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_7131710
_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 rmad
_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      triclinic
_space_group_IT_number           1
_space_group_name_Hall           'P 1'
_space_group_name_H-M_alt        'P 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2022-10-12
_audit_creation_method
;
Olex2 1.5
(compiled 2021.12.09 svn.r5202d8cf for OlexSys, GUI svn.r6439)
;
_audit_update_record
;
2023-02-10 deposited with the CCDC.	2023-05-25 downloaded from the CCDC.
;
_cell_angle_alpha                85.4911(12)
_cell_angle_beta                 88.8333(15)
_cell_angle_gamma                77.8317(15)
_cell_formula_units_Z            2
_cell_length_a                   5.06945(11)
_cell_length_b                   9.75039(14)
_cell_length_c                   19.4424(3)
_cell_measurement_reflns_used    21583
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      76.7300
_cell_measurement_theta_min      2.2510
_cell_volume                     936.51(3)
_computing_cell_refinement       'CrysAlisPro 1.171.41.122a (Rigaku OD, 2021)'
_computing_data_collection       'CrysAlisPro 1.171.41.122a (Rigaku OD, 2021)'
_computing_data_reduction        'CrysAlisPro 1.171.41.122a (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  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'XT  (Sheldrick, 2015)'
_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 0.998
_diffrn_measured_fraction_theta_max 0.936
_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   -120.00 -63.00   0.50    1.26    --  -47.76-140.00  73.00  114
  2  \w   -120.00 -70.00   0.50    1.26    --  -47.76-130.00-113.00  100
  3  \w    -90.00 -16.00   0.50    1.26    --  -47.76 130.00 -41.00  148
  4  \w     43.00 104.00   0.50    1.26    --   47.76-140.00  73.00  122
  5  \w     37.00  98.00   0.50    1.26    --   47.76-130.00-113.00  122
  6  \w   -163.00 -70.00   0.50    5.04    --  -91.75-130.00-113.00  186
  7  \w   -156.00 -63.00   0.50    5.04    --  -91.75-140.00  73.00  186
  8  \w     85.00 173.00   0.50    5.04    --  107.31 140.00 132.00  176
  9  \w     92.00 178.00   0.50    5.04    --  107.31 130.00 -41.00  172
 10  \w     37.00 116.00   0.50    5.04    --  107.31-130.00-113.00  158
 11  \w     43.00 123.00   0.50    5.04    --  107.31-140.00  73.00  160
 12  \w    -54.00 -27.00   0.50    1.26    --   10.00 153.00  40.83   54
 13  \w      4.00  34.00   0.50    1.26    --   34.00  93.00  53.43   60
 14  \w      2.00  29.00   0.50    1.26    --   34.00  96.00 104.74   54
 15  \w   -121.00 -34.00   0.50    1.26    --  -47.76 -38.00 120.00  174
 16  \w   -120.00 -25.00   0.50    1.26    --  -47.76 -77.00 -30.00  190
 17  \w    -97.00 -21.00   0.50    1.26    --  -47.76 140.00 132.00  152
 18  \w   -120.00 -73.00   0.50    1.26    --  -47.76-125.00-180.00   94
 19  \w     25.00 121.00   0.50    1.26    --   47.76  77.00 120.00  192
 20  \w     33.00 120.00   0.50    1.26    --   47.76  57.00 -60.00  174
 21  \w     25.00 121.00   0.50    1.26    --   47.76  77.00 -30.00  192
 22  \w     36.00 121.00   0.50    1.26    --   47.76  38.00-120.00  170
 23  \w     25.00 121.00   0.50    1.26    --   47.76  77.00 -60.00  192
 24  \w     36.00 121.00   0.50    1.26    --   47.76  38.00 -60.00  170
 25  \w     28.00 122.00   0.50    1.26    --   50.00  75.00  44.40  188
 26  \w     31.00 126.00   0.50    1.26    --   54.00  77.00-117.00  190
 27  \w     32.00 126.00   0.50    1.26    --   54.00  75.00  77.25  188
