Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients
Babor, Martin; Nievergelt, Philipp P.; Čejka, Jan; Zvoníček, Vít; Spingler, Bernhard; IUCrJ 6 (2019) 145–151; doi:10.1107/S2052252518017876

data_1550455
_publ_section_title
;
 Microbatch under-oil salt screening of organic cations: single-crystal
 growth of active pharmaceutical ingredients
;
_journal_issue                   1
_journal_name_full               IUCrJ
_journal_page_first              145
_journal_page_last               151
_journal_paper_doi               10.1107/S2052252518017876
_journal_volume                  6
_journal_year                    2019
_chemical_absolute_configuration rmad
_chemical_formula_moiety         '2(C10 H16 N O), C4 H4 O5, H2 O'
_chemical_formula_sum            'C24 H38 N2 O8'
_chemical_formula_weight         482.56
_space_group_crystal_system      triclinic
_space_group_IT_number           1
_space_group_name_Hall           'P 1'
_space_group_name_H-M_alt        'P 1'
_symmetry_space_group_name_Hall  'P 1'
_symmetry_space_group_name_H-M   'P 1'
_atom_sites_solution_hydrogens   mixed
_audit_creation_date             2018-09-21
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                94.7215(8)
_cell_angle_beta                 96.6693(8)
_cell_angle_gamma                109.5246(11)
_cell_formula_units_Z            1
_cell_length_a                   5.82130(7)
_cell_length_b                   7.27088(8)
_cell_length_c                   15.90214(13)
_cell_measurement_reflns_used    16192
_cell_measurement_temperature    159.99(10)
_cell_measurement_theta_max      78.6150
_cell_measurement_theta_min      5.6250
_cell_volume                     624.781(12)
_computing_cell_refinement       'CrysAlisPro 1.171.40.16c (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.40.16c (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.40.16c (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)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      159.99(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_type            'Pilatus 200K'
_diffrn_measured_fraction_theta_full 0.951
_diffrn_measured_fraction_theta_max 0.931
_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     35.00 123.00   0.50    0.60    --   50.46  57.00  30.00  176
  2  \w     92.00 125.00   0.50    2.40    --  102.00  48.00  42.46   66
  3  \w    134.00 160.00   0.50    2.40    --  107.75  45.00  60.00   52
  4  \w    141.00 175.00   0.50    2.40    --  107.75  45.00  90.00   68
  5  \w    146.00 172.00   0.50    2.40    --  107.75  45.00 150.00   52
  6  \w    146.00 178.00   0.50    2.40    --  107.75  45.00 120.00   64
  7  \w    123.00 159.00   0.50    2.40    --  107.75  15.00 120.00   72
  8  \w    116.00 151.00   0.50    2.40    --  107.75  30.00  90.00   70
  9  \w    114.00 178.00   0.50    2.40    --  107.75  30.00  30.00  128
 10  \w    152.00 178.00   0.50    2.40    --  107.75  58.00 -28.47   52
 11  \w    153.00 178.00   0.50    2.40    --  107.75  15.00 -60.00   50
 12  \w    153.00 178.00   0.50    2.40    --  107.75  45.00-120.00   50
 13  \w    138.00 164.00   0.50    2.40    --  107.75  45.00-150.00   52
 14  \w    110.00 162.00   0.50    2.40    --  107.75  30.00-120.00  104
 15  \w    108.00 150.00   0.50    2.40    --  107.75  15.00 -30.00   84
 16  \w     97.00 124.00   0.50    2.40    --  107.75  45.00  60.00   54
 17  \w     94.00 120.00   0.50    2.40    --  107.75  45.00  30.00   52
 18  \w     92.00 135.00   0.50    2.40    --  107.75  58.00 -28.47   86
 19  \w    100.00 125.00   0.50    2.40    --  107.75  15.00 -60.00   50
 20  \w     95.00 158.00   0.50    2.40    --  107.75  45.00   0.00  126
 21  \w     94.00 129.00   0.50    2.40    --  107.75  45.00  90.00   70
 22  \w    102.00 144.00   0.50    2.40    --  107.75  30.00 150.00   84
 23  \w     95.00 141.00   0.50    2.40    --  107.75  45.00 150.00   92
 24  \w     99.00 124.00   0.50    2.40    --  107.75  45.00 120.00   50
 25  \w     79.00 120.00   0.50    2.40    --  107.75  -6.00  54.81   82
 26  \w     84.00 111.00   0.50    2.40    --  107.75 -60.00  51.39   54
 27  \w     76.00 102.00   0.50    2.40    --  107.75 -59.00 129.58   52
 28  \w     41.00  94.00   0.50    2.40    --  107.75 -58.00  76.83  106
 29  \w     43.00  69.00   0.50    2.40    --  107.75 -57.00  89.40   52
