Novel multicomponent crystal forms of artesunate
Madu, Shadrack J.; Wang, Ke; Fábián, László; Li, Mingzhong; CrystEngComm 27 (2025) 7146–7169; doi:10.1039/D5CE00279F

data_7251047
_publ_section_title
;
 Novel multicomponent crystal forms of artesunate
;
_journal_issue                   44
_journal_name_full               CrystEngComm
_journal_page_first              7146
_journal_page_last               7169
_journal_paper_doi               10.1039/D5CE00279F
_journal_volume                  27
_journal_year                    2025
_chemical_absolute_configuration rmad
_chemical_formula_moiety         'C19 H28 O8, C7 H7 N O2'
_chemical_formula_sum            'C26 H35 N O10'
_chemical_formula_weight         521.55
_chemical_name_common            'artesunate 4-aminobenzoic acid'
_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             2025-09-11
_audit_creation_method
; 
Olex2 1.5 
(compiled 2025.07.13 svn.rb7424ae for OlexSys, GUI svn.r7314) 
;
_audit_update_record
;
2025-10-07 deposited with the CCDC.	2025-10-15 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 96.1350(10)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   5.69290(10)
_cell_length_b                   17.0162(2)
_cell_length_c                   13.4451(2)
_cell_measurement_reflns_used    10715
_cell_measurement_temperature    100.00(11)
_cell_measurement_theta_max      76.4160
_cell_measurement_theta_min      3.2700
_cell_volume                     1294.99(3)
_computing_cell_refinement       'CrysAlisPro 1.171.42.84a (Rigaku OD, 2023)'
_computing_data_collection       'CrysAlisPro 1.171.42.84a (Rigaku OD, 2023)'
_computing_data_reduction        'CrysAlisPro 1.171.42.84a (Rigaku OD, 2023)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.00(11)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.943
_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    -51.00 -20.00   0.50    0.66    --  -91.75  45.00  30.00   62
  2  \w    -51.00 -22.00   0.50    0.66    --  -91.75  61.00 -30.00   58
  3  \w    -50.00 -21.00   0.50    0.66    --  -91.75  45.00 -90.00   58
  4  \w    -62.00  23.00   0.50    0.16    --  -47.29  57.00-180.00  170
  5  \w    -50.00 -21.00   0.50    0.66    --  -91.75  45.00-180.00   58
  6  \w    -49.00 -20.00   0.50    0.66    --  -91.75  45.00 -60.00   58
  7  \w    -51.00 -22.00   0.50    0.66    --  -91.75  45.00  90.00   58
  8  \w    -48.00 -21.00   0.50    0.66    --  -91.75  45.00 150.00   54
  9  \w     -6.00  26.00   0.50    0.16    --  -47.29  37.00  60.00   64
 10  \w    121.00 177.00   0.50    0.66    --  106.64  61.00 -90.00  112
 11  \w    130.00 167.00   0.50    0.66    --  106.64  61.00-120.00   74
 12  \w     96.00 176.00   0.50    0.66    --  106.64 125.00 -60.00  160
 13  \w    146.00 172.00   0.50    0.66    --  106.64  83.00 -31.00   52
 14  \w    101.00 133.00   0.50    0.66    --  106.64  83.00 -31.00   64
 15  \w    101.00 131.00   0.50    0.66    --  106.64  15.00 -90.00   60
 16  \w     41.00  66.00   0.50    0.66    --  106.64 -61.00  60.00   50
 17  \w     44.00  71.00   0.50    0.66    --  106.64 -61.00 120.00   54
 18  \w     35.00  71.00   0.50    0.66    --  106.64 -61.00 -30.00   72
 19  \w    -27.00  19.00   0.50    0.16    --   47.29 -19.00 -90.00   92
 20  \w    -15.00  18.00   0.50    0.16    --   47.29 -19.00 -60.00   66
 21  \w     50.00 101.00   0.50    0.66    --  106.64 -83.00-151.00  102
 22  \w     44.00 105.00   0.50    0.66    --  106.64 -94.00-150.00  122
 23  \w     66.00 107.00   0.50    0.66    --  106.64-125.00  30.00   82
 24  \w     39.00  73.00   0.50    0.66    --  106.64-125.00 -30.00   68
 25  \w      2.00  32.00   0.50    0.16    --   47.29 -83.00-151.00   60
 26  \w    -72.00   7.00   0.50    0.16    --  -47.29  83.00 -31.00  158
