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_7248802
_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 H3 N2 O4, C14.37 H20.49 N4 O3.37'
_chemical_formula_sum            'C20.37 H23.49 N6 O7.37'
_chemical_formula_weight         470.37
_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             2023-07-24
_audit_creation_method
;
Olex2 1.5
(compiled 2023.03.06 svn.rbb2c1857 for OlexSys, GUI svn.r6748)
;
_audit_update_record
;
2023-07-24 deposited with the CCDC.	2024-05-27 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 111.155(3)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   14.4664(4)
_cell_length_b                   12.6295(2)
_cell_length_c                   12.7478(4)
_cell_measurement_reflns_used    18514
_cell_measurement_temperature    113.15
_cell_measurement_theta_max      34.6680
_cell_measurement_theta_min      2.1940
_cell_volume                     2172.10(11)
_computing_cell_refinement       'CrysAlisPro 1.171.42.49 (Rigaku OD, 2022)'
_computing_data_collection       'CrysAlisPro 1.171.42.49 (Rigaku OD, 2022)'
_computing_data_reduction        'CrysAlisPro 1.171.42.49 (Rigaku OD, 2022)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      113.15
_diffrn_detector                 'CCD plate'
_diffrn_measured_fraction_theta_full 0.996
_diffrn_measured_fraction_theta_max 0.998
_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   -110.00  70.00   0.50   12.00    --  -20.00   0.00   0.00  360
  2  \w   -110.00   5.00   0.50   12.00    --  -20.00 -70.00  90.00  230
  3  \w   -110.00 -21.00   0.50   12.00    --  -20.00 -70.00   0.00  178
  4  \w    -90.00   7.00   0.50   12.00    --  -20.00 -70.00 180.00  194
;
_diffrn_measurement_device       'abstract diffractometer'
_diffrn_measurement_device_type  'Rigaku Saturn 944'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0447977000
_diffrn_orient_matrix_UB_12      0.0287641000
_diffrn_orient_matrix_UB_13      0.0124242000
_diffrn_orient_matrix_UB_21      0.0272121000
_diffrn_orient_matrix_UB_22      -0.0480111000
_diffrn_orient_matrix_UB_23      0.0123413000
_diffrn_orient_matrix_UB_31      -0.0042390000
_diffrn_orient_matrix_UB_32      -0.0041040000
_diffrn_orient_matrix_UB_33      -0.0570782000
_diffrn_radiation_monochromator  confocal
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0854
_diffrn_reflns_av_unetI/netI     0.0450
_diffrn_reflns_Laue_measured_fraction_full 0.996
_diffrn_reflns_Laue_measured_fraction_max 0.998
_diffrn_reflns_limit_h_max       19
_diffrn_reflns_limit_h_min       -20
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       17
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            30763
_diffrn_reflns_point_group_measured_fraction_full 0.996
_diffrn_reflns_point_group_measured_fraction_max 0.998
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         29.575
_diffrn_reflns_theta_min         2.209
_diffrn_source                   'rotating anode'
_diffrn_source_type              'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.112
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.85538
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.49 (Rigaku Oxford Diffraction, 2022)
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    1.438
_exptl_crystal_description       prism
_exptl_crystal_F_000             987
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: Methanol'
_exptl_crystal_size_max          0.38
_exptl_crystal_size_mid          0.16
_exptl_crystal_size_min          0.14
_refine_diff_density_max         0.400
_refine_diff_density_min         -0.271
_refine_diff_density_rms         0.058
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.020
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     416
_refine_ls_number_reflns         6083
_refine_ls_number_restraints     31
_refine_ls_restrained_S_all      1.025
_refine_ls_R_factor_all          0.0623
_refine_ls_R_factor_gt           0.0512
_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^)+(0.0727P)^2^+0.7274P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1301
_refine_ls_wR_factor_ref         0.1395
_reflns_Friedel_coverage         0.000
_reflns_number_gt                5064
_reflns_number_total             6083
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4ce00345d2.cif
_cod_data_source_block           r20230530d_autored
_cod_depositor_comments
'Adding full bibliography for 7248797--7248804.cif.'
_cod_database_code               7248802
_shelx_shelxl_version_number     2018/3
_reflns_odcompleteness_completeness 93.19
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     34.72
_olex2_refinement_description
;
1. Restrained distances
 O1-C12 \\sim O1A-C12A \\sim O2-C13 \\sim O2A-C13A \\sim O3-C14 \\sim O3A-C14A
 with sigma of 0.01
 C5-C6 \\sim C5-C6A
 with sigma of 0.01
 C8-O1 \\sim C8A-O1A \\sim C9-O2 \\sim C9A-O2A \\sim C10-O3 \\sim C10A-O3A
 with sigma of 0.01
2. Uiso/Uaniso restraints and constraints
Uanis(C6) = Uanis(C6A)
Uanis(C7) = Uanis(C7A)
Uanis(C11) = Uanis(C11A)
3. Others
 Sof(H5BD)=Sof(H5BC)=Sof(O1A)=Sof(O2A)=Sof(O3A)=Sof(C6A)=Sof(C7A)=Sof(H7A)=
 Sof(C8A)=Sof(C9A)=Sof(C10A)=Sof(C11A)=Sof(H11A)=Sof(C12A)=Sof(H12D)=Sof(H12E)=
 Sof(H12F)=Sof(C13A)=Sof(H13D)=Sof(H13E)=Sof(H13F)=Sof(C14A)=Sof(H14D)=
 Sof(H14E)=Sof(H14F)=1-FVAR(1)
 Sof(H5AB)=Sof(H5AA)=Sof(O1)=Sof(O2)=Sof(O3)=Sof(C6)=Sof(C7)=Sof(H7)=Sof(C8)=
 Sof(C9)=Sof(C10)=Sof(C11)=Sof(H11)=Sof(C12)=Sof(H12A)=Sof(H12B)=Sof(H12C)=
 Sof(C13)=Sof(H13A)=Sof(H13B)=Sof(H13C)=Sof(C14)=Sof(H14A)=Sof(H14B)=Sof(H14C)=
 FVAR(1)
 Sof(O8)=Sof(H8)=Sof(C21)=Sof(H21A)=Sof(H21B)=Sof(H21C)=FVAR(2)
4.a Secondary CH2 refined with riding coordinates:
 C5(H5AB,H5AA), C5(H5BD,H5BC)
4.b Aromatic/amide H refined with riding coordinates:
 C17(H17), C18(H18), C2(H2A), C7(H7), C11(H11), C7A(H7A), C11A(H11A)
4.c Fitted hexagon refined as free rotating group:
 C6(C7,C8,C9,C10,C11), C6A(C7A,C8A,C9A,C10A,C11A)
4.d Idealised Me refined as rotating group:
 C12(H12A,H12B,H12C), C13(H13A,H13B,H13C), C14(H14A,H14B,H14C), C12A(H12D,H12E,
 H12F), C13A(H13D,H13E,H13F), C14A(H14D,H14E,H14F), C21(H21A,H21B,H21C)
4.e Idealised tetrahedral OH refined as rotating group:
 O8(H8)
;
_shelx_res_checksum              40086
_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
- Detector area scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 3.850
_oxdiff_exptl_absorpt_empirical_full_min 0.397