Solid-state characterization and solubility enhancement of apremilast drug‒drug cocrystals
Wang, Feng-Yuan; Zhang, Qi; Zhang, Zaiyong; Gong, Xiaoyi; Wang, Jian-Rong; Mei, Xuefeng; CrystEngComm 20 (2018) 5945–; doi:10.1039/C8CE00689J

data_7231342
_publ_section_title
;
 Solid-state characterization and solubility enhancement of apremilast
 drug--drug cocrystals
;
_journal_issue                   39
_journal_name_full               CrystEngComm
_journal_page_first              5945
_journal_paper_doi               10.1039/C8CE00689J
_journal_volume                  20
_journal_year                    2018
_chemical_formula_moiety         '2(C22 H24 N2 O7 S), 0.5(C14 H14 N8 O4)'
_chemical_formula_sum            'C51 H55 N8 O16 S2'
_chemical_formula_weight         1100.15
_space_group_crystal_system      tetragonal
_space_group_IT_number           92
_space_group_name_Hall           'P 4abw 2nw'
_space_group_name_H-M_alt        'P 41 21 2'
_symmetry_space_group_name_Hall  'P 4abw 2nw'
_symmetry_space_group_name_H-M   'P 41 21 2'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2018-07-26
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2018-07-26 deposited with the CCDC.
2018-08-09 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   13.1300(3)
_cell_length_b                   13.1300(3)
_cell_length_c                   28.8287(6)
_cell_measurement_reflns_used    9991
_cell_measurement_temperature    50
_cell_measurement_theta_max      26.03
_cell_measurement_theta_min      2.30
_cell_volume                     4969.98(19)
_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      50
_diffrn_measured_fraction_theta_full 0.975
_diffrn_measured_fraction_theta_max 0.975
_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  0.0363
_diffrn_reflns_av_unetI/netI     0.0324
_diffrn_reflns_Laue_measured_fraction_full 0.975
_diffrn_reflns_Laue_measured_fraction_max 0.975
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       34
_diffrn_reflns_limit_l_min       -33
_diffrn_reflns_number            14128
_diffrn_reflns_point_group_measured_fraction_full 0.980
_diffrn_reflns_point_group_measured_fraction_max 0.980
_diffrn_reflns_theta_full        25.010
_diffrn_reflns_theta_max         25.010
_diffrn_reflns_theta_min         2.194
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.190
_exptl_absorpt_correction_type   none
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.470
_exptl_crystal_description       block
_exptl_crystal_F_000             2308
_exptl_crystal_size_max          0.15
_exptl_crystal_size_mid          0.13
_exptl_crystal_size_min          0.11
_refine_diff_density_max         1.314
_refine_diff_density_min         -2.899
_refine_diff_density_rms         0.154
_refine_ls_abs_structure_details
;
 Flack x determined using 1568 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.08(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.050
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     155
_refine_ls_number_reflns         4289
_refine_ls_number_restraints     20
_refine_ls_restrained_S_all      1.145
_refine_ls_R_factor_all          0.1237
_refine_ls_R_factor_gt           0.1208
_refine_ls_shift/su_max          0.004
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1437P)^2^+45.6606P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2959
_refine_ls_wR_factor_ref         0.2985
_reflns_Friedel_coverage         0.705
_reflns_Friedel_fraction_full    0.987
_reflns_Friedel_fraction_max     0.987
_reflns_number_gt                4135
_reflns_number_total             4289
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c8ce00689j2.cif
_cod_data_source_block           2018713
_cod_depositor_comments
'Adding full bibliography for 7231341--7231342.cif.'
_cod_original_cell_volume        4970.0(2)
_cod_database_code               7231342
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.979
_shelx_estimated_absorpt_t_min   0.972
_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
2. Restrained distances
 C28-N6 = C28-N5 = N5-C25 = C26-C25 = N6-C26
 1.3 with sigma of 0.01
 C26-C27 = C27-N3 = N3-C24 = C24-N4 = N4-C23 = C25-N4
 1.48 with sigma of 0.01
 C27-O9
 1.28 with sigma of 0.02
 N3-C26
 2.4 with sigma of 0.02
3. Rigid bond restraints
 N2, C3
 with sigma for 1-2 distances of 0.005 and sigma for 1-3 distances of 0.005
4. Uiso/Uaniso restraints and constraints
N2 \\sim C3: within 2A with sigma of 0.005 and sigma for terminal atoms of 0.01
Uanis(N3) = Uanis(N4) = Uanis(N5) = Uanis(N6)
Uanis(C29) = Uanis(C28) = Uanis(C25) = Uanis(C26) = Uanis(C27) = Uanis(C24) =
Uanis(C23)
Uanis(O9) = Uanis(O5) = Uanis(O4) = Uanis(O3) = Uanis(O2) = Uanis(O1)
Uanis(N5) = Uanis(N6) = Uanis(N3) = Uanis(N4) = Uanis(O6) = Uanis(O7) =
Uanis(N1) = Uanis(N2)
Uanis(C24) = Uanis(C27) = Uanis(C26) = Uanis(C25) = Uanis(C28) = Uanis(C29) =
Uanis(C23) = Uanis(C22) = Uanis(C17) = Uanis(C18) = Uanis(C20) = Uanis(C21) =
Uanis(C19) = Uanis(C14) = Uanis(C15) = Uanis(C16) = Uanis(C12) = Uanis(C11) =
Uanis(C13) = Uanis(C7) = Uanis(C10) = Uanis(C9) = Uanis(C8) = Uanis(C6) =
Uanis(C5) = Uanis(C4) = Uanis(C3) = Uanis(C2) = Uanis(C1)
Uanis(O8) = Uanis(O9) = Uanis(O5) = Uanis(O2) = Uanis(O3) = Uanis(O4) =
Uanis(O1)
5. Others
 Fixed Sof: C26(0.5) C25(0.5) N5(0.5) C28(0.5) H28(0.5) N6(0.5) C29(0.5)
 H29A(0.5) H29B(0.5) H29C(0.5) C27(0.5) N3(0.5) C24(0.5) N4(0.5) C23(0.5)
 H23A(0.5) H23B(0.5) H23C(0.5) O9(0.5)
6.a Ternary CH refined with riding coordinates:
 C11(H11)
6.b Secondary CH2 refined with riding coordinates:
 C12(H12A,H12B), C20(H20A,H20B)
6.c Aromatic/amide H refined with riding coordinates:
 C6(H6), C4(H4), C19(H19), C5(H5), C16(H16), C15(H15), C28(H28), N2(H2)
6.d Fitted pentagon refined as free rotating group:
 C26(C25,N5,C28,N6)
6.e Idealised Me refined as rotating group:
 C1(H1A,H1B,H1C), C13(H13A,H13B,H13C), C21(H21A,H21B,H21C), C22(H22A,H22B,
 H22C), C29(H29A,H29B,H29C), C23(H23A,H23B,H23C)
;
_shelx_res_checksum              59318
_olex2_submission_special_instructions 'No special instructions were received'