 27  \w    -68.00 -21.00   0.50    0.66    --  -91.75  83.00 -31.00   94
 28  \w   -113.00 -37.00   0.50    0.16    --  -47.29 -37.00 120.00  152
 29  \w   -161.00-115.00   0.50    0.66    --  -91.75 -61.00 150.00   92
 30  \w   -161.00-103.00   0.50    0.66    --  -91.75 -61.00 120.00  116
 31  \w   -163.00-111.00   0.50    0.66    --  -91.75 -77.00  90.00  104
 32  \w   -162.00-126.00   0.50    0.66    --  -91.75 -45.00  60.00   72
 33  \w   -124.00 -78.00   0.50    0.66    --  -91.75 -15.00  90.00   92
 34  \w   -106.00 -79.00   0.50    0.66    --  -91.75 -45.00  60.00   54
 35  \w   -111.00 -84.00   0.50    0.66    --  -91.75 -15.00  30.00   54
 36  \w   -164.00-138.00   0.50    0.66    --  -91.75 -15.00  30.00   52
 37  \w   -123.00 -82.00   0.50    0.66    --  -91.75 -45.00 -90.00   82
 38  \w   -132.00 -80.00   0.50    0.66    --  -91.75 -45.00-120.00  104
 39  \w   -145.00-120.00   0.50    0.66    --  -91.75 -83.00-151.00   50
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0432758000
_diffrn_orient_matrix_UB_12      0.0020506000
_diffrn_orient_matrix_UB_13      0.1111480000
_diffrn_orient_matrix_UB_21      0.1299539000
_diffrn_orient_matrix_UB_22      0.0793893000
_diffrn_orient_matrix_UB_23      0.0124077000
_diffrn_orient_matrix_UB_31      -0.2351915000
_diffrn_orient_matrix_UB_32      0.0434452000
_diffrn_orient_matrix_UB_33      -0.0278804000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0361
_diffrn_reflns_av_unetI/netI     0.0337
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.943
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       21
_diffrn_reflns_limit_k_min       -20
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            14940
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.912
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.419
_diffrn_reflns_theta_min         3.306
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.861
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.85477
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
; 
CrysAlisPro 1.171.42.84a (Rigaku Oxford Diffraction, 2023) 
Empirical absorption correction using spherical harmonics, 
implemented in SCALE3 ABSPACK scaling algorithm. 
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.338
_exptl_crystal_description       block
_exptl_crystal_F_000             556
_exptl_crystal_size_max          0.300
_exptl_crystal_size_mid          0.200
_exptl_crystal_size_min          0.050
_refine_diff_density_max         0.179
_refine_diff_density_min         -0.171
_refine_diff_density_rms         0.032
_refine_ls_abs_structure_details
; 
 Flack x determined using 2118 quotients [(I+)-(I-)]/[(I+)+(I-)] 
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259). 
;
_refine_ls_abs_structure_Flack   0.09(8)
_refine_ls_extinction_coef       0.0027(4)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2018/3 (Sheldrick 2018)'
_refine_ls_goodness_of_fit_ref   1.033
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     424
_refine_ls_number_reflns         5007
_refine_ls_number_restraints     243
_refine_ls_restrained_S_all      1.040
_refine_ls_R_factor_all          0.0352
_refine_ls_R_factor_gt           0.0339
_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^)+(0.0345P)^2^+0.3023P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0836
_refine_ls_wR_factor_ref         0.0847
_reflns_Friedel_coverage         0.870
_reflns_Friedel_fraction_full    0.997
_reflns_Friedel_fraction_max     0.880
_reflns_number_gt                4810
_reflns_number_total             5007
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ce00279f2.cif
_cod_data_source_block           rev2
_cod_depositor_comments
'Adding full bibliography for 7251047--7251052.cif.'
