Exploring the solubility of novel lamotrigine drug–drug salts: the role of pH and structural variability
Yu, Xinyi; Li, Jianting; Wu, Chenyu; Yang, Dezhi; Li, Liang; Lu, Yang; Zhou, Zhengzheng; CrystEngComm 27 (2025) 820–832; doi:10.1039/D4CE01111B

data_7249751
_publ_section_title
;
 Exploring the solubility of novel lamotrigine drug--drug salts: the role
 of pH and structural variability
;
_journal_issue                   6
_journal_name_full               CrystEngComm
_journal_page_first              820
_journal_page_last               832
_journal_paper_doi               10.1039/D4CE01111B
_journal_volume                  27
_journal_year                    2025
_chemical_formula_moiety         'C9 H8 Cl2 N5, C15 H14 N O2, C2 H6 O'
_chemical_formula_sum            'C26 H28 Cl2 N6 O3'
_chemical_formula_weight         543.46
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_symmetry_Int_Tables_number      2
_audit_creation_date             2024-08-28
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2024-08-28 deposited with the CCDC.	2025-01-09 downloaded from the CCDC.
;
_cell_angle_alpha                75.104(7)
_cell_angle_beta                 73.770(8)
_cell_angle_gamma                75.903(8)
_cell_formula_units_Z            2
_cell_length_a                   8.9451(9)
_cell_length_b                   10.4421(9)
_cell_length_c                   15.1087(13)
_cell_measurement_reflns_used    3171
_cell_measurement_temperature    150.00(10)
_cell_measurement_theta_max      73.8170
_cell_measurement_theta_min      3.0890
_cell_volume                     1286.8(2)
_computing_cell_refinement       'CrysAlisPro 1.171.38.43f (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.43f (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.43f (Rigaku OD, 2015)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'olex2.refine (Bourhis et al., 2015)'
_computing_structure_solution    'SHELXT  (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      150.00(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.2684
_diffrn_detector_type            AtlasS2
_diffrn_measured_fraction_theta_full 0.9610
_diffrn_measured_fraction_theta_max 0.9610
_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    -56.00  33.00   1.00    1.00    --  -41.42  38.00-150.00   89
  2  \w     33.00  83.00   1.00    1.00    --   41.42-125.00 -60.00   50
  3  \w     34.00 133.00   1.00    2.00    --  107.51 -45.00-150.00   99
  4  \w     79.00 153.00   1.00    2.00    --  107.51  15.00-180.00   74
  5  \w    110.00 163.00   1.00    2.00    --  107.51 125.00 -30.00   53
  6  \w     85.00 157.00   1.00    2.00    --  107.51  30.00  30.00   72
  7  \w     82.00 121.00   1.00    2.00    --  107.51  61.00  60.00   39
  8  \w     79.00 172.00   1.00    2.00    --  107.51  30.00 -90.00   93
  9  \w     73.00 101.00   1.00    2.00    --  107.51 -94.00-180.00   28
 10  \w     70.00 131.00   1.00    2.00    --  107.51 -61.00 -60.00   61
 11  \w     70.00 115.00   1.00    2.00    --  107.51-125.00 -60.00   45
 12  \w     43.00 105.00   1.00    2.00    --  107.51 -94.00 -30.00   62
 13  \w     35.00 134.00   1.00    2.00    --  107.51 -61.00  60.00   99
 14  \w     78.00 119.00   1.00    2.00    --  107.51-125.00 120.00   41
 15  \w    -91.00  -3.00   1.00    1.00    --  -41.42 125.00  30.00   88
 16  \w   -106.00 -42.00   1.00    1.00    --  -41.42 -38.00   0.00   64
 17  \w   -114.00 -14.00   1.00    1.00    --  -41.42 -57.00 -90.00  100
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, AtlasS2'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.1053139000
_diffrn_orient_matrix_UB_12      -0.1261310000
_diffrn_orient_matrix_UB_13      -0.0348139000
_diffrn_orient_matrix_UB_21      -0.0257468000
_diffrn_orient_matrix_UB_22      0.0625505000
_diffrn_orient_matrix_UB_23      -0.0999313000
_diffrn_orient_matrix_UB_31      0.1468500000
_diffrn_orient_matrix_UB_32      0.0656776000
_diffrn_orient_matrix_UB_33      -0.0237494000
_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  0.0495
_diffrn_reflns_av_unetI/netI     0.0662
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            9020
_diffrn_reflns_theta_full        74.3521
_diffrn_reflns_theta_max         74.35
_diffrn_reflns_theta_min         3.11
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.609
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.45651
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.43f (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            yellow
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.4024
_exptl_crystal_description       block
_exptl_crystal_F_000             571.0789
_exptl_crystal_size_max          0.13
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.9781
_refine_diff_density_min         -0.7712
_refine_diff_density_rms         0.1712
_refine_ls_d_res_high            0.8006
_refine_ls_d_res_low             14.2047
_refine_ls_goodness_of_fit_ref   1.0663
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_constraints    47
_refine_ls_number_parameters     338
_refine_ls_number_reflns         5026
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.0663
_refine_ls_R_factor_all          0.0956
_refine_ls_R_factor_gt           0.0745
_refine_ls_shift/su_max          0.0000
_refine_ls_shift/su_mean         0.0000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1402P)^2^+0.9572P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2117
_refine_ls_wR_factor_ref         0.2345
_reflns_Friedel_coverage         0.0
_reflns_limit_h_max              11
_reflns_limit_h_min              -10
_reflns_limit_k_max              13
_reflns_limit_k_min              -12
_reflns_limit_l_max              18
_reflns_limit_l_min              0
_reflns_number_gt                3896
_reflns_number_total             5026
_reflns_threshold_expression     I>=2u(I)
_cod_data_source_file            d4ce01111b2.cif
_cod_data_source_block           04-1222
_cod_depositor_comments
'Adding full bibliography for 7249749--7249752.cif.'
_cod_database_code               7249751
_chemical_oxdiff_formula         'C24 H24 N24 O24 Cl0 '
_reflns_odcompleteness_completeness 99.98
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_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.a Secondary CH2 refined with riding coordinates:
 C25(H25a,H25b)
2.b Aromatic/amide H refined with riding coordinates:
 N2(H2), C4(H4), C5(H5), C6(H6a), N6(H6), C11(H11), C12(H12), C13(H13),
 C20(H20), C19(H19), C18(H18), C17(H17)
2.c X=CH2 refined with riding coordinates:
 N5(H5a,H5b), N4(H4a,H4b)
2.d Idealised Me refined as rotating group:
 C24(H24a,H24b,H24c), C23(H23a,H23b,H23c), C26(H26a,H26b,H26c)
2.e Idealised tetrahedral OH refined as rotating group:
 O3(H3)
;
_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 2.067
_oxdiff_exptl_absorpt_empirical_full_min 0.440