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_1558874
_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
'2(C12 H18 Cl0.5 F1.5 N O1.5), 2(C1.5 H3.5 N0.5 O0.5)'
_chemical_formula_sum            'C27 H43 Cl F3 N3 O4'
_chemical_formula_weight         566.09
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2020-01-22
_audit_creation_method
;
Olex2 1.3
(compiled 2019.09.11 svn.r3662 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                90.279(3)
_cell_angle_beta                 98.533(3)
_cell_angle_gamma                100.758(2)
_cell_formula_units_Z            4
_cell_length_a                   10.4481(3)
_cell_length_b                   13.0857(4)
_cell_length_c                   21.6967(8)
_cell_measurement_reflns_used    7982
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      72.6020
_cell_measurement_theta_min      3.9580
_cell_volume                     2880.37(16)
_computing_cell_refinement       'CrysAlisPro 1.171.40.35a (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.40.35a (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.40.35a (Rigaku OD, 2018)'
_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    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100(2)
_diffrn_detector                 'CCD area detector'
_diffrn_detector_area_resol_mean 10.5861
_diffrn_detector_type            'Agilent Diffraction Atlas detector'
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.971
_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  35.00   1.00    9.00    --  -38.01  19.00 -60.00   30
  2  \w     -3.00  31.00   1.00    9.00    --  -38.01  19.00 -30.00   34
  3  \w      8.00  45.00   1.00    9.00    --  -38.01  19.00 -90.00   37
  4  \w     -5.00  30.00   1.00    9.00    --  -38.01  19.00-180.00   35
  5  \w     -5.00  45.00   1.00    9.00    --  -38.01  19.00-150.00   50
  6  \w      7.00  45.00   1.00    9.00    --  -38.01  19.00-120.00   38
  7  \w     66.00 125.00   1.00    9.00    --   38.01 178.00 120.00   59
  8  \w      6.00  78.00   1.00    9.00    --   38.01 -99.00 120.00   72
  9  \w     17.00  78.00   1.00    9.00    --   38.01 -99.00-120.00   61
 10  \w     42.00 109.00   1.00   36.00    --  107.94-112.00 150.00   67
 11  \w    153.00 178.00   1.00   36.00    --  107.94 112.00 -60.00   25
 12  \w     62.00 145.00   1.00   36.00    --  107.94 178.00-180.00   83
 13  \w    101.00 164.00   1.00   36.00    --  107.94  45.00   0.00   63
 14  \w     35.00  72.00   1.00   36.00    --  107.94 -45.00 -90.00   37
 15  \w     35.00  62.00   1.00   36.00    --  107.94 -61.00 150.00   27
 16  \w     45.00  71.00   1.00   36.00    --  107.94 -45.00   0.00   26
 17  \w    108.00 152.00   1.00   36.00    --  107.94  77.00-150.00   44
 18  \w     31.00 109.00   1.00   36.00    --  107.94-112.00 -30.00   78
 19  \w     28.00  57.00   1.00   36.00    --  107.94 -30.00-180.00   29
 20  \w     34.00  66.00   1.00   36.00    --  107.94 -45.00 -60.00   32
 21  \w     28.00  57.00   1.00   36.00    --  107.94 -30.00  60.00   29
 22  \w     46.00  72.00   1.00   36.00    --  107.94 -45.00  90.00   26
 23  \w     33.00 109.00   1.00   36.00    --  107.94-112.00-120.00   76
 24  \w    110.00 142.00   1.00   36.00    --  107.94 112.00 -60.00   32
 25  \w     47.00  86.00   1.00   36.00    --  107.94 -61.00-150.00   39
 26  \w     76.00 109.00   1.00   36.00    --  107.94-112.00   0.00   33
 27  \w     63.00 128.00   1.00   36.00    --  107.94 178.00 120.00   65
 28  \w     74.00 173.00   1.00   36.00    --  107.94  30.00 -60.00   99
;
_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      0.0744965000
_diffrn_orient_matrix_UB_12      0.1136225000
_diffrn_orient_matrix_UB_13      0.0027660000
_diffrn_orient_matrix_UB_21      0.0012051000
_diffrn_orient_matrix_UB_22      0.0051546000
_diffrn_orient_matrix_UB_23      0.0710400000
_diffrn_orient_matrix_UB_31      0.1323151000
_diffrn_orient_matrix_UB_32      -0.0379455000
_diffrn_orient_matrix_UB_33      0.0103241000
_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  0.0258
_diffrn_reflns_av_unetI/netI     0.0370
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.971
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       26
_diffrn_reflns_limit_l_min       -25
_diffrn_reflns_number            20897
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.971
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         72.738
_diffrn_reflns_theta_min         3.951
