Inorganic salts of topiroxostat: metastable tautomeric form and improved pharmaceutical performance
Li, Jiangying; Ma, Haowen; Shi, Xiaoju; Jiao, Ting; Wang, Lin; Nie, Meiling; Wang, Xiaojuan; Deng, Zongwu; Zhang, Hailu; CrystEngComm 27 (2025) 2534–2544; doi:10.1039/D5CE00073D

data_7250116
_publ_section_title
;
 Inorganic salts of topiroxostat: metastable tautomeric form and improved
 pharmaceutical performance
;
_journal_issue                   16
_journal_name_full               CrystEngComm
_journal_page_first              2534
_journal_page_last               2544
_journal_paper_doi               10.1039/D5CE00073D
_journal_volume                  27
_journal_year                    2025
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C13 H9 N6, H O4 S'
_chemical_formula_sum            'C13 H10 N6 O4 S'
_chemical_formula_weight         346.33
_chemical_name_systematic        'FYX--H2SO4 II'
_space_group_crystal_system      orthorhombic
_space_group_IT_number           34
_space_group_name_Hall           'P 2 -2n'
_space_group_name_H-M_alt        'P n n 2'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2024-11-22
_audit_creation_method
;
Olex2 1.5
(compiled 2024.02.16 svn.r378c4104 for OlexSys, GUI svn.r6928)
;
_audit_update_record
;
2024-11-25 deposited with the CCDC.	2025-03-17 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   25.4485(8)
_cell_length_b                   12.9002(5)
_cell_length_c                   4.46615(12)
_cell_measurement_reflns_used    5905
_cell_measurement_temperature    273.00(10)
_cell_measurement_theta_max      72.9530
_cell_measurement_theta_min      3.4570
_cell_volume                     1466.20(8)
_computing_cell_refinement       'CrysAlisPro 1.171.43.136a (Rigaku OD, 2024)'
_computing_data_collection       'CrysAlisPro 1.171.43.136a (Rigaku OD, 2024)'
_computing_data_reduction        'CrysAlisPro 1.171.43.136a (Rigaku OD, 2024)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      air
_diffrn_ambient_temperature      273.00(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            'HyPix-Arc 150'
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.996
_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    -48.00 -23.00   0.50    0.20    --  -77.79  63.00 120.00   50
  2  \w    -54.00 -27.00   0.50    0.20    --  -77.79  63.00  90.00   54
  3  \w    -56.00 -26.00   0.50    0.20    --  -77.79  63.00   0.00   60
  4  \w    -55.00 -26.00   0.50    0.20    --  -77.79  63.00-150.00   58
  5  \w     64.00 110.00   0.50    0.20    --   93.74  12.00 -90.00   92
  6  \w    106.00 138.00   0.50    0.20    --   93.74  77.00-150.00   64
  7  \w    110.00 142.00   0.50    0.20    --   93.74  77.00 -60.00   64
  8  \w    105.00 131.00   0.50    0.20    --   93.74  63.00 -60.00   52
  9  \w    102.00 140.00   0.50    0.20    --   93.74  50.00 -30.00   76
 10  \w    128.00 154.00   0.50    0.20    --   93.74  12.00 -90.00   52
 11  \w    111.00 138.00   0.50    0.20    --   93.74  77.00  30.00   54
 12  \w     65.00  90.00   0.50    0.20    --   93.74  15.00 116.00   50
 13  \w     39.00  65.00   0.50    0.20    --   51.16  15.00 116.00   52
 14  \w     99.00 136.00   0.50    0.20    --   93.74  77.00  90.00   74
 15  \w    107.00 132.00   0.50    0.20    --   93.74 134.00 155.00   50
 16  \w     97.00 123.00   0.50    0.20    --   93.74 111.00 150.00   52
 17  \w     99.00 124.00   0.50    0.20    --   93.74 111.00-100.00   50
 18  \w    120.00 151.00   0.50    0.20    --   93.74 111.00-150.00   62
 19  \w     -1.00  24.00   0.50    0.20    --   57.24 -45.00   0.00   50
 20  \w     45.00  70.00   0.50    0.20    --   93.74 -77.00   0.00   50
 21  \w     44.00  69.00   0.50    0.20    --   93.74 -77.00  60.00   50
 22  \w     44.00  69.00   0.50    0.20    --   93.74 -77.00 120.00   50
 23  \w     -7.00  26.00   0.50    0.20    --   51.16 -45.00 150.00   66
 24  \w     46.00  71.00   0.50    0.20    --   93.74 -77.00  30.00   50
 25  \w     45.00  70.00   0.50    0.20    --   93.74 -77.00 -30.00   50
 26  \w      0.00  25.00   0.50    0.20    --   57.24 -45.00 -30.00   50
 27  \w     44.00  69.00   0.50    0.20    --   93.74 -77.00-120.00   50
 28  \w     70.00  95.00   0.50    0.20    --   93.74-135.00 -90.00   50
 29  \w     36.00  91.00   0.50    0.20    --   93.74-111.00-180.00  110
 30  \w     46.00  71.00   0.50    0.20    --   93.74-134.00  88.00   50
 31  \w     18.00  43.00   0.50    0.20    --   51.16-111.00 165.00   50
