Optimization of physicochemical properties of theophylline by forming cocrystals with amino acids
Li, Qi; Xie, Yifei; Wang, Zhipeng; Li, Shuang; Yang, Shiying; Yang, Dezhi; Zhang, Li; Du, Guanhua; Lu, Yang; RSC Advances 14 (2024) 40006–40017; doi:10.1039/D4RA06804A

data_7249709
_publ_section_title
;
 Optimization of physicochemical properties of theophylline by forming
 cocrystals with amino acids
;
_journal_issue                   54
_journal_name_full               'RSC Advances'
_journal_page_first              40006
_journal_page_last               40017
_journal_paper_doi               10.1039/D4RA06804A
_journal_volume                  14
_journal_year                    2024
_chemical_absolute_configuration rm
_chemical_formula_moiety         'C7 H8 N4 O2, C6 H14 N4 O2, 2(H2 O)'
_chemical_formula_sum            'C13 H26 N8 O6'
_chemical_formula_weight         390.42
_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   mixed
_audit_creation_date             2024-06-17
_audit_creation_method
;
Olex2 1.5
(compiled 2024.02.16 svn.r378c4104 for OlexSys, GUI svn.r6928)
;
_audit_update_record
;
2024-12-01 deposited with the CCDC.	2024-12-16 downloaded from the CCDC.
;
_cell_angle_alpha                72.564(3)
_cell_angle_beta                 81.718(3)
_cell_angle_gamma                72.804(3)
_cell_formula_units_Z            1
_cell_length_a                   5.8709(2)
_cell_length_b                   7.7140(3)
_cell_length_c                   11.1553(3)
_cell_measurement_reflns_used    5170
_cell_measurement_temperature    301.9(5)
_cell_measurement_theta_max      75.1290
_cell_measurement_theta_min      3.9360
_cell_volume                     459.59(3)
_computing_cell_refinement       'CrysAlisPro 1.171.42.59a (Rigaku OD, 2022)'
_computing_data_collection       'CrysAlisPro 1.171.42.59a (Rigaku OD, 2022)'
_computing_data_reduction        'CrysAlisPro 1.171.42.59a (Rigaku OD, 2022)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2019/2 (Sheldrick, 2015)'
_computing_structure_solution    2018.3
_diffrn_ambient_environment      air
_diffrn_ambient_temperature      301.9(5)
_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 0.963
_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  26.00   0.50    0.59    --  -46.53  91.00 115.00  204
  2  \w    -25.00  76.00   0.50    0.59    --   46.53 -91.00   1.00  202
  3  \w   -174.00 -79.00   0.50    2.35    -- -103.00 -91.00   1.00  190
  4  \w   -105.00 -30.00   0.50    2.35    -- -103.00  91.00 115.00  150
  5  \w     85.00 176.00   0.50    2.35    --  104.54  91.00 115.00  182
  6  \w    -23.00  29.00   0.50    0.59    --  -46.53  19.00   0.00  104
  7  \w   -118.00 -73.00   0.50    0.59    --  -46.53-125.00  90.00   90
  8  \w    -26.00  46.00   0.50    0.59    --   46.53 -38.00  90.00  144
  9  \w    -28.00  29.00   0.50    0.59    --   46.53 -19.00   0.00  114
 10  \w    -68.00 -30.00   0.50    2.35    -- -103.00  61.00 120.00   76
 11  \w    -68.00 -30.00   0.50    2.35    -- -103.00  61.00  90.00   76
 12  \w   -174.00 -83.00   0.50    2.35    -- -103.00 -95.00 120.00  182
 13  \w   -174.00 -86.00   0.50    2.35    -- -103.00 -61.00  30.00  176
 14  \w    -68.00 -30.00   0.50    2.35    -- -103.00  61.00 -30.00   76
 15  \w    -68.00 -30.00   0.50    2.35    -- -103.00  61.00-180.00   76
 16  \w    -68.00 -30.00   0.50    2.35    -- -103.00  61.00-120.00   76
 17  \w     32.00 105.00   0.50    2.35    --  104.54 -95.00 -90.00  146
 18  \w     32.00  74.00   0.50    2.35    --  104.54 -61.00   0.00   84
 19  \w     32.00 111.00   0.50    2.35    --  104.54-125.00-180.00  158
 20  \w     32.00 108.00   0.50    2.35    --  104.54 -77.00-180.00  152
 21  \w     32.00 111.00   0.50    2.35    --  104.54-125.00-120.00  158
 22  \w     91.00 178.00   0.50    2.35    --  104.54  15.00 -90.00  174
 23  \w     92.00 178.00   0.50    2.35    --  104.54  30.00-180.00  172
 24  \w     32.00  74.00   0.50    2.35    --  104.54 -61.00 -90.00   84
 25  \w     32.00 105.00   0.50    2.35    --  104.54 -95.00 -30.00  146
 26  \w     88.00 176.00   0.50    2.35    --  104.54  61.00  30.00  176
 27  \w     32.00 111.00   0.50    2.35    --  104.54-125.00   0.00  158
