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_1570565
_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 Ga N10 S2, 1(N O3), 1(O)'
_chemical_formula_sum            'C30 H34 Ga N11 O4 S2'
_chemical_formula_weight         746.52
_chemical_name_systematic        Ga(Dp4e4mT)2
_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     direct
_audit_creation_date             2018-11-14
_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                92.486(2)
_cell_angle_beta                 102.138(2)
_cell_angle_gamma                94.766(2)
_cell_formula_units_Z            2
_cell_length_a                   8.7832(3)
_cell_length_b                   11.7181(3)
_cell_length_c                   17.1171(4)
_cell_measurement_reflns_used    13149
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      73.7190
_cell_measurement_theta_min      4.4400
_cell_volume                     1713.04(8)
_computing_cell_refinement       'CrysAlisPro 1.171.39.46e (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.46e (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.46e (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    'ShelXS (Sheldrick, 2008)'
_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 0.982
_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      1.00  26.00   1.00    5.00    --   40.00  92.00-133.89   25
  2  \w   -130.00 -92.00   1.00    5.00    --  -40.45   0.00-120.00   38
  3  \w    -86.00  42.00   1.00    5.00    --  -40.45   0.00-120.00  128
  4  \w    -50.00  35.00   1.00    5.00    --  -40.45  38.00 -60.00   85
  5  \w   -112.00 -15.00   1.00    5.00    --  -40.45 -38.00 150.00   97
  6  \w      2.00  27.00   1.00    5.00    --   40.45  91.00 -21.88   25
  7  \w     69.00 127.00   1.00    5.00    --   40.45-178.00-120.00   58
  8  \w     12.00  39.00   1.00    5.00    --   40.45  57.00  60.00   27
  9  \w     11.00  40.00   1.00    5.00    --   40.45  57.00-150.00   29
 10  \w     56.00 123.00   1.00    5.00    --   40.45-178.00  90.00   67
 11  \w     73.00 124.00   1.00    5.00    --   40.45 178.00 -30.00   51
 12  \w      7.00  32.00   1.00    5.00    --   44.00  89.00  86.94   25
 13  \w     13.00  38.00   1.00    5.00    --   48.00  83.00 168.17   25
 14  \w     12.00  38.00   1.00    5.00    --   48.00  84.00-127.99   26
 15  \w     18.00  43.00   1.00    5.00    --   52.00  79.00 124.66   25
 16  \w     17.00  42.00   1.00    5.00    --   52.00  81.00 -31.39   25
 17  \w     18.00  43.00   1.00    5.00    --   52.00  79.00  37.94   25
 18  \w     33.00  60.00   1.00    5.00    --   64.00  76.00 -48.79   27
 19  \w     30.00  57.00   1.00    5.00    --   64.00  77.00 115.69   27
 20  \w     33.00  60.00   1.00    5.00    --   64.00  77.00 150.42   27
 21  \w     34.00  61.00   1.00    5.00    --   64.00  76.00  29.10   27
 22  \w     31.00  57.00   1.00    5.00    --   64.00  75.00  68.42   26
 23  \w     31.00  57.00   1.00    5.00    --   64.00  76.00 -95.23   26
 24  \w     35.00  77.00   1.00    5.00    --   68.00  77.00-150.39   42
 25  \w     92.00 146.00   1.00    5.00    --   68.00  77.00-150.39   54
 26  \w     35.00  62.00   1.00    5.00    --   68.00  76.00 -25.45   27
 27  \w     41.00  71.00   1.00    5.00    --   72.00  75.00 119.14   30
 28  \w     38.00  65.00   1.00    5.00    --   72.00  77.00  69.82   27
 29  \w     44.00  71.00   1.00   20.00    --   76.00  70.00 -77.75   27
 30  \w     44.00  71.00   1.00   20.00    --   76.00  76.00  -5.27   27
 31  \w     50.00 125.00   1.00   20.00    --   80.00  75.00 159.56   75
 32  \w     49.00 101.00   1.00   20.00    --   80.00  70.00 136.15   52
 33  \w     51.00  76.00   1.00   20.00    --   80.00  59.00  44.28   25
 34  \w     48.00  73.00   1.00   20.00    --   80.00  75.00 -37.75   25
 35  \w     50.00  78.00   1.00   20.00    --   84.00  77.00 -88.53   28
 36  \w     53.00  80.00   1.00   20.00    --   84.00  66.00  75.85   27
 37  \w     62.00  87.00   1.00   20.00    --   92.00  66.00  38.24   25
 38  \w     77.00 175.00   1.00   20.00    --  108.56  77.00  60.00   98
