Comprehensive Structure‒Activity Profiling of Micheliolide and its Targeted Proteome in Leukemia Cells via Probe-Guided Late-Stage C‒H Functionalization
Alwaseem, Hanan; Giovani, Simone; Crotti, Michele; Welle, Kevin; Jordan, Craig T.; Ghaemmaghami, Sina; Fasan, Rudi; ACS Central Science  (2021) –; doi:10.1021/acscentsci.0c01624

data_4518637
_publ_section_title
;
 Comprehensive Structure--Activity Profiling of Micheliolide and its
 Targeted Proteome in Leukemia Cells via Probe-Guided Late-Stage C--H
 Functionalization
;
_journal_name_full               'ACS Central Science'
_journal_paper_doi               10.1021/acscentsci.0c01624
_journal_year                    2021
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C15 H20 O4'
_chemical_formula_sum            'C15 H20 O4'
_chemical_formula_weight         264.31
_space_group_crystal_system      orthorhombic
_space_group_IT_number           20
_space_group_name_Hall           'C 2c 2'
_space_group_name_H-M_alt        'C 2 2 21'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_atom_sites_solution_secondary   difmap
_audit_creation_date             2020-09-25
_audit_creation_method
;
Olex2 1.3-ac4
(compiled 2020.03.28 svn.rd84adfe8 for Rigaku Oxford Diffraction, GUI svn.r6032)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   10.39540(10)
_cell_length_b                   15.0420(2)
_cell_length_c                   16.9395(3)
_cell_measurement_reflns_used    12058
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      77.6200
_cell_measurement_theta_min      5.1630
_cell_volume                     2648.79(6)
_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 1.3-ac4 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3-ac4 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015b)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015a)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.00(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.991
_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    -86.00   1.00   0.50    0.06    --  -49.62 111.00-111.00  174
  2  \w     21.00  88.00   0.50    0.06    --   49.62-111.00 154.00  134
  3  \w   -156.00 -78.00   0.50    0.22    --  -84.25-111.00 154.00  156
  4  \w    -85.00 -12.00   0.50    0.22    --  -84.25 111.00-111.00  146
  5  \w     34.00 111.00   0.50    0.22    --  105.75-111.00 154.00  154
  6  \w    100.00 178.00   0.50    0.22    --  105.75 111.00-111.00  156
  7  \w    -57.00  22.00   0.50    0.06    --  -49.62  38.00 -60.00  158
  8  \w   -121.00 -70.00   0.50    0.06    --  -49.62-125.00 -60.00  102
  9  \w     31.00  95.00   0.50    0.06    --   49.62-125.00 120.00  128
 10  \w     33.00  82.00   0.50    0.22    --  105.75 -15.00-180.00   98
 11  \w     34.00  72.00   0.50    0.22    --  105.75 -30.00-180.00   76
 12  \w     34.00  72.00   0.50    0.22    --  105.75 -30.00  90.00   76
 13  \w     98.00 178.00   0.50    0.22    --  105.75  30.00 -30.00  160
 14  \w     34.00  72.00   0.50    0.22    --  105.75 -30.00 -30.00   76
 15  \w     34.00  90.00   0.50    0.22    --  105.75 -45.00  30.00  112
 16  \w     34.00  90.00   0.50    0.22    --  105.75 -45.00-120.00  112
 17  \w     34.00  90.00   0.50    0.22    --  105.75 -45.00-180.00  112
 18  \w     34.00  90.00   0.50    0.22    --  105.75 -45.00 -30.00  112
 19  \w     34.00  90.00   0.50    0.22    --  105.75 -45.00 150.00  112
 20  \w     99.00 176.00   0.50    0.22    --  105.75  15.00 120.00  154
 21  \w    101.00 152.00   0.50    0.22    --  105.75  45.00 -90.00  102
 22  \w     46.00  72.00   0.50    0.22    --  105.75 -45.00   0.00   52
 23  \w     38.00  64.00   0.50    0.22    --  105.75 -15.00 -90.00   52
;
_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      -0.0143792000
_diffrn_orient_matrix_UB_12      -0.0410763000
_diffrn_orient_matrix_UB_13      0.0828475000
_diffrn_orient_matrix_UB_21      0.0980478000
_diffrn_orient_matrix_UB_22      0.0673104000
_diffrn_orient_matrix_UB_23      0.0327817000
_diffrn_orient_matrix_UB_31      -0.1101744000
_diffrn_orient_matrix_UB_32      0.0653317000
_diffrn_orient_matrix_UB_33      0.0183435000
_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  0.0347
_diffrn_reflns_av_unetI/netI     0.0225
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.991
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       19
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -20
_diffrn_reflns_number            13923
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.984
_diffrn_reflns_theta_full        74.504
_diffrn_reflns_theta_max         77.864
_diffrn_reflns_theta_min         5.172
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.778
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.21033
_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            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.326
_exptl_crystal_description       block
_exptl_crystal_F_000             1136
_exptl_crystal_size_max          0.36
_exptl_crystal_size_mid          0.284
_exptl_crystal_size_min          0.154
_refine_diff_density_max         0.225
_refine_diff_density_min         -0.157
_refine_diff_density_rms         0.045
_refine_ls_abs_structure_details
;
 Refined as an inversion twin.
;
_refine_ls_abs_structure_Flack   0.2(2)
_refine_ls_extinction_coef       0.00059(11)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2018/3 (Sheldrick 2018)'
_refine_ls_goodness_of_fit_ref   1.073
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     195
_refine_ls_number_reflns         2792
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.073
_refine_ls_R_factor_all          0.0313
_refine_ls_R_factor_gt           0.0308
_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^)+(0.0425P)^2^+1.0692P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0784
_refine_ls_wR_factor_ref         0.0790
_reflns_Friedel_coverage         0.762
_reflns_Friedel_fraction_full    0.999
_reflns_Friedel_fraction_max     0.975
_reflns_number_gt                2748
_reflns_number_total             2792
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            oc0c01624_si_001.cif
_cod_data_source_block           fasha01
_cod_database_code               4518637
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.890
_shelx_estimated_absorpt_t_min   0.767
_reflns_odcompleteness_completeness 99.94
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     74.33
_olex2_refinement_description
;
1. Twinned data refinement
 Scales: 0.8(2)
 0.2(2)
2. 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, All O(H,H) groups
3. Others
 Fixed Sof: H3A(0.5) H3B(0.5) H4A(0.5) H4B(0.5)
4.a Ternary CH refined with riding coordinates:
 C5(H5), C6(H6), C7(H7)
4.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C3(H3C,H3D), C8(H8A,H8B), C9(H9A,H9B), C14(H14A,H14B)
4.c Idealised Me refined as rotating group:
 C15(H15A,H15B,H15C)
;
_shelx_res_checksum              60989
_shelx_hkl_checksum              7492
_olex2_submission_original_sample_id fasha01
_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 3.764
_oxdiff_exptl_absorpt_empirical_full_min 0.564