 28  \w     33.00 126.00   0.50    1.26    --   54.00  72.00  65.42  186
 29  \w     32.00 126.00   0.50    1.26    --   54.00  76.00-151.27  188
 30  \w   -131.00 -36.00   0.50    1.26    --  -58.00 -74.00-141.81  190
 31  \w     37.00 131.00   0.50    1.26    --   58.00  74.00-169.50  188
 32  \w   -135.00 -45.00   0.50    1.26    --  -62.00 -63.00 -45.81  180
 33  \w   -135.00 -44.00   0.50    1.26    --  -62.00 -65.00-177.54  182
 34  \w   -135.00 -43.00   0.50    1.26    --  -62.00 -67.00-149.23  184
 35  \w     39.00 135.00   0.50    1.26    --   62.00  77.00 154.31  192
 36  \w   -139.00 -49.00   0.50    1.26    --  -66.00 -62.00 -20.03  180
 37  \w     44.00 139.00   0.50    1.26    --   66.00  75.00 149.00  190
 38  \w     43.00 139.00   0.50    1.26    --   66.00  77.00 -66.62  192
 39  \w   -143.00 -52.00   0.50    5.04    --  -70.00 -65.00 134.70  182
 40  \w   -142.00 -54.00   0.50    5.04    --  -70.00 -60.00  44.91  176
 41  \w   -142.00 -55.00   0.50    5.04    --  -70.00 -57.00 -68.23  174
 42  \w     47.00  73.00   0.50    1.26    --   70.00  77.00 128.59   52
 43  \w    -85.00 -54.00   0.50    5.04    --  -70.00 -62.00  29.04   62
 44  \w    -81.00 -55.00   0.50    5.04    --  -70.00 -60.00 168.05   52
 45  \w    -80.00 -54.00   0.50    5.04    --  -70.00 -59.00 138.78   52
 46  \w    -83.00 -57.00   0.50    5.04    --  -74.00 -63.00  14.13   52
 47  \w    -81.00 -56.00   0.50    5.04    --  -74.00 -65.00 -43.64   50
 48  \w    -81.00 -55.00   0.50    5.04    --  -74.00 -67.00-109.23   52
 49  \w    -82.00 -57.00   0.50    5.04    --  -74.00 -62.00 -18.24   50
 50  \w    -83.00 -57.00   0.50    5.04    --  -74.00 -63.00-132.60   52
 51  \w    -89.00 -63.00   0.50    5.04    --  -78.00 -60.00  40.92   52
 52  \w    -94.00 -68.00   0.50    5.04    --  -78.00 -58.00-160.38   52
 53  \w    -88.00 -62.00   0.50    5.04    --  -78.00 -65.00 113.17   52
 54  \w    -89.00 -63.00   0.50    5.04    --  -78.00 -57.00 172.42   52
 55  \w    -83.00 -57.00   0.50    5.04    --  -78.00 -72.00 110.65   52
 56  \w    -87.00 -61.00   0.50    5.04    --  -78.00 -62.00 129.02   52
 57  \w    -92.00 -66.00   0.50    5.04    --  -82.00 -62.00  31.93   52
 58  \w    -92.00 -67.00   0.50    5.04    --  -82.00 -57.00 158.42   50
 59  \w    -92.00 -67.00   0.50    5.04    --  -82.00 -58.00-149.09   50
 60  \w    -91.00 -65.00   0.50    5.04    --  -82.00 -64.00 -17.40   52
 61  \w    -92.00 -66.00   0.50    5.04    --  -82.00 -62.00 123.86   52
 62  \w    -86.00 -61.00   0.50    5.04    --  -82.00 -72.00 -92.50   50
 63  \w   -155.00-124.00   0.50    5.04    --  -86.00 -76.00 105.45   62
 64  \w   -117.00 -63.00   0.50    5.04    --  -86.00 -76.00 105.45  108
 65  \w    -97.00 -71.00   0.50    5.04    --  -91.75 -73.00  10.23   52
 66  \w   -163.00-105.00   0.50    5.04    --  -91.75 -73.00  10.23  116
 67  \w   -106.00 -71.00   0.50    5.04    --  -91.75 -77.00 -30.00   70
 68  \w   -163.00 -69.00   0.50    5.04    --  -91.75 -77.00   0.00  188
 69  \w   -142.00-116.00   0.50    5.04    --  -91.75 -77.00 -66.97   52
 70  \w   -160.00-135.00   0.50    5.04    --  -91.75 -77.00 -30.00   50
 71  \w   -122.00 -69.00   0.50    5.04    --  -91.75 -77.00  60.00  106
 72  \w   -162.00-136.00   0.50    5.04    --  -91.75 -68.00 -90.17   52
 73  \w   -152.00-126.00   0.50    5.04    --  -91.75 -65.00 -28.98   52
 74  \w   -130.00 -80.00   0.50    5.04    --  -91.75 -57.00-150.00  100
 75  \w   -104.00 -73.00   0.50    5.04    --  -91.75 -66.00 118.34   62
