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_7231341
_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), C6 H6 N2 O'
_chemical_formula_sum            'C50 H54 N6 O15 S2'
_chemical_formula_weight         1043.11
_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
_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                   12.9994(8)
_cell_length_b                   12.9994(8)
_cell_length_c                   29.744(2)
_cell_measurement_reflns_used    6723
_cell_measurement_temperature    170(2)
_cell_measurement_theta_max      21.83
_cell_measurement_theta_min      2.22
_cell_volume                     5026.3(6)
_computing_cell_refinement       'SAINT v7.68A (Bruker, 2009)'
_computing_data_reduction        'SAINT v7.68A (Bruker, 2009)'
_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 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_temperature      170.0
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.994
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0671
_diffrn_reflns_av_unetI/netI     0.0472
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.994
_diffrn_reflns_limit_h_max       16
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       34
_diffrn_reflns_limit_l_min       -38
_diffrn_reflns_number            46922
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.995
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         27.525
_diffrn_reflns_theta_min         1.710
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.181
_exptl_absorpt_correction_T_max  0.7456
_exptl_absorpt_correction_T_min  0.6516
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2008/1 (Bruker,2008) was used for absorption correction.
wR2(int) was 0.1080 before and 0.0631 after correction.
The Ratio of minimum to maximum transmission is 0.8739.
The \l/2 correction factor is 0.0015.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.378
_exptl_crystal_description       block
_exptl_crystal_F_000             2192
_exptl_crystal_size_max          0.25
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.11
_refine_diff_density_max         0.509
_refine_diff_density_min         -0.642
_refine_diff_density_rms         0.060
_refine_ls_abs_structure_details
;
 Flack x determined using 1356 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.01(4)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.060
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     362
_refine_ls_number_reflns         5752
_refine_ls_number_restraints     156
_refine_ls_restrained_S_all      1.140
_refine_ls_R_factor_all          0.0949
_refine_ls_R_factor_gt           0.0600
_refine_ls_shift/su_max          0.003
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0969P)^2^+1.1805P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1552
_refine_ls_wR_factor_ref         0.1776
_reflns_Friedel_coverage         0.720
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.996
_reflns_number_gt                4024
_reflns_number_total             5752
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c8ce00689j2.cif
_cod_data_source_block           mo_2016513_0m
_cod_depositor_comments
'Adding full bibliography for 7231341--7231342.cif.'
_cod_original_cell_volume        5026.3(7)
_cod_database_code               7231341
_shelx_shelxl_version_number     2018/3
_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
2. Restrained distances
 C46-C50
 1.5 with sigma of 0.02
 C47-C50
 2.5 with sigma of 0.02
 C50-C45
 2.5 with sigma of 0.02
 C46-O15
 2.8 with sigma of 0.02
 N6-O15
 2.4 with sigma of 0.02
 O15-N6
 2.256 with sigma of 0.02
 N6-C46
 2.4 with sigma of 0.02
 N6-C45
 2.7 with sigma of 0.02
 N6-C50
 1.316 with sigma of 0.02
 O15-C50
 1.245 with sigma of 0.02
 O15-C47
 2.8 with sigma of 0.02
 O15-C46
 2.38 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
C45 \\sim N5 \\sim C49 \\sim C48 \\sim C47 \\sim C46 \\sim O15 \\sim C50 \\sim
N6: within 2A with sigma of 0.005 and sigma for terminal atoms of 0.01
Uanis(C45) \\sim Ueq, Uanis(N5) \\sim Ueq, Uanis(C49) \\sim Ueq, Uanis(C48)
\\sim Ueq, Uanis(C47) \\sim Ueq, Uanis(C46) \\sim Ueq: with sigma of 0.005 and
sigma for terminal atoms of 0.01
Uanis(C50) \\sim Ueq, Uanis(O15) \\sim Ueq, Uanis(N6) \\sim Ueq: with sigma of
0.005 and sigma for terminal atoms of 0.01
4. Rigid body (RIGU) restrains
 C46, C47, C48, C49, N5, C45
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
5. Others
 Fixed Sof: C45(0.5) H45(0.5) N5(0.5) C49(0.5) H49(0.5) C48(0.5) H48(0.5)
 C47(0.5) H47(0.5) C46(0.5) O15(0.5) C50(0.5) N6(0.5) H6A(0.5) H6B(0.5)
6.a Ternary CH refined with riding coordinates:
 C1(H1)
6.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C10(H10A,H10B)
6.c Aromatic/amide H refined with riding coordinates:
 N2(H2), C5(H5), C9(H9), C8(H8), C18(H18), C16(H16), C17(H17), C45(H45),
 C49(H49), C48(H48), C47(H47)
6.d Fitted hexagon refined as free rotating group:
 C45(N5,C49,C48,C47,C46)
6.e X=CH2 refined with riding coordinates:
 N6(H6A,H6B)
6.f Idealised Me refined as rotating group:
 C22(H22A,H22B,H22C), C3(H3A,H3B,H3C), C12(H12A,H12B,H12C), C11(H11A,H11B,H11C)
;
_shelx_res_checksum              33453
_olex2_submission_special_instructions 'No special instructions were received'