Improving the solubility and bioavailability of anti-hepatitis B drug PEC via PEC–fumaric acid cocrystal
Li, Long; Yin, Xian-Hong; Diao, Kai-Sheng; RSC Advances 10 (2020) 36125–36134; doi:10.1039/D0RA06608G

data_7241347
_publ_section_title
;
 Improving the solubility and bioavailability of anti-hepatitis B drug PEC
 via PEC--fumaric acid cocrystal
;
_journal_issue                   59
_journal_name_full               'RSC Advances'
_journal_page_first              36125
_journal_page_last               36134
_journal_paper_doi               10.1039/D0RA06608G
_journal_volume                  10
_journal_year                    2020
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C24 H29 N6 O4 P, C4 H4 O4'
_chemical_formula_sum            'C28 H33 N6 O8 P'
_chemical_formula_weight         612.57
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     iterative
_audit_creation_date             2020-06-15
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2020-07-13 deposited with the CCDC.	2020-09-24 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 96.021(5)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   13.7013(6)
_cell_length_b                   6.4058(4)
_cell_length_c                   17.3373(10)
_cell_measurement_reflns_used    1851
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      28.6060
_cell_measurement_theta_min      3.6400
_cell_volume                     1513.26(15)
_computing_cell_refinement
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.34 (release 22-05-2014 CrysAlis171 .NET)
(compiled May 22 2014,16:03:01)
;
_computing_data_collection
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.34 (release 22-05-2014 CrysAlis171 .NET)
(compiled May 22 2014,16:03:01)
;
_computing_data_reduction
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.34 (release 22-05-2014 CrysAlis171 .NET)
(compiled May 22 2014,16:03:01)
;
_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
;
Superflip (Palatinus & Chapuis, 2007;Palatinus & van der Lee, 2008;
Palatinus et al., 2012)
;
_diffrn_ambient_temperature      293.15
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 16.0874
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.998
_diffrn_measurement_details
;
  1 omega  -22.00    4.00   1.0000    7.0000
omega____ theta____ kappa____ phi______ frames
    -      -15.4773  -99.0000 -120.0000 26

  2 omega  -83.00    0.00   1.0000    7.0000
omega____ theta____ kappa____ phi______ frames
    -      -15.4773  -57.0000 -120.0000 83

  3 omega  -84.00  -53.00   1.0000    7.0000
omega____ theta____ kappa____ phi______ frames
    -      -15.4773  -19.0000  -60.0000 31

  4 omega  -83.00    1.00   1.0000    7.0000
omega____ theta____ kappa____ phi______ frames
    -      -15.4773  -38.0000  150.0000 84
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Eos'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      -0.0051822000
_diffrn_orient_matrix_UB_12      0.0198038000
_diffrn_orient_matrix_UB_13      -0.0404864000
_diffrn_orient_matrix_UB_21      0.0516730000
_diffrn_orient_matrix_UB_22      -0.0054760000
_diffrn_orient_matrix_UB_23      -0.0001559000
_diffrn_orient_matrix_UB_31      -0.0035516000
_diffrn_orient_matrix_UB_32      -0.1088142000
_diffrn_orient_matrix_UB_33      -0.0073239000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0256
_diffrn_reflns_av_unetI/netI     0.0531
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.998
_diffrn_reflns_limit_h_max       17
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -5
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            7082
_diffrn_reflns_point_group_measured_fraction_full 0.770
_diffrn_reflns_point_group_measured_fraction_max 0.752
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.369
_diffrn_reflns_theta_min         2.990
_diffrn_source                   'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.149
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.85046
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.34 (release 22-05-2014 CrysAlis171 .NET)
(compiled May 22 2014,16:03:01)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_density_diffrn    1.344
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       needle
_exptl_crystal_F_000             644
_exptl_crystal_size_max          0.35
_exptl_crystal_size_mid          0.3
_exptl_crystal_size_min          0.25
_refine_diff_density_max         0.263
_refine_diff_density_min         -0.274
_refine_diff_density_rms         0.043
_refine_ls_abs_structure_details
;
 Flack x determined using 944 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.06(9)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.024
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     401
_refine_ls_number_reflns         4629
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.024
_refine_ls_R_factor_all          0.0596
_refine_ls_R_factor_gt           0.0456
_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^)+(0.0486P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0985
_refine_ls_wR_factor_ref         0.1093
_reflns_Friedel_coverage         0.378
_reflns_Friedel_fraction_full    0.494
_reflns_Friedel_fraction_max     0.455
_reflns_number_gt                3761
_reflns_number_total             4629
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d0ra06608g2.cif
_cod_data_source_block           200615_s1_kl_ll_a256
_cod_original_cell_volume        1513.25(14)
_cod_database_code               7241347
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         c12h12n2o3p1
_shelx_estimated_absorpt_t_max   0.964
_shelx_estimated_absorpt_t_min   0.950
_reflns_odcompleteness_completeness 99.76
_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 Ternary CH refined with riding coordinates:
 C7(H7)
2.b Secondary CH2 refined with riding coordinates:
 C6(H6A,H6B), C9(H9A,H9B), C10(H10A,H10B), C11(H11A,H11B), C12(H12A,H12B)
2.c Aromatic/amide H refined with riding coordinates:
 C3(H3), C5(H5), C14(H14), C15(H15), C16(H16), C17(H17), C18(H18), C20(H20),
 C21(H21), C22(H22), C23(H23), C24(H24), C26(H26), C27(H27)
2.d X=CH2 refined with riding coordinates:
 N5(H5A,H5B)
2.e Idealised Me refined as rotating group:
 C8(H8A,H8B,H8C)
;
_shelx_res_checksum              83047
_olex2_submission_special_instructions 'No special instructions were received'