 76  \w   -119.00 -73.00   0.50    5.04    --  -91.75 -68.00-169.54   92
 77  \w   -143.00-117.00   0.50    5.04    --  -91.75 -66.00 118.34   52
 78  \w   -113.00 -87.00   0.50    5.04    --  -91.75 -57.00 150.00   52
 79  \w   -163.00-129.00   0.50    5.04    --  -91.75 -68.00-169.54   68
 80  \w   -121.00 -69.00   0.50    5.04    --  -91.75 -77.00  90.00  104
 81  \w   -162.00-127.00   0.50    5.04    --  -91.75 -77.00  90.00   70
 82  \w    -99.00 -73.00   0.50    5.04    --  -91.75 -68.00 -90.17   52
 83  \w    -95.00 -69.00   0.50    5.04    --  -91.75 -76.00 123.07   52
 84  \w   -109.00 -74.00   0.50    5.04    --  -91.75 -63.00 -38.96   70
 85  \w   -163.00-113.00   0.50    5.04    --  -91.75 -63.00 -38.96  100
 86  \w   -154.00 -74.00   0.50    5.04    --  -91.75 -63.00-126.69  160
 87  \w   -163.00 -75.00   0.50    5.04    --  -91.75 -62.00  58.05  176
 88  \w   -104.00 -76.00   0.50    5.04    --  -91.75 -77.00-180.00   56
 89  \w   -161.00-109.00   0.50    5.04    --  -91.75 -77.00-180.00  104
 90  \w   -106.00 -69.00   0.50    5.04    --  -91.75 -77.00 -66.97   74
 91  \w   -112.00 -75.00   0.50    5.04    --  -91.75 -61.00-118.67   74
 92  \w   -106.00 -72.00   0.50    5.04    --  -91.75 -70.00 -97.26   68
 93  \w   -111.00 -73.00   0.50    5.04    --  -91.75 -71.00 -54.15   76
 94  \w   -154.00-119.00   0.50    5.04    --  -91.75 -70.00 -97.26   70
 95  \w    -99.00 -71.00   0.50    5.04    --  -91.75 -73.00 143.15   56
 96  \w   -162.00 -72.00   0.50    5.04    --  -91.75 -73.00  42.72  180
 97  \w   -163.00-107.00   0.50    5.04    --  -91.75 -73.00 143.15  112
 98  \w   -158.00-133.00   0.50    5.04    --  -91.75 -57.00 150.00   50
 99  \w   -162.00-121.00   0.50    5.04    --  -91.75 -71.00 -54.15   82
100  \w   -103.00 -77.00   0.50    5.04    --  -91.75 -65.00 -28.98   52
101  \w     35.00 103.00   0.50    5.04    --  107.31 -99.00-180.00  136
102  \w     35.00 107.00   0.50    5.04    --  107.31 -77.00  30.00  144
103  \w    144.00 177.00   0.50    5.04    --  107.31 125.00  90.00   66
104  \w     37.00  68.00   0.50    5.04    --  107.31 -57.00-150.00   62
105  \w     67.00 106.00   0.50    5.04    --  107.31 -99.00 -90.00   78
106  \w     38.00  64.00   0.50    5.04    --  107.31 -99.00 -90.00   52
107  \w     80.00 106.00   0.50    5.04    --  107.31 -99.00 -60.00   52
108  \w     35.00  71.00   0.50    5.04    --  107.31 -99.00 -60.00   72
109  \w     79.00 105.00   0.50    5.04    --  107.31 -99.00-120.00   52
110  \w     35.00  67.00   0.50    5.04    --  107.31 -57.00 -30.00   64
111  \w     79.00 104.00   0.50    5.04    --  107.31 -77.00  60.00   50
112  \w     73.00 101.00   0.50    5.04    --  107.31 -77.00  90.00   56
113  \w     36.00  68.00   0.50    5.04    --  107.31 -77.00  90.00   64
114  \w     46.00  75.00   0.50    5.04    --  107.31 -77.00  60.00   58
115  \w     36.00  68.00   0.50    5.04    --  107.31 -57.00 -90.00   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      0.1352285000
_diffrn_orient_matrix_UB_12      -0.1501558000
_diffrn_orient_matrix_UB_13      -0.0174268000
_diffrn_orient_matrix_UB_21      0.0397556000
_diffrn_orient_matrix_UB_22      -0.0447778000
_diffrn_orient_matrix_UB_23      0.0774935000
_diffrn_orient_matrix_UB_31      -0.2771510000
_diffrn_orient_matrix_UB_32      -0.0415385000
_diffrn_orient_matrix_UB_33      0.0029714000
_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  0.0880
_diffrn_reflns_av_unetI/netI     0.0507
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.936
_diffrn_reflns_limit_h_max       5
