Co-Crystals of Zwitterionic GABA API’s Pregabalin and Phenibut: Properties and Application
Komisarek, Daniel; Haj Hassani Sohi, Takin; Vasylyeva, Vera; CrystEngComm  (2022) –; doi:10.1039/D2CE01416E

data_7245864
_publ_section_title
;
 Co-Crystals of Zwitterionic GABA API&#x2019;s Pregabalin and Phenibut:
 Properties and Application
;
_journal_name_full               CrystEngComm
_journal_paper_doi               10.1039/D2CE01416E
_journal_year                    2022
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C8 H17 N O2, C8 H8 O3'
_chemical_formula_sum            'C16 H25 N O5'
_chemical_formula_weight         311.37
_chemical_name_common            '(R)-Pregabalin (R)-Mandelic Acid'
_chemical_name_systematic
'(R)-3-isobutyl-\^I^3^-aminobutyric acid (R)-2-Hydroxy-2-phenylacetic 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   difmap
_atom_sites_solution_primary     dual
_audit_creation_date             2021-09-08
_audit_creation_method
;
Olex2 1.3
(compiled 2020.11.12 svn.r5f609507 for OlexSys, GUI svn.r6272)
;
_audit_update_record
;
2022-05-03 deposited with the CCDC.	2022-11-17 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90.4830(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.25270(10)
_cell_length_b                   27.3848(3)
_cell_length_c                   9.96030(10)
_cell_measurement_reflns_used    33130
_cell_measurement_temperature    99.97(16)
_cell_measurement_theta_max      77.3600
_cell_measurement_theta_min      3.2050
_cell_volume                     1705.43(4)
_computing_cell_refinement       'CrysAlisPro 1.171.41.92a (Rigaku OD, 2020)'
_computing_data_collection       'CrysAlisPro 1.171.41.92a (Rigaku OD, 2020)'
_computing_data_reduction        'CrysAlisPro 1.171.41.92a (Rigaku OD, 2020)'
_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 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      99.97(16)
_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 0.939
_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     48.00  85.00   0.50    0.11    --   49.27  19.00 150.00   74
  2  \w     44.00  77.00   0.50    0.11    --   66.00  77.00  93.24   66
  3  \w     41.00  66.00   0.50    0.11    --   62.00  77.00  -1.48   50
  4  \w     41.00  66.00   0.50    0.11    --   62.00  77.00 -33.85   50
  5  \w    -72.00 -20.00   0.50    0.44    --  -90.00  77.00  30.00  104
  6  \w    -54.00 -28.00   0.50    0.44    --  -90.00  57.00  30.00   52
  7  \w    -70.00 -24.00   0.50    0.44    --  -90.00  57.00 150.00   92
  8  \w   -107.00 -76.00   0.50    0.44    --  -90.00  77.00  30.00   62
  9  \w    -46.00 -20.00   0.50    0.44    --  -90.00  38.00 -30.00   52
 10  \w    -47.00 -21.00   0.50    0.44    --  -90.00  38.00 -60.00   52
 11  \w    -71.00 -22.00   0.50    0.44    --  -90.00  57.00-120.00   98
 12  \w     15.00  40.00   0.50    0.11    --   42.00  89.00 173.01   50
 13  \w    -54.00 -29.00   0.50    0.11    --   10.00 154.00 179.88   50
 14  \w    -15.00  14.00   0.50    0.11    --   18.00 101.00  22.11   58
 15  \w     -1.00  24.00   0.50    0.11    --   30.00  96.00  19.77   50
 16  \w     14.00  39.00   0.50    0.11    --   42.00  91.00  14.46   50
 17  \w     -2.00  25.00   0.50    0.11    --   30.00  98.00-164.21   54
