Novel pharmaceutical co-crystals of gefitinib: synthesis, dissolution, cytotoxicity, and theoretical studies
Shaik, Althaf; Bhagwat, Pranav Umesh; Palanisamy, Parimaladevi; Chhabria, Dimple; Dubey, Pankaj; Kirubakaran, Sivapriya; Thiruvenkatam, Vijay; CrystEngComm 25 (2023) 2570–2581; doi:10.1039/D3CE00056G

data_7246501
_publ_section_title
;
 Novel pharmaceutical co-crystals of gefitinib: synthesis, dissolution,
 cytotoxicity, and theoretical studies
;
_journal_issue                   17
_journal_name_full               CrystEngComm
_journal_page_first              2570
_journal_page_last               2581
_journal_paper_doi               10.1039/D3CE00056G
_journal_volume                  25
_journal_year                    2023
_chemical_formula_moiety         'C22 H23 Cl F N4 O3, C6 H8 O2, H2 O'
_chemical_formula_sum            'C28 H33 Cl F N4 O6'
_chemical_formula_weight         576.03
_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             2019-01-01
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2019-01-08 deposited with the CCDC.	2023-03-22 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 93.749(7)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   10.930(2)
_cell_length_b                   7.2541(14)
_cell_length_c                   35.222(6)
_cell_measurement_reflns_used    5556
_cell_measurement_temperature    150(2)
_cell_measurement_theta_max      25.48
_cell_measurement_theta_min      2.32
_cell_volume                     2786.7(9)
_computing_cell_refinement       'SAINT V8.38A (?, 2016)'
_computing_data_reduction        'SAINT V8.38A (?, 2016)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      150.0
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.995
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0999
_diffrn_reflns_av_unetI/netI     0.0830
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.995
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       47
_diffrn_reflns_limit_l_min       -46
_diffrn_reflns_number            36316
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.995
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         28.342
_diffrn_reflns_theta_min         2.318
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.193
_exptl_absorpt_correction_T_max  0.7457
_exptl_absorpt_correction_T_min  0.6154
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.1360 before and 0.0795 after correction. The Ratio of minimum to maximum transmission is 0.8253. The \l/2 correction factor is Not present.'
_exptl_crystal_colour            transparant
_exptl_crystal_density_diffrn    1.373
_exptl_crystal_description       block
_exptl_crystal_F_000             1212
_exptl_crystal_size_max          0.297
_exptl_crystal_size_mid          0.092
_exptl_crystal_size_min          0.09
_refine_diff_density_max         0.448
_refine_diff_density_min         -0.388
_refine_diff_density_rms         0.080
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.069
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     367
_refine_ls_number_reflns         6931
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.069
_refine_ls_R_factor_all          0.1306
_refine_ls_R_factor_gt           0.0716
_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^)+(0.0976P)^2^+2.1071P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1863
_refine_ls_wR_factor_ref         0.2222
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4091
_reflns_number_total             6931
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3ce00056g2.cif
_cod_data_source_block           gsalt_0m
_cod_depositor_comments
;
Adding full bibliography for 7246500--7246502.cif.

2025-04-02
Z value and formula fixed to values more according to usual
chemical conventions.                 miguel
;
_cod_original_formula_sum            'C56 H66 Cl2 F2 N8 O12'
_cod_original_formula_weight         1152.06
_cod_original_formula_moiety     '2(C22 H23 Cl F N4 O3), 2(C6 H8 O2), 2(H2 O)'
_cod_original_formula_units_Z            2
_cod_original_cell_volume        2786.8(9)
_cod_database_code               7246501
_shelx_shelxl_version_number     2017/1
_shelx_estimated_absorpt_t_max   0.983
_shelx_estimated_absorpt_t_min   0.945
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups, All O(H,H) groups
2.a Free rotating group:
 O1S(H1SA,H1SB)
2.b Secondary CH2 refined with riding coordinates:
 C15(H15A,H15B), C17(H17A,H17B), C18(H18A,H18B), C19(H19A,H19B), C20(H20A,
 H20B), C22(H22A,H22B)
2.c Aromatic/amide H refined with riding coordinates:
 N3(H3), C2B(H2BA), C3(H3A), C3B(H3B), C4B(H4B), C5B(H5B), C6(H6), C7(H7),
 C10(H10), C11(H11), C14(H14), C21(H21)
2.d Idealised Me refined as rotating group:
 C1B(H1BA,H1BB,H1BC), C16(H16A,H16B,H16C)
2.e Idealised tetrahedral OH refined as rotating group:
 O2B(H2B)
;
_shelx_res_checksum              51677
_shelx_hkl_checksum              12111
_olex2_submission_special_instructions 'No special instructions were received'