Enhancing the dissolution and bacteriostatic activity of trimethoprim through salt formation
Hu, Xingchen; Xiao, Yuntian; Qi, Luguang; Bai, Yunhe; Sun, Ying; Ye, Yang; Xie, Chuang; CrystEngComm 25 (2023) 3445–3459; doi:10.1039/D3CE00128H

data_7246781
_publ_section_title
;
 Enhancing the dissolution and bacteriostatic activity of trimethoprim
 through salt formation
;
_journal_issue                   23
_journal_name_full               CrystEngComm
_journal_page_first              3445
_journal_page_last               3459
_journal_paper_doi               10.1039/D3CE00128H
_journal_volume                  25
_journal_year                    2023
_chemical_formula_moiety         'C9 H9 O5, 0.163(H2 O), C14 H19 N4 O3'
_chemical_formula_sum            'C23 H28.33 N4 O8.16'
_chemical_formula_weight         491.42
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2yn'
_space_group_name_H-M_alt        'P 1 21/n 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2023-03-28
_audit_creation_method
;
Olex2 1.5
(compiled 2022.04.07 svn.rca3783a0 for OlexSys, GUI svn.r6498)
;
_audit_update_record
;
2023-04-03 deposited with the CCDC.	2023-04-28 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 94.608(3)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   12.1553(5)
_cell_length_b                   8.8076(3)
_cell_length_c                   22.3040(7)
_cell_measurement_reflns_used    9927
_cell_measurement_temperature    113.15
_cell_measurement_theta_max      33.6070
_cell_measurement_theta_min      1.8630
_cell_volume                     2380.13(15)
_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 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_temperature      113.15
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 1.000
_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   -120.00  60.00   1.00    1.00    --  -30.00  45.00   0.00  180
  2  \w   -120.00  30.00   1.00    1.00    --  -30.00  45.00  90.00  150
  3  \w   -120.00   0.00   1.00    1.00    --  -30.00  45.00 180.00  120
;
_diffrn_measurement_device       'abstract diffractometer'
_diffrn_measurement_device_type  'Rigaku Saturn 70 CCD'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0412
_diffrn_reflns_av_unetI/netI     0.0333
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 1.000
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       27
_diffrn_reflns_limit_l_min       -27
_diffrn_reflns_number            18662
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 1.000
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.372
_diffrn_reflns_theta_min         1.832
_exptl_absorpt_coefficient_mu    0.105
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.93023
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'CrysAlisPro 1.171.39.46 (Rigaku Oxford Diffraction, 2018)'
_exptl_crystal_density_diffrn    1.371
_exptl_crystal_description       block
_exptl_crystal_F_000             1038
_exptl_crystal_size_max          0.23
_exptl_crystal_size_mid          0.2
_exptl_crystal_size_min          0.17
_refine_diff_density_max         0.284
_refine_diff_density_min         -0.269
_refine_diff_density_rms         0.047
_refine_ls_extinction_coef       0.0103(10)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2018/3 (Sheldrick 2018)'
_refine_ls_goodness_of_fit_ref   1.023
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     458
_refine_ls_number_reflns         4860
_refine_ls_number_restraints     600
_refine_ls_restrained_S_all      1.019
_refine_ls_R_factor_all          0.0532
_refine_ls_R_factor_gt           0.0425
_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^)+(0.0488P)^2^+0.9516P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1034
_refine_ls_wR_factor_ref         0.1115
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4023
_reflns_number_total             4860
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3ce00128h2.cif
_cod_data_source_block           r20210618c
_cod_depositor_comments
'Adding full bibliography for 7246781--7246785.cif.'