 30  \w     39.00  86.00   0.50    2.40    --  107.75 -52.00 139.96   94
 31  \w     30.00  55.00   0.50    2.40    --  107.75 -30.00  60.00   50
 32  \w     38.00 104.00   0.50    2.40    --  107.75 -60.00  20.05  132
 33  \w     87.00 114.00   0.50    2.40    --  107.75 -15.00 -60.00   54
 34  \w     80.00 109.00   0.50    2.40    --  107.75 -60.00 -45.07   58
 35  \w     53.00  85.00   0.50    2.40    --   90.00 -60.00-151.75   64
 36  \w     73.00 123.00   0.50    2.40    --  107.75 -60.00-150.94  100
 37  \w     67.00  98.00   0.50    2.40    --  107.75 -58.00-179.05   62
 38  \w     51.00 102.00   0.50    2.40    --  107.75 -59.00 -78.83  102
 39  \w     37.00  63.00   0.50    2.40    --  107.75 -58.00-179.05   52
 40  \w     37.00  62.00   0.50    2.40    --  107.75 -60.00-150.94   50
 41  \w     32.00  65.00   0.50    2.40    --  107.75 -30.00-150.00   66
 42  \w     31.00  68.00   0.50    2.40    --  107.75 -30.00-120.00   74
 43  \w     33.00  68.00   0.50    2.40    --  107.75 -30.00-180.00   70
 44  \w     97.00 124.00   0.50    2.40    --  107.75  45.00-150.00   54
 45  \w     97.00 123.00   0.50    2.40    --  107.75  45.00 -90.00   52
 46  \w     94.00 122.00   0.50    2.40    --  107.75  45.00 -60.00   56
 47  \w     98.00 139.00   0.50    2.40    --  107.75  45.00-120.00   82
 48  \w     95.00 176.00   0.50    2.40    --  107.75  45.00-180.00  162
 49  \w     96.00 145.00   0.50    2.40    --  107.75  45.00 -30.00   98
 50  \w     66.00  97.00   0.50    2.40    --   82.00  60.00-104.77   62
 51  \w     35.00 123.00   0.50    0.60    --   50.46  57.00-120.00  176
 52  \w     35.00 123.00   0.50    0.60    --   50.46  57.00-180.00  176
 53  \w     35.00 122.00   0.50    0.60    --   50.46  60.00-109.26  174
 54  \w     33.00  70.00   0.50    2.40    --  107.75 -45.00 -30.00   74
 55  \w     37.00  63.00   0.50    2.40    --  107.75 -60.00  51.39   52
 56  \w     35.00  93.00   0.50    2.40    --  107.75 -57.00 104.89  116
 57  \w     36.00  73.00   0.50    2.40    --  107.75 -59.00 129.58   74
 58  \w     30.00  73.00   0.50    2.40    --  107.75  -6.00  54.81   86
 59  \w     38.00  84.00   0.50    2.40    --  107.75 -57.00 -33.73   92
 60  \w     36.00  66.00   0.50    2.40    --  107.75 -60.00 -45.07   60
 61  \w     -6.00  82.00   0.50    0.60    --   66.00 -60.00-120.29  176
 62  \w    -22.00  66.00   0.50    0.60    --   50.46 -57.00 120.00  176
 63  \w     35.00 123.00   0.50    0.60    --   50.46  57.00 150.00  176
 64  \w     10.00  98.00   0.50    0.60    --   26.00  59.00 164.77  176
 65  \w    -65.00 -20.00   0.50    2.40    --  -86.25  59.00  97.75   90
 66  \w   -103.00 -76.00   0.50    2.40    --  -86.25 -56.00 106.55   54
 67  \w    -98.00 -71.00   0.50    2.40    --  -86.25 -60.00 123.27   54
 68  \w    -97.00 -71.00   0.50    2.40    --  -86.25 -58.00  75.39   52
 69  \w    -96.00 -71.00   0.50    2.40    --  -86.25 -59.00  38.58   50
 70  \w    -98.00 -70.00   0.50    2.40    --  -82.00 -59.00 -12.71   56
 71  \w    -98.00 -73.00   0.50    2.40    --  -86.25 -60.00 -68.11   50
 72  \w    -95.00 -68.00   0.50    2.40    --  -82.00 -58.00 -85.23   54
 73  \w    -95.00 -67.00   0.50    2.40    --  -82.00 -57.00 -97.74   56
 74  \w    -89.00 -63.00   0.50    2.40    --  -78.00 -60.00-178.80   52
 75  \w    -99.00 -71.00   0.50    2.40    --  -86.25 -56.00-113.80   56
 76  \w   -102.00 -74.00   0.50    2.40    --  -86.25 -54.00-158.17   56
 77  \w   -114.00 -26.00   0.50    0.60    --  -42.00 -59.00 -88.70  176
 78  \w   -102.00 -70.00   0.50    2.40    --  -82.00 -59.00 -45.36   64
 79  \w    -98.00 -71.00   0.50    2.40    --  -86.25 -60.00  18.04   54
 80  \w   -105.00 -71.00   0.50    2.40    --  -86.25 -59.00  65.56   68
 81  \w    -99.00 -73.00   0.50    2.40    --  -86.25 -60.00 153.02   52
 82  \w   -102.00 -72.00   0.50    2.40    --  -86.25 -60.00 174.82   60
 83  \w   -128.00 -38.00   0.50    0.60    --  -50.46 -38.00  60.00  180
 84  \w   -118.00 -30.00   0.50    0.60    --  -46.00 -60.00  13.51  176
 85  \w   -122.00 -34.00   0.50    0.60    --  -50.00 -59.00-114.16  176
 86  \w   -126.00 -39.00   0.50    0.60    --  -54.00 -58.00  40.19  174
 87  \w   -131.00 -38.00   0.50    0.60    --  -50.46 -19.00 -60.00  186
 88  \w    -82.00 -57.00   0.50    2.40    --  -86.25  60.00-170.23   50
