Differential transmetallation of complexes of the anti-cancer thiosemicarbazone, Dp4e4mT: effects on anti-proliferative efficacy, redox activity, oxy-myoglobin and oxy-hemoglobin oxidation.
Dharmasivam, Mahendiran; Kaya, Busra; Wijesinghe, Tharushi P.; Richardson, Vera; Harmer, Jeffrey R.; Gonzalvez, Miguel A.; Lewis, William; Azad, Mahan Gholam; Bernhardt, Paul V.; Richardson, Des R.; Chemical science 15 (2024) 974–990; doi:10.1039/d3sc05723b

data_1570567
_publ_section_title
;
 Differential transmetallation of complexes of the anti-cancer
 thiosemicarbazone, Dp4e4mT: effects on anti-proliferative efficacy, redox
 activity, oxy-myoglobin and oxy-hemoglobin oxidation.
;
_journal_issue                   3
_journal_name_full               'Chemical science'
_journal_page_first              974
_journal_page_last               990
_journal_paper_doi               10.1039/d3sc05723b
_journal_volume                  15
_journal_year                    2024
_chemical_formula_moiety         'C15 H16 Cl N5 Pd S'
_chemical_formula_sum            'C15 H16 Cl N5 Pd S'
_chemical_formula_weight         440.24
_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     iterative
_audit_creation_date             2018-09-19
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2019-10-17 deposited with the CCDC.	2023-12-07 downloaded from the CCDC.
;
_cell_angle_alpha                73.219(2)
_cell_angle_beta                 81.923(2)
_cell_angle_gamma                69.997(3)
_cell_formula_units_Z            4
_cell_length_a                   10.0507(3)
_cell_length_b                   10.5184(3)
_cell_length_c                   17.5993(4)
_cell_measurement_reflns_used    20714
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      73.0620
_cell_measurement_theta_min      4.6270
_cell_volume                     1672.06(9)
_computing_cell_refinement       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_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    'olex2.solve (Bourhis et al., 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100(2)
_diffrn_detector                 'CCD area detector'
_diffrn_detector_area_resol_mean 10.5861
_diffrn_detector_type            'Agilent Diffraction Atlas detector'
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.984
_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   -129.00 -34.00   1.00    2.00    --  -40.45 178.00-120.00   95
  2  \w    -50.00  35.00   1.00    2.00    --  -40.45  38.00-150.00   85
  3  \w   -129.00 -34.00   1.00    2.00    --  -40.45 178.00-180.00   95
  4  \w   -114.00 -11.00   1.00    2.00    --  -40.45 -57.00  60.00  103
  5  \w     46.00 123.00   1.00    2.00    --   40.45-166.00 -25.00   77
  6  \w     32.00  98.00   1.00    8.00    --  106.66 -45.00 150.00   66
  7  \w     32.00  98.00   1.00    8.00    --  106.66 -45.00  60.00   66
  8  \w     28.00 140.00   1.00    8.00    --  106.66 -77.00 -30.00  112
  9  \w     32.00 118.00   1.00    8.00    --  106.66-125.00   0.00   86
 10  \w     32.00  98.00   1.00    8.00    --  106.66 -45.00-150.00   66
 11  \w     29.00  91.00   1.00    8.00    --  106.66 -30.00 -30.00   62
 12  \w     29.00  91.00   1.00    8.00    --  106.66 -30.00  90.00   62
 13  \w     94.00 178.00   1.00    8.00    --  106.66 125.00  30.00   84
 14  \w     73.00 178.00   1.00    8.00    --  106.66  77.00 120.00  105
 15  \w     23.00 110.00   1.00    8.00    --  106.66 -95.00-180.00   87
 16  \w     23.00 110.00   1.00    8.00    --  106.66 -95.00  90.00   87
 17  \w     17.00 178.00   1.00    8.00    --  106.66   0.00 -60.00  161
 18  \w   -119.00  -7.00   1.00    2.00    --  -40.45 -77.00-150.00  112
 19  \w   -123.00 -44.00   1.00    2.00    --  -40.45-166.00 -25.00   79
 20  \w   -114.00 -11.00   1.00    2.00    --  -40.45 -57.00-120.00  103
 21  \w   -114.00 -11.00   1.00    2.00    --  -40.45 -57.00 -30.00  103
 22  \w   -114.00 -11.00   1.00    2.00    --  -40.45 -57.00 150.00  103
 23  \w     79.00 178.00   1.00    8.00    --  106.66  45.00  90.00   99
 24  \w     73.00 178.00   1.00    8.00    --  106.66  77.00  30.00  105
 25  \w     45.00 178.00   1.00    8.00    --  106.66  15.00  60.00  133
 26  \w     73.00 178.00   1.00    8.00    --  106.66  77.00 -60.00  105
 27  \w     73.00 178.00   1.00    8.00    --  106.66  77.00-150.00  105
 28  \w     76.00 178.00   1.00    8.00    --  106.66  61.00 -90.00  102
 29  \w     73.00 178.00   1.00    8.00    --  106.66  77.00   0.00  105
 30  \w     73.00 178.00   1.00    8.00    --  106.66  77.00  90.00  105
 31  \w     76.00 178.00   1.00    8.00    --  106.66  61.00 150.00  102
 32  \w     76.00 178.00   1.00    8.00    --  106.66  61.00-180.00  102
 33  \w   -116.00 -14.00   1.00    2.00    --  -40.45 -38.00-180.00  102
 34  \w   -119.00  -7.00   1.00    2.00    --  -40.45 -77.00-120.00  112
 35  \w   -119.00  -7.00   1.00    2.00    --  -40.45 -77.00 -30.00  112
 36  \w   -119.00  -7.00   1.00    2.00    --  -40.45 -77.00  30.00  112
 37  \w   -119.00  -7.00   1.00    2.00    --  -40.45 -77.00 120.00  112
 38  \w     76.00 178.00   1.00    8.00    --  106.66  61.00-120.00  102
 39  \w     76.00 178.00   1.00    8.00    --  106.66  61.00 120.00  102
 40  \w     73.00 178.00   1.00    8.00    --  106.66  77.00 -30.00  105
