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_7249750
_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, C14 H10 Cl2 N O2'
_chemical_formula_sum            'C23 H17 Cl4 N6 O2'
_chemical_formula_weight         551.22
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   geom
_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                105.074(4)
_cell_angle_beta                 91.002(3)
_cell_angle_gamma                99.969(4)
_cell_formula_units_Z            4
_cell_length_a                   12.8844(5)
_cell_length_b                   13.7991(8)
_cell_length_c                   14.5572(4)
_cell_measurement_reflns_used    6053
_cell_measurement_temperature    150.00(10)
_cell_measurement_theta_max      72.4020
_cell_measurement_theta_min      3.1130
_cell_volume                     2456.06(19)
_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  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_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 0.999
_diffrn_measured_fraction_theta_max 0.967
_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    -28.00   0.00   1.00    1.00    --   40.73 -57.00 120.00   28
  2  \w      4.00  63.00   1.00    1.00    --   40.73 -57.00 120.00   59
  3  \w     49.00  92.00   1.00    1.00    --   40.73-125.00  30.00   43
  4  \w     72.00 107.00   1.00    1.00    --  107.58 -94.00 -60.00   35
  5  \w     82.00 120.00   1.00    1.00    --  107.58-125.00-120.00   38
  6  \w     46.00 136.00   1.00    1.00    --  107.58 -30.00   0.00   90
  7  \w     81.00 150.00   1.00    1.00    --  107.58  30.00 -60.00   69
  8  \w     93.00 128.00   1.00    1.00    --  107.58 -45.00 120.00   35
  9  \w     47.00 124.00   1.00    1.00    --  107.58 -30.00  90.00   77
 10  \w     40.00 119.00   1.00    1.00    --  107.58-125.00  90.00   79
 11  \w     39.00 134.00   1.00    1.00    --  107.58 -77.00  90.00   95
 12  \w     36.00 119.00   1.00    1.00    --  107.58 -61.00 -90.00   83
 13  \w     38.00  86.00   1.00    1.00    --  107.58 -77.00-120.00   48
 14  \w     28.00 153.00   1.00    1.00    --  107.58 -15.00 -90.00  125
 15  \w     24.00  79.00   1.00    1.00    --   40.73-125.00-150.00   55
 16  \w      9.00  48.00   1.00    1.00    --   40.73 -99.00 -90.00   39
 17  \w   -109.00 -18.00   1.00    1.00    --  -40.73 -38.00  30.00   91
 18  \w   -114.00 -21.00   1.00    1.00    --  -40.73 -38.00 -60.00   93
 19  \w    -32.00  -7.00   1.00    1.00    --  -40.73 125.00-180.00   25
;
_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      -0.0777553000
_diffrn_orient_matrix_UB_12      0.0738851000
_diffrn_orient_matrix_UB_13      0.0036433000
_diffrn_orient_matrix_UB_21      0.0921704000
_diffrn_orient_matrix_UB_22      0.0914712000
_diffrn_orient_matrix_UB_23      0.0310483000
_diffrn_orient_matrix_UB_31      0.0161477000
_diffrn_orient_matrix_UB_32      -0.0032531000
_diffrn_orient_matrix_UB_33      -0.1052942000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0452
_diffrn_reflns_av_unetI/netI     0.0641
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.967
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       11
_diffrn_reflns_limit_l_min       -17
_diffrn_reflns_number            17321
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.967
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         73.903
_diffrn_reflns_theta_min         3.151
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    4.672
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.47548
_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            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.491
_exptl_crystal_description       block
_exptl_crystal_F_000             1124
_exptl_crystal_size_max          0.14
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.08
_refine_diff_density_max         1.073
_refine_diff_density_min         -0.732
_refine_diff_density_rms         0.111
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.049
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     650
_refine_ls_number_reflns         9628
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.049
_refine_ls_R_factor_all          0.1084
_refine_ls_R_factor_gt           0.0935
_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^)+(0.0890P)^2^+14.3299P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2357
_refine_ls_wR_factor_ref         0.2462
_reflns_Friedel_coverage         0.000
_reflns_number_gt                7877
_reflns_number_total             9628
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4ce01111b2.cif
_cod_data_source_block           02-1222
_cod_depositor_comments
'Adding full bibliography for 7249749--7249752.cif.'
_cod_database_code               7249750
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.706
_shelx_estimated_absorpt_t_min   0.561
_reflns_odcompleteness_completeness 99.99
_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
2. Others
 Sof(Cl7)=Sof(Cl8)=Sof(H25)=Sof(H26)=1-FVAR(1)
 Sof(Cl5)=Sof(Cl6)=Sof(H27)=Sof(H29)=FVAR(1)
3.a Secondary CH2 refined with riding coordinates:
 C22(H22A,H22B), C45(H45A,H45B)
3.b Aromatic/amide H refined with riding coordinates:
 N2(H2), C4(H4), C5(H5), C6(H6A), N6(H6), C12(H12), C13(H13), C14(H14),
 C17(H17), C18(H18), C19(H19), C20(H20), N8(H8), C25(H25), C26(H26), C27(H27),
 C28(H28), C29(H29), N12(H12A), C35(H35), C36(H36), C37(H37), C40(H40),
 C41(H41), C42(H42), C43(H43)
3.c X=CH2 refined with riding coordinates:
 N4(H4A,H4B), N5(H5A,H5B), N10(H10A,H10B), N11(H11A,H11B)
;
_shelx_res_checksum              60560
_shelx_hkl_checksum              50208
_shelx_fab_checksum              13003
_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 1.575
_oxdiff_exptl_absorpt_empirical_full_min 0.635