Crystal engineering of the cystic fibrosis drug ivacaftor: salts, solvates and hydrate forms with solubility and stability studies
Doguparthi, Naga Prathyusha; Kanagavel, Manimurugan; Samreen, Sabiqa; Navya, Yaramala; Soujanya, Yarasi; Swain, Debasish; Nechipadappu, Sunil Kumar; CrystEngComm 28 (2026) 1621–1635; doi:10.1039/D5CE01068C

data_7251472
_publ_section_title
;
 Crystal engineering of the cystic fibrosis drug ivacaftor: salts,
 solvates and hydrate forms with solubility and stability studies
;
_journal_issue                   10
_journal_name_full               CrystEngComm
_journal_page_first              1621
_journal_page_last               1635
_journal_paper_doi               10.1039/D5CE01068C
_journal_volume                  28
_journal_year                    2026
_chemical_formula_moiety         'C24 H28 N2 O3, 2(C2 H4 O2)'
_chemical_formula_sum            'C28 H36 N2 O7'
_chemical_formula_weight         512.59
_chemical_name_systematic        'ivacaftor di acetic acid solvate'
_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     difmap
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-2019/3
_audit_update_record
;
2025-10-10 deposited with the CCDC.	2026-01-28 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 109.131(7)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   17.796(2)
_cell_length_b                   6.5459(9)
_cell_length_c                   25.136(3)
_cell_measurement_reflns_used    6001
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      66.89
_cell_measurement_theta_min      5.26
_cell_volume                     2766.4(6)
_computing_cell_refinement       '<i>SAINT</i> (Bruker, 2016)'
_computing_data_collection       '<i>APEX3</i> (Bruker, 2016)'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-2018/3 (Sheldrick, 2018)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      100(2)
_diffrn_measured_fraction_theta_full 0.966
_diffrn_measured_fraction_theta_max 0.966
_diffrn_measurement_device_type  'Bruker D8 VENTURE PHOTON-III C14'
_diffrn_measurement_method       '\w and \f'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0888
_diffrn_reflns_av_unetI/netI     0.0720
_diffrn_reflns_Laue_measured_fraction_full 0.966
_diffrn_reflns_Laue_measured_fraction_max 0.966
_diffrn_reflns_limit_h_max       19
_diffrn_reflns_limit_h_min       -20
_diffrn_reflns_limit_k_max       7
_diffrn_reflns_limit_k_min       -7
_diffrn_reflns_limit_l_max       29
_diffrn_reflns_limit_l_min       -28
_diffrn_reflns_number            15955
_diffrn_reflns_point_group_measured_fraction_full 0.966
_diffrn_reflns_point_group_measured_fraction_max 0.966
_diffrn_reflns_theta_full        62.998
_diffrn_reflns_theta_max         62.998
_diffrn_reflns_theta_min         3.686
_exptl_absorpt_coefficient_mu    0.725
_exptl_absorpt_correction_T_max  0.7461
_exptl_absorpt_correction_T_min  0.6832
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
 SADABS 2016/2: Krause, L., Herbst-Irmer, R., Sheldrick G.M. & Stalke D.,
 J. Appl. Cryst. 48 (2015) 3-10
;
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.231
_exptl_crystal_description       plate
_exptl_crystal_F_000             1096
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: acetic acid'
_exptl_crystal_size_max          0.200
_exptl_crystal_size_mid          0.110
_exptl_crystal_size_min          0.100
_refine_diff_density_max         0.184
_refine_diff_density_min         -0.215
_refine_diff_density_rms         0.044
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.039
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     360
_refine_ls_number_reflns         4333
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.039
_refine_ls_R_factor_all          0.0805
_refine_ls_R_factor_gt           0.0477
_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^)+(0.0781P)^2^+0.2664P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1268
_refine_ls_wR_factor_ref         0.1400
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3195
_reflns_number_total             4333
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ce01068c2.cif
_cod_data_source_block           cu_VA216_0m_IVA-DACA
_cod_depositor_comments
'Adding full bibliography for 7251465--7251473.cif.'
_cod_original_cell_volume        2766.5(7)
_cod_original_sg_symbol_H-M      'P 21/n'
_cod_database_code               7251472
_shelx_shelxl_version_number     2019/3
_shelx_estimated_absorpt_t_min   0.869
_shelx_estimated_absorpt_t_max   0.931
_shelx_res_checksum              29415