Organometallic Small Molecule Kinase Inhibitors – Direct Incorporation of Re and 99mTc into Opaganib®
Alberto, Roger; Lengacher, Raphael; Wang, Youchao; Braband, Henrik; Blacque, Olivier; Gasser, Gilles; Chemical Communications  (2021) –; doi:10.1039/D1CC03678E

data_7129276
_publ_section_title
;
 Organometallic Small Molecule Kinase Inhibitors -- Direct Incorporation
 of Re and 99mTc into Opaganib&#x00AE;
;
_journal_name_full               'Chemical Communications'
_journal_paper_doi               10.1039/D1CC03678E
_journal_year                    2021
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C15 H15 Cl O2'
_chemical_formula_sum            'C15 H15 Cl O2'
_chemical_formula_weight         262.72
_space_group_crystal_system      orthorhombic
_space_group_IT_number           29
_space_group_name_Hall           'P 2c -2ac'
_space_group_name_H-M_alt        'P c a 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2021-04-06
_audit_creation_method
;
Olex2 1.3
(compiled 2020.11.12 svn.r5f609507 for OlexSys, GUI svn.r6272)
;
_audit_update_record
;
2021-07-06 deposited with the CCDC.	2021-11-19 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   25.9451(7)
_cell_length_b                   4.24250(10)
_cell_length_c                   11.7127(3)
_cell_measurement_reflns_used    7092
_cell_measurement_temperature    160(1)
_cell_measurement_theta_max      75.9660
_cell_measurement_theta_min      3.3830
_cell_volume                     1289.24(6)
_computing_cell_refinement       'CrysAlisPro 1.171.40.68a (Rigaku OD, 2019)'
_computing_data_collection       'CrysAlisPro 1.171.40.68a (Rigaku OD, 2019)'
_computing_data_reduction        'CrysAlisPro 1.171.40.68a (Rigaku OD, 2019)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL (Sheldrick, 2015b)'
_computing_structure_solution    'SHELXT (Sheldrick, 2015a)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      160(1)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.3801
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.996
_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    -79.00  37.00   0.80    0.80    --  -41.74  19.00 120.00  145
  2  \w    -64.00  30.40   0.80    0.80    --  -41.74  37.00-150.00  118
  3  \w     10.00  41.20   0.80    0.80    --   41.74  78.00  54.93   39
  4  \w    -31.00  63.40   0.80    0.80    --   41.74 -37.00 -90.00  118
  5  \w     27.00  95.80   0.80    0.80    --   41.74-125.00 -60.00   86
  6  \w    -31.00  63.40   0.80    0.80    --   41.74 -37.00 120.00  118
  7  \w    103.00 177.40   0.80    1.50    --  111.00  77.00  90.00   93
  8  \w     31.00 155.00   0.80    1.50    --  111.00 -15.00 -30.00  155
  9  \w     41.00 123.40   0.80    1.50    --  111.00-140.00  58.84  103
 10  \w     36.00 108.00   0.80    1.50    --  111.00-111.00 -60.00   90
 11  \w     36.00 108.00   0.80    1.50    --  111.00-111.00  30.00   90
 12  \w     31.00 155.00   0.80    1.50    --  111.00 -15.00-180.00  155
 13  \w     36.00 108.00   0.80    1.50    --  111.00-111.00-150.00   90
 14  \w     41.00 138.60   0.80    1.50    --  111.00 -61.00 -30.00  122
 15  \w     40.00 134.40   0.80    1.50    --  111.00 -45.00 150.00  118
 16  \w     87.00 177.40   0.80    1.50    --  111.00  45.00   0.00  113
 17  \w    104.00 177.60   0.80    1.50    --  111.00 111.00 -60.00   92
 18  \w     40.00 134.40   0.80    1.50    --  111.00 -45.00   0.00  118
 19  \w     36.00 108.00   0.80    1.50    --  111.00-111.00-120.00   90
 20  \w     36.00 108.00   0.80    1.50    --  111.00-111.00-180.00   90
 21  \w     30.00 106.00   0.80    1.50    --  111.00 -94.00  30.00   95
 22  \w     36.00 108.00   0.80    1.50    --  111.00-111.00 120.00   90
 23  \w     36.00 108.00   0.80    1.50    --  111.00-111.00 -30.00   90
 24  \w    104.00 177.60   0.80    1.50    --  111.00 111.00 -30.00   92
