A quaternary solid-form of ritonavir: an oxalate salt oxalic acid co-crystal acetone solvate
Wang, Chang; Turner, Thomas D.; Ma, Cai Y.; Pask, Christopher M.; Rosbottom, Ian; Hong, Richard S.; Sheikh, Ahmad Y.; Yin, Qiuxiang; Roberts, Kevin J.; CrystEngComm 25 (2023) 1782–1791; doi:10.1039/D2CE01612E

data_7246276
_publ_section_title
;
 A quaternary solid-form of ritonavir: an oxalate salt oxalic acid
 co-crystal acetone solvate
;
_journal_issue                   12
_journal_name_full               CrystEngComm
_journal_page_first              1782
_journal_page_last               1791
_journal_paper_doi               10.1039/D2CE01612E
_journal_volume                  25
_journal_year                    2023
_chemical_absolute_configuration ad
_chemical_formula_moiety
'C37 H49 N6 O5 S2, C2 H O4, 0.5(C2 H2 O4), 0.5(C3 H6 O)'
_chemical_formula_sum            'C41.5 H54 N6 O11.5 S2'
_chemical_formula_weight         885.02
_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     dual
_audit_creation_date             2019-03-28
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2020-06-11 deposited with the CCDC.	2023-02-14 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 91.994(3)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   5.2615(2)
_cell_length_b                   25.2098(9)
_cell_length_c                   16.6111(6)
_cell_measurement_reflns_used    6386
_cell_measurement_temperature    150.01(10)
_cell_measurement_theta_max      72.9630
_cell_measurement_theta_min      4.3820
_cell_volume                     2201.98(14)
_computing_cell_refinement       'CrysAlisPro 1.171.39.43c (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.43c (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.43c (Rigaku OD, 2018)'
_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      150.01(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.3095
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.984
_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    -91.00 -21.00   1.00   15.00    --  -41.04 -37.00 -60.00   70
  2  \w    -54.00  30.00   1.00   15.00    --  -41.04  37.00  60.00   84
  3  \w   -109.00 -71.00   1.00   15.00    --  -41.04 -37.00 120.00   38
  4  \w   -112.00 -19.00   1.00   15.00    --  -41.04 -37.00-120.00   93
  5  \w      1.00  64.00   1.00   15.00    --   41.04 -57.00 120.00   63
  6  \w    -26.00   0.00   1.00   15.00    --   41.04 -57.00 120.00   26
  7  \w     80.00 173.00   1.00   60.00    --  106.02  45.00  90.00   93
  8  \w    136.00 177.00   1.00   60.00    --  106.02  30.00 -90.00   41
  9  \w     68.00 134.00   1.00   60.00    --  106.02 -61.00  30.00   66
 10  \w     82.00 172.00   1.00   60.00    --  106.02  30.00-180.00   90
 11  \w     78.00 112.00   1.00   60.00    --  106.02  61.00 -60.00   34
 12  \w     80.00 115.00   1.00   60.00    --  106.02  45.00   0.00   35
 13  \w    150.00 177.00   1.00   60.00    --  106.02  61.00 -90.00   27
 14  \w     40.00 122.00   1.00   60.00    --  106.02 -45.00-120.00   82
 15  \w     90.00 134.00   1.00   60.00    --  106.02 -30.00 -90.00   44
 16  \w     78.00 116.00   1.00   60.00    --  106.02  61.00 -90.00   38
 17  \w     81.00 176.00   1.00   60.00    --  106.02  45.00  30.00   95
 18  \w     77.00 103.00   1.00   60.00    --  106.02  61.00   0.00   26
 19  \w     40.00  65.00   1.00   60.00    --  106.02 -30.00 -90.00   25
 20  \w     65.00 131.00   1.00   60.00    --  106.02 -45.00  90.00   66
 21  \w     78.00 103.00   1.00   60.00    --  106.02  61.00 -30.00   25
 22  \w     82.00 166.00   1.00   60.00    --  106.02  45.00 -30.00   84
 23  \w     78.00 105.00   1.00   60.00    --  106.02  61.00 -33.86   27
 24  \w     78.00 103.00   1.00   60.00    --  106.02  61.00 -40.01   25
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.2089756000
_diffrn_orient_matrix_UB_12      -0.0355017000
_diffrn_orient_matrix_UB_13      -0.0339216000
_diffrn_orient_matrix_UB_21      0.1850753000
_diffrn_orient_matrix_UB_22      0.0180246000
_diffrn_orient_matrix_UB_23      0.0685132000
_diffrn_orient_matrix_UB_31      -0.0882006000