 39  \w     27.00 107.00   1.00   20.00    --  108.56 -95.00  60.00   80
 40  \w     75.00 176.00   1.00   20.00    --  108.56  77.00   0.00  101
 41  \w     75.00 154.00   1.00   20.00    --  108.56  77.00-120.00   79
 42  \w     56.00 115.00   1.00   20.00    --  108.56-125.00  30.00   59
 43  \w    121.00 151.00   1.00   20.00    --  108.56  61.00-180.00   30
 44  \w     91.00 118.00   1.00   20.00    --  108.56-125.00 -90.00   27
 45  \w     78.00 107.00   1.00   20.00    --  108.56  61.00-180.00   29
 46  \w     76.00 164.00   1.00   20.00    --  108.56  77.00-150.00   88
 47  \w     75.00 102.00   1.00   20.00    --  108.56  77.00-180.00   27
 48  \w     52.00  93.00   1.00   20.00    --  108.56 -45.00  30.00   41
 49  \w     76.00 148.00   1.00   20.00    --  108.56  77.00 -90.00   72
 50  \w    113.00 172.00   1.00   20.00    --  108.56  77.00 150.00   59
 51  \w     75.00 101.00   1.00   20.00    --  108.56  77.00 150.00   26
 52  \w     28.00 109.00   1.00   20.00    --  108.56 -95.00 150.00   81
 53  \w     75.00 168.00   1.00   20.00    --  108.56  77.00  90.00   93
 54  \w    114.00 163.00   1.00   20.00    --  108.56  77.00 -30.00   49
 55  \w     53.00 141.00   1.00   20.00    --  108.56 -77.00-150.00   88
 56  \w     75.00 111.00   1.00   20.00    --  108.56  77.00 -30.00   36
 57  \w     78.00 137.00   1.00   20.00    --  108.56  61.00-150.00   59
 58  \w     75.00 175.00   1.00   20.00    --  108.56  77.00 -60.00  100
 59  \w     77.00 174.00   1.00   20.00    --  108.56  77.00  30.00   97
 60  \w     64.00  94.00   1.00   20.00    --  108.56 -45.00 120.00   30
 61  \w     75.00 164.00   1.00   20.00    --  108.56  77.00 120.00   89
;
_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      -0.1666141000
_diffrn_orient_matrix_UB_12      0.0375555000
_diffrn_orient_matrix_UB_13      -0.0098501000
_diffrn_orient_matrix_UB_21      0.0387569000
_diffrn_orient_matrix_UB_22      0.0476789000
_diffrn_orient_matrix_UB_23      0.0879292000
_diffrn_orient_matrix_UB_31      0.0567005000
_diffrn_orient_matrix_UB_32      0.1174249000
_diffrn_orient_matrix_UB_33      -0.0260682000
_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  0.0325
_diffrn_reflns_av_unetI/netI     0.0246
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.982
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            29333
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.982
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.209
_diffrn_reflns_theta_min         3.793
_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    2.682
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.833
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46e (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 yellow'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.447
_exptl_crystal_description       plate
_exptl_crystal_F_000             772
_exptl_crystal_recrystallization_method
'The material was recrystallised from methanol by slow evaporation'
_exptl_crystal_size_max          0.112
_exptl_crystal_size_mid          0.092
_exptl_crystal_size_min          0.046
_refine_diff_density_max         1.288
_refine_diff_density_min         -0.799
_refine_diff_density_rms         0.081
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.042
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     561
_refine_ls_number_reflns         6839
_refine_ls_number_restraints     358
_refine_ls_restrained_S_all      1.040
_refine_ls_R_factor_all          0.0497
_refine_ls_R_factor_gt           0.0432
_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^)+(0.0749P)^2^+1.9419P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1204
_refine_ls_wR_factor_ref         0.1265
_reflns_Friedel_coverage         0.000
_reflns_number_gt                6008
_reflns_number_total             6839
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3sc05723b2.cif
_cod_data_source_block           drr18_s1692
_cod_depositor_comments
'Adding full bibliography for 1570562--1570567.cif.'