 18  \w    -75.00 -49.00   0.50    0.11    --  -49.27 146.00-177.00   52
 19  \w    -63.00 -36.00   0.50    0.44    --  -90.00 125.00  16.00   54
 20  \w    -73.00 -48.00   0.50    0.11    --  -49.27 125.00  16.00   50
 21  \w    -51.00 -19.00   0.50    0.11    --   -2.00 134.00  79.15   64
 22  \w    -53.00 -28.00   0.50    0.11    --  -49.27 -77.00 -60.00   50
 23  \w    -70.00 -28.00   0.50    0.11    --  -49.27 -77.00-120.00   84
 24  \w   -106.00 -77.00   0.50    0.11    --  -49.27 -77.00 -60.00   58
 25  \w    -54.00 -28.00   0.50    0.11    --  -49.27 -77.00 120.00   52
 26  \w    -53.00 -28.00   0.50    0.11    --  -49.27 -77.00  90.00   50
 27  \w    -54.00 -28.00   0.50    0.11    --  -49.27 -77.00  60.00   52
 28  \w    -56.00 -28.00   0.50    0.11    --  -49.27 -77.00  30.00   56
 29  \w   -110.00 -84.00   0.50    0.11    --  -49.27 -77.00 120.00   52
 30  \w    -56.00 -30.00   0.50    0.11    --  -49.27 -77.00   0.00   52
 31  \w    -76.00 -38.00   0.50    0.11    --  -49.27 -19.00 -30.00   76
 32  \w    -53.00 -28.00   0.50    0.11    --  -49.27 -77.00 -90.00   50
 33  \w    -54.00 -28.00   0.50    0.11    --  -49.27 -77.00-150.00   52
 34  \w    -63.00 -28.00   0.50    0.11    --  -49.27 -77.00-180.00   70
 35  \w    -83.00 -48.00   0.50    0.44    --  -70.00 -77.00-159.98   70
 36  \w   -103.00 -69.00   0.50    0.44    --  -90.00 -77.00   0.00   68
 37  \w   -159.00 -68.00   0.50    0.44    --  -90.00 -77.00 -30.00  182
 38  \w   -159.00-129.00   0.50    0.44    --  -90.00 -77.00 150.00   60
 39  \w   -140.00 -64.00   0.50    0.44    --  -86.00 -77.00 135.64  152
 40  \w   -105.00 -68.00   0.50    0.44    --  -90.00 -77.00 150.00   74
 41  \w    -95.00 -68.00   0.50    0.44    --  -90.00 -77.00  53.61   54
 42  \w    -93.00 -68.00   0.50    0.44    --  -90.00 -77.00  60.00   50
 43  \w   -121.00 -72.00   0.50    0.44    --  -90.00 -77.00 120.00   98
 44  \w   -153.00-127.00   0.50    0.44    --  -90.00 -77.00 120.00   52
 45  \w   -147.00 -98.00   0.50    0.44    --  -90.00 -77.00  60.00   98
 46  \w    -93.00 -68.00   0.50    0.44    --  -90.00 -77.00-150.00   50
 47  \w    -96.00 -69.00   0.50    0.44    --  -90.00 -77.00-180.00   54
 48  \w    -95.00 -68.00   0.50    0.44    --  -90.00 -77.00-170.52   54
 49  \w   -161.00-105.00   0.50    0.44    --  -90.00 -77.00-170.52  112
 50  \w   -156.00-116.00   0.50    0.44    --  -90.00 -77.00-180.00   80
 51  \w   -130.00-104.00   0.50    0.44    --  -90.00 -77.00-150.00   52
 52  \w   -102.00 -65.00   0.50    0.44    --  -86.00 -76.00-139.52   74
 53  \w   -158.00-107.00   0.50    0.44    --  -86.00 -76.00-139.52  102
 54  \w    -67.00 -41.00   0.50    0.11    --  -62.00 -74.00 -19.16   52
 55  \w    -95.00 -69.00   0.50    0.44    --  -90.00 -75.00  45.15   52
 56  \w    -84.00 -57.00   0.50    0.44    --  -78.00 -74.00  64.26   54
 57  \w   -122.00 -69.00   0.50    0.44    --  -90.00 -76.00  97.16  106
 58  \w   -145.00-119.00   0.50    0.44    --  -90.00 -74.00 160.12   52
 59  \w   -100.00 -69.00   0.50    0.44    --  -90.00 -74.00 160.12   62
 60  \w   -160.00-104.00   0.50    0.44    --  -90.00 -77.00  53.61  112
 61  \w   -143.00-117.00   0.50    0.44    --  -78.00 -73.00-101.52   52
 62  \w    -83.00 -57.00   0.50    0.44    --  -78.00 -74.00-127.15   52
