Investigation of the In Vitro Anticancer Potential of Bis(imino)acenaphthene-N-Heterocyclic Carbene Transition Metal Complexes Revealed TrxR Inhibition and Triggering of Immunogenic Cell Death (ICD) for Allyl Palladates
Donati, Chiara; Hashim, Ishfaq Ibni; Pozsoni, Nestor Bracho; Bourda, Laurens; Van Hecke, Kristof; Cazin, Catherine S. J.; Visentin, Fabiano; Nolan, Steven P.; Gandin, Valentina; Scattolin, Thomas; RSC Medicinal Chemistry  (2025) –; doi:10.1039/D5MD00039D

data_7250130
_publ_section_title
;
 Investigation of the In Vitro Anticancer Potential of
 Bis(imino)acenaphthene-N-Heterocyclic Carbene Transition Metal Complexes
 Revealed TrxR Inhibition and Triggering of Immunogenic Cell Death (ICD)
 for Allyl Palladates
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D5MD00039D
_journal_year                    2025
_chemical_formula_moiety         'C3 H5 Cl2 Pd, 2(C H2 Cl2), C37 H41 N2'
_chemical_formula_sum            'C42 H50 Cl6 N2 Pd'
_chemical_formula_weight         901.94
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2yn'
_space_group_name_H-M_alt        'P 1 21/n 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2022-11-10
_audit_creation_method
;
Olex2 1.5
(compiled 2022.04.07 svn.rca3783a0 for OlexSys, GUI svn.r6498)
;
_audit_update_record
;
2025-01-07 deposited with the CCDC.	2025-03-17 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 99.8290(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   12.76020(10)
_cell_length_b                   15.6164(2)
_cell_length_c                   21.3741(2)
_cell_measurement_reflns_used    13938
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      73.6620
_cell_measurement_theta_min      3.4740
_cell_volume                     4196.66(8)
_computing_cell_refinement       'CrysAlisPro 1.171.41.112a (Rigaku OD, 2021)'
_computing_data_collection       'CrysAlisPro 1.171.41.112a (Rigaku OD, 2021)'
_computing_data_reduction        'CrysAlisPro 1.171.41.112a (Rigaku OD, 2021)'
_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_environment      N~2~
_diffrn_ambient_temperature      100.0(1)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.4839
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.986
_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    -66.00  33.00   1.00    1.50    --  -41.28  38.00-120.00   99
  2  \w    -66.00  33.00   1.00    1.50    --  -41.28  38.00 120.00   99
  3  \w    -87.00  -6.00   1.00    1.50    --  -41.28 125.00-180.00   81
  4  \w     33.00 132.00   1.00    7.50    --  106.28 -45.00 -60.00   99
  5  \w     30.00 139.00   1.00    7.50    --  106.28 -77.00  60.00  109
  6  \w     97.00 177.00   1.00    7.50    --  106.28 125.00  30.00   80
  7  \w    103.00 178.00   1.00    7.50    --  106.28  77.00  60.00   75
  8  \w     78.00 178.00   1.00    7.50    --  106.28  30.00-180.00  100
  9  \w    103.00 178.00   1.00    7.50    --  106.28  77.00  90.00   75
 10  \w     13.00 114.00   1.00    1.50    --   41.28  57.00-150.00  101
 11  \w     13.00 114.00   1.00    1.50    --   41.28  57.00 -30.00  101
 12  \w     13.00 114.00   1.00    1.50    --   41.28  57.00 120.00  101
 13  \w     77.00 178.00   1.00    7.50    --  106.28  61.00  30.00  101
 14  \w     77.00 178.00   1.00    7.50    --  106.28  61.00-120.00  101
 15  \w     35.00 112.00   1.00    7.50    --  106.28-125.00 -90.00   77
 16  \w     35.00 112.00   1.00    7.50    --  106.28-125.00  30.00   77
 17  \w     54.00 178.00   1.00    7.50    --  106.28  15.00   0.00  124
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.1173808000
_diffrn_orient_matrix_UB_12      -0.0218225000
_diffrn_orient_matrix_UB_13      -0.0013547000
_diffrn_orient_matrix_UB_21      0.0347220000
_diffrn_orient_matrix_UB_22      0.0585152000
_diffrn_orient_matrix_UB_23      0.0578356000
_diffrn_orient_matrix_UB_31      -0.0070601000