 41  \w     76.00 178.00   1.00    8.00    --  106.66  61.00  30.00  102
 42  \w     76.00 178.00   1.00    8.00    --  106.66  61.00  90.00  102
 43  \w     76.00 178.00   1.00    8.00    --  106.66  61.00 -60.00  102
 44  \w     73.00  98.00   1.00    8.00    --  106.66  77.00 150.00   25
 45  \w     76.00 178.00   1.00    8.00    --  106.66  61.00-150.00  102
;
_diffrn_measurement_device       '\k-geometry diffractometer'
_diffrn_measurement_device_type  'SuperNova-Duo, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0030191000
_diffrn_orient_matrix_UB_12      0.0023074000
_diffrn_orient_matrix_UB_13      0.0873610000
_diffrn_orient_matrix_UB_21      -0.0706655000
_diffrn_orient_matrix_UB_22      0.1600993000
_diffrn_orient_matrix_UB_23      -0.0233577000
_diffrn_orient_matrix_UB_31      -0.1471814000
_diffrn_orient_matrix_UB_32      -0.0199749000
_diffrn_orient_matrix_UB_33      0.0141344000
_diffrn_radiation_collimation    'focusing mirrors'
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_radiation_wavelength_determination fundamental
_diffrn_reflns_av_R_equivalents  0.0520
_diffrn_reflns_av_unetI/netI     0.0268
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.984
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            41878
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.984
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         73.375
_diffrn_reflns_theta_min         4.631
_diffrn_source                   'microfocus sealed tube'
_diffrn_source_current           0.8
_diffrn_source_power             0.04
_diffrn_source_target            Cu
_diffrn_source_type              'Agilent Diffraction microfocus tube'
_diffrn_source_voltage           50
_exptl_absorpt_coefficient_mu    11.634
_exptl_absorpt_correction_T_max  0.982
_exptl_absorpt_correction_T_min  0.301
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46 (Rigaku Oxford Diffraction, 2018)
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 orange'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    orange
_exptl_crystal_density_diffrn    1.749
_exptl_crystal_description       plate
_exptl_crystal_F_000             880
_exptl_crystal_recrystallization_method 'crystallised form methanol'
_exptl_crystal_size_max          0.162
_exptl_crystal_size_mid          0.093
_exptl_crystal_size_min          0.021
_refine_diff_density_max         1.091
_refine_diff_density_min         -0.645
_refine_diff_density_rms         0.101
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.059
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     419
_refine_ls_number_reflns         6610
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.059
_refine_ls_R_factor_all          0.0343
_refine_ls_R_factor_gt           0.0307
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0488P)^2^+1.4296P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0803
_refine_ls_wR_factor_ref         0.0830
_reflns_Friedel_coverage         0.000
_reflns_number_gt                5979
_reflns_number_total             6610
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3sc05723b2.cif
_cod_data_source_block           drr18_s1675
_cod_depositor_comments
'Adding full bibliography for 1570562--1570567.cif.'
_cod_original_cell_volume        1672.07(8)
_cod_database_code               1570567
_sydney_internal_submission_code drr18_s1675
_sydney_internal_submission_date 2018-09-12
_sydney_internal_submission_number s1675
_sydney_internal_client_code     dm1
_sydney_internal_client_email    mahendiran.dharmasivam@sydney.edu.au
_sydney_internal_client_name     'Mahendiran Dharmasivam'
_sydney_internal_supervisor_code drr
_sydney_internal_supervisor_name 'Des Richardson'
_sydney_internal_collection_date 2018-09-17
_sydney_internal_collection_user wlew0588
_sydney_internal_process_date    2018-09-19
_sydney_internal_process_user    wlew0588
_sydney_internal_solution_date   2018-09-19
_sydney_internal_solution_user   wlew0588
_sydney_internal_refine_date     2018-09-19
_sydney_internal_refine_user     wlew0588
_sydney_internal_check_and_archive_date 2018-09-19
_sydney_internal_check_user      wlew0588
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C15H17ClN5SPd
_chemical_oxdiff_usercomment     drr18_s1675
_reflns_odcompleteness_completeness 99.98
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.49
_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.a Secondary CH2 refined with riding coordinates:
 C15(H15A,H15B), C35(H35A,H35B)
2.b Aromatic/amide H refined with riding coordinates:
 C1(H1), C2(H2), C3(H3), C4(H4), C8(H8), C9(H9), C10(H10), C11(H11), C21(H21),
 C22(H22), C23(H23), C24(H24), C28(H28), C29(H29), C30(H30), C31(H31)
2.c Idealised Me refined as rotating group:
 C14(H14A,H14B,H14C), C16(H16A,H16B,H16C), C34(H34A,H34B,H34C), C36(H36A,H36B,
 H36C)
;
_shelx_res_checksum              25374
_shelx_hkl_checksum              90828
_olex2_date_sample_data_collection 2018-09-17
_olex2_date_sample_submission    2018-09-12
_olex2_exptl_crystal_mounting_method 'in paratone on a loop'
_olex2_submission_original_sample_id Pd(Dp4e4mT)Cl
_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 1.721
_oxdiff_exptl_absorpt_empirical_full_min 0.681