Investigation of Poor Solubility of a Salt-Cocrystal Hydrate: A Case Study of the Common-Ion Effect in Betrixaban, an Anticoagulant Drug.
Devarapalli, Ramesh; Indukuri, Anjaneyaraju; Bollineni, Manjunath; Mondal, Amit; Reddy, C. Malla; Chennuru, Ramanaiah; Molecular pharmaceutics 18 (2021) 1138–1149; doi:10.1021/acs.molpharmaceut.0c01045

data_1560809
_publ_section_title
;
 Investigation of Poor Solubility of a Salt-Cocrystal Hydrate: A Case
 Study of the Common-Ion Effect in Betrixaban, an Anticoagulant Drug.
;
_journal_issue                   3
_journal_name_full               'Molecular pharmaceutics'
_journal_page_first              1138
_journal_page_last               1149
_journal_paper_doi               10.1021/acs.molpharmaceut.0c01045
_journal_volume                  18
_journal_year                    2021
_chemical_formula_moiety         'C23 H23 Cl N5 O3, 2(C4 H4 O4), C4 H3 O4, H2 O'
_chemical_formula_sum            'C35 H36 Cl N5 O16'
_chemical_formula_weight         818.14
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2ybc'
_space_group_name_H-M_alt        'P 1 21/c 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2020-02-22
_audit_creation_method
;
Olex2 1.3
(compiled Nov 21 2019 18:26:39 for OlexSys, GUI svn.r6003)
;
_cell_angle_alpha                90
_cell_angle_beta                 95.6750(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   21.1662(2)
_cell_length_b                   7.28220(10)
_cell_length_c                   23.8529(2)
_cell_measurement_reflns_used    16140
_cell_measurement_temperature    100
_cell_measurement_theta_max      66.1050
_cell_measurement_theta_min      3.7290
_cell_volume                     3658.58(7)
_computing_cell_refinement       'CrysAlisPro 1.171.38.43 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.43 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.43 (Rigaku OD, 2015)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      100
_diffrn_detector_area_resol_mean 7.9580
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.989
_diffrn_measured_fraction_theta_max 0.989
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
--------------------------------------------------------------------------
  1  \w    -50.00  64.00   1.00    2.00    --   26.21 -57.00 150.00  114
  2  \w    -50.00  64.00   1.00    2.00    --   26.21 -57.00  90.00  114
  3  \w    -12.00 102.00   1.00    2.00    --   26.21  57.00 -60.00  114
  4  \w    -50.00  64.00   1.00    2.00    --   26.21 -57.00   0.00  114
  5  \w    100.00 153.00   1.00    4.00    --   67.10 111.00 120.00   53
  6  \w    100.00 153.00   1.00    4.00    --   67.10 111.00-180.00   53
  7  \w    100.00 153.00   1.00    4.00    --   67.10 111.00-120.00   53
  8  \w     20.00 147.00   1.00    4.00    --   67.10  45.00 150.00  127
  9  \w     20.00 147.00   1.00    4.00    --   67.10  45.00  60.00  127
 10  \w     12.00 116.00   1.00    4.00    --   67.10-111.00-180.00  104
 11  \w    100.00 153.00   1.00    4.00    --   67.10 111.00 -30.00   53
 12  \w     97.00 148.00   1.00    4.00    --   67.10 122.00   9.00   51
 13  \w     86.00 178.00   1.00    8.00    --  108.00 138.00-120.00   92
 14  \w     29.00 145.00   1.00    8.00    --  108.00 -65.00  60.00  116
 15  \w     21.00 113.00   1.00    8.00    --  108.00-104.00   0.00   92
 16  \w     24.00 117.00   1.00    8.00    --  108.00-116.00 111.30   93
 17  \w     28.00 158.00   1.00    8.00    --  108.00 -43.00 -30.00  130
 18  \w     21.00 113.00   1.00    8.00    --  108.00-104.00-150.00   92
 19  \w    101.00 178.00   1.00    8.00    --  108.00 104.00-180.00   77
 20  \w     29.00 145.00   1.00    8.00    --  108.00 -65.00 -30.00  116
 21  \w    101.00 178.00   1.00    8.00    --  108.00 104.00  60.00   77
 22  \w     21.00 113.00   1.00    8.00    --  108.00-104.00 -60.00   92
