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_7249752
_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 H9 F3 N O2'
_chemical_formula_sum            'C23 H17 Cl2 F3 N6 O2'
_chemical_formula_weight         537.331
_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                73.590(6)
_cell_angle_beta                 76.902(7)
_cell_angle_gamma                88.509(6)
_cell_formula_units_Z            2
_cell_length_a                   9.2015(9)
_cell_length_b                   11.6771(7)
_cell_length_c                   14.8897(10)
_cell_measurement_reflns_used    3159
_cell_measurement_temperature    149.9(2)
_cell_measurement_theta_max      27.4040
_cell_measurement_theta_min      2.4070
_cell_volume                     1493.5(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      149.9(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.2684
_diffrn_detector_type            AtlasS2
_diffrn_measured_fraction_theta_full 0.9989
_diffrn_measured_fraction_theta_max 0.9989
_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    -13.00  85.00   1.00    4.00    --   11.90  57.00 -90.00   98
  2  \w     36.00  61.00   1.00    4.00    --   11.90 178.00  90.00   25
  3  \w    -15.00  79.00   1.00    4.00    --   11.90  77.00  30.00   94
  4  \w    -56.00  38.00   1.00    4.00    --   11.90 -57.00 120.00   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      0.0583031000
_diffrn_orient_matrix_UB_12      -0.0407989000
_diffrn_orient_matrix_UB_13      -0.0019749000
_diffrn_orient_matrix_UB_21      -0.0523521000
_diffrn_orient_matrix_UB_22      -0.0482426000
_diffrn_orient_matrix_UB_23      0.0252466000
_diffrn_orient_matrix_UB_31      -0.0115842000
_diffrn_orient_matrix_UB_32      -0.0049442000
_diffrn_orient_matrix_UB_33      -0.0442816000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Mo K\a'
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0361
_diffrn_reflns_av_unetI/netI     0.0678
_diffrn_reflns_Laue_measured_fraction_full 0.9989
_diffrn_reflns_Laue_measured_fraction_max 0.9989
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -17
_diffrn_reflns_number            12436
_diffrn_reflns_point_group_measured_fraction_full 0.9989
_diffrn_reflns_point_group_measured_fraction_max 0.9989
_diffrn_reflns_theta_full        24.9984
_diffrn_reflns_theta_max         25.00
_diffrn_reflns_theta_min         2.27
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.264
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.55583
_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    1.195
_exptl_crystal_description       block
_exptl_crystal_F_000             548.989
_exptl_crystal_size_max          0.13
_exptl_crystal_size_mid          0.11
_exptl_crystal_size_min          0.09
_refine_diff_density_max         0.9961
_refine_diff_density_min         -0.5958
_refine_diff_density_rms         0.0962
_refine_ls_d_res_high            0.8409
_refine_ls_d_res_low             8.9547
_refine_ls_goodness_of_fit_ref   1.0409
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_constraints    34
_refine_ls_number_parameters     347
_refine_ls_number_reflns         5253
_refine_ls_number_restraints     49
_refine_ls_restrained_S_all      1.0358
_refine_ls_R_factor_all          0.0878
_refine_ls_R_factor_gt           0.0720
_refine_ls_shift/su_max          -0.0009
_refine_ls_shift/su_mean         0.0000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1159P)^2^+1.3377P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1978
_refine_ls_wR_factor_ref         0.2132
_reflns_Friedel_coverage         0.0
_reflns_limit_h_max              10
_reflns_limit_h_min              -10
_reflns_limit_k_max              13
_reflns_limit_k_min              -13
_reflns_limit_l_max              17
_reflns_limit_l_min              0
_reflns_number_gt                4018
_reflns_number_total             5253
_reflns_threshold_expression     I>=2u(I)
_cod_data_source_file            d4ce01111b2.cif
_cod_data_source_block           n01
_cod_depositor_comments
'Adding full bibliography for 7249749--7249752.cif.'
_cod_database_code               7249752
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All N(H) groups, All N(H,H) groups
2. Restrained distances
 F2-C10 \\sim F3B-C10
 with sigma of 0.02
 F3-C10 \\sim F1B-C10
 with sigma of 0.02
 F1-C10 \\sim F2B-C10
 with sigma of 0.02
3. Rigid bond restraints
 C5, C4
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
 C5, C6
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
4. Uiso/Uaniso restraints and constraints
C5 \\sim C4: within 2A with sigma of 0.002 and sigma for terminal atoms of
0.004 within 2A
C6: within 2A with sigma of 0.001 and sigma for terminal atoms of 0.002 within
2A
Uanis(C5) = Uanis(C6)
5. Rigid body (RIGU) restrains
 F2, F3, F1, C10
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.002
 F3B, F2B, F1B, C10
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.002
6. Others
 Sof(F3B)=Sof(F1B)=Sof(F2B)=1-FVAR(1)
 Sof(F2)=Sof(F1)=Sof(F3)=FVAR(1)
7.a Aromatic/amide H refined with riding coordinates:
 N2(H2), N6(H6), C6(H6a), C19(H19), C12(H12), C22(H22), C21(H21), C14(H14),
 C20(H20), C16(H16), C15(H15), C5(H5), C4(H4)
7.b X=CH2 refined with riding coordinates:
 N5(H5a,H5b), N4(H4a,H4b)
;
_smtbx_masks_void_probe_radius   1.2
_smtbx_masks_void_truncation_radius 1.2
_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 2.170
_oxdiff_exptl_absorpt_empirical_full_min 0.542