Structurally optimised BODIPY derivatives for imaging of mitochondrial dysfunction in cancer and heart cells
Shubhanchi Nigam; Benjamin P. Burke; Laura H. Davies; Juozas Domarkas; Jennifer F. Wallis; Paul G. Waddell; Jennifer S. Waby; David M. Benoit; Anne-Marie Seymour; Christopher Cawthorne; Lee J. Higham; Stephen J. Archibald; Chem.Commun. 52 (2016) 7114–; doi:

data_7119003
_publ_section_title
;
 Structurally optimised BODIPY derivatives for imaging of mitochondrial
 dysfunction in cancer and heart cells
;
_journal_name_full               Chem.Commun.
_journal_page_first              7114
_journal_volume                  52
_journal_year                    2016
_chemical_formula_moiety         'Br, 3(C H Cl3), C41 H62 B F N2 P'
_chemical_formula_sum            'C44 H65 B Br Cl9 F N2 P'
_chemical_formula_weight         1081.72
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2ybc'
_space_group_name_H-M_alt        'P 1 21/c 1'
_symmetry_space_group_name_Hall  '-P 2ybc'
_symmetry_space_group_name_H-M   'P 1 21/c 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_audit_creation_date             2016-03-30
_audit_creation_method
;
Olex2 1.2
(compiled 2015.01.26 svn.r3151 for OlexSys, GUI svn.r4998)
;
_audit_update_record
;
2016-04-18 deposited with the CCDC.
2016-04-25 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 109.127(3)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   24.7264(7)
_cell_length_b                   9.6603(2)
_cell_length_c                   23.4725(7)
_cell_measurement_reflns_used    5479
_cell_measurement_temperature    150.0(2)
_cell_measurement_theta_max      65.8490
_cell_measurement_theta_min      3.7560
_cell_volume                     5297.2(3)
_computing_cell_refinement       'CrysAlisPro 1.171.38.42b (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.42b (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.42b (Rigaku OD, 2015)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL (Sheldrick, 2008)'
_computing_structure_solution    'XT (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      150.0(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.3968
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.994
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  1  \w    -34.00  68.00   1.00   20.00    --   41.59 -38.00   0.00  102
  2  \w     12.00 116.00   1.00   20.00    --   41.59  57.00 150.00  104
  3  \w      9.00  83.00   1.00   80.00    --   93.50 -94.00-180.00   74
  4  \w     16.00 124.00   1.00   80.00    --   93.50 -30.00  90.00  108
  5  \w      9.00  83.00   1.00   80.00    --   93.50 -94.00 120.00   74
  6  \w     10.00 155.00   1.00   80.00    --   93.50 -15.00 150.00  145
  7  \w     19.00  96.00   1.00   80.00    --   93.50-125.00  90.00   77
  8  \w     87.00 113.00   1.00   80.00    --   93.50 -93.00  96.24   26
  9  \w    103.00 160.00   1.00   80.00    --   93.50  45.00 -30.00   57
 10  \w     34.00  60.00   1.00   80.00    --   93.50 -89.00  44.59   26
 11  \w     76.00 123.00   1.00   80.00    --   93.50 -89.00  44.59   47
 12  \w     68.00 118.00   1.00   80.00    --   93.50 -45.00  30.00   50
 13  \w    105.00 131.00   1.00   80.00    --   93.50 125.00-180.00   26
 14  \w     16.00  72.00   1.00   80.00    --   93.50 -93.00  96.24   56
 15  \w     66.00 104.00   1.00   80.00    --   93.50 -61.00  90.00   38
 16  \w    146.00 172.00   1.00   80.00    --   93.50  77.00  60.00   26
 17  \w     21.00  53.00   1.00   80.00    --   93.50 -88.00-165.15   32
 18  \w     83.00 109.00   1.00   80.00    --   93.50 -88.00-165.15   26
 19  \w     80.00 127.00   1.00   80.00    --   93.50  77.00  60.00   47
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Atlas, Gemini ultra'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0588324000
_diffrn_orient_matrix_UB_12      0.0013935000
_diffrn_orient_matrix_UB_13      0.0499408000
_diffrn_orient_matrix_UB_21      0.0293354000
_diffrn_orient_matrix_UB_22      0.0247429000
_diffrn_orient_matrix_UB_23      -0.0477761000
_diffrn_orient_matrix_UB_31      -0.0051258000
_diffrn_orient_matrix_UB_32      0.1575078000
_diffrn_orient_matrix_UB_33      0.0071235000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0860
_diffrn_reflns_av_unetI/netI     0.0607
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.994
_diffrn_reflns_limit_h_max       29
_diffrn_reflns_limit_h_min       -29
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       27
_diffrn_reflns_limit_l_min       -27
_diffrn_reflns_number            38266
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.994
_diffrn_reflns_theta_full        66.500
_diffrn_reflns_theta_max         66.983
_diffrn_reflns_theta_min         3.784
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance Ultra (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    5.794
_exptl_absorpt_correction_T_max  0.971
_exptl_absorpt_correction_T_min  0.718
_exptl_absorpt_correction_type   analytical
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.42b (Rigaku Oxford Diffraction, 2015)
Analytical numeric absorption correction using a multifaceted crystal
            model based on expressions derived by R.C. Clark & J.S. Reid.
