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_1570563
_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         'C30 H33 Cu N10 S2, Cl O4, H2 O'
_chemical_formula_sum            'C30 H35 Cl Cu N10 O5 S2'
_chemical_formula_weight         778.79
_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   mixed
_atom_sites_solution_primary     iterative
_audit_creation_date             2019-12-17
_audit_creation_method
;
Olex2 1.3
(compiled 2019.09.11 svn.r3662 for OlexSys, GUI svn.r6003)
;
_audit_update_record
;
2020-02-07 deposited with the CCDC.	2023-12-07 downloaded from the CCDC.
;
_cell_angle_alpha                73.376(3)
_cell_angle_beta                 77.366(3)
_cell_angle_gamma                86.693(3)
_cell_formula_units_Z            2
_cell_length_a                   9.5625(3)
_cell_length_b                   13.6735(4)
_cell_length_c                   13.8397(5)
_cell_measurement_reflns_used    7494
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      72.6270
_cell_measurement_theta_min      4.7270
_cell_volume                     1691.94(10)
_computing_cell_refinement       'CrysAlisPro 1.171.40.35a (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.40.35a (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.40.35a (Rigaku OD, 2018)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'olex2.solve 1.3 (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 0.980
_diffrn_measured_fraction_theta_max 0.961
_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    -44.00  38.00   1.00    7.50    --  -38.19  57.00 -90.00   82
  2  \w   -116.00  -9.00   1.00    7.50    --  -38.19 -38.00 120.00  107
  3  \w     -5.00  45.00   1.00    7.50    --  -38.19  19.00-120.00   50
  4  \w     -5.00  45.00   1.00    7.50    --  -38.19  19.00 -90.00   50
  5  \w   -126.00 -37.00   1.00    7.50    --  -38.19 178.00-180.00   89
  6  \w     -2.00  24.00   1.00    7.50    --   38.19  91.00-178.73   26
  7  \w      0.00  31.00   1.00    7.50    --   38.19  87.00 136.23   31
  8  \w    103.00 178.00   1.00   30.00    --  107.94  77.00-150.00   75
  9  \w     32.00  93.00   1.00   30.00    --  107.94 -61.00  90.00   61
 10  \w     28.00 109.00   1.00   30.00    --  107.94-111.00-150.00   81
 11  \w     31.00  72.00   1.00   30.00    --  107.94 -45.00-180.00   41
 12  \w     28.00 109.00   1.00   30.00    --  107.94-111.00  30.00   81
 13  \w     32.00  93.00   1.00   30.00    --  107.94 -61.00 -60.00   61
 14  \w     23.00 106.00   1.00   30.00    --  107.94 -95.00-120.00   83
 15  \w     28.00  57.00   1.00   30.00    --  107.94 -30.00   0.00   29
 16  \w    104.00 178.00   1.00   30.00    --  107.94 111.00-120.00   74
 17  \w     28.00 109.00   1.00   30.00    --  107.94-111.00 -60.00   81
 18  \w     28.00  57.00   1.00   30.00    --  107.94 -30.00  90.00   29
 19  \w     28.00  57.00   1.00   30.00    --  107.94 -30.00 150.00   29
 20  \w     28.00  57.00   1.00   30.00    --  107.94 -30.00-150.00   29
 21  \w     28.00 109.00   1.00   30.00    --  107.94-111.00 150.00   81
 22  \w     31.00  72.00   1.00   30.00    --  107.94 -45.00-120.00   41
 23  \w     20.00  52.00   1.00   30.00    --  107.94  -6.00 -34.00   32
 24  \w     35.00  69.00   1.00   30.00    --  107.94 -45.00 120.00   34
 25  \w     26.00 126.00   1.00   30.00    --  107.94 -77.00  30.00  100
 26  \w     38.00 159.00   1.00   30.00    --  107.94  15.00   0.00  121
;
_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      -0.1333317000
_diffrn_orient_matrix_UB_12      0.0052945000
_diffrn_orient_matrix_UB_13      -0.0467692000
_diffrn_orient_matrix_UB_21      0.0973713000
_diffrn_orient_matrix_UB_22      0.0071334000
_diffrn_orient_matrix_UB_23      -0.1063983000
_diffrn_orient_matrix_UB_31      -0.0009640000
_diffrn_orient_matrix_UB_32      -0.1172479000
_diffrn_orient_matrix_UB_33      0.0248776000
_diffrn_radiation_collimation    'focusing mirrors'
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_radiation_wavelength_determination fundamental
_diffrn_radiation_xray_symbol    K-L~2,3~
_diffrn_reflns_av_R_equivalents  0.0221
_diffrn_reflns_av_unetI/netI     0.0278
_diffrn_reflns_Laue_measured_fraction_full 0.980
_diffrn_reflns_Laue_measured_fraction_max 0.961
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -17
_diffrn_reflns_number            15295
_diffrn_reflns_point_group_measured_fraction_full 0.980
_diffrn_reflns_point_group_measured_fraction_max 0.961
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         72.773
_diffrn_reflns_theta_min         4.069
_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    3.265
_exptl_absorpt_correction_T_max  0.927
_exptl_absorpt_correction_T_min  0.821
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.35a (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 dark brown'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   dark
_exptl_crystal_colour_primary    brown
_exptl_crystal_density_diffrn    1.529
_exptl_crystal_description       block
_exptl_crystal_F_000             806
_exptl_crystal_recrystallization_method 'crystallised from an ethanol solution'
_exptl_crystal_size_max          0.099
_exptl_crystal_size_mid          0.066
_exptl_crystal_size_min          0.046
_refine_diff_density_max         0.586
_refine_diff_density_min         -0.706
_refine_diff_density_rms         0.069
_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     474
_refine_ls_number_reflns         6469
_refine_ls_number_restraints     22
_refine_ls_restrained_S_all      1.036
_refine_ls_R_factor_all          0.0467
_refine_ls_R_factor_gt           0.0406
_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^)+(0.0664P)^2^+1.1950P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1087
_refine_ls_wR_factor_ref         0.1148
_reflns_Friedel_coverage         0.000
_reflns_number_gt                5677
_reflns_number_total             6469
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3sc05723b2.cif
_cod_data_source_block           drr19_s1943
_cod_depositor_comments
'Adding full bibliography for 1570562--1570567.cif.'
