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_1570564
_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 H32 N10 S2 Zn'
_chemical_formula_sum            'C30 H32 N10 S2 Zn'
_chemical_formula_weight         662.14
_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             2018-09-11
_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                109.844(9)
_cell_angle_beta                 91.411(7)
_cell_angle_gamma                103.463(9)
_cell_formula_units_Z            2
_cell_length_a                   10.7315(10)
_cell_length_b                   10.8268(12)
_cell_length_c                   14.7436(13)
_cell_measurement_reflns_used    5736
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      73.4040
_cell_measurement_theta_min      4.2060
_cell_volume                     1556.9(3)
_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 0.998
_diffrn_measured_fraction_theta_max 0.959
_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    -86.00  32.00   2.00    2.00    --  -40.45  19.00 150.00   59
  2  \w    -24.00  32.00   2.00    2.00    --  -40.45  38.00-180.00   28
  3  \w    -50.00  36.00   2.00    2.00    --  -40.45  38.00  30.00   43
  4  \w     66.00  92.00   2.00    2.00    --   40.45-178.00 -30.00   13
  5  \w     58.00 126.00   2.00    2.00    --   40.45 178.00   0.00   34
  6  \w     82.00 128.00   2.00    2.00    --   40.45 178.00-180.00   23
  7  \w    100.00 128.00   2.00    2.00    --   40.45-178.00 -30.00   14
  8  \w     69.00  97.00   2.00    2.00    --  107.93 -45.00-150.00   14
  9  \w     77.00 177.00   2.00    2.00    --  107.93  30.00  90.00   50
 10  \w     52.00 122.00   2.00    2.00    --  107.93 -61.00   0.00   35
 11  \w     54.00 100.00   2.00    2.00    --  107.93-125.00-180.00   23
 12  \w     80.00 178.00   2.00    2.00    --  107.93  30.00   0.00   49
 13  \w     65.00  91.00   2.00    2.00    --  107.93 -30.00  30.00   13
 14  \w     35.00  75.00   2.00    2.00    --  107.93 -45.00 -30.00   20
 15  \w     30.00  80.00   2.00    2.00    --  107.93 -30.00  90.00   25
 16  \w     84.00 116.00   2.00    2.00    --  107.93-125.00  90.00   16
 17  \w     26.00 102.00   2.00    2.00    --  107.93 -95.00 -30.00   38
 18  \w     29.00 125.00   2.00    2.00    --  107.93 -77.00-180.00   48
 19  \w     30.00  88.00   2.00    2.00    --  107.93 -30.00-180.00   29
 20  \w     90.00 116.00   2.00    2.00    --  107.93-125.00-150.00   13
 21  \w     92.00 116.00   2.00    2.00    --  107.93-125.00 -60.00   12
 22  \w     56.00  82.00   2.00    2.00    --  107.93 -30.00 -90.00   13
;
_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      -0.1129602000
_diffrn_orient_matrix_UB_12      -0.0574715000
_diffrn_orient_matrix_UB_13      0.0489172000
_diffrn_orient_matrix_UB_21      0.0200798000
_diffrn_orient_matrix_UB_22      -0.1434277000
_diffrn_orient_matrix_UB_23      -0.0475297000
_diffrn_orient_matrix_UB_31      0.0943901000
_diffrn_orient_matrix_UB_32      0.0249158000
_diffrn_orient_matrix_UB_33      0.0885936000
_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  0.0205
_diffrn_reflns_av_unetI/netI     0.0272
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.959
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            10830
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.959
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.230
_diffrn_reflns_theta_min         4.264
_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    2.656
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.196
_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    1.412
_exptl_crystal_description       block
_exptl_crystal_F_000             688
_exptl_crystal_recrystallization_method
'crystallised from a solution in methanol'
_exptl_crystal_size_max          0.511
_exptl_crystal_size_mid          0.385
_exptl_crystal_size_min          0.171
_refine_diff_density_max         0.720
_refine_diff_density_min         -0.493
_refine_diff_density_rms         0.059
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.054
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     450
_refine_ls_number_reflns         6092
_refine_ls_number_restraints     249
_refine_ls_restrained_S_all      1.044
_refine_ls_R_factor_all          0.0408
_refine_ls_R_factor_gt           0.0362
_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^)+(0.0444P)^2^+1.2470P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0938
_refine_ls_wR_factor_ref         0.0969
_reflns_Friedel_coverage         0.000
_reflns_number_gt                5433
_reflns_number_total             6092
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3sc05723b2.cif
_cod_data_source_block           drr18_s1671
_cod_depositor_comments
'Adding full bibliography for 1570562--1570567.cif.'