(Clark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887-897)
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    1.356
_exptl_crystal_description       plate
_exptl_crystal_F_000             2240
_exptl_crystal_size_max          0.47
_exptl_crystal_size_mid          0.06
_exptl_crystal_size_min          0.02
_refine_diff_density_max         0.702
_refine_diff_density_min         -1.049
_refine_diff_density_rms         0.079
_refine_ls_extinction_coef       .
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.020
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     549
_refine_ls_number_reflns         9392
_refine_ls_number_restraints     41
_refine_ls_restrained_S_all      1.019
_refine_ls_R_factor_all          0.1093
_refine_ls_R_factor_gt           0.0685
_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^)+(0.1035P)^2^+3.8861P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1786
_refine_ls_wR_factor_ref         0.2101
_reflns_Friedel_coverage         0.000
_reflns_Friedel_fraction_full    .
_reflns_Friedel_fraction_max     .
_reflns_number_gt                5931
_reflns_number_total             9392
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c5cc08325g2.cif
_cod_data_source_block           ljh160010_3_fa
_cod_database_code               7119003
_shelxl_version_number           2014/6
_chemical_oxdiff_formula         'C41 H62 B1 Br1 F1 N2 P1'
_reflns_odcompleteness_completeness 99.88
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.49
_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,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 Cl7B-C53B \\sim Cl7A-C53A
 with sigma of 0.02
 Cl9A-C53A \\sim Cl9B-C53B
 with sigma of 0.02
 Cl8A-C53A \\sim Cl8B-C53B
 with sigma of 0.02
 Cl7B-Cl9B \\sim Cl9A-Cl7A
 with sigma of 0.02
 Cl9A-Cl8A \\sim Cl9B-Cl8B
 with sigma of 0.02
 Cl8A-Cl7A \\sim Cl7B-Cl8B
 with sigma of 0.02
 F1C-C39C \\sim F1D-C39D \\sim F1A-C39A \\sim F1B-C39B
 with sigma of 0.02
 C43-C31B \\sim C43-C38C \\sim C39C-C38C
 with sigma of 0.02
 C37D-C31B \\sim C38D-C37D \\sim C39D-C38D
 with sigma of 0.02
 C37A-C31A \\sim C38A-C37A \\sim C39A-C38A
 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
Uanis(C53B) = Uanis(C53A)
Uanis(Cl8B) = Uanis(Cl8A)
Uanis(Cl7B) = Uanis(Cl7A)
Uanis(Cl9B) = Uanis(Cl9A)
Uanis(C31A) = Uanis(C32A) = Uanis(C33A) = Uanis(C34A) = Uanis(C35A) =
Uanis(C36A) = Uanis(C37A) = Uanis(C38A) = Uanis(C39A) = Uanis(F1A) =
Uanis(C37B) = Uanis(C38B) = Uanis(F1B) = Uanis(C37A) = Uanis(C39B)
Uanis(C43) = Uanis(C38C) = Uanis(C39C) = Uanis(F1C) = Uanis(C37D) = Uanis(C38D)