 23  \w     27.00 178.00   1.00    8.00    --  108.00  24.00 158.00  151
 24  \w     69.00 178.00   1.00    8.00    --  108.00  54.00-180.00  109
 25  \w     68.00 178.00   1.00    8.00    --  108.00  72.00 141.01  110
 26  \w     26.00 121.00   1.00    8.00    --  108.00-124.00  95.79   95
 27  \w     69.00 178.00   1.00    8.00    --  108.00  54.00 150.00  109
 28  \w    101.00 178.00   1.00    8.00    --  108.00 104.00   0.00   77
 29  \w     86.00 178.00   1.00    8.00    --  108.00 138.00 -90.00   92
 30  \w     28.00 158.00   1.00    8.00    --  108.00 -43.00 120.00  130
 31  \w    -12.00 102.00   1.00    2.00    --   26.21  57.00  30.00  114
 32  \w    -12.00 102.00   1.00    2.00    --   26.21  57.00-120.00  114
 33  \w     57.00 120.00   1.00    2.00    --   26.21 178.00  60.00   63
 34  \w    -17.00  47.00   1.00    2.00    --   26.21  77.00  60.00   64
 35  \w    -17.00 111.00   1.00    2.00    --   26.21  77.00 120.00  128
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, Eos'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0313
_diffrn_reflns_av_unetI/netI     0.0267
_diffrn_reflns_Laue_measured_fraction_full 0.989
_diffrn_reflns_Laue_measured_fraction_max 0.989
_diffrn_reflns_limit_h_max       25
_diffrn_reflns_limit_h_min       -24
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -5
_diffrn_reflns_limit_l_max       28
_diffrn_reflns_limit_l_min       -28
_diffrn_reflns_number            29309
_diffrn_reflns_point_group_measured_fraction_full 0.989
_diffrn_reflns_point_group_measured_fraction_max 0.989
_diffrn_reflns_theta_full        66.284
_diffrn_reflns_theta_max         66.284
_diffrn_reflns_theta_min         3.724
_exptl_absorpt_coefficient_mu    1.655
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.76858
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.43 (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear whiteish colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   whiteish
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.485
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       block
_exptl_crystal_F_000             1704
_exptl_crystal_size_max          0.25
_exptl_crystal_size_mid          0.2
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.482
_refine_diff_density_min         -0.301
_refine_diff_density_rms         0.049
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.039
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     525
_refine_ls_number_reflns         6362
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.039
_refine_ls_R_factor_all          0.0432
_refine_ls_R_factor_gt           0.0358
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0457P)^2^+1.8700P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0865
_refine_ls_wR_factor_ref         0.0894
_reflns_Friedel_coverage         0.000
_reflns_number_gt                5581
_reflns_number_total             6362
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            mp0c01045_si_003.cif
_cod_data_source_block           bm_salt-cocrystal
_cod_database_code               1560809
_shelx_shelxl_version_number     2018/3
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All N(H) groups, All N(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups, All O(H,H) groups
2.a Free rotating group:
 O16(H16a,H16b)
2.b Aromatic/amide H refined with riding coordinates:
 N2(H2), N3(H3), C2(H2a), C3(H3a), C4(H4), C8(H8), C10(H10), C11(H11),
 C16(H16), C17(H17), C19(H19), C20(H20), C33(H33), C34(H34), C29(H29), C30(H30),
  C25(H25), C26(H26)
2.c X=CH2 refined with riding coordinates:
 N4(H4a,H4b)
2.d Idealised Me refined as rotating group:
 C13(H13a,H13b,H13c), C22(H22a,H22b,H22c), C23(H23a,H23b,H23c)
2.e Idealised tetrahedral OH refined as rotating group:
 O12(H12), O15(H15), O8(H8a), O11(H11a), O7(H7)
;
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;