   30.0000 92

 45 omega   81.00  178.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336   38.0000 -150.0000 97

 46 omega   40.00  178.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      112.6336   12.0000  150.0000 138
;
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, Eos'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      0.0716370000
_diffrn_orient_matrix_UB_12      -0.0804628000
_diffrn_orient_matrix_UB_13      0.0823204000
_diffrn_orient_matrix_UB_21      0.0376093000
_diffrn_orient_matrix_UB_22      -0.0772010000
_diffrn_orient_matrix_UB_23      -0.0585143000
_diffrn_orient_matrix_UB_31      0.1450309000
_diffrn_orient_matrix_UB_32      0.0665524000
_diffrn_orient_matrix_UB_33      -0.0665930000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.5418
_diffrn_reflns_av_R_equivalents  0.0264
_diffrn_reflns_av_unetI/netI     0.0289
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -17
_diffrn_reflns_number            17732
_diffrn_reflns_theta_full        71.91
_diffrn_reflns_theta_max         71.91
_diffrn_reflns_theta_min         3.47
_diffrn_source                   'SuperNova (Cu) X-ray Source'
_diffrn_source_current           n/a
_diffrn_source_voltage           n/a
_exptl_absorpt_coefficient_mu    2.241
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.75580
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.36.24 (release 03-12-2012 CrysAlis171 .NET)
(compiled Dec  3 2012,18:21:49)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.360
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       prism
_exptl_crystal_F_000             690
_exptl_crystal_size_max          0.4
_exptl_crystal_size_mid          0.3
_exptl_crystal_size_min          0.2
_refine_diff_density_max         0.519
_refine_diff_density_min         -0.461
_refine_diff_density_rms         0.051
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.636
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     426
_refine_ls_number_reflns         6206
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.636
_refine_ls_R_factor_all          0.0921
_refine_ls_R_factor_gt           0.0712
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.1000P)^2^+0.0000P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2319
_refine_ls_wR_factor_ref         0.2489
_reflns_number_gt                4585
_reflns_number_total             6206
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            mp9b01178_si_003.cif
_cod_data_source_block           keto-paba
_cod_original_cell_volume        1620.45(13)
_cod_database_code               1557269
_chemical_oxdiff_formula         'c26 h28 cl2 n4 o4'
_reflns_odcompleteness_completeness 99.45
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97