_cod_database_code               1570564
_sydney_internal_submission_code drr18_s1671
_sydney_internal_submission_date 2018-09-03
_sydney_internal_submission_number s1671
_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 2018-09-10
_sydney_internal_collection_user wlew0588
_sydney_internal_process_date    2018-09-10
_sydney_internal_process_user    wlew0588
_sydney_internal_solution_date   2018-09-10
_sydney_internal_solution_user   wlew0588
_sydney_internal_refine_date     2018-09-10
_sydney_internal_refine_user     wlew0588
_sydney_internal_check_and_archive_date 2018-09-11
_sydney_internal_check_user      wlew0588
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C30H34N10S2Zn
_chemical_oxdiff_usercomment     drr18_s1671
_shelx_estimated_absorpt_t_max   0.659
_shelx_estimated_absorpt_t_min   0.344
_reflns_odcompleteness_completeness 99.87
_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 C(H,H,H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 C16-C15 \\sim C35A-C34 \\sim C35-C34
 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
N22 \\sim N22A \\sim C27 \\sim C28 \\sim C28A \\sim C29 \\sim C29A \\sim C30
\\sim C30A \\sim C31 \\sim C31A \\sim C34 \\sim C35 \\sim C35A: within 2A with
sigma of 0.01 and sigma for terminal atoms of 0.02
4. Rigid body (RIGU) restrains
 N22, N22A, C27, C28, C28A, C29, C29A, C30, C30A, C31, C31A, C34, C35, C35A
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
5. Others
 Sof(N22A)=Sof(C28A)=Sof(H28A)=Sof(C29A)=Sof(H29A)=Sof(C31A)=Sof(H31A)=1-FVAR(1)
 Sof(N22)=Sof(C28)=Sof(H28)=Sof(C29)=Sof(H29)=Sof(C31)=Sof(H31)=FVAR(1)
 Sof(C30A)=Sof(H30A)=1-FVAR(2)
 Sof(C30)=Sof(H30)=FVAR(2)
 Sof(H34C)=Sof(H34D)=Sof(C35A)=Sof(H35D)=Sof(H35E)=Sof(H35F)=1-FVAR(3)
 Sof(H34A)=Sof(H34B)=Sof(C35)=Sof(H35A)=Sof(H35B)=Sof(H35C)=FVAR(3)
6.a Secondary CH2 refined with riding coordinates:
 C15(H15A,H15B), C34(H34A,H34B), C34(H34C,H34D)
6.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), C28A(H28A), C29(H29), C29A(H29A),
 C30(H30), C30A(H30A), C31(H31), C31A(H31A)
6.c Idealised Me refined as rotating group:
 C14(H14A,H14B,H14C), C16(H16A,H16B,H16C), C35(H35A,H35B,H35C), C35A(H35D,H35E,
 H35F), C36(H36A,H36B,H36C)
;
_shelx_res_checksum              28581
_shelx_hkl_checksum              33928
_olex2_date_sample_data_collection 2018-09-10
_olex2_date_sample_submission    2018-09-03
_olex2_exptl_crystal_mounting_method 'in paratone on a loop'
_olex2_submission_original_sample_id drr180903a
_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 1.277
_oxdiff_exptl_absorpt_empirical_full_min 0.786