_cod_database_code               7246781
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.982
_shelx_estimated_absorpt_t_min   0.976
_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) groups, All O(H,H) groups
2. Restrained distances
 O5-H5
 0.84 with sigma of 0.01
 N1-H1A = N1-H1B = N2-H2A = N2-H2B = N4-H4
 0.88 with sigma of 0.01
 H1A-H1B = H2A-H2B
 1.5 with sigma of 0.01
 O7-C17 \\sim O8A-C19A
 with sigma of 0.02
 O7-C21 \\sim O8A-C22A
 with sigma of 0.02
 O8-C19 \\sim O7A-C17A
 with sigma of 0.02
 O8-C22 \\sim O7A-C21A
 with sigma of 0.02
 O9-C18 \\sim O9A-C18A
 with sigma of 0.02
 C16-C17 \\sim C20A-C19A
 with sigma of 0.02
 C20-C19 \\sim C16A-C17A
 with sigma of 0.02
 C19-C18 \\sim C17A-C18A
 with sigma of 0.02
 C18-C17 \\sim C18A-C19A
 with sigma of 0.02
 O7-C16 \\sim O8A-C20A
 with sigma of 0.04
 O7-C18 \\sim O8A-C18A
 with sigma of 0.04
 O8-C20 \\sim O7A-C16A
 with sigma of 0.04
 O8-C18 \\sim O7A-C18A
 with sigma of 0.04
 O9-C19 \\sim O9A-C17A
 with sigma of 0.04
 O9-C17 \\sim O9A-C19A
 with sigma of 0.04
 C16-C20 \\sim C20A-C16A
 with sigma of 0.04
 C16-C18 \\sim C20A-C18A
 with sigma of 0.04
 C20-C18 \\sim C16A-C18A
 with sigma of 0.04
 C19-C22 \\sim C17A-C21A
 with sigma of 0.04
 C19-C17 \\sim C17A-C19A
 with sigma of 0.04
 C17-C21 \\sim C19A-C22A
 with sigma of 0.04
 C15-C16 \\sim C15A-C20A
 with sigma of 0.02
 C15-C20 \\sim C15A-C16A
 with sigma of 0.02
 C15-C19 \\sim C15A-C17A
 with sigma of 0.04
 C15-C17 \\sim C15A-C19A
 with sigma of 0.04
 C14-C16 \\sim C14-C20A
 with sigma of 0.04
 C14-C20 \\sim C14-C16A
 with sigma of 0.04
 C14-C15 \\sim C14-C15A
 with sigma of 0.02
 C15-C14 \\sim C14A-C15A
 with sigma of 0.01
 O9-C23 \\sim O9A-C23A
 with sigma of 0.02
 C18-C23 \\sim C18A-C23A
 with sigma of 0.04
3. Uiso/Uaniso restraints and constraints
O7 \\sim O8 \\sim O9 \\sim C14 \\sim C15 \\sim C16 \\sim C17 \\sim C18 \\sim
C19 \\sim C20 \\sim C21 \\sim C22 \\sim C23 \\sim O7A \\sim O8A \\sim O9A \\sim
C14A \\sim C20A \\sim C15A \\sim C16A \\sim C17A \\sim C18A \\sim C19A \\sim
C21A \\sim C22A \\sim C23A: within 2A with sigma of 0.005 and sigma for
terminal atoms of 0.01 within 2A
Uanis(O7) \\sim Ueq, Uanis(O8) \\sim Ueq, Uanis(O9) \\sim Ueq, Uanis(C14) \\sim
Ueq, Uanis(C15) \\sim Ueq, Uanis(C16) \\sim Ueq, Uanis(C17) \\sim Ueq,
Uanis(C18) \\sim Ueq, Uanis(C19) \\sim Ueq, Uanis(C20) \\sim Ueq, Uanis(C21)
\\sim Ueq, Uanis(C22) \\sim Ueq, Uanis(C23) \\sim Ueq, Uanis(O7A) \\sim Ueq,
Uanis(O8A) \\sim Ueq, Uanis(O9A) \\sim Ueq, Uanis(C14A) \\sim Ueq, Uanis(C20A)
\\sim Ueq, Uanis(C15A) \\sim Ueq, Uanis(C16A) \\sim Ueq, Uanis(C17A) \\sim Ueq,
Uanis(C18A) \\sim Ueq, Uanis(C19A) \\sim Ueq, Uanis(C21A) \\sim Ueq,
Uanis(C22A) \\sim Ueq, Uanis(C23A) \\sim Ueq: with sigma of 0.005 and sigma for
terminal atoms of 0.01
4. Others
 Sof(O7A)=Sof(O8A)=Sof(O9A)=Sof(C14A)=Sof(H14C)=Sof(H14D)=Sof(C20A)=Sof(H20A)=
 Sof(C15A)=Sof(C16A)=Sof(H16A)=Sof(C17A)=Sof(C18A)=Sof(C19A)=Sof(C21A)=
 Sof(H21D)=Sof(H21E)=Sof(H21F)=Sof(C22A)=Sof(H22D)=Sof(H22E)=Sof(H22F)=
 Sof(C23A)=Sof(H23D)=Sof(H23E)=Sof(H23F)=1-FVAR(1)
 Sof(O7)=Sof(O8)=Sof(O9)=Sof(C14)=Sof(H14A)=Sof(H14B)=Sof(C15)=Sof(C16)=
 Sof(H16)=Sof(C17)=Sof(C18)=Sof(C19)=Sof(C20)=Sof(H20)=Sof(C21)=Sof(H21A)=
 Sof(H21B)=Sof(H21C)=Sof(C22)=Sof(H22A)=Sof(H22B)=Sof(H22C)=Sof(C23)=Sof(H23A)=
 Sof(H23B)=Sof(H23C)=FVAR(1)
 Sof(O6)=Sof(H6A)=Sof(H6B)=FVAR(2)
5.a Riding coordinates:
 O6(H6A,H6B)
5.b Secondary CH2 refined with riding coordinates:
 C14(H14A,H14B), C14A(H14C,H14D)
5.c Me refined with riding coordinates:
 C9(H9A,H9B,H9C)
5.d Aromatic/amide H refined with riding coordinates:
 C3(H3), C7(H7), C12(H12), C16(H16), C20(H20), C20A(H20A), C16A(H16A)
5.e Fitted hexagon refined as free rotating group:
 C20A(C15A,C16A,C17A,C18A,C19A)
5.f Idealised Me refined as rotating group:
 C8(H8A,H8B,H8C), C21(H21A,H21B,H21C), C22(H22A,H22B,H22C), C23(H23A,H23B,
 H23C), C21A(H21D,H21E,H21F), C22A(H22D,H22E,H22F), C23A(H23D,H23E,H23F)
;
_shelx_res_checksum              94786
_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
;