Anticancer Organorhodium and -iridium Complexes with Low Toxicity in vivo but High Potency in vitro: DNA Damage, Reactive Oxygen Species Formation, and Haemolytic Activity
Parveen, Shahida; Hanif, Muhammad; Leung, Euphemia; Tong, Kelvin; Yang, Annie; Astin, Jonathan; De Zoysa , Gayan Heruka; Steel , Tasha R.; Goodman, David; Movassaghi, Sanam; Soehnel, Tilo; Sarojini, Vijayalekshmi; Jamieson, Stephen; Hartinger, Christian; Chemical Communications  (2019) –; doi:10.1039/C9CC03822A

data_7124094
_publ_section_title
;
 Anticancer Organorhodium and -iridium Complexes with Low Toxicity in vivo
 but High Potency in vitro: DNA Damage, Reactive Oxygen Species Formation,
 and Haemolytic Activity
;
_journal_name_full               'Chemical Communications'
_journal_paper_doi               10.1039/C9CC03822A
_journal_year                    2019
_chemical_formula_moiety         'C36 H48 Cl2 Ir2 N2 O4, 2(C H4 O)'
_chemical_formula_sum            'C38 H56 Cl2 Ir2 N2 O6'
_chemical_formula_weight         1092.14
_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'
_symmetry_space_group_name_Hall  '-P 2yn'
_symmetry_space_group_name_H-M   'P 1 21/n 1'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2019-03-29
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3510 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2019-05-13 deposited with the CCDC.    2019-08-23 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 97.4552(14)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   7.8857(2)
_cell_length_b                   14.3838(3)
_cell_length_c                   17.7206(4)
_cell_measurement_reflns_used    9886
_cell_measurement_temperature    100
_cell_measurement_theta_max      30.831
_cell_measurement_theta_min      2.711
_cell_volume                     1992.99(8)
_computing_cell_refinement       'SAINT V8.32B (?, 2016)'
_computing_data_reduction        'SAINT V8.32B (?, 2016)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_diffrn_ambient_temperature      100
_diffrn_detector                 'Bruker APEX2 area detector'
_diffrn_detector_area_resol_mean 7.9
_diffrn_detector_type            'CCD area detector'
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_device       'three-circle diffractometer'
_diffrn_measurement_device_type  'BRUKER APEXII'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  'mirror optics'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0528
_diffrn_reflns_av_unetI/netI     0.0458
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       19
_diffrn_reflns_limit_k_min       -18
_diffrn_reflns_limit_l_max       24
_diffrn_reflns_limit_l_min       -24
_diffrn_reflns_number            25662
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.999
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         29.573
_diffrn_reflns_theta_min         2.710
_diffrn_source                   'microfocus sealed X-ray tube'
_diffrn_source_type              'Incoatec I\ms'
_exptl_absorpt_coefficient_mu    6.850
_exptl_absorpt_correction_T_max  0.7462
_exptl_absorpt_correction_T_min  0.5513
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2012/1 (Bruker,2012) was used for absorption correction.
wR2(int) was 0.0890 before and 0.0663 after correction.
The Ratio of minimum to maximum transmission is 0.7388.
The \l/2 correction factor is 0.0015.
;
_exptl_crystal_colour            'clear light yellow'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.820
_exptl_crystal_description       irregular
_exptl_crystal_F_000             1068
_exptl_crystal_size_max          0.32
_exptl_crystal_size_mid          0.28
_exptl_crystal_size_min          0.24
_refine_diff_density_max         1.500
_refine_diff_density_min         -1.197
_refine_diff_density_rms         0.154
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.057
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     243
_refine_ls_number_reflns         5579
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.057
_refine_ls_R_factor_all          0.0415
_refine_ls_R_factor_gt           0.0311
_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^)+(0.0276P)^2^+0.7512P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0643
_refine_ls_wR_factor_ref         0.0680
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4651
_reflns_number_total             5579
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c9cc03822a2.cif
_cod_data_source_block           d4_ir2a_0m
_cod_database_code               7124094
_shelx_shelxl_version_number     2016/6
_shelx_estimated_absorpt_t_max   0.290
_shelx_estimated_absorpt_t_min   0.218
_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, All O(H) groups
2. Restrained distances
 C18-O3 \\sim C19-O4
 with sigma of 0.01
3. Uiso/Uaniso restraints and constraints
Uanis(C18) = Uanis(C19)
Uanis(O3) = Uanis(O4)
4. Others
 Sof(O4)=Sof(H4)=Sof(C19)=Sof(H19A)=Sof(H19B)=Sof(H19C)=1-FVAR(1)
 Sof(O3)=Sof(H3)=Sof(C18)=Sof(H18A)=Sof(H18B)=Sof(H18C)=FVAR(1)
5.a Secondary CH2 refined with riding coordinates:
 C1'(H1'A,H1'B), C2'(H2'A,H2'B)
5.b Aromatic/amide H refined with riding coordinates:
 C5(H5), C6(H6)
5.c Idealised Me refined as rotating group:
 C7(H7A,H7B,H7C), C9(H9A,H9B,H9C), C11(H11A,H11B,H11C), C13(H13A,H13B,H13C),
 C15(H15A,H15B,H15C), C17(H17A,H17B,H17C), C18(H18A,H18B,H18C), C19(H19A,H19B,
 H19C)
5.d Idealised tetrahedral OH refined as rotating group:
 O3(H3), O4(H4)
;
_olex2_submission_special_instructions 'No special instructions were received'