_cod_database_code               1570565
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C30H34GaN11O4S2
_chemical_oxdiff_usercomment     ' '
_reflns_odcompleteness_completeness 99.95
_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
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 O3-O1 = O1-O2 = O2-O3 = O3A-O1A = O1A-O2A = O2A-O3A = O1C-O2C = O2C-O3C = O3C-
 O1C = O3B-O2B = O2B-O1B = O1B-O3B
 2.148 with sigma of 0.001
 O3A-N11A = O2-N11 = O3-N11 = O1A-N11A = O1-N11 = O2A-N11A = N11C-O1C = N11C-
 O2C = N11C-O3C = N11B-O3B = N11B-O2B = N11B-O1B
 1.245 with sigma of 0.001
 S2-C27A \\sim S2-C27
 with sigma of 0.02
 C29-C30 \\sim C29A-C30A
 with sigma of 0.02
 C28A-C27A \\sim C27-C28
 with sigma of 0.02
 C28-C29 \\sim C28A-C29A
 with sigma of 0.02
 C29-C27 \\sim C27A-C29A
 with sigma of 0.02
 N9-N8 \\sim N9A-N8
 with sigma of 0.02
 N9A-C27A \\sim N9-C27
 with sigma of 0.02
 N10-C27 \\sim N10A-C27A
 with sigma of 0.02
 N10A-C28A \\sim N10-C28
 with sigma of 0.02
 N10A-C29A \\sim N10-C29
 with sigma of 0.02
 C30A-N10A \\sim C30-N10
 with sigma of 0.02
3. Restrained planarity
 O1, O2, O3, N11
 with sigma of 0.1
 O1B, O2B, O3B, N11B
 with sigma of 0.01
 O1C, O2C, O3C, N11C
 with sigma of 0.01
 O1A, O2A, O3A, N11A
 with sigma of 0.1
4. Uiso/Uaniso restraints and constraints
O4 \\sim O4A \\sim O4B: within 2A with sigma of 0.01 and sigma for terminal
atoms of 0.02
N9A \\sim N10A \\sim C27A \\sim C28A \\sim C29A \\sim C30A: within 2A with
sigma of 0.01 and sigma for terminal atoms of 0.02
O1 \\sim O2 \\sim O3 \\sim N11 \\sim O1A \\sim O2A \\sim O3A \\sim N11A \\sim
O1B \\sim O2B \\sim O3B \\sim N11B \\sim O1C \\sim O2C \\sim O3C \\sim N11C:
within 2A with sigma of 0.01 and sigma for terminal atoms of 0.02
5. Rigid body (RIGU) restrains
 O1, O2, O3, N11, O1A, O2A, O3A, N11A, O1B, O2B, O3B, N11B, O1C, O2C, O3C,
 N11C, O4, O4A, O4B
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
6. Others
 1*[Sof(O1)+Sof(O2)+Sof(O3)+Sof(N11)]+1*[Sof(O1A)+Sof(O2A)+Sof(O3A)+Sof(N11A)]+
 1*[Sof(O1C)+Sof(O2C)+Sof(O3C)+Sof(N11C)]+1*[Sof(O1B)+Sof(O2B)+Sof(O3B)+
