Reversible interconversion of pharmaceutical salt polymorphs facilitated by mechanical methods.
Ma, Liulei; Zheng, Qixuan; Unruh, Daniel K.; Hutchins, Kristin M.; Chemical communications (Cambridge, England) 59 (2023) 7779–7782; doi:10.1039/d3cc02188b

data_7131709
_publ_section_title
;
 Reversible interconversion of pharmaceutical salt polymorphs facilitated
 by mechanical methods.
;
_journal_issue                   50
_journal_name_full               'Chemical communications (Cambridge, England)'
_journal_page_first              7779
_journal_page_last               7782
_journal_paper_doi               10.1039/d3cc02188b
_journal_volume                  59
_journal_year                    2023
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C14 H19 N4 O3, C3 H5 O3'
_chemical_formula_sum            'C17 H24 N4 O6'
_chemical_formula_weight         380.40
_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   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2021-12-15
_audit_creation_method
;
Olex2 1.5
(compiled 2021.11.18 svn.ra9532c28 for OlexSys, GUI svn.r6429)
;
_audit_update_record
;
2023-02-10 deposited with the CCDC.	2023-05-25 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 95.2640(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   5.09750(10)
_cell_length_b                   36.4142(5)
_cell_length_c                   10.00430(10)
_cell_measurement_reflns_used    9993
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      76.2290
_cell_measurement_theta_min      4.5810
_cell_volume                     1849.18(5)
_computing_cell_refinement       'CrysAlisPro 1.171.41.120a (Rigaku OD, 2021)'
_computing_data_collection       'CrysAlisPro 1.171.41.120a (Rigaku OD, 2021)'
_computing_data_reduction        'CrysAlisPro 1.171.41.120a (Rigaku OD, 2021)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL  (Sheldrick, 2008)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.00(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.952
_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    -76.00  25.00   0.50    6.91    --  -47.76  90.00 -15.00  202
  2  \w    -20.00  77.00   0.50    6.91    --   47.76 -90.00-130.00  194
  3  \w   -163.00 -79.00   0.50   25.00    --  -91.75 -90.00-130.00  168
  4  \w    -79.00 -19.00   0.50   25.00    --  -91.75  90.00 -15.00  120
  5  \w     35.00 105.00   0.50   25.00    --  107.31 -90.00-130.00  140
  6  \w    101.00 178.00   0.50   25.00    --  107.31  90.00 -15.00  154
  7  \w   -120.00 -73.00   0.50    6.91    --  -47.76-125.00   0.00   94
  8  \w   -120.00 -73.00   0.50    6.91    --  -47.76-125.00  30.00   94
  9  \w   -120.00 -73.00   0.50    6.91    --  -47.76-125.00 -30.00   94
 10  \w    -25.00  28.00   0.50    6.91    --  -47.76  19.00 -90.00  106
 11  \w    -85.00 -19.00   0.50   25.00    --  -91.75 125.00   0.00  132
 12  \w    -64.00 -19.00   0.50   25.00    --  -91.75  57.00 -30.00   90
 13  \w    -64.00 -19.00   0.50   25.00    --  -91.75  57.00 -60.00   90
 14  \w    -64.00 -19.00   0.50   25.00    --  -91.75  57.00   0.00   90
 15  \w    -64.00 -19.00   0.50   25.00    --  -91.75  57.00-180.00   90
 16  \w    -82.00 -37.00   0.50   25.00    --  -91.75 125.00 120.00   90
 17  \w     96.00 167.00   0.50   25.00    --  107.31  19.00 -90.00  142
 18  \w     35.00  62.00   0.50   25.00    --  107.31 -57.00 120.00   54
 19  \w     82.00 107.00   0.50   25.00    --  107.31 -77.00  30.00   50
 20  \w     37.00  67.00   0.50   25.00    --  107.31 -57.00  30.00   60
 21  \w     37.00 107.00   0.50   25.00    --  107.31 -77.00-120.00  140
 22  \w    100.00 169.00   0.50   25.00    --  107.31 125.00  60.00  138
 23  \w     35.00  68.00   0.50   25.00    --  107.31 -57.00  60.00   66
 24  \w     36.00  66.00   0.50   25.00    --  107.31 -57.00  90.00   60
 25  \w     36.00  68.00   0.50   25.00    --  107.31 -77.00  30.00   64
;
_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      0.0354371000
_diffrn_orient_matrix_UB_12      -0.0108238000
_diffrn_orient_matrix_UB_13      -0.1461196000
_diffrn_orient_matrix_UB_21      -0.1199596000
_diffrn_orient_matrix_UB_22      0.0369927000
_diffrn_orient_matrix_UB_23      -0.0489027000
_diffrn_orient_matrix_UB_31      0.2765179000
_diffrn_orient_matrix_UB_32      0.0174453000
_diffrn_orient_matrix_UB_33      0.0130164000
_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  0.0321
_diffrn_reflns_av_unetI/netI     0.0335
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.952
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -4
_diffrn_reflns_limit_k_max       45
_diffrn_reflns_limit_k_min       -43
_diffrn_reflns_limit_l_max       12
_diffrn_reflns_limit_l_min       -12
_diffrn_reflns_number            18312
_diffrn_reflns_point_group_measured_fraction_full 0.836
_diffrn_reflns_point_group_measured_fraction_max 0.775
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.207
_diffrn_reflns_theta_min         2.427
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.878
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.725
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.41.120a (Rigaku Oxford Diffraction, 2021)
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            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.366
_exptl_crystal_description       needle
_exptl_crystal_F_000             808
_exptl_crystal_size_max          0.161
_exptl_crystal_size_mid          0.033
_exptl_crystal_size_min          0.021
_refine_diff_density_max         0.269
_refine_diff_density_min         -0.208
_refine_diff_density_rms         0.043
_refine_ls_abs_structure_details
;
 Refined as an inversion twin.