 28  \w     32.00 106.00   0.50    2.35    --  104.54 -91.00   1.00  148
 29  \w   -118.00 -24.00   0.50    0.59    --  -46.53 -77.00 -30.00  188
 30  \w   -118.00 -32.00   0.50    0.59    --  -46.53 -57.00  60.00  172
 31  \w     32.00 118.00   0.50    0.59    --   46.53  57.00  30.00  172
 32  \w     24.00 118.00   0.50    0.59    --   46.53  77.00-120.00  188
 33  \w     24.00 118.00   0.50    0.59    --   46.53  77.00-180.00  188
 34  \w     24.00 118.00   0.50    0.59    --   46.53  77.00 -60.00  188
 35  \w     24.00 118.00   0.50    0.59    --   46.53  77.00  90.00  188
 36  \w   -174.00 -86.00   0.50    2.35    -- -103.00 -61.00 150.00  176
 37  \w     92.00 178.00   0.50    2.35    --  104.54  30.00-150.00  172
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy R, DW system, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.1485389000
_diffrn_orient_matrix_UB_12      0.1463099000
_diffrn_orient_matrix_UB_13      0.0690588000
_diffrn_orient_matrix_UB_21      0.1554859000
_diffrn_orient_matrix_UB_22      -0.1009683000
_diffrn_orient_matrix_UB_23      0.1138357000
_diffrn_orient_matrix_UB_31      0.1717345000
_diffrn_orient_matrix_UB_32      0.1248699000
_diffrn_orient_matrix_UB_33      -0.0574752000
_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  0.0554
_diffrn_reflns_av_unetI/netI     0.0475
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.963
_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       13
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            8049
_diffrn_reflns_point_group_measured_fraction_full 0.856
_diffrn_reflns_point_group_measured_fraction_max 0.803
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.318
_diffrn_reflns_theta_min         4.162
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.956
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.60737
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.59a (Rigaku Oxford Diffraction, 2022)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.411
_exptl_crystal_description       blocked
_exptl_crystal_F_000             208
_exptl_crystal_size_max          0.23
_exptl_crystal_size_mid          0.21
_exptl_crystal_size_min          0.13
_refine_diff_density_max         0.243
_refine_diff_density_min         -0.258
_refine_diff_density_rms         0.058
_refine_ls_abs_structure_details
;
 Flack x determined using 1037 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.1(2)
_refine_ls_extinction_coef       0.008(3)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2019/2 (Sheldrick 2019)'
_refine_ls_goodness_of_fit_ref   1.060
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     262
_refine_ls_number_reflns         3092
_refine_ls_number_restraints     5
_refine_ls_restrained_S_all      1.060
_refine_ls_R_factor_all          0.0486
_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^)+(0.0858P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1155
_refine_ls_wR_factor_ref         0.1198
_reflns_Friedel_coverage         0.668
_reflns_Friedel_fraction_full    0.714
_reflns_Friedel_fraction_max     0.643
_reflns_number_gt                2806
_reflns_number_total             3092
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4ra06804a2.cif
_cod_data_source_block           samp7047b
_cod_database_code               7249709
_shelx_shelxl_version_number     2019/2
_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, All
  N(H,H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2. Restrained distances
 O1W-H1WA
 0.85 with sigma of 0.02
 O2W-H2WA
 0.85 with sigma of 0.02
3.a Ternary CH refined with riding coordinates:
 C1S(H1S)
3.b Secondary CH2 refined with riding coordinates:
 C2S(H2SA,H2SB), C3S(H3SC,H3SD), C4S(H4SC,H4SD)
3.c Aromatic/amide H refined with riding coordinates:
 N4(H4), C5(H5)
3.d X=CH2 refined with riding coordinates:
 N3S(H3SA,H3SB), N4S(H4SA,H4SB)
3.e Idealised Me refined as rotating group:
 C6(H6A,H6B,H6C), C7(H7A,H7B,H7C), N1S(H1SA,H1SB,H1SC)
;
_shelx_res_checksum              61141
_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 3.681
_oxdiff_exptl_absorpt_empirical_full_min 0.198