A Selective and Cell-Permeable Mitochondrial Calcium Uniporter (MCU) Inhibitor Preserves Mitochondrial Bioenergetics after Hypoxia/Reoxygenation Injury.
Woods, Joshua J.; Nemani, Neeharika; Shanmughapriya, Santhanam; Kumar, Akshay; Zhang, MengQi; Nathan, Sarah R.; Thomas, Manfred; Carvalho, Edmund; Ramachandran, Karthik; Srikantan, Subramanya; Stathopulos, Peter B.; Wilson, Justin J.; Madesh, Muniswamy; ACS central science 5 (2019) 153–166; doi:10.1021/acscentsci.8b00773

data_4514921
_publ_section_title
;
 A Selective and Cell-Permeable Mitochondrial Calcium Uniporter (MCU)
 Inhibitor Preserves Mitochondrial Bioenergetics after
 Hypoxia/Reoxygenation Injury.
;
_journal_issue                   1
_journal_name_full               'ACS central science'
_journal_page_first              153
_journal_page_last               166
_journal_paper_doi               10.1021/acscentsci.8b00773
_journal_volume                  5
_journal_year                    2019
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C8 H32 Cl2 N9 Ru2, O, 3(Cl)'
_chemical_formula_sum            'C8 H32 Cl5 N9 O Ru2'
_chemical_formula_weight         649.81
_space_group_crystal_system      hexagonal
_space_group_IT_number           179
_space_group_name_Hall           'P 65 2 (0 0 1)'
_space_group_name_H-M_alt        'P 65 2 2'
_symmetry_space_group_name_Hall  'P 65 2 (0 0 1)'
_symmetry_space_group_name_H-M   'P 65 2 2'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2017-04-24
_audit_creation_method
;
Olex2 1.2-ac3
(compiled 2016.08.26 svn.r3337 for Rigaku Oxford Diffraction, GUI svn.r5221)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                120
_cell_formula_units_Z            6
_cell_length_a                   10.00360(10)
_cell_length_b                   10.00360(10)
_cell_length_c                   37.9277(3)
_cell_measurement_reflns_used    15736
_cell_measurement_temperature    100.01(10)
_cell_measurement_theta_max      77.9330
_cell_measurement_theta_min      5.0570
_cell_volume                     3287.00(5)
_computing_cell_refinement       'CrysAlisPro 1.171.39.27b (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.39.27b (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.39.27b (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    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.01(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 1.000
_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     34.00  60.00   0.50    1.50    --   47.80  57.00 -40.00   52
  2  \w     97.00 154.00   0.50    3.00    --  107.75  35.00 -51.00  114
  3  \w    148.00 174.00   0.50    3.00    --  107.75  77.00   0.00   52
  4  \w    144.00 170.00   0.50    3.00    --  107.75  30.00   0.00   52
  5  \w    125.00 157.00   0.50    3.00    --  107.75  23.00-103.00   64
  6  \w    104.00 178.00   0.50    3.00    --  107.75  30.00 -30.00  148
  7  \w    111.00 164.00   0.50    3.00    --  107.75  15.00 -90.00  106
  8  \w     93.00 141.00   0.50    3.00    --  107.75  77.00   0.00   96
  9  \w    128.00 162.00   0.50    3.00    --  107.75  15.00 120.00   68
 10  \w     97.00 142.00   0.50    3.00    --  107.75  30.00 150.00   90
 11  \w     87.00 118.00   0.50    3.00    --  107.75 -35.00 151.00   62
 12  \w     40.00 121.00   0.50    3.00    --  107.75 -57.00 177.00  162
 13  \w     36.00  76.00   0.50    3.00    --  107.75 -35.00 151.00   80
 14  \w     36.00  88.00   0.50    3.00    --  107.75 -77.00 -30.00  104
 15  \w     45.00  85.00   0.50    3.00    --  107.75 -94.00 -30.00   80
 16  \w     74.00 100.00   0.50    3.00    --  107.75 -15.00-150.00   52
 17  \w    -32.00  23.00   0.50    1.50    --  -47.80  37.00 -90.00  110
 18  \w   -119.00 -71.00   0.50    1.50    --  -47.80-125.00   0.00   96
 19  \w   -119.00 -70.00   0.50    1.50    --  -47.80-125.00-120.00   98
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0496820000
_diffrn_orient_matrix_UB_12      -0.0434905000
_diffrn_orient_matrix_UB_13      -0.0386975000
_diffrn_orient_matrix_UB_21      0.0636528000
_diffrn_orient_matrix_UB_22      -0.1119575000
_diffrn_orient_matrix_UB_23      0.0005556000
_diffrn_orient_matrix_UB_31      -0.1584048000
_diffrn_orient_matrix_UB_32      -0.1310759000
_diffrn_orient_matrix_UB_33      0.0123612000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0337
_diffrn_reflns_av_unetI/netI     0.0142
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 1.000
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       46
_diffrn_reflns_limit_l_min       -41
_diffrn_reflns_number            19483
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 1.000
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         70.068
_diffrn_reflns_theta_min         5.105
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    16.940
_exptl_absorpt_correction_T_max  0.479
_exptl_absorpt_correction_T_min  0.146
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.27b (Rigaku Oxford Diffraction, 2015)
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_density_diffrn    1.970
_exptl_crystal_description       needle
_exptl_crystal_F_000             1944
_exptl_crystal_size_max          0.184
_exptl_crystal_size_mid          0.050
_exptl_crystal_size_min          0.049
_refine_diff_density_max         0.506
_refine_diff_density_min         -0.438
_refine_diff_density_rms         0.075
_refine_ls_abs_structure_details
;
 Flack x determined using 735 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.011(6)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.070
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     119
_refine_ls_number_reflns         2088
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.070
_refine_ls_R_factor_all          0.0171
_refine_ls_R_factor_gt           0.0168
_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^)+(0.0244P)^2^+3.4113P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0427
_refine_ls_wR_factor_ref         0.0430
_reflns_Friedel_coverage         0.552
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     1.000
_reflns_number_gt                2069
_reflns_number_total             2088
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            oc8b00773_si_002.cif
_cod_data_source_block           C-3
_cod_original_cell_volume        3287.00(7)
_cod_database_code               4514921
_shelx_shelxl_version_number     2016/6
_chemical_oxdiff_formula         'Ru2 N9 C8 H32 Cl5 O'
_chemical_oxdiff_usercomment     'Crystallized from EtOH/HCl/H2O'
_reflns_odcompleteness_completeness 99.86
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     69.95
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H,H) groups, All N(H,H) groups
2. Others
 Fixed Sof: O1(0.5)
3.a Secondary CH2 refined with riding coordinates:
 N2(H2A,H2B), N3(H3A,H3B), N4(H4A,H4B), N5(H5A,H5B), C1(H1A,H1B), C2(H2C,H2D),
 C3(H3C,H3D), C4(H4C,H4D)
;
_shelx_res_checksum              46882
_shelx_hkl_checksum              79935
_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 1.927
_oxdiff_exptl_absorpt_empirical_full_min 0.670