_diffrn_orient_matrix_UB_32      -0.0763239000
_diffrn_orient_matrix_UB_33      0.0447324000
_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  0.0803
_diffrn_reflns_av_unetI/netI     0.0524
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.986
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -19
_diffrn_reflns_limit_l_max       26
_diffrn_reflns_limit_l_min       -26
_diffrn_reflns_number            40172
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.986
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         73.933
_diffrn_reflns_theta_min         3.523
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    7.320
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.578
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.41.112a (Rigaku Oxford Diffraction, 2021)
Numerical absorption correction based on gaussian integration over
a multifaceted crystal model
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear yellow'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.428
_exptl_crystal_description       irregular
_exptl_crystal_F_000             1856
_exptl_crystal_size_max          0.2
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.939
_refine_diff_density_min         -0.919
_refine_diff_density_rms         0.086
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.021
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     506
_refine_ls_number_reflns         8393
_refine_ls_number_restraints     18
_refine_ls_restrained_S_all      1.021
_refine_ls_R_factor_all          0.0596
_refine_ls_R_factor_gt           0.0425
_refine_ls_shift/su_max          0.003
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0609P)^2^+0.7708P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1049
_refine_ls_wR_factor_ref         0.1164
_reflns_Friedel_coverage         0.000
_reflns_number_gt                6594
_reflns_number_total             8393
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5md00039d2.cif
_cod_data_source_block           161_01_dcmhex
_cod_database_code               7250130
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C41H35N2PdCl2
_shelx_estimated_absorpt_t_max   0.711
_shelx_estimated_absorpt_t_min   0.322
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Uiso/Uaniso restraints and constraints
Uanis(C38A) = Uanis(C38B)
Uanis(C39A) = Uanis(C39B)
Uanis(C40A) = Uanis(C40B)
3. Rigid body (RIGU) restrains
 C38A, C39A, C40A
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001
 C38B, C39B, C40B
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001
4. Others
 Sof(C38B)=Sof(H38C)=Sof(H38D)=Sof(C39B)=Sof(H39B)=Sof(C40B)=Sof(H40C)=
 Sof(H40D)=1-FVAR(1)
 Sof(C38A)=Sof(H38A)=Sof(H38B)=Sof(C39A)=Sof(H39A)=Sof(C40A)=Sof(H40A)=
 Sof(H40B)=FVAR(1)
 Sof(Cl5B)=Sof(Cl6B)=Sof(C42B)=Sof(H42C)=Sof(H42D)=1-FVAR(2)
 Sof(Cl5A)=Sof(Cl6A)=Sof(C42A)=Sof(H42A)=Sof(H42B)=FVAR(2)
5.a Ternary CH refined with riding coordinates:
 C39A(H39A), C39B(H39B), C20(H20), C23(H23), C32(H32), C35(H35)
5.b Secondary CH2 refined with riding coordinates:
 C38A(H38A,H38B), C40A(H40A,H40B), C38B(H38C,H38D), C40B(H40C,H40D), C41(H41A,
 H41B), C42A(H42A,H42B), C42B(H42C,H42D)
5.c Aromatic/amide H refined with riding coordinates:
 C1(H1), C4(H4), C5(H5), C6(H6), C8(H8), C9(H9), C10(H10), C16(H16), C17(H17),
 C18(H18), C28(H28), C29(H29), C30(H30)
5.d Idealised Me refined as rotating group:
 C21(H21A,H21B,H21C), C22(H22A,H22B,H22C), C24(H24A,H24B,H24C), C25(H25A,H25B,
 H25C), C33(H33A,H33B,H33C), C34(H34A,H34B,H34C), C36(H36A,H36B,H36C), C37(H37A,
 H37B,H37C)
;
_shelx_res_checksum              29253
_olex2_date_sample_data_collection 2022-10-21
_olex2_exptl_crystal_mounting_method 'Mounted on a LythoLoop'
_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 3.447
_oxdiff_exptl_absorpt_empirical_full_min 0.345