A current insight into the drug–drug molecular adducts of an anti-cancer drug vandetanib with various NSAIDs
Abishek, K. G.; Kenguva, Gowtham; Giri, Lopamudra; Venkat Shivaji Ramarao, E. V.; Dhilli Rao, Gorja; Dandela, Rambabu; CrystEngComm 27 (2025) 2998–3005; doi:10.1039/D5CE00070J

data_7250630
_publ_section_title
;
 A current insight into the drug--drug molecular adducts of an anti-cancer
 drug vandetanib with various NSAIDs
;
_journal_issue                   19
_journal_name_full               CrystEngComm
_journal_page_first              2998
_journal_page_last               3005
_journal_paper_doi               10.1039/D5CE00070J
_journal_volume                  27
_journal_year                    2025
_chemical_formula_moiety         'C22 H25 Br F N4 O2, C13 H17 O2'
_chemical_formula_sum            'C35 H42 Br F N4 O4'
_chemical_formula_weight         681.63
_chemical_name_common            'Vandetanib Ibuprofen'
_chemical_name_systematic
'4-(((4-((4-bromo-2-fluorophenyl)amino)-6-methoxyquinazolin-7-yl)oxy)methyl)-1-methylpiperidin-1-ium 2-(4-isobutylphenyl)propanoate'
_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
_atom_sites_solution_primary     dual
_audit_creation_date             2023-12-28
_audit_creation_method
;
Olex2 1.5
(compiled 2023.08.24 svn.re1ec1418 for OlexSys, GUI svn.r6817)
;
_audit_update_record
;
2024-05-27 deposited with the CCDC.	2025-04-16 downloaded from the CCDC.
;
_cell_angle_alpha                94.774(8)
_cell_angle_beta                 105.146(8)
_cell_angle_gamma                94.739(7)
_cell_formula_units_Z            2
_cell_length_a                   10.192(3)
_cell_length_b                   13.023(4)
_cell_length_c                   13.452(4)
_cell_measurement_reflns_used    9919
_cell_measurement_temperature    298.15
_cell_measurement_theta_max      26.28
_cell_measurement_theta_min      2.25
_cell_volume                     1707.3(9)
_computing_cell_refinement       'SAINT V8.40B (?, 2016)'
_computing_data_collection       'Bruker APEX4'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      298.15
_diffrn_detector_area_resol_mean 8
_diffrn_measured_fraction_theta_full 0.996
_diffrn_measured_fraction_theta_max 0.995
_diffrn_measurement_device_type  'Bruker D8 quest photon detector'
_diffrn_measurement_method       'Omega and Phi scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0946
_diffrn_reflns_av_unetI/netI     0.0598
_diffrn_reflns_Laue_measured_fraction_full 0.996
_diffrn_reflns_Laue_measured_fraction_max 0.995
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       17
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            54637
_diffrn_reflns_point_group_measured_fraction_full 0.996
_diffrn_reflns_point_group_measured_fraction_max 0.995
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         27.598
_diffrn_reflns_theta_min         2.248
_diffrn_source                   microfocus
_diffrn_source_current           1.4
_diffrn_source_power             0.07
_diffrn_source_voltage           50.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    1.252
_exptl_absorpt_correction_T_max  0.7456
_exptl_absorpt_correction_T_min  0.5802
_exptl_absorpt_correction_type   none
_exptl_absorpt_process_details
;
SADABS-2016/2 (Bruker,2016/2) was used for absorption correction.
wR2(int) was 0.1201 before and 0.0815 after correction.
The Ratio of minimum to maximum transmission is 0.7782.
The \l/2 correction factor is Not present.
;
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.326
_exptl_crystal_description       block
_exptl_crystal_F_000             712
_exptl_crystal_size_max          0.26
_exptl_crystal_size_mid          0.24
_exptl_crystal_size_min          0.22
_refine_diff_density_max         0.830
_refine_diff_density_min         -1.061
_refine_diff_density_rms         0.066
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.026
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     393
_refine_ls_number_reflns         7898
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.026
_refine_ls_R_factor_all          0.1242
_refine_ls_R_factor_gt           0.0728
_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^)+(0.0940P)^2^+1.9388P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1808
_refine_ls_wR_factor_ref         0.2135
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4753
_reflns_number_total             7898
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ce00070j2.cif
_cod_data_source_block           vndb_ibp_0m
_cod_original_cell_volume        1707.2(9)
_cod_database_code               7250630
_shelx_shelxl_version_number     2018/3
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Uiso/Uaniso restraints and constraints
Uanis(C1) = Uanis(C3) = Uanis(C2)
Uanis(C35) = Uanis(C1)
3.a Ternary CH refined with riding coordinates:
 N1(H1), C8(H8), C1(H1A), C32(H32)
3.b Secondary CH2 refined with riding coordinates:
 C6(H6A,H6B), C7(H7A,H7B), C9(H9A,H9B), C10(H10A,H10B), C11(H11A,H11B),
 C35(H35A,H35B)
3.c Aromatic/amide H refined with riding coordinates:
 N4(H4), C13(H13), C16(H16), C19(H19), C23(H23), C24(H24), C25(H25), C27(H27),
 C28(H28), C30(H30), C31(H31)
3.d Idealised Me refined as rotating group:
 C5(H5A,H5B,H5C), C18(H18A,H18B,H18C), C2(H2A,H2B,H2C), C3(H3A,H3B,H3C),
 C34(H34A,H34B,H34C)
;
_shelx_res_checksum              96723
_olex2_submission_special_instructions 'No special instructions were received'