= Uanis(C39D) = Uanis(F1D) = Uanis(C31B) = Uanis(C32B) = Uanis(C33B) =
Uanis(C34B) = Uanis(C35B) = Uanis(C36B)
4. Same fragment restrains
{C37D, C38D, C39D, F1D} sigma for 1-2: 0.02, 1-3: 0.02
as
{C43, C38C, C39C, F1C}
{C37A, C38A, C39A, F1A} sigma for 1-2: 0.02, 1-3: 0.02
as
{C37B, C38B, C39B, F1B}
5. Others
 Fixed Sof: H31B(0.25) H31C(0.25) H31D(0.25) H31E(0.25) H31A(0.5) H31F(0.25)
 H31G(0.25) H31H(0.25) H31I(0.25) H31J(0.5) Cl7B(0.64946) Cl8B(0.64946)
 Cl9B(0.64946) C43(0.25) H43A(0.25) H43B(0.25) C38C(0.25) H38A(0.25) H38B(0.25)
 C39C(0.25) H39A(0.25) H39B(0.25) F1C(0.25) C32A(0.5) H32A(0.5) H32B(0.5)
 C33A(0.5) H33A(0.5) H33B(0.5) C34A(0.5) H34A(0.5) H34B(0.5) C35A(0.5)
 H35A(0.5) H35B(0.5) C36A(0.5) H36A(0.5) H36B(0.5) C53B(0.64946) H53B(0.64946)
 Cl7A(0.35054) Cl8A(0.35054) Cl9A(0.35054) C37A(0.25) H37A(0.25) H37B(0.25)
 C38A(0.25) H38C(0.25) H38D(0.25) C39A(0.25) H39C(0.25) H39D(0.25) F1A(0.25)
 C37D(0.25) H37C(0.25) H37D(0.25) C38D(0.25) H38E(0.25) H38F(0.25) C39D(0.25)
 H39E(0.25) H39F(0.25) F1D(0.25) C53A(0.35054) H53A(0.35054) C37B(0.25)
 H37E(0.25) H37F(0.25) C38B(0.25) H38G(0.25) H38H(0.25) C39B(0.25) H39G(0.25)
 H39H(0.25) F1B(0.25) C32B(0.5) H32C(0.5) H32D(0.5) C33B(0.5) H33C(0.5)
 H33D(0.5) C34B(0.5) H34C(0.5) H34D(0.5) C35B(0.5) H35C(0.5) H35D(0.5)
 C36B(0.5) H36C(0.5) H36D(0.5)
6.a Ternary CH refined with riding coordinates:
 C25(H25), C31A(H31A), C31B(H31J), C51(H51), C52(H52), C53B(H53B), C53A(H53A)
6.b Secondary CH2 refined with riding coordinates:
 C12(H12A,H12B), C16(H16A,H16B), C26(H26A,H26B), C27(H27A,H27B), C28(H28A,
 H28B), C29(H29A,H29B), C30(H30A,H30B), C31A(H31B,H31C), C31A(H31D,H31E),
 C31B(H31F,H31G), C31B(H31H,H31I), C43(H43A,H43B), C38C(H38A,H38B), C39C(H39A,
 H39B), C32A(H32A,H32B), C33A(H33A,H33B), C34A(H34A,H34B), C35A(H35A,H35B),
 C36A(H36A,H36B), C37A(H37A,H37B), C38A(H38C,H38D), C39A(H39C,H39D), C37D(H37C,
 H37D), C38D(H38E,H38F), C39D(H39E,H39F), C37B(H37E,H37F), C38B(H38G,H38H),
 C39B(H39G,H39H), C32B(H32C,H32D), C33B(H33C,H33D), C34B(H34C,H34D), C35B(H35C,
 H35D), C36B(H36C,H36D)
6.c Aromatic/amide H refined with riding coordinates:
 C20(H20), C21(H21), C23(H23), C24(H24)
6.d Idealised Me refined as rotating group:
 C11(H11A,H11B,H11C), C13(H13A,H13B,H13C), C14(H14A,H14B,H14C), C15(H15A,H15B,
 H15C), C17(H17A,H17B,H17C), C18(H18A,H18B,H18C), C49(H49A,H49B,H49C), C50(H50A,
 H50B,H50C)
;
_shelx_res_checksum              70647
_shelx_hkl_checksum              25464
_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 2.303
_oxdiff_exptl_absorpt_empirical_full_min 0.567