_diffrn_orient_matrix_UB_32      -0.0463985000
_diffrn_orient_matrix_UB_33      0.0526473000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0444
_diffrn_reflns_av_unetI/netI     0.0585
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.984
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       31
_diffrn_reflns_limit_k_min       -30
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -20
_diffrn_reflns_number            17561
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.967
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         73.738
_diffrn_reflns_theta_min         3.506
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.657
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.541
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.43c (Rigaku Oxford Diffraction, 2018)
Numerical absorption correction based on gaussian integration over
			a multifaceted crystal model
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.335
_exptl_crystal_description       prism
_exptl_crystal_F_000             938
_exptl_crystal_size_max          0.29
_exptl_crystal_size_mid          0.06
_exptl_crystal_size_min          0.03
_refine_diff_density_max         0.441
_refine_diff_density_min         -0.370
_refine_diff_density_rms         0.053
_refine_ls_abs_structure_details
;
 Flack x determined using 2982 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.014(12)
_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     558
_refine_ls_number_reflns         8613
_refine_ls_number_restraints     45
_refine_ls_restrained_S_all      1.031
_refine_ls_R_factor_all          0.0612
_refine_ls_R_factor_gt           0.0513
_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^)+(0.0665P)^2^+0.4500P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1248
_refine_ls_wR_factor_ref         0.1313
_reflns_Friedel_coverage         0.920
_reflns_Friedel_fraction_full    0.994
_reflns_Friedel_fraction_max     0.950
_reflns_number_gt                7439
_reflns_number_total             8613
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d2ce01612e2.cif
_cod_data_source_block           ritonavir
_cod_depositor_comments          'Adding full bibliography for 7246276.cif.'
_cod_original_cell_volume        2201.99(14)
_cod_original_formula_sum        'C41.50 H54 N6 O11.50 S2'
_cod_database_code               7246276
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         'C83  H108  N12  O23  S4  '
_shelx_estimated_absorpt_t_max   0.952
_shelx_estimated_absorpt_t_min   0.645
_reflns_odcompleteness_completeness 99.93
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2. Restrained distances
 O11-C40 = O13-C41
 1.3 with sigma of 0.02
 O10-C40 = O12-C41
 1.22 with sigma of 0.02
 C41-C40
 1.51 with sigma of 0.02
 O14-C42
 1.22 with sigma of 0.02
 C43-C42 = C44-C42
 1.52 with sigma of 0.02
3. Rigid body (RIGU) restrains
 C8, C9, C10, C11, C12, C13
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
4. Others
 Fixed Sof: O10(0.5) O11(0.5) H11A(0.5) O12(0.5) O13(0.5) H13A(0.5) C40(0.5)
 C41(0.5) O14(0.5) C42(0.5) C43(0.5) H43A(0.5) H43B(0.5) H43C(0.5) C44(0.5)
 H44A(0.5) H44B(0.5) H44C(0.5)
5.a Ternary CH refined with riding coordinates:
 C6(H6A), C14(H14), C16(H16), C25(H25), C26(H26), C35(H35)
5.b Secondary CH2 refined with riding coordinates:
 C4(H4A,H4B), C7(H7A,H7B), C15(H15A,H15B), C17(H17A,H17B), C31(H31A,H31B)
5.c Me refined with riding coordinates:
 C43(H43A,H43B,H43C), C44(H44A,H44B,H44C)
5.d Aromatic/amide H refined with riding coordinates:
 N2(H2), N4(H4), N6(H6), C1(H1), C2(H2A), C9(H9), C10(H10), C11(H11), C12(H12),
  C13(H13), C19(H19), C20(H20), C21(H21), C22(H22), C23(H23), C33(H33)
5.e Idealised Me refined as rotating group:
 C27(H27A,H27B,H27C), C28(H28A,H28B,H28C), C30(H30A,H30B,H30C), C36(H36A,H36B,
 H36C), C37(H37A,H37B,H37C)
5.f Idealised tetrahedral OH refined as rotating group:
 O3(H3), O9(H9A), O11(H11A), O13(H13A)
;
_olex2_date_sample_data_collection 2018-10-22
_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 1.345
_oxdiff_exptl_absorpt_empirical_full_min 0.834