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_4514920
_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_formula_moiety         'Cl2 H24 N9 Ru2, 3(Cl), 2(O)'
_chemical_formula_sum            'Cl5 H24 N9 O2 Ru2'
_chemical_formula_weight         561.67
_space_group_crystal_system      monoclinic
_space_group_IT_number           12
_space_group_name_Hall           '-I 2y'
_space_group_name_H-M_alt        'I 1 2/m 1'
_symmetry_space_group_name_Hall  '-I 2y'
_symmetry_space_group_name_H-M   'I 1 2/m 1'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2018-08-23
_audit_creation_method
;
Olex2 1.2
(compiled May 18 2018 14:05:52 for OlexSys, GUI svn.r5486)
;
_cell_angle_alpha                90
_cell_angle_beta                 91.5930(10)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   8.52770(10)
_cell_length_b                   7.67950(10)
_cell_length_c                   13.57150(10)
_cell_measurement_reflns_used    13418
_cell_measurement_temperature    100.01(10)
_cell_measurement_theta_max      76.8500
_cell_measurement_theta_min      6.0250
_cell_volume                     888.433(17)
_computing_cell_refinement       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.46 (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    '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   -119.00 -70.00   0.50    0.08    --  -48.30-126.00 -47.00   98
  2  \w   -105.00 -20.00   0.50    0.08    --  -48.30 144.00-162.00  170
  3  \w   -119.00 -57.00   0.50    0.08    --  -48.30-144.00 144.00  124
  4  \w     42.00 106.00   0.50    0.08    --   48.30-144.00 144.00  128
  5  \w     32.00  95.00   0.50    0.08    --   48.30-126.00 -47.00  126
  6  \w   -105.00 -20.00   0.50    0.31    --  -86.25 144.00-162.00  170
  7  \w   -158.00 -57.00   0.50    0.31    --  -86.25-144.00 144.00  202
  8  \w   -158.00 -70.00   0.50    0.31    --  -86.25-126.00 -47.00  176
  9  \w    -92.00 -14.00   0.50    0.31    --  -86.25 126.00  29.00  156
 10  \w     42.00 131.00   0.50    0.31    --  107.75-144.00 144.00  178
 11  \w     79.00 175.00   0.50    0.31    --  107.75 144.00-162.00  192
 12  \w     92.00 178.00   0.50    0.31    --  107.75 126.00  29.00  172
 13  \w     36.00 118.00   0.50    0.31    --  107.75-126.00 -47.00  164
 14  \w    -38.00 -11.00   0.50    0.08    --   10.00 127.00  80.85   54
 15  \w    -12.00  17.00   0.50    0.08    --   22.00 102.00-156.84   58
 16  \w      0.00  37.00   0.50    0.08    --   30.00  94.00   8.91   74
 17  \w   -119.00 -27.00   0.50    0.08    --  -48.30 -77.00 120.00  184
 18  \w   -119.00 -27.00   0.50    0.08    --  -48.30 -77.00 -90.00  184
 19  \w   -121.00 -37.00   0.50    0.08    --  -48.30 -37.00   0.00  168
 20  \w   -119.00 -27.00   0.50    0.08    --  -48.30 -77.00-180.00  184
 21  \w   -119.00 -27.00   0.50    0.08    --  -48.30 -77.00  90.00  184
 22  \w     38.00 123.00   0.50    0.08    --   48.30  19.00 -90.00  170
 23  \w     38.00 121.00   0.50    0.08    --   48.30  37.00  60.00  166
 24  \w     27.00 121.00   0.50    0.08    --   50.00  81.00   5.69  188
 25  \w     30.00 121.00   0.50    0.08    --   50.00  72.00 110.14  182
 26  \w     32.00 125.00   0.50    0.08    --   54.00  77.00-149.26  186
 27  \w     34.00 125.00   0.50    0.08    --   54.00  73.00 -91.87  182
