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_1560810
_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, C4 H3 O4'
_chemical_formula_sum            'C27 H26 Cl N5 O7'
_chemical_formula_weight         567.98
_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   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2020-03-29
_audit_creation_method
;
Olex2 1.3
(compiled 2020.02.04 svn.rd84adfe8 for OlexSys, GUI svn.r6032)
;
_cell_angle_alpha                73.184(2)
_cell_angle_beta                 75.634(2)
_cell_angle_gamma                89.646(2)
_cell_formula_units_Z            4
_cell_length_a                   10.2717(3)
_cell_length_b                   14.0080(4)
_cell_length_c                   19.5347(5)
_cell_measurement_reflns_used    20025
_cell_measurement_temperature    100
_cell_measurement_theta_max      66.1790
_cell_measurement_theta_min      2.4260
_cell_volume                     2599.91(13)
_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 2014/4 (Sheldrick, 2014)'
_diffrn_ambient_temperature      100
_diffrn_measured_fraction_theta_full 0.995
_diffrn_measured_fraction_theta_max 0.995
_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  0.0335
_diffrn_reflns_av_unetI/netI     0.0301
_diffrn_reflns_Laue_measured_fraction_full 0.995
_diffrn_reflns_Laue_measured_fraction_max 0.995
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       23
_diffrn_reflns_limit_l_min       -22
_diffrn_reflns_number            36169
_diffrn_reflns_point_group_measured_fraction_full 0.995
_diffrn_reflns_point_group_measured_fraction_max 0.995
_diffrn_reflns_theta_full        66.286
_diffrn_reflns_theta_max         66.286
_diffrn_reflns_theta_min         3.304
_diffrn_source                   'micro-focus sealed X-ray tube'
_exptl_absorpt_coefficient_mu    1.797
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.94054
_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            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.451
_exptl_crystal_description       block
_exptl_crystal_F_000             1184
_exptl_crystal_size_max          0.34
_exptl_crystal_size_mid          0.22
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.326
_refine_diff_density_min         -0.284
_refine_diff_density_rms         0.046
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.034
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     749
_refine_ls_number_reflns         9089
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.034
_refine_ls_R_factor_all          0.0347
_refine_ls_R_factor_gt           0.0311
_refine_ls_shift/su_max          0.002
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0412P)^2^+0.7570P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0787
_refine_ls_wR_factor_ref         0.0816
_reflns_Friedel_coverage         0.000
_reflns_number_gt                8287
_reflns_number_total             9089
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            mp0c01045_si_002.cif
_cod_data_source_block           bm_salt
_cod_original_cell_volume        2599.92(13)
_cod_database_code               1560810
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.841
_shelx_estimated_absorpt_t_min   0.580
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2.a Aromatic/amide H refined with riding coordinates:
 N2A(H2A), C2A(H2Aa), C3A(H3Aa), C4A(H4A), C8A(H8A), C10A(H10A), C11A(H11A),
 C16A(H16A), C17A(H17A), C19A(H19A), C20A(H20A), N2B(H2B), N3B(H3B), C2B(H2Ba),
 C3B(H3Ba), C4B(H4B), C8B(H8B), C10B(H10B), C11B(H11B), C16B(H16B), C17B(H17B),
 C19B(H19B), C20B(H20B), C25A(H25A), C26A(H26A), C25B(H25B), C26B(H26B)
2.b Idealised Me refined as rotating group:
 C13A(H13a,H13b,H13c), C22A(H22a,H22b,H22c), C23A(H23a,H23b,H23c), C13B(H13d,
 H13e,H13f), C22B(H22d,H22e,H22f), C23B(H23d,H23e,H23f)
2.c Idealised tetrahedral OH refined as rotating group:
 O5A(H5A), O5B(H5B)
;
_olex2_submission_special_instructions 'No special instructions were received'