_cod_original_cell_volume        1691.94(11)
_cod_database_code               1570563
_sydney_internal_submission_code drr19_s1943
_sydney_internal_submission_date 2019-11-07
_sydney_internal_submission_number s1943
_sydney_internal_client_code     dm1
_sydney_internal_client_email    mdha3758@chem.usyd.edu.au
_sydney_internal_client_name     'Mahendiran Dharmasivam'
_sydney_internal_supervisor_code drr
_sydney_internal_supervisor_name 'Des Richardson'
_sydney_internal_collection_date 2019-11-29
_sydney_internal_collection_user wlew0588
_sydney_internal_process_date    2019-12-12
_sydney_internal_process_user    wlew0588
_sydney_internal_solution_date   2019-12-12
_sydney_internal_solution_user   wlew0588
_sydney_internal_refine_date     2019-12-13
_sydney_internal_refine_user     wlew0588
_sydney_internal_check_and_archive_date 2019-12-17
_sydney_internal_check_user      wlew0588
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C30H34ClCuN10O5S2
_chemical_oxdiff_usercomment     C19H21N4O2SCu
_shelx_estimated_absorpt_t_max   0.864
_shelx_estimated_absorpt_t_min   0.738
_reflns_odcompleteness_completeness 97.99
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     67.13
_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, All O(H,H) groups
2. Restrained distances
 N6A-C19 \\sim N6-C17
 with sigma of 0.02
 N6-C19 \\sim N6A-C19A
 with sigma of 0.02
 C17-C18 \\sim C18A-C19
 with sigma of 0.02
3. Restrained planarity
 N6A, C16, C19, C19A
 with sigma of 0.1
4. Rigid body (RIGU) restrains
 N6, N6A, C17, C18, C18A, C19, C19A
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
5. Others
 Sof(N6A)=Sof(C18A)=Sof(H18D)=Sof(H18E)=Sof(H18F)=Sof(H19D)=Sof(H19E)=
 Sof(C19A)=Sof(H19F)=Sof(H19G)=Sof(H19H)=1-FVAR(1)
 Sof(N6)=Sof(C17)=Sof(H17A)=Sof(H17B)=Sof(C18)=Sof(H18A)=Sof(H18B)=Sof(H18C)=
 Sof(H19A)=Sof(H19B)=Sof(H19C)=FVAR(1)
6.a Free rotating group:
 O5(H5A,H5B)
6.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C17(H17A,H17B), C19(H19D,H19E)
6.c Aromatic/amide H refined with riding coordinates:
 N2(H2), C7(H7), C8(H8), C9(H9), C10(H10), C12(H12), C13(H13), C14(H14),
 C15(H15), C22(H22), C23(H23), C24(H24), C25(H25), C27(H27), C28(H28), C29(H29),
  C30(H30)
6.d Idealised Me refined as rotating group:
 C3(H3A,H3B,H3C), C4(H4A,H4B,H4C), C18(H18A,H18B,H18C), C18A(H18D,H18E,H18F),
 C19(H19A,H19B,H19C), C19A(H19F,H19G,H19H)
;
_shelx_res_checksum              50171
_shelx_hkl_checksum              9488
_olex2_date_sample_data_collection 2019-11-29
_olex2_date_sample_submission    2019-11-07
_olex2_exptl_crystal_mounting_method 'in paratone on a micromount'
_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 1.371
_oxdiff_exptl_absorpt_empirical_full_min 0.853