 28  \w     39.00 130.00   0.50    0.08    --   58.00  71.00  41.93  182
 29  \w     37.00 130.00   0.50    0.08    --   58.00  76.00  86.52  186
 30  \w     39.00 134.00   0.50    0.08    --   62.00  80.00 143.67  190
 31  \w   -138.00 -50.00   0.50    0.08    --  -66.00 -63.00  78.60  176
 32  \w     44.00  75.00   0.50    0.08    --   66.00  78.00 -73.89   62
 33  \w    113.00 138.00   0.50    0.08    --   66.00  78.00 -73.89   50
 34  \w    -76.00 -50.00   0.50    0.31    --  -70.00 -83.00  60.82   52
 35  \w    -84.00 -58.00   0.50    0.31    --  -74.00 -62.00 -23.51   52
 36  \w    -77.00 -51.00   0.50    0.31    --  -74.00 -81.00  98.11   52
 37  \w    -88.00 -58.00   0.50    0.31    --  -74.00 -62.00-169.26   60
 38  \w    -83.00 -57.00   0.50    0.31    --  -74.00 -66.00 149.76   52
 39  \w    -83.00 -57.00   0.50    0.31    --  -74.00 -65.00 171.75   52
 40  \w    -74.00 -49.00   0.50    0.31    --  -74.00 -83.00 -95.64   50
 41  \w    -82.00 -57.00   0.50    0.31    --  -78.00 -74.00 -42.50   50
 42  \w    -83.00 -57.00   0.50    0.31    --  -78.00 -74.00-131.22   52
 43  \w    -96.00 -64.00   0.50    0.31    --  -78.00 -58.00 -47.37   64
 44  \w    -99.00 -69.00   0.50    0.31    --  -86.25 -69.00-108.67   60
 45  \w    -97.00 -64.00   0.50    0.31    --  -86.25 -77.00  30.00   66
 46  \w   -111.00 -64.00   0.50    0.31    --  -86.25 -77.00 -60.00   94
 47  \w    -94.00 -65.00   0.50    0.31    --  -86.25 -76.00  66.03   58
 48  \w    -96.00 -66.00   0.50    0.31    --  -86.25 -74.00 133.03   60
 49  \w    -92.00 -66.00   0.50    0.31    --  -86.25 -82.00  25.16   52
 50  \w    -92.00 -66.00   0.50    0.31    --  -86.25 -77.00 -30.00   52
 51  \w    -91.00 -65.00   0.50    0.31    --  -86.25 -77.00   0.00   52
 52  \w    -98.00 -66.00   0.50    0.31    --  -86.25 -74.00 154.00   64
 53  \w   -149.00-123.00   0.50    0.31    --  -86.25 -77.00   0.00   52
 54  \w   -107.00 -65.00   0.50    0.31    --  -86.25 -77.00  90.00   84
 55  \w   -106.00 -67.00   0.50    0.31    --  -86.25 -70.00 179.88   78
 56  \w    -91.00 -65.00   0.50    0.31    --  -86.25 -77.00-150.00   52
 57  \w    152.00 178.00   0.50    0.31    --  107.75  77.00 150.00   52
 58  \w     81.00 107.00   0.50    0.31    --  107.75 -94.00   0.00   52
 59  \w     87.00 145.00   0.50    0.31    --  107.75  77.00 150.00  116
 60  \w     89.00 116.00   0.50    0.31    --  107.75  77.00  90.00   54
 61  \w     36.00  69.00   0.50    0.31    --  107.75 -30.00 -60.00   66
 62  \w    136.00 177.00   0.50    0.31    --  107.75  45.00 -60.00   82
 63  \w     37.00  85.00   0.50    0.31    --  107.75 -61.00-180.00   96
 64  \w     64.00 129.00   0.50    0.31    --  107.75 -77.00  90.00  130
 65  \w    130.00 175.00   0.50    0.31    --  107.75  77.00  30.00   90
 66  \w     37.00  75.00   0.50    0.31    --  107.75 -94.00   0.00   76
 67  \w     95.00 120.00   0.50    0.31    --  107.75  61.00-120.00   50
 68  \w     86.00 120.00   0.50    0.31    --  107.75  77.00 -30.00   68
 69  \w    127.00 153.00   0.50    0.31    --  107.75  77.00 -30.00   52
 70  \w     95.00 120.00   0.50    0.31    --  107.75  61.00 -90.00   50
 71  \w     92.00 118.00   0.50    0.31    --  107.75  77.00  30.00   52
 72  \w    111.00 175.00   0.50    0.31    --  107.75  15.00-150.00  128
