A potent fluorescent transmembrane HCl transporter perturbs cellular pH and promotes cancer cell death.
Fares, Mohamed; Wu, Xin; McNaughton, Daniel A.; Gilchrist, Alexander M.; Lewis, William; Keller, Paul A.; Arias-Betancur, Alain; Fontova, Pere; Pérez-Tomás, Ricardo; Gale, Philip A.; Organic & biomolecular chemistry 21 (2023) 2509–2515; doi:10.1039/d3ob00128h

data_7159230
_publ_section_title
;
 A potent fluorescent transmembrane HCl transporter perturbs cellular pH
 and promotes cancer cell death.
;
_journal_issue                   12
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              2509
_journal_page_last               2515
_journal_paper_doi               10.1039/d3ob00128h
_journal_volume                  21
_journal_year                    2023
_chemical_formula_moiety         'C24 H20 N4 O4, 1[C2H6O]'
_chemical_formula_sum            'C26 H26 N4 O5'
_chemical_formula_weight         474.51
_space_group_crystal_system      monoclinic
_space_group_IT_number           13
_space_group_name_Hall           '-P 2yc'
_space_group_name_H-M_alt        'P 1 2/c 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     iterative
_audit_creation_date             2020-01-13
_audit_creation_method
;
Olex2 1.3
(compiled 2019.09.11 svn.r3662 for OlexSys, GUI svn.r6003)
;
_audit_update_record
;
2020-04-27 deposited with the CCDC.	2023-02-24 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90.234(4)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   28.2772(10)
_cell_length_b                   11.1135(9)
_cell_length_c                   7.9823(3)
_cell_measurement_reflns_used    2046
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      70.5320
_cell_measurement_theta_min      3.9560
_cell_volume                     2508.5(2)
_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    '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 10.5861
_diffrn_detector_type            'Agilent Diffraction Atlas detector'
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.983
_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     -3.00  41.00   1.00   30.00    --  -38.19  19.00-150.00   44
  2  \w    -26.00  58.00   1.00   30.00    --   38.19 -38.00   0.00   84
  3  \w     91.00 119.00   1.00   30.00    --   38.19 178.00 -30.00   28
  4  \w     29.00  57.00   1.00  120.00    --  107.32 -30.00   0.00   28
  5  \w     28.00  54.00   1.00  120.00    --  107.32 -30.00  30.00   26
  6  \w     28.00  57.00   1.00  120.00    --  107.32 -30.00 120.00   29
  7  \w     94.00 133.00   1.00  120.00    --  107.32  45.00-150.00   39
  8  \w     43.00  69.00   1.00  120.00    --  107.32 -45.00 -60.00   26
  9  \w     24.00 102.00   1.00  120.00    --  107.32 -95.00 -60.00   78
 10  \w    135.00 160.00   1.00  120.00    --  107.32  45.00-150.00   25
 11  \w    135.00 165.00   1.00  120.00    --  107.32 111.00 150.00   30
 12  \w    -64.00 -39.00   1.00   30.00    --  -38.32-178.00  30.00   25
 13  \w   -128.00-102.00   1.00   30.00    --  -38.32-178.00  30.00   26
 14  \w    -90.00 -37.00   1.00   30.00    --  -38.32 178.00 150.00   53
 15  \w     29.00  56.00   1.00  120.00    --  107.32 -30.00-150.00   27
 16  \w     57.00 109.00   1.00  120.00    --  107.32-111.00  30.00   52
 17  \w     29.00  56.00   1.00  120.00    --  107.32 -30.00  60.00   27
 18  \w     31.00  57.00   1.00  120.00    --  107.32 -30.00  90.00   26
 19  \w     28.00  53.00   1.00  120.00    --  107.32 -30.00 -60.00   25
 20  \w    124.00 161.00   1.00  120.00    --  107.32 144.00-158.00   37
 21  \w     38.00  64.00   1.00  120.00    --  107.32 -45.00 -90.00   26
 22  \w     73.00  99.00   1.00  120.00    --  107.32  30.00-120.00   26
 23  \w    113.00 163.00   1.00  120.00    --  107.32  30.00-120.00   50
 24  \w     55.00  81.00   1.00  120.00    --  107.32 -61.00   0.00   26
 25  \w     -5.00  20.00   1.00   30.00    --  -39.07  19.00-120.00   25
 26  \w     79.00 105.00   1.00  120.00    --  107.94-111.00  60.00   26
 27  \w     31.00  56.00   1.00  120.00    --  107.94 -45.00-180.00   25
 28  \w   -115.00  -8.00   1.00   30.00    --  -39.07 -57.00 120.00  107
 29  \w    -21.00  38.00   1.00   30.00    --  -39.07  38.00   0.00   59
 30  \w   -115.00  -8.00   1.00   30.00    --  -39.07 -57.00 -90.00  107
 31  \w   -115.00  -8.00   1.00   30.00    --  -39.07 -57.00-180.00  107
 32  \w    -21.00  38.00   1.00   30.00    --  -39.07  38.00 150.00   59
 33  \w   -115.00  -8.00   1.00   30.00    --  -39.07 -57.00  30.00  107
 34  \w     75.00 121.00   1.00   30.00    --   39.07 161.00  99.00   46
 35  \w     31.00  56.00   1.00  120.00    --  107.94  15.00 120.00   25
;
_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      -0.0051107000
_diffrn_orient_matrix_UB_12      -0.1378192000
_diffrn_orient_matrix_UB_13      -0.0089305000
_diffrn_orient_matrix_UB_21      -0.0537282000
