New bedaquiline salt with improved bioavailability and reduced food effect
Zhang, Xiaowen; Meng, Dongshuo; Zang, Zongwu; Xu, Zhiru; Liu, Yu; CrystEngComm 26 (2024) 5071–5077; doi:10.1039/D4CE00567H

data_7249181
_publ_section_title
;
 New bedaquiline salt with improved bioavailability and reduced food
 effect
;
_journal_issue                   36
_journal_name_full               CrystEngComm
_journal_page_first              5071
_journal_page_last               5077
_journal_paper_doi               10.1039/D4CE00567H
_journal_volume                  26
_journal_year                    2024
_chemical_absolute_configuration rm
_chemical_formula_moiety         'C32 H32 Br N2 O2, C7 H4 N O3 S, H2 O, C2 H3 N'
_chemical_formula_sum            'C41 H41 Br N4 O6 S'
_chemical_formula_weight         797.75
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     iterative
_atom_sites_solution_secondary   difmap
_audit_creation_date             2024-05-18
_audit_creation_method
;
Olex2 1.5
(compiled 2023.08.24 svn.re1ec1418 for OlexSys, GUI svn.r6817)
;
_audit_update_record
;
2024-05-20 deposited with the CCDC.	2024-08-07 downloaded from the CCDC.
;
_cell_angle_alpha                90.00
_cell_angle_beta                 90.00
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   9.0487(4)
_cell_length_b                   16.0617(10)
_cell_length_c                   26.2120(16)
_cell_measurement_reflns_used    3495
_cell_measurement_temperature    100
_cell_measurement_theta_max      23.893
_cell_measurement_theta_min      2.381
_cell_volume                     3809.6(4)
_computing_cell_refinement       'SAINT V8.40A (?, 2016)'
_computing_data_reduction        'SAINT V8.40A (?, 2016)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL  (Sheldrick, 2008)'
_computing_structure_solution    'olex2.solve 1.5 (Bourhis et al., 2015)'
_diffrn_ambient_temperature      100
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.997
_diffrn_measurement_device_type  'D8 VENTURE'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0855
_diffrn_reflns_av_unetI/netI     0.1257
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       20
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       32
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            20424
_diffrn_reflns_theta_full        26.41
_diffrn_reflns_theta_max         26.41
_diffrn_reflns_theta_min         2.01
_diffrn_source                   'fine-focus sealed tube'
_diffrn_source_current           1.4
_diffrn_source_power             0.07
_diffrn_source_voltage           50.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    1.187
_exptl_absorpt_correction_T_max  0.7454
_exptl_absorpt_correction_T_min  0.4716
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.1085 before and 0.0871 after correction. The Ratio of minimum to maximum transmission is 0.6327. The \l/2 correction factor is Not present.'
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.391
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       block
_exptl_crystal_F_000             1656
_exptl_crystal_size_max          0.12
_exptl_crystal_size_mid          0.08
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.365
_refine_diff_density_min         -0.505
_refine_diff_density_rms         0.088
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   -0.003(8)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.998
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     486
_refine_ls_number_reflns         7785
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      0.998
_refine_ls_R_factor_all          0.0950
_refine_ls_R_factor_gt           0.0514
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0000P)^2^+0.0000P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0820
_refine_ls_wR_factor_ref         0.0997
_reflns_number_gt                5488
_reflns_number_total             7785
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            d4ce00567h2.cif
_cod_data_source_block           mo_20231074_0m
_cod_depositor_comments          'Adding full bibliography for 7249181.cif.'
_cod_database_code               7249181
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(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:
 O008(H00B,H00D)
2.b Ternary CH refined with riding coordinates:
 N00A(H00A), C00P(H00P)
2.c Secondary CH2 refined with riding coordinates:
 C010(H01A,H01B), C012(H01C,H01D)
2.d Aromatic/amide H refined with riding coordinates:
 C00C(H00C), C00G(H00G), C00H(H00H), C00I(H00I), C00J(H00J), C00L(H00L),
 C00O(H00O), C00R(H00R), C00S(H00S), C00U(H00U), C00X(H00X), C00Y(H00Y),
 C00Z(H00Z), C014(H014), C015(H015), C016(H016), C017(H017), C01A(H01P),
 C01B(H01H), C01D(H01I)
2.e Idealised Me refined as rotating group:
 C018(H01E,H01F,H01G), C01E(H01J,H01K,H01L), C01G(H01Q,H01R,H01S), C01H(H01M,
 H01N,H01O)
2.f Idealised tetrahedral OH refined as rotating group:
 O005(H005)
;
_olex2_submission_special_instructions 'No special instructions were received'