 73  \w     36.00  73.00   0.50    0.31    --  107.75 -45.00-180.00   74
 74  \w    106.00 131.00   0.50    0.31    --  107.75  45.00 -30.00   50
 75  \w     86.00 135.00   0.50    0.31    --  107.75  77.00 -60.00   98
 76  \w     58.00  97.00   0.50    0.31    --  107.75 -77.00 -90.00   78
 77  \w     79.00 104.00   0.50    0.31    --  107.75 -94.00  90.00   50
 78  \w     80.00 108.00   0.50    0.31    --  107.75 -94.00-150.00   56
 79  \w    133.00 168.00   0.50    0.31    --  107.75  77.00-180.00   70
 80  \w     83.00 108.00   0.50    0.31    --  107.75 -94.00 150.00   50
 81  \w    153.00 178.00   0.50    0.31    --  107.75  61.00  60.00   50
 82  \w     93.00 124.00   0.50    0.31    --  107.75  61.00  60.00   62
 83  \w     90.00 122.00   0.50    0.31    --  107.75  77.00-180.00   64
 84  \w     97.00 148.00   0.50    0.31    --  107.75  77.00-120.00  102
 85  \w     39.00  65.00   0.50    0.31    --  107.75 -94.00 150.00   52
 86  \w     58.00 120.00   0.50    0.31    --  107.75 -61.00-150.00  124
 87  \w     41.00  77.00   0.50    0.31    --  107.75 -45.00-120.00   72
 88  \w    103.00 162.00   0.50    0.31    --  107.75  45.00  90.00  118
 89  \w     37.00  79.00   0.50    0.31    --  107.75-125.00 150.00   84
 90  \w     87.00 140.00   0.50    0.31    --  107.75  77.00 -90.00  106
 91  \w     94.00 139.00   0.50    0.31    --  107.75  77.00   0.00   90
 92  \w     43.00  68.00   0.50    0.31    --  107.75 -45.00 -30.00   50
 93  \w    153.00 178.00   0.50    0.31    --  107.75  61.00  90.00   50
 94  \w     52.00 102.00   0.50    0.31    --  107.75 -61.00 120.00  100
 95  \w    108.00 156.00   0.50    0.31    --  107.75 125.00 -60.00   96
 96  \w     93.00 138.00   0.50    0.31    --  107.75  61.00  90.00   90
 97  \w    134.00 178.00   0.50    0.31    --  107.75  77.00-150.00   88
 98  \w     93.00 150.00   0.50    0.31    --  107.75  61.00  30.00  114
 99  \w    138.00 175.00   0.50    0.31    --  107.75  45.00 120.00   74
100  \w    104.00 133.00   0.50    0.31    --  107.75  45.00 120.00   58
101  \w     54.00  79.00   0.50    0.31    --  107.75 -94.00-180.00   50
102  \w     81.00 109.00   0.50    0.31    --  107.75 -94.00-180.00   56
103  \w     86.00 125.00   0.50    0.31    --  107.75  77.00-150.00   78
104  \w     43.00 116.00   0.50    0.31    --  107.75-125.00-180.00  146
105  \w     80.00 110.00   0.50    0.31    --  107.75-113.00  82.80   60
106  \w     71.00  97.00   0.50    0.31    --  107.75-125.00  30.00   52
107  \w    142.00 168.00   0.50    0.31    --  107.75  61.00   0.00   52
108  \w     97.00 132.00   0.50    0.31    --  107.75  45.00  30.00   70
109  \w     97.00 130.00   0.50    0.31    --  107.75  45.00  60.00   66
110  \w    104.00 133.00   0.50    0.31    --  107.75  30.00 -60.00   58
111  \w    103.00 129.00   0.50    0.31    --  107.75  30.00  30.00   52
112  \w     94.00 132.00   0.50    0.31    --  107.75  61.00   0.00   76
113  \w     37.00  87.00   0.50    0.31    --  107.75 -77.00  30.00  100
114  \w    102.00 141.00   0.50    0.31    --  107.75  61.00 150.00   78
115  \w     93.00 144.00   0.50    0.31    --  107.75  60.00 -30.08  102
116  \w     43.00  77.00   0.50    0.31    --  107.75 -45.00  30.00   68
117  \w     98.00 143.00   0.50    0.31    --  107.75  45.00-120.00   90