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       23
_diffrn_reflns_limit_l_min       -23
_diffrn_reflns_number            37542
_diffrn_reflns_point_group_measured_fraction_full 0.956
_diffrn_reflns_point_group_measured_fraction_max 0.866
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.883
_diffrn_reflns_theta_min         2.280
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.867
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.820
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.41.122a (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    1.349
_exptl_crystal_description       irregular
_exptl_crystal_F_000             404
_exptl_crystal_size_max          0.147
_exptl_crystal_size_mid          0.06
_exptl_crystal_size_min          0.046
_refine_diff_density_max         0.233
_refine_diff_density_min         -0.260
_refine_diff_density_rms         0.046
_refine_ls_abs_structure_details
;
 Flack x determined using 2572 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.08(13)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.062
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     554
_refine_ls_number_reflns         6872
_refine_ls_number_restraints     69
_refine_ls_restrained_S_all      1.059
_refine_ls_R_factor_all          0.0513
_refine_ls_R_factor_gt           0.0430
_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^)+(0.0733P)^2^+0.0824P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1084
_refine_ls_wR_factor_ref         0.1156
_reflns_Friedel_coverage         0.850
_reflns_Friedel_fraction_full    0.914
_reflns_Friedel_fraction_max     0.796
_reflns_number_gt                6183
_reflns_number_total             6872
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3cc02188b2.cif
_cod_data_source_block           TMP_DLA_b
_cod_depositor_comments
'Adding full bibliography for 7131709--7131712.cif.'
_cod_original_cell_volume        936.52(3)
_cod_database_code               7131710
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C36  H36  N8  O8  '
_chemical_oxdiff_usercomment     'TMP + DLA'
_shelx_estimated_absorpt_t_max   0.961
_shelx_estimated_absorpt_t_min   0.883
_olex2_refinement_description
;
1. 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
2. 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
3. Others
 Sof(O10B)=Sof(O11B)=Sof(O12B)=Sof(H12B)=Sof(C32B)=Sof(C33B)=Sof(H33B)=
 Sof(C34B)=Sof(H34D)=Sof(H34E)=Sof(H34F)=1-FVAR(1)
 Sof(O10A)=Sof(O11A)=Sof(O12A)=Sof(H12A)=Sof(C32A)=Sof(C33A)=Sof(H33A)=
 Sof(C34A)=Sof(H34A)=Sof(H34B)=Sof(H34C)=FVAR(1)
4.a Ternary CH refined with riding coordinates:
 C30(H30), C33A(H33A), C33B(H33B)
4.b Secondary CH2 refined with riding coordinates:
 C10(H10A,H10B), C24(H24A,H24B)
4.c Aromatic/amide H refined with riding coordinates:
 N5(H5), C4(H4), C6(H6), C14(H14), N1(H1), C18(H18), C20(H20), C28(H28)
4.d X=CH2 refined with riding coordinates:
 N8(H8A,H8B), N6(H6A,H6B), N4(H4A,H4B), N2(H2A,H2B)
4.e Idealised Me refined as rotating group:
 C7(H7A,H7B,H7C), C8(H8C,H8D,H8E), 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)
4.f Idealised tetrahedral OH refined as rotating group:
 O9(H9), O12A(H12A), O12B(H12B)
;
_shelx_res_checksum              26359
_shelx_hkl_checksum              42405
_olex2_exptl_crystal_mounting_method 'Hampton Research 20 micron nylon CryoLoop'
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_diffrn_reflns_filtered   2790
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 2.594
_oxdiff_exptl_absorpt_empirical_full_min 0.486