_cod_database_code               7251047
_shelx_shelxl_version_number     2018/3
_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. Restrained distances 
 O9B-H9B = O9C-H9B = O21-H21 
 0.84 with sigma of 0.02 
 C1B-C2B \\sim C1C-C2C 
 with sigma of 0.02 
 C1B-C6B \\sim C1C-C6C 
 with sigma of 0.02 
 C1B-C7B \\sim C1C-C7C 
 with sigma of 0.02 
 C2B-C3B \\sim C2C-C3C 
 with sigma of 0.02 
 C3B-C4B \\sim C3C-C4C 
 with sigma of 0.02 
 C4B-N4B \\sim C4C-N4C 
 with sigma of 0.02 
 C4B-C5B \\sim C4C-C5C 
 with sigma of 0.02 
 C5B-C6B \\sim C5C-C6C 
 with sigma of 0.02 
 C7B-O8B \\sim C7C-O8C 
 with sigma of 0.02 
 C7B-O9B \\sim C7C-O9C 
 with sigma of 0.02 
 C1B-C3B \\sim C1C-C3C 
 with sigma of 0.04 
 C1B-C5B \\sim C1C-C5C 
 with sigma of 0.04 
 C1B-O8B \\sim C1C-O8C 
 with sigma of 0.04 
 C1B-O9B \\sim C1C-O9C 
 with sigma of 0.04 
 C2B-C4B \\sim C2C-C4C 
 with sigma of 0.04 
 C2B-C6B \\sim C2C-C6C 
 with sigma of 0.04 
 C2B-C7B \\sim C2C-C7C 
 with sigma of 0.04 
 C3B-N4B \\sim C3C-N4C 
 with sigma of 0.04 
 C3B-C5B \\sim C3C-C5C 
 with sigma of 0.04 
 C4B-C6B \\sim C4C-C6C 
 with sigma of 0.04 
 N4B-C5B \\sim N4C-C5C 
 with sigma of 0.04 
 C6B-C7B \\sim C6C-C7C 
 with sigma of 0.04 
 O8B-O9B \\sim O8C-O9C 
 with sigma of 0.04 
 C6-C7 \\sim C6-C7D 
 with sigma of 0.02 
 C7-C8 \\sim C7D-C8D 
 with sigma of 0.02 
 C8-C8A \\sim C8D-C8E 
 with sigma of 0.02 
 C8A-C9 \\sim C8E-C9D 
 with sigma of 0.02 
 C8A-C12A \\sim C8E-C12A 
 with sigma of 0.02 
 C9-C9M \\sim C9D-C9N 
 with sigma of 0.02 
 C9-C10 \\sim C9D-C10 
 with sigma of 0.02 
 C6-C8 \\sim C6-C8D 
 with sigma of 0.04 
 C7-C8A \\sim C7D-C8E 
 with sigma of 0.04 
 C8-C9 \\sim C8D-C9D 
 with sigma of 0.04 
 C8-C12A \\sim C8D-C12A 
 with sigma of 0.04 
 C8A-C9M \\sim C8E-C9N 
 with sigma of 0.04 
 C8A-C10 \\sim C8E-C10 
 with sigma of 0.04 
 C9-C12A \\sim C9D-C12A 
 with sigma of 0.04 
 C9M-C10 \\sim C9N-C10 
 with sigma of 0.04 
3. Uiso/Uaniso restraints and constraints 
Uanis(C1B) = Uanis(C1C) 
Uanis(C2B) = Uanis(C2C) 
Uanis(C6B) = Uanis(C6C) 
Uanis(C7B) = Uanis(C7C) 
