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_7058873
_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, H2 O, C8 H12 N2'
_chemical_formula_sum            'C28 H38 N2 O3'
_chemical_formula_weight         450.60
_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
_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
;
2019-09-14 deposited with the CCDC.    2019-10-03 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 94.771(5)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   7.3836(5)
_cell_length_b                   21.3958(14)
_cell_length_c                   32.4582(19)
_cell_measurement_reflns_used    4555
_cell_measurement_temperature    173.00(10)
_cell_measurement_theta_max      27.9240
_cell_measurement_theta_min      3.5910
_cell_volume                     5109.9(6)
_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      N~2~
_diffrn_ambient_temperature      173.00(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 16.1213
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.996
_diffrn_measured_fraction_theta_max 0.858
_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    -15.00  20.20   0.80    5.00    --  -16.28 -99.00 120.00   44
  2  \w     30.00  55.60   0.80    5.00    --   15.49-119.00  36.00   32
  3  \w     30.00  57.20   0.80    5.00    --   15.49-157.00-118.00   34
  4  \w     -3.00  85.00   0.80    5.00    --   15.49  38.00 150.00  110
  5  \w     42.00  69.20   0.80    5.00    --   15.49 178.00   0.00   34
  6  \w     38.00  83.60   0.80    5.00    --   15.49 178.00 -60.00   57
  7  \w     60.00  84.80   0.80    5.00    --   15.49 178.00-150.00   31
  8  \w    -88.00 -63.20   0.80    5.00    --  -16.28 157.00 -83.00   31
  9  \w    -25.00  15.00   0.80    5.00    --  -16.28 -99.00 -90.00   50
;
_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      0.0185237000
_diffrn_orient_matrix_UB_12      -0.0318453000
_diffrn_orient_matrix_UB_13      -0.0040768000
_diffrn_orient_matrix_UB_21      0.0010993000
_diffrn_orient_matrix_UB_22      0.0069257000
_diffrn_orient_matrix_UB_23      -0.0213413000
_diffrn_orient_matrix_UB_31      0.0946091000
_diffrn_orient_matrix_UB_32      0.0061190000
_diffrn_orient_matrix_UB_33      0.0029077000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0309
_diffrn_reflns_av_unetI/netI     0.0645
_diffrn_reflns_Laue_measured_fraction_full 0.996
_diffrn_reflns_Laue_measured_fraction_max 0.858
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       29
_diffrn_reflns_limit_k_min       -25
_diffrn_reflns_limit_l_max       44
_diffrn_reflns_limit_l_min       -41
_diffrn_reflns_number            19064
_diffrn_reflns_point_group_measured_fraction_full 0.889
_diffrn_reflns_point_group_measured_fraction_max 0.729
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         29.372
_diffrn_reflns_theta_min         3.357
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.076
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.73443
_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    1.171
_exptl_crystal_description       block
_exptl_crystal_F_000             1952
_exptl_crystal_size_max          0.31
_exptl_crystal_size_mid          0.22
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.377
_refine_diff_density_min         -0.357
_refine_diff_density_rms         0.046
_refine_ls_abs_structure_details
;
 Flack x determined using 2181 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   -0.7(7)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.034
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     623
_refine_ls_number_reflns         10272
_refine_ls_number_restraints     4
_refine_ls_restrained_S_all      1.055
_refine_ls_R_factor_all          0.1026
_refine_ls_R_factor_gt           0.0680
_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^)+(0.0730P)^2^+2.1477P]
 where P=(Fo^2^+2Fc^2^)/3
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1513
_refine_ls_wR_factor_ref         0.1789
_reflns_Friedel_coverage         0.657
_reflns_Friedel_fraction_full    0.774
_reflns_Friedel_fraction_max     0.593
_reflns_number_gt                6979
_reflns_number_total             10272
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c9nj04147h2.cif
_cod_data_source_block           EE-TET-H2O
_cod_depositor_comments
'Adding full bibliography for 7058869--7058873.cif.'
_cod_database_code               7058873
_shelxl_version_number           2013-2
_shelx_estimated_absorpt_t_max   0.992
_shelx_estimated_absorpt_t_min   0.977
_reflns_odcompleteness_completeness 99.64
_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, All O(H) groups, All O(H,H) groups
2. Restrained distances
 H4XA-H1AA_$1
 2.1 with sigma of 0.005
 H3XB-H1AA
 2.1 with sigma of 0.005
 H1BA-H1XA_$2
 2.1 with sigma of 0.005
3. Others
 Fixed Sof: H1XA(0.5) H1XB(0.5) H3XA(0.5) H3XB(0.5) H2XA(0.5) H2XB(0.5)
 O4X(0.5) H4XA(0.5) H4XB(0.5)
4.a Riding coordinates:
 O1X(H1XA,H1XB), O3X(H3XA,H3XB), O2X(H2XA,H2XB), O4X(H4XA,H4XB)
4.b Ternary CH refined with riding coordinates:
 C8A(H8A), C9A(H9A), C14A(H14A), C8B(H8B), C9B(H9B), C14B(H14B)
4.c Secondary CH2 refined with riding coordinates:
 C6A(H6AA,H6AB), C7A(H7AB,H7AA), C11A(H11A,H11B), C12A(H12A,H12B), C15A(H15A,
 H15B), C16A(H16A,H16B), C6B(H6BA,H6BB), C7B(H7BA,H7BB), C11B(H11C,H11D),
 C12B(H12C,H12D), C15B(H15D,H15C), C16B(H16C,H16D)
4.d Aromatic/amide H refined with riding coordinates:
 C1A(H1A), C2A(H2A), C4A(H4A), C1B(H1B), C2B(H2B), C4B(H4B)
4.e Idealised Me refined as rotating group:
 C18A(H18A,H18B,H18C), C18B(H18D,H18E,H18F), C28A(H28A,H28B,H28C), C29A(H29A,
 H29B,H29C), C26A(H26A,H26B,H26C), C27A(H27A,H27B,H27C), C26B(H26D,H26E,H26F),
 C29B(H29D,H29E,H29F), C27B(H27D,H27E,H27F), C28B(H28D,H28E,H28F)
4.f Idealised tetrahedral OH refined as rotating group:
 O1A(H1AA), O1B(H1BA)
4.g :
 C21A(H21A), C21B(H21B)
;
_shelx_res_checksum              71348
_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 2.062
_oxdiff_exptl_absorpt_empirical_full_min 0.580