_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    1.656
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.727
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.35a (Rigaku Oxford Diffraction, 2018)
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    1.305
_exptl_crystal_description       plate
_exptl_crystal_F_000             1208
_exptl_crystal_size_max          0.186
_exptl_crystal_size_mid          0.094
_exptl_crystal_size_min          0.041
_refine_diff_density_max         0.267
_refine_diff_density_min         -0.353
_refine_diff_density_rms         0.048
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.027
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     784
_refine_ls_number_reflns         11109
_refine_ls_number_restraints     379
_refine_ls_restrained_S_all      1.027
_refine_ls_R_factor_all          0.0549
_refine_ls_R_factor_gt           0.0406
_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^)+(0.0576P)^2^+0.4065P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1042
_refine_ls_wR_factor_ref         0.1141
_reflns_Friedel_coverage         0.000
_reflns_number_gt                8785
_reflns_number_total             11109
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d0sc02777d2.cif
_cod_data_source_block           pag20_s1973
_cod_database_code               1558874
_sydney_internal_submission_code pag20_s1973
_sydney_internal_submission_date 2020-01-13
_sydney_internal_submission_number s1973
_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 2020-01-21
_sydney_internal_collection_user wlew0588
_sydney_internal_process_date    2020-01-22
_sydney_internal_process_user    wlew0588
_sydney_internal_solution_date   2020-01-22
_sydney_internal_solution_user   wlew0588
_sydney_internal_refine_date     2020-01-22
_sydney_internal_refine_user     wlew0588
_sydney_internal_check_and_archive_date 2020-01-22
_sydney_internal_check_user      wlew0588
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C27 H42 Cl F3 N4 O4'
_chemical_oxdiff_usercomment     29CsOH-2
_shelx_estimated_absorpt_t_max   0.935
_shelx_estimated_absorpt_t_min   0.748
_reflns_odcompleteness_completeness 99.93
_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 C(H,H,H) groups, All O(H) groups
2. Restrained distances
 F1-F2 \\sim F2-F3 \\sim F3-F1 \\sim F1A-F2A \\sim F2A-F3A \\sim F3A-F1A \\sim
F4-F5 \\sim F5-F6 \\sim F6-F4 ~
 F4A-F5A \\sim F5A-F6A \\sim F6A-F4A
 with sigma of 0.02
 C5-C24 \\sim C24A-C3 \\sim C48A-C27 \\sim C29-C48
 with sigma of 0.02
 F4-C48 \\sim F5-C48 \\sim F6-C48 \\sim F6A-C48A \\sim F4A-C48A \\sim F5A-C48A
\\sim F1-C24 \\sim F3-C24 ~
 F2-C24 \\sim F1A-C24A \\sim F3A-C24A \\sim F2A-C24A
 with sigma of 0.02
 Cl1-C3 \\sim Cl1A-C5 \\sim Cl2A-C29 \\sim Cl2-C27
 with sigma of 0.02
3. Restrained planarity
 C29, C30, C26, C25, C27, C28, Cl2A
 with sigma of 0.1
4. Uiso/Uaniso restraints and constraints
Cl1 \\sim Cl1A \\sim F1 \\sim F1A \\sim F2 \\sim F2A \\sim F3 \\sim F3A \\sim
C24 \\sim C24A \\sim Cl2 \\sim Cl2A \\sim F4 \\sim F4A \\sim F5 \\sim F5A \\sim
F6 \\sim F6A \\sim C48 \\sim C48A: within 2A with sigma of 0.01 and sigma for
terminal atoms of 0.02 within 2A
5. Rigid body (RIGU) restrains
 Cl1, Cl1A, F1, F1A, F2, F2A, F3, F3A, C24, C24A, Cl2, Cl2A, F4, F4A, F5, F5A,
 F6, F6A, C48, C48A
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
6. Others
 Sof(Cl1A)=Sof(F1A)=Sof(F2A)=Sof(F3A)=Sof(C24A)=1-FVAR(1)
 Sof(Cl1)=Sof(F1)=Sof(F2)=Sof(F3)=Sof(C24)=FVAR(1)
 Sof(Cl2A)=Sof(F4A)=Sof(F5A)=Sof(F6A)=Sof(C48A)=1-FVAR(2)
 Sof(Cl2)=Sof(F4)=Sof(F5)=Sof(F6)=Sof(C48)=FVAR(2)
7.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), C32(H32A,H32B), C33(H33A,H33B), C34(H34A,H34B), C35(H35A,H35B),
 C36(H36A,H36B), C37(H37A,H37B), C38(H38A,H38B), C39(H39A,H39B), C40(H40A,H40B),
  C41(H41A,H41B), C42(H42A,H42B), C43(H43A,H43B), C44(H44A,H44B), C45(H45A,
 H45B), C46(H46A,H46B)
7.b Aromatic/amide H refined with riding coordinates:
 C2(H2B), C4(H4), C6(H6), C26(H26), C28(H28), C30(H30), C49(H49), C52(H52)
7.c Idealised Me refined as rotating group:
 C50(H50A,H50B,H50C), C51(H51A,H51B,H51C), C53(H53A,H53B,H53C), C54(H54A,H54B,
 H54C)
;
_shelx_res_checksum              44113
_olex2_date_sample_data_collection 2020-01-21
_olex2_date_sample_submission    2020-01-13
_olex2_exptl_crystal_mounting_method 'in paratone on a micromount'
_olex2_submission_original_sample_id 29CsOH-2
_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 1.191
_oxdiff_exptl_absorpt_empirical_full_min 0.842