Ethinyl estradiol cocrystals assembled by chain structures: improvement in stability and solubility
Du, Rongkai; Xu, Juan; Zhang, Lei; Ning, Lifeng; Li, Shan; New Journal of Chemistry 43 (2019) 16889–; doi:10.1039/C9NJ04147H

data_7058871
_publ_section_title
;
 Ethinyl estradiol cocrystals assembled by chain structures: improvement
 in stability and solubility
;
_journal_issue                   43
_journal_name_full               'New Journal of Chemistry'
_journal_page_first              16889
_journal_paper_doi               10.1039/C9NJ04147H
_journal_volume                  43
_journal_year                    2019
_chemical_absolute_configuration syn
_chemical_formula_moiety         'C20 H24 O2, 2(C2 H5 N)'
_chemical_formula_sum            'C24 H34 N2 O2'
_chemical_formula_weight         382.53
_space_group_crystal_system      monoclinic
_space_group_IT_number           5
_space_group_name_Hall           'C 2y'
_space_group_name_H-M_alt        'C 1 2 1'
_symmetry_space_group_name_Hall  'C 2y'
_symmetry_space_group_name_H-M   'C 1 2 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2019-07-03
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2019-07-05 deposited with the CCDC.    2019-10-03 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 91.921(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   11.9146(13)
_cell_length_b                   6.9435(8)
_cell_length_c                   26.361(3)
_cell_measurement_reflns_used    1339
_cell_measurement_temperature    173.00(15)
_cell_measurement_theta_max      26.4000
_cell_measurement_theta_min      3.6950
_cell_volume                     2179.6(4)
_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_environment      air
_diffrn_ambient_temperature      173.00(15)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 16.1213
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.824
_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    -29.00  65.00   1.00    7.50    --   15.49   0.00   0.00   94
  2  \w      8.00  77.00   1.00    7.50    --   15.49  38.00  60.00   69
  3  \w     58.00  88.00   1.00    7.50    --   15.49 178.00 -30.00   30
  4  \w    -23.00   5.00   1.00    7.50    --  -16.28-102.00 -39.00   28
;
_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      -0.0237395000
_diffrn_orient_matrix_UB_12      0.0052729000
_diffrn_orient_matrix_UB_13      -0.0250033000
_diffrn_orient_matrix_UB_21      0.0262326000
_diffrn_orient_matrix_UB_22      -0.0884975000
_diffrn_orient_matrix_UB_23      -0.0060232000
_diffrn_orient_matrix_UB_31      -0.0479596000
_diffrn_orient_matrix_UB_32      -0.0508293000
_diffrn_orient_matrix_UB_33      0.0078858000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0231
_diffrn_reflns_av_unetI/netI     0.0426
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.824
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       7
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       36
_diffrn_reflns_limit_l_min       -33
_diffrn_reflns_number            5217
_diffrn_reflns_point_group_measured_fraction_full 0.786
_diffrn_reflns_point_group_measured_fraction_max 0.615
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         29.394
_diffrn_reflns_theta_min         3.396
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.074
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.63182
_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 colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.166
_exptl_crystal_description       plate
_exptl_crystal_F_000             832
_exptl_crystal_size_max          0.3
_exptl_crystal_size_mid          0.26
_exptl_crystal_size_min          0.12
_refine_diff_density_max         0.524
_refine_diff_density_min         -0.246
_refine_diff_density_rms         0.044
_refine_ls_abs_structure_details
;
 Flack x determined using 723 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   -0.3(10)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.054
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     284
_refine_ls_number_reflns         3725
_refine_ls_number_restraints     2
_refine_ls_restrained_S_all      1.054
_refine_ls_R_factor_all          0.0815
_refine_ls_R_factor_gt           0.0629
_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^)+(0.0736P)^2^+1.5555P]
 where P=(Fo^2^+2Fc^2^)/3
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1570
_refine_ls_wR_factor_ref         0.1717
_reflns_Friedel_coverage         0.385
_reflns_Friedel_fraction_full    0.533
_reflns_Friedel_fraction_max     0.371
_reflns_number_gt                2898
_reflns_number_total             3725
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c9nj04147h2.cif
_cod_data_source_block           EE-PZ
_cod_depositor_comments
'Adding full bibliography for 7058869--7058873.cif.'
_cod_database_code               7058871
_shelxl_version_number           2013-2
_shelx_estimated_absorpt_t_max   0.991
_shelx_estimated_absorpt_t_min   0.978
_reflns_odcompleteness_completeness 99.79
_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
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 N1-H1B
 0.86 with sigma of 0.01
3. Others
 Sof(H25C)=Sof(H25D)=Sof(H24C)=Sof(H24D)=Sof(N2B)=Sof(H2B)=1-FVAR(1)
 Sof(H25A)=Sof(H25B)=Sof(H24A)=Sof(H24B)=Sof(N2A)=Sof(H2AA)=FVAR(1)
4.a Everything fixed:
 H1B
4.b Ternary CH refined with riding coordinates:
 C14(H14), C9(H9), C8(H8)
4.c Secondary CH2 refined with riding coordinates:
 C16(H16A,H16B), C15(H15A,H15B), C12(H12A,H12B), C11(H11A,H11B), C7(H7A,H7B),
 C6(H6A,H6B), C23(H23A,H23B), C22(H22A,H22B), C25(H25C,H25D), C25(H25A,H25B),
 C24(H24C,H24D), C24(H24A,H24B)
4.d Aromatic/amide H refined with riding coordinates:
 C1(H1A), C2(H2A), C4(H4)
4.e Idealised Me refined as rotating group:
 C18(H18A,H18B,H18C)
4.f :
 C21(H21)
;
_shelx_res_checksum              36464
_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 1.702
_oxdiff_exptl_absorpt_empirical_full_min 0.548