Theoretical and experimental study of pharmaceutical salts: a case of trimethoprim
Zhang, Liang; Wu, Di; Zhang, Menglong; Yu, Fuhai; Bao, Ying; Xie, Chuang; Hou, Baohong; Jing, Dingding; Zhang, Chuntao; Chen, Wei; CrystEngComm 26 (2024) 3808–3822; doi:10.1039/D4CE00345D

data_7248801
_publ_section_title
;
 Theoretical and experimental study of pharmaceutical salts: a case of
 trimethoprim
;
_journal_issue                   28
_journal_name_full               CrystEngComm
_journal_page_first              3808
_journal_page_last               3822
_journal_paper_doi               10.1039/D4CE00345D
_journal_volume                  26
_journal_year                    2024
_chemical_formula_moiety         'C6 H2 N2 O4, H2 O, 2(C14 H19 N4 O3)'
_chemical_formula_sum            'C34 H42 N10 O11'
_chemical_formula_weight         766.77
_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             2023-08-08
_audit_creation_method
;
Olex2 1.5
(compiled 2023.03.06 svn.rbb2c1857 for OlexSys, GUI svn.r6748)
;
_audit_update_record
;
2023-08-14 deposited with the CCDC.	2024-05-27 downloaded from the CCDC.
;
_cell_angle_alpha                67.818(6)
_cell_angle_beta                 84.598(5)
_cell_angle_gamma                84.690(6)
_cell_formula_units_Z            2
_cell_length_a                   10.6038(7)
_cell_length_b                   12.9331(11)
_cell_length_c                   14.4781(8)
_cell_measurement_reflns_used    4392
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      75.3090
_cell_measurement_theta_min      3.7030
_cell_volume                     1826.9(2)
_computing_cell_refinement       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2013/2 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      293(2)
_diffrn_detector                 'CCD plate'
_diffrn_measured_fraction_theta_full 0.982
_diffrn_measured_fraction_theta_max 0.951
_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     42.00  92.00   1.00   15.00    --    5.00  38.00 150.00   50
  2  \w     -6.00  20.00   1.00   15.00    --    5.00  38.00 150.00   26
  3  \w    -82.00  21.00   1.00   15.00    --  -49.00  38.00 -90.00  103
  4  \w    -76.00 -24.00   1.00   15.00    --  -49.00 -57.00 -60.00   52
  5  \w   -133.00 -16.00   1.00   15.00    --  -49.00 -38.00  60.00  117
  6  \w     11.00  37.00   1.00   15.00    --  -49.00  67.00 153.41   26
  7  \w    -79.00 -13.00   1.00   15.00    --  -49.00  67.00 153.41   66
  8  \w    -68.00  40.00   1.00   15.00    --  -49.00  69.00 -29.32  108
  9  \w   -140.00-114.00   1.00   19.00    -- -110.00  72.00-180.00   26
 10  \w   -176.00 -80.00   1.00   19.00    -- -110.00 -72.00 120.00   96
 11  \w   -114.00 -21.00   1.00   19.00    -- -110.00  57.00  30.00   93
 12  \w   -199.00 -60.00   1.00   19.00    -- -110.00 -19.00  60.00  139
 13  \w   -101.00 -57.00   1.00   19.00    -- -110.00  72.00 150.00   44
 14  \w    -65.00 -22.00   1.00   19.00    -- -110.00  72.00-180.00   43
 15  \w   -157.00-124.00   1.00   19.00    -- -110.00 -72.00-150.00   33
 16  \w   -144.00 -45.00   1.00   19.00    -- -110.00  72.00  30.00   99
 17  \w   -199.00-168.00   1.00   19.00    -- -110.00 -38.00-180.00   31
 18  \w   -118.00 -92.00   1.00   19.00    -- -110.00  72.00 120.00   26
 19  \w   -196.00 -96.00   1.00   19.00    -- -110.00 -72.00 -30.00  100
 20  \w   -141.00-115.00   1.00   19.00    -- -110.00 -38.00-180.00   26
 21  \w   -104.00 -67.00   1.00   19.00    -- -110.00  72.00 -30.00   37
 22  \w   -122.00 -72.00   1.00   19.00    -- -110.00  72.00-150.00   50
 23  \w   -198.00 -66.00   1.00   19.00    -- -110.00 -19.00   0.00  132
 24  \w   -122.00 -96.00   1.00   19.00    -- -110.00  72.00   0.00   26
 25  \w   -138.00 -21.00   1.00   19.00    -- -110.00  72.00 -90.00  117
 26  \w   -106.00 -60.00   1.00   19.00    -- -110.00  72.00  90.00   46
