Pharmaceutical salt and salt hydrates of vortioxetine with sulfonic acid to ameliorate the solubility and hygroscopicity via the charge-assisted hydrogen bond assembly
Du, Rongkai; Xu, Juan; Li, Jing; Zhang, Lei; Ning, Lifeng; Li, Shan; New Journal of Chemistry 45 (2021) 1474–1481; doi:10.1039/D0NJ05052K

data_7060266
_publ_section_title
;
 Pharmaceutical salt and salt hydrates of vortioxetine with sulfonic acid
 to ameliorate the solubility and hygroscopicity via the charge-assisted
 hydrogen bond assembly
;
_journal_issue                   3
_journal_name_full               'New Journal of Chemistry'
_journal_page_first              1474
_journal_page_last               1481
_journal_paper_doi               10.1039/D0NJ05052K
_journal_volume                  45
_journal_year                    2021
_chemical_formula_moiety         'C6 H6 N O3 S, C18 H23 N2 S'
_chemical_formula_sum            'C24 H29 N3 O3 S2'
_chemical_formula_weight         471.62
_space_group_crystal_system      orthorhombic
_space_group_IT_number           33
_space_group_name_Hall           'P 2c -2n'
_space_group_name_H-M_alt        'P n a 21'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2019-08-20
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2019-10-06 deposited with the CCDC.	2020-12-07 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   15.7632(16)
_cell_length_b                   6.4133(6)
_cell_length_c                   46.610(4)
_cell_measurement_reflns_used    3133
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      23.2940
_cell_measurement_theta_min      4.0710
_cell_volume                     4712.0(8)
_computing_cell_refinement       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_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      293(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 8.0606
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.974
_diffrn_measured_fraction_theta_max 0.998
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
  1  \w     43.00  81.25   0.75    7.50    --   15.49  57.00 -30.00   51
  2  \w    -14.00  12.25   0.75    7.50    --  -16.28  19.00-180.00   35
  3  \w    -51.00  13.50   0.75    7.50    --   15.49 -77.00-150.00   86
  4  \w    -25.00  10.25   0.75    7.50    --  -16.28 -99.00  30.00   47
  5  \w    -44.00 -18.50   0.75    7.50    --  -16.28  90.00 104.00   34
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Eos, Gemini'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0098367000
_diffrn_orient_matrix_UB_12      -0.0495496000
_diffrn_orient_matrix_UB_13      -0.0279078000
_diffrn_orient_matrix_UB_21      0.0111000000
_diffrn_orient_matrix_UB_22      -0.0133623000
_diffrn_orient_matrix_UB_23      -0.0302409000
_diffrn_orient_matrix_UB_31      0.0034476000
_diffrn_orient_matrix_UB_32      -0.0979999000
_diffrn_orient_matrix_UB_33      0.0181221000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0983
_diffrn_reflns_av_unetI/netI     0.1403
_diffrn_reflns_Laue_measured_fraction_full 0.974
_diffrn_reflns_Laue_measured_fraction_max 0.998
_diffrn_reflns_limit_h_max       18
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       6
_diffrn_reflns_limit_k_min       -7
_diffrn_reflns_limit_l_max       55
_diffrn_reflns_limit_l_min       -40
_diffrn_reflns_number            15469
_diffrn_reflns_point_group_measured_fraction_full 0.776
_diffrn_reflns_point_group_measured_fraction_max 0.794
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         25.026
_diffrn_reflns_theta_min         3.385
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.257
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.51379
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.41 (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light yellow'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.330
_exptl_crystal_description       plate
_exptl_crystal_F_000             2000
_exptl_crystal_size_max          0.24
_exptl_crystal_size_mid          0.22
_exptl_crystal_size_min          0.12
_refine_diff_density_max         0.341
_refine_diff_density_min         -0.829
_refine_diff_density_rms         0.074
_refine_ls_abs_structure_details
;
 Flack x determined using 1043 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   0.54(13)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.042
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     583
_refine_ls_number_reflns         6626
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.042
_refine_ls_R_factor_all          0.1292
_refine_ls_R_factor_gt           0.0853
_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^)+(0.0583P)^2^]
 where P=(Fo^2^+2Fc^2^)/3
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1600
_refine_ls_wR_factor_ref         0.1854
_reflns_Friedel_coverage         0.571
_reflns_Friedel_fraction_full    0.572
_reflns_Friedel_fraction_max     0.586
_reflns_number_gt                4303
_reflns_number_total             6626
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d0nj05052k2.cif
_cod_data_source_block           VOT-SA
_cod_depositor_comments
'Adding full bibliography for 7060266--7060269.cif.'
_cod_original_cell_volume        4712.0(7)
_cod_database_code               7060266
_shelxl_version_number           2013-2
_shelx_estimated_absorpt_t_max   0.970
_shelx_estimated_absorpt_t_min   0.941
_reflns_odcompleteness_completeness 99.55
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     26.32
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2.a Rotating group:
 N3B(H3BC,H3BD), N3A(H3AC,H3AD)
2.b Secondary CH2 refined with riding coordinates:
 C1A(H1AC,H1AD), N1A(H1AA,H1AB), C2A(H2AA,H2AB), C3A(H3AA,H3AB), C4A(H4AA,
 H4AB), C1B(H1BC,H1BD), N1B(H1BA,H1BB), C2B(H2BA,H2BB), C3B(H3BA,H3BB),
 C4B(H4BA,H4BB)
2.c Aromatic/amide H refined with riding coordinates:
 C20B(H20B), C21B(H21B), C23B(H23B), C24B(H24B), C6A(H6A), C7A(H7A), C8A(H8A),
 C9A(H9A), C13A(H13A), C15A(H15A), C16A(H16A), C6B(H6B), C7B(H7B), C8B(H8B),
 C9B(H9B), C13B(H13B), C15B(H15B), C16B(H16B), C20A(H20A), C21A(H21A),
 C23A(H23A), C24A(H24A)
2.d Idealised Me refined as rotating group:
 C17A(H17A,H17B,H17C), C18A(H18A,H18B,H18C), C17B(H17D,H17E,H17F), C18B(H18D,
 H18E,H18F)
;
_shelx_res_checksum              41835
_shelx_hkl_checksum              40052
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.409
_oxdiff_exptl_absorpt_empirical_full_min 0.689