 89  \w   -126.00 -39.00   0.50    0.60    --  -54.00 -58.00-158.34  174
 90  \w   -142.00 -54.00   0.50    2.40    --  -70.00 -60.00 -16.61  176
 91  \w   -131.00 -38.00   0.50    0.60    --  -50.46 -19.00  90.00  186
 92  \w   -126.00-100.00   0.50    2.40    --  -86.25 -59.00  38.58   52
 93  \w   -126.00-100.00   0.50    2.40    --  -86.25 -58.00  75.39   52
 94  \w   -134.00 -46.00   0.50    0.60    --  -62.00 -60.00  72.08  176
 95  \w   -146.00 -58.00   0.50    2.40    --  -74.00 -59.00  23.87  176
 96  \w   -146.00 -58.00   0.50    2.40    --  -74.00 -60.00 -51.46  176
 97  \w   -152.00-125.00   0.50    2.40    --  -82.00 -57.00 -97.74   54
 98  \w   -150.00 -62.00   0.50    2.40    --  -78.00 -60.00 147.36  176
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, Pilatus 200K'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0265503000
_diffrn_orient_matrix_UB_12      -0.0106884000
_diffrn_orient_matrix_UB_13      -0.0979728000
_diffrn_orient_matrix_UB_21      0.0804748000
_diffrn_orient_matrix_UB_22      -0.1815815000
_diffrn_orient_matrix_UB_23      -0.0045260000
_diffrn_orient_matrix_UB_31      -0.2711991000
_diffrn_orient_matrix_UB_32      -0.1353257000
_diffrn_orient_matrix_UB_33      -0.0075118000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0318
_diffrn_reflns_av_unetI/netI     0.0233
_diffrn_reflns_Laue_measured_fraction_full 0.951
_diffrn_reflns_Laue_measured_fraction_max 0.931
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -20
_diffrn_reflns_number            19924
_diffrn_reflns_point_group_measured_fraction_full 0.926
_diffrn_reflns_point_group_measured_fraction_max 0.888
_diffrn_reflns_theta_full        69.500
_diffrn_reflns_theta_max         78.859
_diffrn_reflns_theta_min         2.821
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.794
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.463
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.16c (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    1.283
_exptl_crystal_description       plate
_exptl_crystal_F_000             260
_exptl_crystal_size_max          0.3
_exptl_crystal_size_mid          0.21
_exptl_crystal_size_min          0.014
_refine_diff_density_max         0.155
_refine_diff_density_min         -0.182
_refine_diff_density_rms         0.031
_refine_ls_abs_structure_details
;
 Flack x determined using 2188 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.00(6)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.063
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     322
_refine_ls_number_reflns         4803
_refine_ls_number_restraints     3
_refine_ls_restrained_S_all      1.063
_refine_ls_R_factor_all          0.0275
_refine_ls_R_factor_gt           0.0270
_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^)+(0.0470P)^2^+0.0580P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0733
_refine_ls_wR_factor_ref         0.0735
_reflns_Friedel_coverage         0.907
_reflns_Friedel_fraction_full    0.901
_reflns_Friedel_fraction_max     0.845
_reflns_number_gt                4709
_reflns_number_total             4803
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            lt5016.cif
_cod_data_source_block           pn180914_uo_eph_1_180814_g4_2
_cod_database_code               1550455
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         'C24 H38 N2 O8'
_shelx_estimated_absorpt_t_max   0.989
_shelx_estimated_absorpt_t_min   0.797
_reflns_odcompleteness_completeness 92.40
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     79.66
_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, All O(H) groups
2.a Ternary CH refined with riding coordinates:
 C1(H1C), C2(H2), C11(H11C), C12(H12), C22(H22)
2.b Secondary CH2 refined with riding coordinates:
 N1(H1A,H1B), N11(H11A,H11B), C23(H23A,H23B)
2.c Aromatic/amide H refined with riding coordinates:
 C6(H6), C7(H7), C8(H8), C9(H9), C10(H10), C16(H16), C17(H17), C18(H18),
 C19(H19), C20(H20)
2.d Idealised Me refined as rotating group:
 C3(H3A,H3B,H3C), C4(H4A,H4B,H4C), C13(H13A,H13B,H13C), C14(H14A,H14B,H14C)
2.e Idealised tetrahedral OH refined as rotating group:
 O1(H1), O11(H11), O23(H23)
;
_shelx_res_checksum              2821
_shelx_hkl_checksum              13594
_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 1.673
_oxdiff_exptl_absorpt_empirical_full_min 0.681