 25  \w     34.00 106.80   0.80    1.50    --  111.00-104.00 -12.32   91
 26  \w     41.00 122.60   0.80    1.50    --  111.00-138.00-170.94  102
 27  \w   -112.00 -16.00   0.80    0.80    --  -41.74 -57.00  60.00  120
 28  \w     11.00  40.60   0.80    0.80    --   41.74  76.00-119.50   37
 29  \w      9.00  41.00   0.80    0.80    --   41.74  82.00 117.07   40
 30  \w     10.00  41.20   0.80    0.80    --   41.74  77.00  -1.86   39
 31  \w     10.00  41.20   0.80    0.80    --   41.74  78.00 -39.84   39
 32  \w     10.00  41.20   0.80    0.80    --   41.74  78.00-153.36   39
 33  \w     87.00 177.40   0.80    1.50    --  111.00  30.00-150.00  113
 34  \w     66.00 178.00   0.80    1.50    --  111.00  15.00 -60.00  140
 35  \w     87.00 177.40   0.80    1.50    --  111.00  45.00  60.00  113
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0521355000
_diffrn_orient_matrix_UB_12      -0.0289264000
_diffrn_orient_matrix_UB_13      0.0621588000
_diffrn_orient_matrix_UB_21      0.0284642000
_diffrn_orient_matrix_UB_22      -0.0361291000
_diffrn_orient_matrix_UB_23      0.1147417000
_diffrn_orient_matrix_UB_31      -0.0013120000
_diffrn_orient_matrix_UB_32      0.3599232000
_diffrn_orient_matrix_UB_33      0.0165482000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0505
_diffrn_reflns_av_unetI/netI     0.0213
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.996
_diffrn_reflns_limit_h_max       32
_diffrn_reflns_limit_h_min       -32
_diffrn_reflns_limit_k_max       5
_diffrn_reflns_limit_k_min       -3
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            18917
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.986
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.313
_diffrn_reflns_theta_min         3.407
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.546
_exptl_absorpt_correction_T_max  0.860
_exptl_absorpt_correction_T_min  0.613
_exptl_absorpt_correction_type   analytical
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.68a (Rigaku Oxford Diffraction, 2019)
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            colourless
_exptl_crystal_density_diffrn    1.354
_exptl_crystal_description       plate
_exptl_crystal_F_000             552
_exptl_crystal_size_max          0.36
_exptl_crystal_size_mid          0.18
_exptl_crystal_size_min          0.06
_refine_diff_density_max         0.425
_refine_diff_density_min         -0.301
_refine_diff_density_rms         0.064
_refine_ls_abs_structure_details
;
 Flack x determined using 1127 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.000(17)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.160
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     165
_refine_ls_number_reflns         2682
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.160
_refine_ls_R_factor_all          0.0565
_refine_ls_R_factor_gt           0.0545
_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^)+(0.0506P)^2^+2.2480P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1522
_refine_ls_wR_factor_ref         0.1533
_reflns_Friedel_coverage         0.882
_reflns_Friedel_fraction_full    0.994
_reflns_Friedel_fraction_max     0.975
_reflns_number_gt                2567
_reflns_number_total             2682
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d1cc03678e2.cif
_cod_data_source_block           3
_cod_database_code               7129276
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.862
_shelx_estimated_absorpt_t_min   0.461
_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
2.a Secondary CH2 refined with riding coordinates:
 C11(H11A,H11B), C14(H14A,H14B)
2.b Aromatic/amide H refined with riding coordinates:
 C2(H2), C3(H3), C5(H5), C6(H6), C8(H8)
2.c Idealised Me refined as rotating group:
 C12(H12A,H12B,H12C), C15(H15A,H15B,H15C)
;
_shelx_res_checksum              50524