 63  \w    -84.00 -58.00   0.50    0.44    --  -78.00 -73.00-118.26   52
 64  \w    -84.00 -58.00   0.50    0.44    --  -78.00 -73.00-109.60   52
 65  \w    -84.00 -58.00   0.50    0.44    --  -78.00 -73.00-101.52   52
 66  \w   -131.00 -70.00   0.50    0.44    --  -90.00 -73.00 -76.08  122
 67  \w   -161.00 -70.00   0.50    0.44    --  -90.00 -72.00 -55.80  182
 68  \w   -101.00 -70.00   0.50    0.44    --  -90.00 -72.00  16.82   62
 69  \w    -85.00 -58.00   0.50    0.44    --  -78.00 -72.00  40.42   54
 70  \w    -84.00 -58.00   0.50    0.44    --  -78.00 -72.00  48.50   52
 71  \w    -88.00 -62.00   0.50    0.44    --  -82.00 -73.00  76.40   52
 72  \w   -161.00-115.00   0.50    0.44    --  -90.00 -72.00  16.82   92
 73  \w   -160.00 -70.00   0.50    0.44    --  -90.00 -72.00   8.10  180
 74  \w   -145.00 -71.00   0.50    0.44    --  -90.00 -71.00 -23.08  148
 75  \w   -135.00-110.00   0.50    0.11    --  -66.00 -71.00-105.47   50
 76  \w    -72.00 -47.00   0.50    0.11    --  -66.00 -71.00-105.47   50
 77  \w    -78.00 -52.00   0.50    0.44    --  -70.00 -68.00 -71.40   52
 78  \w    -87.00 -56.00   0.50    0.44    --  -74.00 -67.00 -89.60   62
 79  \w    -79.00 -52.00   0.50    0.44    --  -70.00 -67.00 -49.60   54
 80  \w    -89.00 -56.00   0.50    0.44    --  -74.00 -67.00 -22.03   66
 81  \w    -78.00 -47.00   0.50    0.11    --  -66.00 -71.00  10.04   62
 82  \w    -78.00 -52.00   0.50    0.44    --  -70.00 -68.00  -1.95   52
 83  \w    -70.00 -44.00   0.50    0.11    --  -62.00 -67.00 127.18   52
 84  \w    -73.00 -46.00   0.50    0.11    --  -62.00 -66.00 152.70   54
 85  \w    -74.00 -49.00   0.50    0.11    --  -66.00 -65.00 104.58   50
 86  \w    -70.00 -45.00   0.50    0.11    --  -62.00 -65.00  72.38   50
 87  \w    -86.00 -59.00   0.50    0.44    --  -74.00 -63.00 136.29   54
 88  \w   -134.00-108.00   0.50    0.11    --  -66.00 -65.00 104.58   52
 89  \w    -71.00 -45.00   0.50    0.11    --  -62.00 -65.00-177.61   52
 90  \w   -136.00 -79.00   0.50    0.44    --  -90.00-125.00 -90.00  114
 91  \w   -128.00 -84.00   0.50    0.44    --  -90.00-125.00 -61.00   88
 92  \w   -112.00 -86.00   0.50    0.11    --  -49.27-125.00 -61.00   52
 93  \w   -141.00 -70.00   0.50    0.44    --  -90.00-146.00 132.00  142
 94  \w    -90.00 -65.00   0.50    0.11    --  -49.27-146.00 132.00   50
 95  \w     39.00  79.00   0.50    0.44    --  109.41 -77.00 120.00   80
 96  \w    101.00 126.00   0.50    0.44    --  109.41 146.00-177.00   50
 97  \w    136.00 161.00   0.50    0.44    --  109.41 125.00  16.00   50
 98  \w     40.00  97.00   0.50    0.44    --  109.41 -77.00-120.00  114
 99  \w     38.00  77.00   0.50    0.44    --  109.41 -77.00 -60.00   78
100  \w     48.00 100.00   0.50    0.44    --  109.41 -77.00 -30.00  104
101  \w     48.00  85.00   0.50    0.11    --   49.27-146.00 132.00   74
102  \w     54.00  90.00   0.50    0.44    --  109.41-146.00 132.00   72
103  \w     97.00 127.00   0.50    0.44    --  109.41-146.00 132.00   60
104  \w     61.00 111.00   0.50    0.44    --  109.41-125.00 120.00  100
105  \w     85.00 111.00   0.50    0.44    --  109.41-125.00 -61.00   52
106  \w     86.00 112.00   0.50    0.44    --  109.41-125.00-120.00   52
107  \w     47.00  72.00   0.50    0.44    --  109.41-125.00-120.00   50
