Mitochondria-targeted spin-labelled luminescent iridium anticancer complexes
Venkatesh, V.; Berrocal-Martin, Raul; Wedge, Christopher J.; Romero-Canelón, Isolda; Sanchez-Cano, Carlos; Song, Ji-Inn; Coverdale, James P. C.; Zhang, Pingyu; Clarkson, Guy J.; Habtemariam, Abraha; Magennis, Steven W.; Deeth, Robert J.; Sadler, Peter J.; Chem. Sci.  (2017) –; doi:10.1039/C7SC03216A

data_1547764
_publ_section_title
;
 Mitochondria-targeted spin-labelled luminescent iridium anticancer
 complexes
;
_journal_name_full               'Chem. Sci.'
_journal_paper_doi               10.1039/C7SC03216A
_journal_year                    2017
_chemical_formula_moiety         'C52 H58 Ir N8 O4, F6 P'
_chemical_formula_sum            'C52 H58 F6 Ir N8 O4 P'
_chemical_formula_weight         1196.23
_space_group_crystal_system      orthorhombic
_space_group_IT_number           36
_space_group_name_Hall           'C 2c -2'
_space_group_name_H-M_alt        'C m c 21'
_symmetry_space_group_name_Hall  'C 2c -2'
_symmetry_space_group_name_H-M   'C m c 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     heavy
_audit_creation_date             2016-03-02
_audit_creation_method
;
Olex2 1.2
(compiled 2016.02.16 svn.r3265 for OlexSys, GUI svn.r5155)
;
_audit_update_record
;
2016-12-10 deposited with the CCDC.
2017-10-20 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   21.7439(8)
_cell_length_b                   20.2524(4)
_cell_length_c                   11.8321(3)
_cell_measurement_reflns_used    7881
_cell_measurement_temperature    150(2)
_cell_measurement_theta_max      24.7370
_cell_measurement_theta_min      2.7320
_cell_volume                     5210.5(3)
_computing_cell_refinement       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_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      150(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.2833
_diffrn_detector_type            Ruby
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.957
_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     35.00 106.00   1.00   80.17    --   17.13 178.00-120.00   71
  2  \w    -25.00  23.00   1.00   80.17    --  -18.22 -99.00 -60.00   48
  3  \w    -90.00  10.00   1.00   80.17    --  -18.22 -57.00  90.00  100
  4  \w    -46.00  55.00   1.00   80.17    --  -18.22  57.00  60.00  101
  5  \w    -94.00 -29.00   1.00   80.17    --  -18.22 -77.00 -30.00   65
  6  \w   -107.00 -57.00   1.00   80.17    --  -18.22-178.00-150.00   50
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Ruby, Gemini'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0198058000
_diffrn_orient_matrix_UB_12      0.0251011000
_diffrn_orient_matrix_UB_13      -0.0178429000
_diffrn_orient_matrix_UB_21      0.0179785000
_diffrn_orient_matrix_UB_22      0.0015140000
_diffrn_orient_matrix_UB_23      -0.0513655000
_diffrn_orient_matrix_UB_31      -0.0226012000
_diffrn_orient_matrix_UB_32      -0.0207699000
_diffrn_orient_matrix_UB_33      -0.0252780000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0823
_diffrn_reflns_av_unetI/netI     0.1022
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.957
_diffrn_reflns_limit_h_max       30
_diffrn_reflns_limit_h_min       -32
_diffrn_reflns_limit_k_max       29
_diffrn_reflns_limit_k_min       -28
_diffrn_reflns_limit_l_max       17
_diffrn_reflns_limit_l_min       -17
_diffrn_reflns_number            34944
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.924
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         32.439
_diffrn_reflns_theta_min         2.647
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    2.667
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.89610
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.41 (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            orange
_exptl_crystal_colour_primary    orange
_exptl_crystal_density_diffrn    1.525
_exptl_crystal_description       block
_exptl_crystal_F_000             2416
_exptl_crystal_size_max          0.24
_exptl_crystal_size_mid          0.06
_exptl_crystal_size_min          0.06
_refine_diff_density_max         0.803
_refine_diff_density_min         -1.675
_refine_diff_density_rms         0.101
_refine_ls_abs_structure_details
;
 Flack x determined using 1609 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).

Flack parameter 0.001(5) Shelx 2014
Hooft y parameter 0.003(6) Olex2
;
_refine_ls_abs_structure_Flack   0.001(5)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.029
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     413
_refine_ls_number_reflns         8874
_refine_ls_number_restraints     247
_refine_ls_restrained_S_all      1.044
_refine_ls_R_factor_all          0.1464
_refine_ls_R_factor_gt           0.0626
_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^)+(0.0525P)^2^+11.8046P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1242
_refine_ls_wR_factor_ref         0.1537
_reflns_Friedel_coverage         0.852
_reflns_Friedel_fraction_full    0.996
_reflns_Friedel_fraction_max     0.888
_reflns_number_gt                4748
_reflns_number_total             8874
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c7sc03216a2.cif
_cod_data_source_block           vv1
_cod_database_code               1547764
_chemical_oxdiff_formula         'C20 H20 N2 O2 Ir'
_reflns_odcompleteness_completeness 99.88
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     30.01
_olex2_refinement_description
;