_diffrn_orient_matrix_UB_22      0.0119977000
_diffrn_orient_matrix_UB_23      0.0266831000
_diffrn_orient_matrix_UB_31      -0.0075212000
_diffrn_orient_matrix_UB_32      0.0080829000
_diffrn_orient_matrix_UB_33      -0.1909596000
_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  0.0918
_diffrn_reflns_av_unetI/netI     0.0957
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.983
_diffrn_reflns_limit_h_max       33
_diffrn_reflns_limit_h_min       -34
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_l_max       6
_diffrn_reflns_limit_l_min       -9
_diffrn_reflns_number            19257
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.983
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         72.655
_diffrn_reflns_theta_min         3.978
_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    0.728
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.568
_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    1.256
_exptl_crystal_description       needle
_exptl_crystal_F_000             1000
_exptl_crystal_recrystallization_method
'crystallised from a mixture of dimethylformamide and ethanol'
_exptl_crystal_size_max          0.432
_exptl_crystal_size_mid          0.019
_exptl_crystal_size_min          0.007
_refine_diff_density_max         0.190
_refine_diff_density_min         -0.192
_refine_diff_density_rms         0.049
_refine_ls_extinction_coef       0.00081(18)
_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   0.931
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     383
_refine_ls_number_reflns         4894
_refine_ls_number_restraints     855
_refine_ls_restrained_S_all      0.889
_refine_ls_R_factor_all          0.1531
_refine_ls_R_factor_gt           0.0661
_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^)+(0.0884P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1579
_refine_ls_wR_factor_ref         0.2088
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2100
_reflns_number_total             4894
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3ob00128h2.cif
_cod_data_source_block           pag19_s1966_sq
_cod_depositor_comments          'Adding full bibliography for 7159230.cif.'
_cod_database_code               7159230
_sydney_internal_submission_code pag19_s1966
_sydney_internal_submission_date 2019-12-11
_sydney_internal_submission_number s1966
_sydney_internal_client_code     mmet
_sydney_internal_client_email    'Mohamed Metwaly'
_sydney_internal_client_name     mmet5356@chem.usyd.edu.au
_sydney_internal_supervisor_code pag
_sydney_internal_supervisor_name 'Phil Gale'
_sydney_internal_collection_date 2019-12-19
_sydney_internal_collection_user wlew0588
_sydney_internal_process_date    2020-01-13
_sydney_internal_process_user    wlew0588
_sydney_internal_solution_date   2020-01-13
_sydney_internal_solution_user   wlew0588
_sydney_internal_refine_date     2020-01-13
_sydney_internal_refine_user     wlew0588
_sydney_internal_check_and_archive_date 2020-01-13
_sydney_internal_check_user      wlew0588
_platon_squeeze_void_probe_radius 1.20
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C24H20N4O4
_chemical_oxdiff_usercomment     HBisUreaCoumarine
_reflns_odcompleteness_completeness 99.94
_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 N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 C8-C6A \\sim C9-C8 \\sim C7-C6 \\sim C9A-C7
 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
All non-hydrogen atoms have similar U: within 2A with sigma of 0.005 and sigma
for terminal atoms of 0.01 within 2A
4. Rigid body (RIGU) restrains
 All non-hydrogen atoms
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
5. Same fragment restrains
{O1, C2, C3, C4, C5, C6, C9, C10, O11, C12} sigma for 1-2: 0.02, 1-3: 0.04
as in
{O1A, C2A, C3A, C4A, C5A, C6A, C9A, C10A, O11A, C12A}
6. Others
 Sof(O1A)=Sof(C2A)=Sof(C3A)=Sof(H3A)=Sof(C4A)=Sof(C5A)=Sof(C6A)=Sof(H6A)=
 Sof(C9A)=Sof(H9A)=Sof(C10A)=Sof(O11A)=Sof(C12A)=Sof(H12D)=Sof(H12E)=Sof(H12F)=
 1-FVAR(1)
 Sof(O1)=Sof(C2)=Sof(C3)=Sof(H3)=Sof(C4)=Sof(C5)=Sof(C6)=Sof(H6)=Sof(C9)=
 Sof(H9)=Sof(C10)=Sof(O11)=Sof(C12)=Sof(H12A)=Sof(H12B)=Sof(H12C)=FVAR(1)
7.a Aromatic/amide H refined with riding coordinates:
 C3(H3), C6(H6), C9(H9), N13(H13), N15(H15), C18(H18), C19(H19), C20(H20),
 C21(H21), C22(H22), N23(H23), N25(H25), C28(H28), C29(H29), C30(H30), C31(H31),
  C32(H32), C3A(H3A), C6A(H6A), C9A(H9A)
7.b Idealised Me refined as rotating group:
 C12(H12A,H12B,H12C), C12A(H12D,H12E,H12F)
;
_shelx_res_checksum              22287
_shelx_fab_checksum              15013
_olex2_date_sample_data_collection 2019-12-19
_olex2_date_sample_submission    2019-12-11
_olex2_exptl_crystal_mounting_method 'in paratone on a micromount'
_olex2_submission_original_sample_id HBisUreaCoumarine
_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 1.375
_oxdiff_exptl_absorpt_empirical_full_min 0.782