 Sof(N11B)]=1 with esd of 0.001
 1*[Sof(O4)]+1*[Sof(O4A)]+1*[Sof(O4B)]=1 with esd of 0.001
 Sof(O1)=Sof(O2)=Sof(O3)=Sof(N11)=FVAR(1)
 Sof(O1A)=Sof(O2A)=Sof(O3A)=Sof(N11A)=FVAR(2)
 Sof(O1C)=Sof(O2C)=Sof(O3C)=Sof(N11C)=FVAR(3)
 Sof(O1B)=Sof(O2B)=Sof(O3B)=Sof(N11B)=FVAR(4)
 U11(O1B)=U11(O2B)=U11(O3B)=U11(N11B)=FVAR(5)
 U22(O1B)=U22(O2B)=U22(O3B)=U22(N11B)=FVAR(6)
 U33(O1B)=U33(O2B)=U33(O3B)=U33(N11B)=FVAR(7)
 U23(O1B)=U23(O2B)=U23(O3B)=U23(N11B)=FVAR(8)
 U13(O1B)=U13(O2B)=U13(O3B)=U13(N11B)=FVAR(9)
 U12(O1B)=U12(O2B)=U12(O3B)=U12(N11B)=FVAR(10)
 U11(O1C)=U11(O2C)=U11(O3C)=U11(N11C)=FVAR(11)
 U22(O1C)=U22(O2C)=U22(O3C)=U22(N11C)=FVAR(12)
 U33(O1C)=U33(O2C)=U33(O3C)=U33(N11C)=FVAR(13)
 U23(O1C)=U23(O2C)=U23(O3C)=U23(N11C)=FVAR(14)
 U13(O1C)=U13(O2C)=U13(O3C)=U13(N11C)=FVAR(15)
 U12(O1C)=U12(O2C)=U12(O3C)=U12(N11C)=FVAR(16)
 Sof(N9A)=Sof(N10A)=Sof(C27A)=Sof(C28A)=Sof(H28D)=Sof(H28E)=Sof(H28F)=
 Sof(C29A)=Sof(H29C)=Sof(H29D)=Sof(C30A)=Sof(H30D)=Sof(H30E)=Sof(H30F)=1-
 FVAR(17)
 Sof(N9)=Sof(N10)=Sof(C27)=Sof(C28)=Sof(H28A)=Sof(H28B)=Sof(H28C)=Sof(C29)=
 Sof(H29A)=Sof(H29B)=Sof(C30)=Sof(H30A)=Sof(H30B)=Sof(H30C)=FVAR(17)
7.a Secondary CH2 refined with riding coordinates:
 C14(H14A,H14B), C29(H29A,H29B), C29A(H29C,H29D)
7.b Aromatic/amide H refined with riding coordinates:
 C1(H1), C2(H2), C3(H3), C4(H4), C8(H8), C9(H9), C10(H10), C11(H11), C16(H16),
 C17(H17), C18(H18), C19(H19), C23(H23), C24(H24), C25(H25), C26(H26)
7.c Idealised Me refined as rotating group:
 C13(H13A,H13B,H13C), C15(H15A,H15B,H15C), C28(H28A,H28B,H28C), C28A(H28D,H28E,
 H28F), C30(H30A,H30B,H30C), C30A(H30D,H30E,H30F)
;
_shelx_res_checksum              19700
_shelx_hkl_checksum              23073
_olex2_date_sample_data_collection 2018-10-17
_olex2_date_sample_submission    2018-10-04
_olex2_diffrn_ambient_temperature_device 'Oxford Cryosystems'
_olex2_exptl_crystal_mounting_method
'The crystal was mounted on a mylar loop with paratone-N oil'
_olex2_submission_original_sample_id drr181004c
_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 1.155
_oxdiff_exptl_absorpt_empirical_full_min 0.884