 27  \w   -101.00 -76.00   1.00   19.00    -- -110.00 -72.00-150.00   25
 28  \w   -184.00-156.00   1.00   19.00    -- -110.00 -19.00-180.00   28
 29  \w   -121.00 -96.00   1.00   19.00    -- -110.00 -19.00-180.00   25
 30  \w   -122.00 -96.00   1.00   19.00    -- -110.00  72.00-120.00   26
 31  \w   -138.00 -34.00   1.00   19.00    -- -110.00  57.00 -90.00  104
 32  \w   -199.00-101.00   1.00   19.00    -- -110.00 -72.00 -60.00   98
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB AFC12 (RCD3): Kappa single'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0030584000
_diffrn_orient_matrix_UB_12      0.1259922000
_diffrn_orient_matrix_UB_13      -0.0202655000
_diffrn_orient_matrix_UB_21      0.0248027000
_diffrn_orient_matrix_UB_22      0.0253295000
_diffrn_orient_matrix_UB_23      -0.1127683000
_diffrn_orient_matrix_UB_31      -0.1440606000
_diffrn_orient_matrix_UB_32      0.0097737000
_diffrn_orient_matrix_UB_33      -0.0114812000
_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  0.0774
_diffrn_reflns_av_unetI/netI     0.0862
_diffrn_reflns_Laue_measured_fraction_full 0.982
_diffrn_reflns_Laue_measured_fraction_max 0.951
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            24796
_diffrn_reflns_point_group_measured_fraction_full 0.982
_diffrn_reflns_point_group_measured_fraction_max 0.951
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         79.451
_diffrn_reflns_theta_min         3.698
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.893
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.47308
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46 (Rigaku Oxford Diffraction, 2018)
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    1.394
_exptl_crystal_description       needle
_exptl_crystal_F_000             808
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: Ethanol'
_exptl_crystal_size_max          0.32
_exptl_crystal_size_mid          0.15
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.435
_refine_diff_density_min         -0.314
_refine_diff_density_rms         0.059
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.026
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     505
_refine_ls_number_reflns         7566
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.026
_refine_ls_R_factor_all          0.0983
_refine_ls_R_factor_gt           0.0600
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
;
 w=1/[\s^2^(Fo^2^)+(0.0680P)^2^+0.9717P]
 where P=(Fo^2^+2Fc^2^)/3
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1517
_refine_ls_wR_factor_ref         0.1786
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4918
_reflns_number_total             7566
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4ce00345d2.cif
_cod_data_source_block           p20230804c
_cod_depositor_comments
'Adding full bibliography for 7248797--7248804.cif.'
_cod_database_code               7248801
_shelxl_version_number           2013-2
_shelx_estimated_absorpt_t_max   0.916
_shelx_estimated_absorpt_t_min   0.763
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,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,H) groups
2.a Free rotating group:
 O004(H00K,H00L)
2.b Secondary CH2 refined with riding coordinates:
 C010(H01L,H01M), C018(H01A,H01B)
2.c Aromatic/amide H refined with riding coordinates:
 N00E(H00E), N00F(H00F), C00W(H00W), C00X(H00X), C00Y(H00Y), C012(H012),
 C013(H013), C015(H015), C016(H016), C01D(H01W)
2.d X=CH2 refined with riding coordinates:
 N00I(H00G,H00H), N00J(H00I,H00J), N00K(H00A,H00B), N00L(H00C,H00D)
2.e Idealised Me refined as rotating group:
 C01E(H01N,H01O,H01P), C01F(H01C,H01D,H01E), C01G(H01F,H01G,H01H), C01H(H01Q,
 H01R,H01S), C01I(H01I,H01J,H01K), C01J(H01T,H01U,H01V)
;
_shelx_res_checksum              97737
_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 2.003
_oxdiff_exptl_absorpt_empirical_full_min 0.469