118  \w     74.00 100.00   0.50    0.31    --  107.75 -61.00   0.00   52
119  \w     66.00  99.00   0.50    0.31    --  107.75 -94.00 -30.00   66
120  \w     38.00  63.00   0.50    0.31    --  107.75 -94.00 -30.00   50
121  \w     87.00 116.00   0.50    0.31    --  107.75 -61.00 -60.00   58
122  \w    102.00 156.00   0.50    0.31    --  107.75  61.00 120.00  108
123  \w     39.00  75.00   0.50    0.31    --  107.75 -45.00 120.00   72
124  \w     37.00  68.00   0.50    0.31    --  107.75 -30.00  60.00   62
;
_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      0.0018141000
_diffrn_orient_matrix_UB_12      0.0322515000
_diffrn_orient_matrix_UB_13      -0.1119943000
_diffrn_orient_matrix_UB_21      -0.0314854000
_diffrn_orient_matrix_UB_22      0.1950435000
_diffrn_orient_matrix_UB_23      0.0171934000
_diffrn_orient_matrix_UB_31      0.1779607000
_diffrn_orient_matrix_UB_32      0.0341326000
_diffrn_orient_matrix_UB_33      0.0074002000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0681
_diffrn_reflns_av_unetI/netI     0.0190
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 1.000
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            17956
_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         69.980
_diffrn_reflns_theta_min         6.054
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    20.796
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.24604
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46 (Rigaku Oxford Diffraction, 2018)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear yellow'
_exptl_crystal_density_diffrn    2.100
_exptl_crystal_description       block
_exptl_crystal_F_000             552
_exptl_crystal_size_max          0.176
_exptl_crystal_size_mid          0.103
_exptl_crystal_size_min          0.053
_refine_diff_density_max         2.597
_refine_diff_density_min         -2.268
_refine_diff_density_rms         0.217
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.066
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     58
_refine_ls_number_reflns         910
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.066
_refine_ls_R_factor_all          0.0550
_refine_ls_R_factor_gt           0.0547
_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^)+(0.0803P)^2^+20.6459P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1425
_refine_ls_wR_factor_ref         0.1427
_reflns_Friedel_coverage         0.000
_reflns_number_gt                899
_reflns_number_total             910
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            oc8b00773_si_002.cif
_cod_data_source_block           C-2
_cod_database_code               4514920
_shelx_shelxl_version_number     2016/6
_chemical_oxdiff_formula         Ru2N9H24Cl3
_chemical_oxdiff_usercomment
'grown by vapor diffusion of dioxane into water'
_reflns_odcompleteness_completeness 97.35
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     80.95
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All N(H,H,H) groups
2. Others
 Fixed Sof: Cl2(0.25)
3.a Idealised Me refined as rotating group:
 N2(H2A,H2B,H2C), N3(H3A,H3B,H3C)
;
_shelx_res_checksum              39162
_shelx_hkl_checksum              8256
_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 3.104
_oxdiff_exptl_absorpt_empirical_full_min 0.515