Aryl urea substituted fatty acids: a new class of protonophoric mitochondrial uncoupler that utilises a synthetic anion transporter
Rawling, Tristan; MacDermott-Opeskin, Hugo; Roseblade, Ariane; Pazderka, Curtis; Clarke, Callum; Bourget, Kirsi; Wu, Xin; Lewis, William; Noble, Benjamin; Gale, Philip A.; O'Mara, Megan L.; Cranfield, Charles; Murray, Michael; Chemical Science  (2020) –; doi:10.1039/D0SC02777D

data_1558873
_publ_section_title
;
 Aryl urea substituted fatty acids: a new class of protonophoric
 mitochondrial uncoupler that utilises a synthetic anion transporter
;
_journal_name_full               'Chemical Science'
_journal_paper_doi               10.1039/D0SC02777D
_journal_year                    2020
_chemical_formula_moiety         'C24 H36 Cl F3 N2 O3'
_chemical_formula_sum            'C24 H36 Cl F3 N2 O3'
_chemical_formula_weight         493.00
_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'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     iterative
_audit_creation_date             2020-01-30
_audit_creation_method
;
Olex2 1.3
(compiled Nov 21 2019 18:26:39 for OlexSys, GUI svn.r6003)
;
_audit_update_record
;
2020-04-22 deposited with the CCDC.	2020-08-11 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 110.706(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   19.0452(4)
_cell_length_b                   7.53882(12)
_cell_length_c                   18.2425(4)
_cell_measurement_reflns_used    8491
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      72.1850
_cell_measurement_theta_min      4.8620
_cell_volume                     2450.04(9)
_computing_cell_refinement       'CrysAlisPro 1.171.40.53a (Rigaku OD, 2019)'
_computing_data_collection       'CrysAlisPro 1.171.40.53a (Rigaku OD, 2019)'
_computing_data_reduction        'CrysAlisPro 1.171.40.53a (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 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'olex2.solve 1.3 (Bourhis et al., 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100(2)
_diffrn_detector                 'CCD area detector'
_diffrn_detector_area_resol_mean 5.2930
_diffrn_detector_type            'Agilent Diffraction Atlas detector'
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.982
_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     -5.00  45.00   1.00   20.00    --  -38.19  19.00 -60.00   50
  2  \w     -5.00  45.00   1.00   20.00    --  -38.19  19.00-180.00   50
  3  \w    -21.00  39.00   1.00   20.00    --  -38.19  38.00 150.00   60
  4  \w    -21.00  39.00   1.00   20.00    --  -38.19  38.00-120.00   60
  5  \w     -5.00  45.00   1.00   20.00    --  -38.19  19.00-150.00   50
  6  \w     61.00 129.00   1.00   20.00    --   38.19 178.00 -60.00   68
  7  \w     74.00 178.00   1.00   80.00    --  107.94  30.00-120.00  104
  8  \w     28.00  57.00   1.00   80.00    --  107.94 -30.00 120.00   29
  9  \w     32.00  93.00   1.00   80.00    --  107.94 -61.00 -30.00   61
 10  \w     26.00 126.00   1.00   80.00    --  107.94 -77.00 120.00  100
 11  \w     28.00  57.00   1.00   80.00    --  107.94 -30.00  60.00   29
 12  \w     28.00  57.00   1.00   80.00    --  107.94 -30.00  90.00   29
 13  \w     31.00  72.00   1.00   80.00    --  107.94 -45.00-150.00   41
 14  \w    103.00 178.00   1.00   80.00    --  107.94  77.00 150.00   75
 15  \w     31.00  72.00   1.00   80.00    --  107.94 -45.00-180.00   41
 16  \w     32.00  93.00   1.00   80.00    --  107.94 -61.00 120.00   61
 17  \w    103.00 178.00   1.00   80.00    --  107.94  77.00  90.00   75
 18  \w   -114.00  -7.00   1.00   20.00    --  -38.19 -57.00-180.00  107
 19  \w   -114.00  -7.00   1.00   20.00    --  -38.19 -57.00  60.00  107
 20  \w   -114.00  -7.00   1.00   20.00    --  -38.19 -57.00 -90.00  107
 21  \w    -21.00   4.00   1.00   20.00    --  -38.19  38.00  60.00   25
 22  \w     61.00 129.00   1.00   20.00    --   38.19 178.00 120.00   68
;
_diffrn_measurement_device       '\k-geometry diffractometer'
_diffrn_measurement_device_type  'SuperNova-Duo, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0010801000
_diffrn_orient_matrix_UB_12      0.1829860000
_diffrn_orient_matrix_UB_13      -0.0380517000
_diffrn_orient_matrix_UB_21      -0.0861093000
_diffrn_orient_matrix_UB_22      -0.0107293000
_diffrn_orient_matrix_UB_23      -0.0383903000
_diffrn_orient_matrix_UB_31      -0.0079150000
_diffrn_orient_matrix_UB_32      0.0901178000
_diffrn_orient_matrix_UB_33      0.0724203000
_diffrn_radiation_collimation    'focusing mirrors'
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_radiation_wavelength_determination fundamental
_diffrn_radiation_xray_symbol    K-L~2,3~
_diffrn_reflns_av_R_equivalents  0.0323
_diffrn_reflns_av_unetI/netI     0.0264
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.982
_diffrn_reflns_limit_h_max       23
_diffrn_reflns_limit_h_min       -23
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -7
_diffrn_reflns_limit_l_max       22