Uanis(C3B) = Uanis(C3C) 
Uanis(N4B) = Uanis(N4C) 
Uanis(C4B) = Uanis(C4C) 
Uanis(C5B) = Uanis(C5C) 
Uanis(O8B) = Uanis(O8C) 
Uanis(O9B) = Uanis(O9C) 
4. Rigid body (RIGU) restrains 
 C7C, C1C, C2C, C6C, C3C, C5C, O8C, O9C, C4C, N4C 
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001 
 C6B, C1B, C2B, C7B, C3B, C5B, O8B, O9B, C4B, N4B 
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001 
 C9, C9M, C8A, C12A, C8, C7, C6 
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001 
 C6, C7D, C8D, C8E, C9D, C10 
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001 
5. Others 
 Sof(C1C)=Sof(C2C)=Sof(H2C)=Sof(C3C)=Sof(H3C)=Sof(C4C)=Sof(N4C)=Sof(H4CA)= 
 Sof(H4CB)=Sof(C5C)=Sof(H5C)=Sof(C6C)=Sof(H6C)=Sof(C7C)=Sof(O8C)=Sof(O9C)=1- 
 FVAR(1) 
 Sof(C1B)=Sof(C2B)=Sof(H2B)=Sof(C3B)=Sof(H3B)=Sof(C4B)=Sof(N4B)=Sof(H4BA)= 
 Sof(H4BB)=Sof(C5B)=Sof(H5BA)=Sof(C6B)=Sof(H6BA)=Sof(C7B)=Sof(O8B)=Sof(O9B)= 
 FVAR(1) 
 Sof(H6B)=Sof(H10A)=Sof(C9D)=Sof(H9D)=Sof(C9N)=Sof(H9NA)=Sof(H9NB)=Sof(H9NC)= 
 Sof(C8E)=Sof(H8E)=Sof(C8D)=Sof(H8DA)=Sof(H8DB)=Sof(C7D)=Sof(H7DA)=Sof(H7DB)=1- 
 FVAR(2) 
 Sof(H6A)=Sof(C7)=Sof(H7A)=Sof(H7B)=Sof(C8)=Sof(H8A)=Sof(H8B)=Sof(C8A)= 
 Sof(H8AA)=Sof(C9)=Sof(H9)=Sof(C9M)=Sof(H9MA)=Sof(H9MB)=Sof(H9MC)=Sof(H10)= 
 FVAR(2) 
6.a Ternary CH refined with riding coordinates: 
 C5A(H5AA), C6(H6A), C6(H6B), C8A(H8AA), C9(H9), C10(H10), C10(H10A), C12(H12), 
  C9D(H9D), C8E(H8E) 
6.b Secondary CH2 refined with riding coordinates: 
 C4(H4A,H4B), C5(H5A,H5B), C7(H7A,H7B), C8(H8A,H8B), C17(H17A,H17B), C18(H18A, 
 H18B), C8D(H8DA,H8DB), C7D(H7DA,H7DB) 
6.c Aromatic/amide H refined with riding coordinates: 
 C2B(H2B), C3B(H3B), C5B(H5BA), C6B(H6BA), C2C(H2C), C3C(H3C), C5C(H5C), 
 C6C(H6C) 
6.d X=CH2 refined with riding coordinates: 
 N4B(H4BA,H4BB), N4C(H4CA,H4CB) 
6.e Idealised Me refined as rotating group: 
 C3M(H3MA,H3MB,H3MC), C6M(H6MA,H6MB,H6MC), C9M(H9MA,H9MB,H9MC), C9N(H9NA,H9NB, 
 H9NC) 
;
_shelx_res_checksum              58668
_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 1.255
_oxdiff_exptl_absorpt_empirical_full_min 0.793