The asymmetric unit contains half an Ir complex and half a PF6 
counterion. The Ir sits on the mirror plane which bisects the 
substituted Bipy. The PF6 also lies on the mirror plane.
The mirror plane lies between the pyridine rings of the 
substituted Bipy between C4 and the symmetry related C4. 
Unfortunately, both the 2-phenyl pyridines of the complex and 
the PF6 were disordered over this mirror plane.
The P10, F11 and F12 sat on the mirror plane and F13 to F16 were 
disordered about the mirror plane.  
The disordered components F13 to F16 were refined behind a 
PART -1 instruction. Several DFIX, DANG and SIMU restraints were 
used to give the disordered components of the PF6 chemically 
reasonable bond angles, bond lengths and thermal parameters.
The two 2-phenyl pyridines were also disordered about the mirror 
plane. The two 2-phenyl pyridines were refined behind a PART -1 
instruction with AFIX 66 constraints and SIMU restraints.  
The assignment of the nitrogen on 2-phenyl pyridine N19-C30 was 
done on thermal parameters. It was not possible to easily assign 
the nitrogen on 2-phenyl pyridine N31 to C41 as the thermal 
parameters for both atoms at position 31 and 41 were very 
similar when refined as nitrogens at either position 31 or 41. 
The 2 phenyl pyridine is probably disordered as N31 and C41 and
C31 and N41 but it was not possible to build a further disordered 
model behind the PART -1 instruction. 
The assignment of the atom at position 31 as a nitrogen is based 
on the slightly lower R factor when refined this way round.
Thermal libration gives the terminal atoms of the nitroxide 
radical rather large thermal parameters so SIMU restraints were 
used to give the terminal methyls of the nitroxide radical more 
reasonable thermal parameters compared to the rest of the 
piperidine ring. The NH was placed at a calculated position. 

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
2. Restrained distances
 P10-F13 = P10-F14 = P10-F15 = P10-F16
 1.6 with sigma of 0.02
 F11-F13 = F11-F14 = F11-F15 = F11-F16 = F12-F13 = F12-F14 = F12-F15
 2.26 with sigma of 0.04
 F12-F16 = F13-F15 = F13-F16 = F14-F15 = F14-F16
 2.26 with sigma of 0.04
3. Restrained planarity
 P10, F13, F14, F15, F16
 with sigma of 0.1
 P10, F11, F12, F15, F16
 with sigma of 0.1
4. Rigid bond restraints
 C11, N12, O12, C13, C15, C16, C17, C18
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001
5. Uiso/Uaniso restraints and constraints
C20 \\sim C21 \\sim C22 \\sim C23 \\sim C24 \\sim C25 \\sim C26 \\sim C27 \\sim
C28 \\sim C29 \\sim C30: within 1.7A with sigma of 0.004 and sigma for terminal
atoms of 0.008
N31 \\sim C32 \\sim C33 \\sim C34 \\sim C35 \\sim C36 \\sim C37 \\sim C38 \\sim
C39 \\sim C40 \\sim C41 \\sim C42: within 1.7A with sigma of 0.004 and sigma
for terminal atoms of 0.008
P10 \\sim F13 \\sim F14 \\sim F15 \\sim F16: within 1.7A with sigma of 0.004
and sigma for terminal atoms of 0.008
C11 \\sim N12 \\sim O12 \\sim C13 \\sim C15 \\sim C16 \\sim C17 \\sim C18:
within 1.7A with sigma of 0.0004 and sigma for terminal atoms of 0.0008
6. Others
 Fixed Sof: N19(0.5) C20(0.5) H20(0.5) C21(0.5) H21(0.5) C22(0.5) H22(0.5)
 C23(0.5) H23(0.5) C24(0.5) C25(0.5) C26(0.5) H26(0.5) C27(0.5) H27(0.5)
 C28(0.5) H28(0.5) C29(0.5) H29(0.5) C30(0.5) N31(0.5) C32(0.5) H32(0.5)
 C33(0.5) H33(0.5) C34(0.5) H34(0.5) C35(0.5) H35(0.5) C36(0.5) C37(0.5)
 C38(0.5) H38(0.5) C39(0.5) H39(0.5) C40(0.5) H40(0.5) C41(0.5) H41(0.5)
 C42(0.5) F13(0.5) F14(0.5) F15(0.5) F16(0.5)
7.a Ternary CH refined with riding coordinates:
 C9(H9)
7.b Secondary CH2 refined with riding coordinates:
 C10(H10A,H10B), C14(H14A,H14B)
7.c Aromatic/amide H refined with riding coordinates:
 C1(H1), C2(H2), C5(H5), N8(H8), C20(H20), C21(H21), C22(H22), C23(H23),
 C26(H26), C27(H27), C28(H28), C29(H29), C32(H32), C33(H33), C34(H34), C35(H35),
  C38(H38), C39(H39), C40(H40), C41(H41)
7.d Fitted hexagon refined as free rotating group:
 N19(C20,C21,C22,C23,C24), C25(C26,C27,C28,C29,C30), N31(C32,C33,C34,C35,C36),
 C37(C38,C39,C40,C41,C42)
7.e Idealised Me refined as rotating group:
 C15(H15A,H15B,H15C), C16(H16A,H16B,H16C), C17(H17A,H17B,H17C), C18(H18A,H18B,
 H18C)
;
_shelx_res_checksum              66867
_shelx_shelxl_version_number     2014/7
_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 1.253
_oxdiff_exptl_absorpt_empirical_full_min 0.906