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_7249749
_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, C13 H8 F3 N2 O2, 2(C2 H6 O)'
_chemical_formula_sum            'C26 H28 Cl2 F3 N7 O4'
_chemical_formula_weight         630.457
_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 1.5
(compiled 2024.01.12 svn.r2f8d729c for OlexSys, GUI svn.r6928)
;
_audit_update_record
;
2024-08-28 deposited with the CCDC.	2025-01-09 downloaded from the CCDC.
;
_cell_angle_alpha                93.057(6)
_cell_angle_beta                 96.405(6)
_cell_angle_gamma                99.535(7)
_cell_formula_units_Z            2
_cell_length_a                   10.7304(9)
_cell_length_b                   11.1991(9)
_cell_length_c                   12.3605(8)
_cell_measurement_reflns_used    3441
_cell_measurement_temperature    150.00(10)
_cell_measurement_theta_max      74.0740
_cell_measurement_theta_min      3.9710
_cell_volume                     1451.8(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 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'olex2.refine 1.5 (Bourhis et al., 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 0.9973
_diffrn_measured_fraction_theta_max 0.9547
_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    -63.00  34.00   1.00    1.00    --  -40.73  38.00  30.00   97
  2  \w     21.00  77.00   1.00    1.00    --   40.73 -99.00  30.00   56
  3  \w     25.00  85.00   1.00    1.00    --   40.73-125.00 -60.00   60
  4  \w     51.00 115.00   1.00    1.00    --  108.83 -61.00  60.00   64
  5  \w     88.00 116.00   1.00    1.00    --  108.83-125.00 -30.00   28
  6  \w     39.00  77.00   1.00    1.00    --  108.83-125.00 -30.00   38
  7  \w     29.00  84.00   1.00    1.00    --  108.83 -95.00  30.00   55
  8  \w     45.00 122.00   1.00    1.00    --  108.83-125.00 120.00   77
  9  \w     34.00 134.00   1.00    1.00    --  108.83 -30.00 150.00  100
 10  \w     82.00 113.00   1.00    1.00    --  108.83  30.00  30.00   31
 11  \w    110.00 137.00   1.00    1.00    --  108.83 110.00 113.00   27
 12  \w    105.00 169.00   1.00    1.00    --  108.83 125.00  90.00   64
 13  \w     80.00 178.00   1.00    1.00    --  108.83  61.00-180.00   98
 14  \w     65.00 119.00   1.00    1.00    --  108.83 -77.00-180.00   54
 15  \w     58.00  94.00   1.00    1.00    --  108.83 -95.00-180.00   36
 16  \w     32.00 150.00   1.00    1.00    --  108.83 -15.00   0.00  118
 17  \w    -66.00  32.00   1.00    1.00    --  -40.73  57.00-120.00   98
 18  \w   -111.00 -17.00   1.00    1.00    --  -40.73 -57.00  90.00   94
;
_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      0.0282273000
_diffrn_orient_matrix_UB_12      -0.1165505000
_diffrn_orient_matrix_UB_13      0.0512634000
_diffrn_orient_matrix_UB_21      -0.0268865000
_diffrn_orient_matrix_UB_22      0.0510576000
_diffrn_orient_matrix_UB_23      0.1116297000
_diffrn_orient_matrix_UB_31      -0.1414061000
_diffrn_orient_matrix_UB_32      -0.0580605000
_diffrn_orient_matrix_UB_33      -0.0269389000
_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  0.0419
_diffrn_reflns_av_unetI/netI     0.0528
_diffrn_reflns_Laue_measured_fraction_full 0.9973
_diffrn_reflns_Laue_measured_fraction_max 0.9547
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            9771
_diffrn_reflns_point_group_measured_fraction_full 0.9973
_diffrn_reflns_point_group_measured_fraction_max 0.9547
_diffrn_reflns_theta_full        67.6840
_diffrn_reflns_theta_max         74.68
_diffrn_reflns_theta_min         3.61
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.584
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.41976
_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    1.442
_exptl_crystal_description       prism
_exptl_crystal_F_000             655.857
_exptl_crystal_size_max          0.14
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.08
_refine_diff_density_max         0.4336
_refine_diff_density_min         -0.7704
_refine_diff_density_rms         0.1052
_refine_ls_d_res_high            0.7993
_refine_ls_d_res_low             12.2503
_refine_ls_goodness_of_fit_ref   1.0501
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_constraints    44
_refine_ls_number_parameters     389
_refine_ls_number_reflns         5684
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.0501
_refine_ls_R_factor_all          0.0837
_refine_ls_R_factor_gt           0.0669
_refine_ls_shift/su_max          0.0008
_refine_ls_shift/su_mean         0.0000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1106P)^2^+0.5556P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1820
_refine_ls_wR_factor_ref         0.2045
_reflns_Friedel_coverage         0.0
_reflns_limit_h_max              12
_reflns_limit_h_min              -13
_reflns_limit_k_max              13
_reflns_limit_k_min              -13
_reflns_limit_l_max              15
_reflns_limit_l_min              0
_reflns_number_gt                4304
_reflns_number_total             5684
_reflns_threshold_expression     I>=2u(I)
_cod_data_source_file            d4ce01111b2.cif
_cod_data_source_block           05
_cod_depositor_comments
'Adding full bibliography for 7249749--7249752.cif.'
_cod_database_code               7249749
_reflns_odcompleteness_completeness 99.81
_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
2.a Secondary CH2 refined with riding coordinates:
 C2S(H2Sa,H2Sb), C3S(H3Sa,H3Sb)
2.b Aromatic/amide H refined with riding coordinates:
 N4(H4a), C16(H16), C17(H17), C18(H18), N2(H2), C2(H2a), C3(H3), C4(H4),
 C7(H7), C9(H9), C10(H10), C11(H11)
2.c X=CH2 refined with riding coordinates:
 N6(H6a,H6b), N7(H7a,H7b)
2.d Idealised Me refined as rotating group:
 C1S(H1Sa,H1Sb,H1Sc), C4S(H4Sa,H4Sb,H4Sc)
;
_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 1.749
_oxdiff_exptl_absorpt_empirical_full_min 0.622