 32  \w     21.00  46.00   0.50    0.20    --   57.24-111.00 165.00   50
 33  \w     46.00  92.00   0.50    0.20    --   93.74-111.00 165.00   92
 34  \w     36.00  66.00   0.50    0.20    --   93.74-111.00-150.00   60
 35  \w     42.00  93.00   0.50    0.20    --   93.74 -91.00-180.00  102
 36  \w     50.00  84.00   0.50    0.20    --   93.74 -91.00-150.00   68
 37  \w     51.00  87.00   0.50    0.20    --   93.74 -91.00-120.00   72
 38  \w     41.00  90.00   0.50    0.20    --   93.74 -91.00 120.00   98
 39  \w     53.00  78.00   0.50    0.20    --   98.00 -83.00  82.55   50
 40  \w   -100.00 -73.00   0.50    0.20    --  -77.79 135.00 -24.00   54
 41  \w    -73.00 -48.00   0.50    0.20    --  -58.89 111.00-100.00   50
 42  \w    -78.00 -21.00   0.50    0.20    --  -77.79 111.00-100.00  114
 43  \w   -128.00 -38.00   0.50    0.20    --  -77.79 -15.00 -53.00  180
 44  \w    -97.00 -49.00   0.50    0.20    --  -52.00 -15.00 -53.00   96
 45  \w   -118.00 -93.00   0.50    0.20    --  -77.79-134.00  88.00   50
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'ROD, Synergy Custom DW system, HyPix-Arc 150'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0501846000
_diffrn_orient_matrix_UB_12      0.0635076000
_diffrn_orient_matrix_UB_13      0.0598069000
_diffrn_orient_matrix_UB_21      0.0315590000
_diffrn_orient_matrix_UB_22      -0.1011321000
_diffrn_orient_matrix_UB_23      0.0363902000
_diffrn_orient_matrix_UB_31      0.0122809000
_diffrn_orient_matrix_UB_32      0.0003196000
_diffrn_orient_matrix_UB_33      -0.3377400000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0340
_diffrn_reflns_av_unetI/netI     0.0274
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.996
_diffrn_reflns_limit_h_max       31
_diffrn_reflns_limit_h_min       -31
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       3
_diffrn_reflns_limit_l_min       -5
_diffrn_reflns_number            13799
_diffrn_reflns_point_group_measured_fraction_full 0.762
_diffrn_reflns_point_group_measured_fraction_max 0.752
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.570
_diffrn_reflns_theta_min         3.473
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.291
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.79498
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'CrysAlisPro 1.171.43.136a (Rigaku Oxford Diffraction, 2024)'
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.569
_exptl_crystal_description       needle
_exptl_crystal_F_000             712
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: methyl alcohol'
_exptl_crystal_size_max          0.13
_exptl_crystal_size_mid          0.08
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.456
_refine_diff_density_min         -0.349
_refine_diff_density_rms         0.047
_refine_ls_abs_structure_details
;
 Flack x determined using 477 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.03(2)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.082
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     218
_refine_ls_number_reflns         2268
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.082
_refine_ls_R_factor_all          0.0448
_refine_ls_R_factor_gt           0.0414
_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^)+(0.0762P)^2^+0.4526P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1197
_refine_ls_wR_factor_ref         0.1224
_reflns_Friedel_coverage         0.333
_reflns_Friedel_fraction_full    0.448
_reflns_Friedel_fraction_max     0.433
_reflns_number_gt                2092
_reflns_number_total             2268
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ce00073d2.cif
_cod_data_source_block           37-cr-20241122c_auto
_cod_depositor_comments
'Adding full bibliography for 7250115--7250119.cif.'
_cod_original_cell_volume        1466.19(8)
_cod_database_code               7250116
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         CHNOS
_shelx_estimated_absorpt_t_max   0.894
_shelx_estimated_absorpt_t_min   0.755
_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 O(H) groups
2.a Aromatic/amide H refined with riding coordinates:
 N3(H3), N6(H6), C3(H3A), C4(H4), C6(H6A), C10(H10), C11(H11), C12(H12),
 C13(H13)
2.b Idealised tetrahedral OH refined as rotating group:
 O1(H1)
;
_shelx_res_checksum              33143
_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
;
_oxdiff_exptl_absorpt_empirical_full_max 1.606
_oxdiff_exptl_absorpt_empirical_full_min 0.556