108  \w     39.00  64.00   0.50    0.44    --  109.41 -99.00-180.00   50
109  \w     70.00  96.00   0.50    0.44    --  109.41 -99.00-180.00   52
110  \w     35.00  96.00   0.50    0.11    --   49.27-125.00 -61.00  122
111  \w     69.00  98.00   0.50    0.44    --  109.41 -99.00 150.00   58
;
_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      -0.0963555000
_diffrn_orient_matrix_UB_12      0.0516403000
_diffrn_orient_matrix_UB_13      0.0103417000
_diffrn_orient_matrix_UB_21      -0.2268312000
_diffrn_orient_matrix_UB_22      -0.0219875000
_diffrn_orient_matrix_UB_23      -0.0039086000
_diffrn_orient_matrix_UB_31      0.0027419000
_diffrn_orient_matrix_UB_32      -0.0040347000
_diffrn_orient_matrix_UB_33      0.1541931000
_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  0.0482
_diffrn_reflns_av_unetI/netI     0.0250
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.939
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       33
_diffrn_reflns_limit_k_min       -34
_diffrn_reflns_limit_l_max       12
_diffrn_reflns_limit_l_min       -10
_diffrn_reflns_number            47481
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.914
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.749
_diffrn_reflns_theta_min         3.228
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.738
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.458
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.41.92a (Rigaku Oxford Diffraction, 2020)
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_density_diffrn    1.213
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       Plate
_exptl_crystal_F_000             672
_exptl_crystal_size_max          0.4
_exptl_crystal_size_mid          0.11
_exptl_crystal_size_min          0.09
_refine_diff_density_max         0.107
_refine_diff_density_min         -0.149
_refine_diff_density_rms         0.032
_refine_ls_abs_structure_details
;
 Flack x determined using 2902 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.02(5)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.035
_refine_ls_hydrogen_treatment    refall
_refine_ls_matrix_type           full
_refine_ls_number_parameters     597
_refine_ls_number_reflns         6627
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.035
_refine_ls_R_factor_all          0.0297
_refine_ls_R_factor_gt           0.0278
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0372P)^2^+0.1974P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0679
_refine_ls_wR_factor_ref         0.0689
_reflns_Friedel_coverage         0.906
_reflns_Friedel_fraction_full    0.998
_reflns_Friedel_fraction_max     0.887
_reflns_number_gt                6330
_reflns_number_total             6627
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d2ce01416e2.cif
_cod_data_source_block           R-PGB_R-MAN
_cod_database_code               7245864
_chemical_oxdiff_formula         'C8 H17 N O2 C8 H8 O3'
_shelx_estimated_absorpt_t_max   0.937
_shelx_estimated_absorpt_t_min   0.757
_olex2_refinement_description
;
;
_shelx_res_checksum              12386
_shelx_hkl_checksum              27948
_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 1.367
_oxdiff_exptl_absorpt_empirical_full_min 0.742