Gefitinib salts/cocrystals with phenolic acids as a promising solid-state approach to improve solubility
Zou, Yao; Meng, Xin; Zhang, Baoxi; Yu, Hongmei; He, Guorong; Gong, Ningbo; Lu, Yang; Du, Guanhua; CrystEngComm 26 (2024) 2112–2122; doi:10.1039/D4CE00039K

data_7248301
_publ_section_title
;
 Gefitinib salts/cocrystals with phenolic acids as a promising solid-state
 approach to improve solubility
;
_journal_issue                   15
_journal_name_full               CrystEngComm
_journal_page_first              2112
_journal_page_last               2122
_journal_paper_doi               10.1039/D4CE00039K
_journal_volume                  26
_journal_year                    2024
_chemical_formula_moiety         'C22 H25 Cl F N4 O3, C7 H3 N2 O6, C7 H4 N2 O6'
_chemical_formula_sum            'C36 H32 Cl F N8 O15'
_chemical_formula_weight         871.14
_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   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2021-11-16
_audit_creation_method
;
Olex2 1.5
(compiled 2021.10.07 svn.r9718050b for OlexSys, GUI svn.r6410)
;
_audit_update_record
;
2023-12-27 deposited with the CCDC.	2024-03-11 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 95.1950(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   7.38070(10)
_cell_length_b                   22.4116(2)
_cell_length_c                   23.00200(10)
_cell_measurement_reflns_used    6327
_cell_measurement_temperature    295(2)
_cell_measurement_theta_max      72.332
_cell_measurement_theta_min      2.758
_cell_volume                     3789.21(6)
_computing_cell_refinement       'CrystalClear (Rigaku Inc., 2008)'
_computing_data_collection       'CrystalClear (Rigaku Inc., 2008)'
_computing_data_reduction        'CrystalClear (Rigaku Inc., 2008)'
_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_temperature      295(2)
_diffrn_detector_area_resol_mean 0
_diffrn_measured_fraction_theta_full 0.988
_diffrn_measured_fraction_theta_max 0.972
_diffrn_measurement_device_type  'Rigaku 002+'
_diffrn_measurement_method       /w/k
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0414
_diffrn_reflns_av_unetI/netI     0.0290
_diffrn_reflns_Laue_measured_fraction_full 0.988
_diffrn_reflns_Laue_measured_fraction_max 0.972
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       27
_diffrn_reflns_limit_k_min       -25
_diffrn_reflns_limit_l_max       27
_diffrn_reflns_limit_l_min       -28
_diffrn_reflns_number            32511
_diffrn_reflns_point_group_measured_fraction_full 0.988
_diffrn_reflns_point_group_measured_fraction_max 0.972
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         72.332
_diffrn_reflns_theta_min         2.758
_diffrn_source                   'fine-focus sealed tube'
_exptl_absorpt_coefficient_mu    1.683
_exptl_absorpt_correction_T_max  0.831
_exptl_absorpt_correction_T_min  0.769
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   ' Higashi, T. (1995).  '
_exptl_crystal_colour            yellow
_exptl_crystal_density_diffrn    1.527
_exptl_crystal_description       needle
_exptl_crystal_F_000             1800
_exptl_crystal_size_max          0.35
_exptl_crystal_size_mid          0.13
_exptl_crystal_size_min          0.11
_refine_diff_density_max         0.325
_refine_diff_density_min         -0.341
_refine_diff_density_rms         0.050
_refine_ls_extinction_coef       0.00099(9)
_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   1.050
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     553
_refine_ls_number_reflns         7281
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.050
_refine_ls_R_factor_all          0.0471
_refine_ls_R_factor_gt           0.0415
_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^)+(0.0575P)^2^+0.8604P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1093
_refine_ls_wR_factor_ref         0.1160
_reflns_Friedel_coverage         0.000
_reflns_number_gt                6327
_reflns_number_total             7281
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4ce00039k2.cif
_cod_data_source_block           6275
_cod_depositor_comments
'Adding full bibliography for 7248298--7248302.cif.'
_cod_database_code               7248301
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.831
_shelx_estimated_absorpt_t_min   0.769
_exptl_absorpt_special_details   sadabs
_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 O(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2.a Ternary CH refined with riding coordinates:
 N4(H4)
2.b Secondary CH2 refined with riding coordinates:
 C15(H15A,H15B), C16(H16A,H16B), C17(H17A,H17B), C18(H18A,H18B), C19(H19A,
 H19B), C20(H20A,H20B), C21(H21A,H21B)
2.c Aromatic/amide H refined with riding coordinates:
 N1(H1), C1(H1A), C4(H4A), C5(H5), C8(H8), C11(H11), C14(H14), C24(H24),
 C26(H26), C28(H28), C31(H31), C33(H33), C35(H35)
2.d Idealised Me refined as rotating group:
 C22(H22A,H22B,H22C)
2.e Idealised tetrahedral OH refined as rotating group:
 O11(H11A)
;
_shelx_res_checksum              22572
_olex2_submission_special_instructions 'No special instructions were received'