;
_refine_ls_abs_structure_Flack   -0.1(2)
_refine_ls_extinction_coef       0.0018(3)
_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   1.058
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     555
_refine_ls_number_reflns         6107
_refine_ls_number_restraints     67
_refine_ls_restrained_S_all      1.054
_refine_ls_R_factor_all          0.0396
_refine_ls_R_factor_gt           0.0344
_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^)+(0.0580P)^2^+0.1770P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0919
_refine_ls_wR_factor_ref         0.0945
_reflns_Friedel_coverage         0.602
_reflns_Friedel_fraction_full    0.667
_reflns_Friedel_fraction_max     0.592
_reflns_number_gt                5538
_reflns_number_total             6107
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3cc02188b2.cif
_cod_data_source_block           TMP_DLA_a
_cod_depositor_comments
'Adding full bibliography for 7131709--7131712.cif.'
_cod_database_code               7131709
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C35  H35  N35  O35  '
_shelx_estimated_absorpt_t_max   0.982
_shelx_estimated_absorpt_t_min   0.872
_olex2_refinement_description
;
1. Twinned data refinement
 Scales: 1.1(2)
 -0.1(2)
2. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups, All N(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
3. Rigid body (RIGU) restrains
 O10A, O11A, O12A, C32A, C33A, C34A, O10B, O11B, O12B, C32B, C33B, C34B
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001
4. Others
 Fixed Sof: O10A(0.5) O11A(0.5) O12A(0.5) H12A(0.5) C32A(0.5) C33A(0.5)
 H33A(0.5) C34A(0.5) H34A(0.5) H34B(0.5) H34C(0.5) O10B(0.5) O11B(0.5)
 O12B(0.5) H12B(0.5) C32B(0.5) C33B(0.5) H33B(0.5) C34B(0.5) H34D(0.5)
 H34E(0.5) H34F(0.5)
5.a Ternary CH refined with riding coordinates:
 C30(H30), C33A(H33A), C33B(H33B)
5.b Secondary CH2 refined with riding coordinates:
 C10(H10A,H10B), C24(H24A,H24B)
5.c Aromatic/amide H refined with riding coordinates:
 N1(H1), C4(H4), C6(H6), C12(H12), N5(H5), C18(H18), C20(H20), C26(H26)
5.d X=CH2 refined with riding coordinates:
 N2(H2A,H2B), N4(H4A,H4B), N6(H6A,H6B), N8(H8D,H8E)
5.e Idealised Me refined as rotating group:
 C7(H7A,H7B,H7C), C8(H8A,H8B,H8C), C9(H9A,H9B,H9C), C21(H21A,H21B,H21C),
 C22(H22A,H22B,H22C), C23(H23A,H23B,H23C), C31(H31A,H31B,H31C), C34A(H34A,H34B,
 H34C), C34B(H34D,H34E,H34F)
5.f Idealised tetrahedral OH refined as rotating group:
 O9(H9), O12A(H12A), O12B(H12B)
;
_shelx_res_checksum              79665
_shelx_hkl_checksum              92225
_olex2_exptl_crystal_mounting_method 'Hampton Research 20 micron nylon CryoLoop'
_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
- Detector area scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.653
_oxdiff_exptl_absorpt_empirical_full_min 0.735