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            16382
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.982
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         72.689
_diffrn_reflns_theta_min         4.892
_diffrn_source                   'microfocus sealed tube'
_diffrn_source_current           0.8
_diffrn_source_power             0.04
_diffrn_source_target            Cu
_diffrn_source_type              'Agilent Diffraction microfocus tube'
_diffrn_source_voltage           50
_exptl_absorpt_coefficient_mu    1.824
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.604
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.53a (Rigaku Oxford Diffraction, 2019)
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 colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.337
_exptl_crystal_description       plank
_exptl_crystal_F_000             1048
_exptl_crystal_recrystallization_method
'The material was recrystallised from a mixture of dimethylformamide and water  by slow evaporation'
_exptl_crystal_size_max          0.397
_exptl_crystal_size_mid          0.054
_exptl_crystal_size_min          0.02
_refine_diff_density_max         0.293
_refine_diff_density_min         -0.351
_refine_diff_density_rms         0.041
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.066
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     382
_refine_ls_number_reflns         4788
_refine_ls_number_restraints     229
_refine_ls_restrained_S_all      1.066
_refine_ls_R_factor_all          0.0458
_refine_ls_R_factor_gt           0.0394
_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^)+(0.0521P)^2^+0.7465P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1019
_refine_ls_wR_factor_ref         0.1066
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4202
_reflns_number_total             4788
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d0sc02777d2.cif
_cod_data_source_block           pag20_s1972
_cod_database_code               1558873
_sydney_internal_submission_code pag20_s1972
_sydney_internal_submission_date 2020-01-14
_sydney_internal_submission_number s1972
_sydney_internal_client_code     xwu
_sydney_internal_client_email    xiwu7916@chem.usyd.edu.au
_sydney_internal_client_name     'Xin Wu'
_sydney_internal_supervisor_code pag
_sydney_internal_supervisor_name 'Phil Gale'
_sydney_internal_collection_date 2020-01-24
_sydney_internal_collection_user wlew0588
_sydney_internal_process_date    2020-01-28
_sydney_internal_process_user    wlew0588
_sydney_internal_solution_date   2020-01-28
_sydney_internal_solution_user   wlew0588
_sydney_internal_refine_date     2020-01-28
_sydney_internal_refine_user     wlew0588
_sydney_internal_check_and_archive_date 2020-01-30
_sydney_internal_check_user      wlew0588
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C24 H36 N3 O3 F3 Cl'
_chemical_oxdiff_usercomment     29CsOH-1
_shelx_estimated_absorpt_t_max   0.964
_shelx_estimated_absorpt_t_min   0.531
_reflns_odcompleteness_completeness 99.89
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     67.13
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All O(H) groups
2. Restrained distances
 F1-F2 \\sim F2-F3 \\sim F3-F1
 with sigma of 0.02
 F1-C24 \\sim F3-C24 \\sim F2-C24
 with sigma of 0.02
 F1-C5 \\sim F2-C5 \\sim F3-C5
 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
C24 \\sim C3 \\sim C5: within 2A with sigma of 0.01 and sigma for terminal
atoms of 0.02 within 2A
Cl1 \\sim F1A \\sim F2A \\sim F3A \\sim C24A \\sim Cl1A \\sim F1 \\sim F2 \\sim
F3 \\sim F4 \\sim F5 \\sim F6 \\sim C24: within 2A with sigma of 0.1 and sigma
for terminal atoms of 0.02 within 2A
4. Rigid body (RIGU) restrains
 C24, C3, C5
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
 Cl1A, F1, F2, F3, F4, F5, F6, C24, Cl1, F1A, F2A, C24A, F3A
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
5. Others
 1*[Sof(F1)+Sof(F2)+Sof(F3)]+1*[Sof(F4)+Sof(F5)+Sof(F6)]-1*[Sof(Cl1)+Sof(Cl1A)+
 Sof(F1A)+Sof(F2A)+Sof(F3A)+Sof(C24)+Sof(C24A)]=0 with esd of 0.001
 Sof(Cl1A)=Sof(F1A)=Sof(F2A)=Sof(F3A)=Sof(C24A)=1-FVAR(1)
 Sof(Cl1)=Sof(C24)=FVAR(1)
 Sof(F1)=Sof(F2)=Sof(F3)=FVAR(2)
 Sof(F4)=Sof(F5)=Sof(F6)=FVAR(3)
6.a Secondary CH2 refined with riding coordinates:
 C8(H8A,H8B), C9(H9A,H9B), C10(H10A,H10B), C11(H11A,H11B), C12(H12A,H12B),
 C13(H13A,H13B), C14(H14A,H14B), C15(H15A,H15B), C16(H16A,H16B), C17(H17A,H17B),
  C18(H18A,H18B), C19(H19A,H19B), C20(H20A,H20B), C21(H21A,H21B), C22(H22A,H22B)
6.b Aromatic/amide H refined with riding coordinates:
 C2(H2B), C4(H4), C6(H6)
;
_shelx_res_checksum              62088
_olex2_date_sample_data_collection 2020-01-24
_olex2_date_sample_submission    2020-01-13
_olex2_diffrn_ambient_temperature_device 'Oxford Cryosystems'
_olex2_exptl_crystal_mounting_method
'The crystal was mounted on a MITIGEN holder with paratone-N oil'
_olex2_submission_original_sample_id 29CsOH-1
_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 1.699
_oxdiff_exptl_absorpt_empirical_full_min 0.737