Enhancing allosteric inhibition of dihydrodipicolinate synthase through the design and synthesis of novel dimeric compounds
Christoff, Rebecca M.; Al Bayer, Mohammad; Soares da Costa, Tatiana P.; Perugini, Matthew A.; Abbott, Belinda M.; RSC Medicinal Chemistry  (2023) –; doi:10.1039/D3MD00044C

data_7247098
_publ_section_title
;
 Enhancing allosteric inhibition of dihydrodipicolinate synthase through
 the design and synthesis of novel dimeric compounds
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D3MD00044C
_journal_year                    2023
_chemical_formula_moiety         'C27 H22 N2 O10 S2'
_chemical_formula_sum            'C27 H22 N2 O10 S2'
_chemical_formula_weight         598.58
_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   geom
_audit_creation_date             2023-01-08
_audit_creation_method
;
Olex2 1.5
(compiled 2022.04.07 svn.rca3783a0 for OlexSys, GUI svn.r6498)
;
_audit_update_record
;
2023-01-08 deposited with the CCDC.	2023-07-04 downloaded from the CCDC.
;
_cell_angle_alpha                76.057(4)
_cell_angle_beta                 83.296(4)
_cell_angle_gamma                84.321(4)
_cell_formula_units_Z            4
_cell_length_a                   13.0431(6)
_cell_length_b                   15.4223(7)
_cell_length_c                   17.5012(7)
_cell_measurement_reflns_used    9404
_cell_measurement_temperature    150
_cell_measurement_theta_max      70.9420
_cell_measurement_theta_min      4.0890
_cell_volume                     3384.2(3)
_computing_cell_refinement       'CrysAlisPro 1.171.40.53 (Rigaku OD, 2019)'
_computing_data_collection       'CrysAlisPro 1.171.40.53 (Rigaku OD, 2019)'
_computing_data_reduction        'CrysAlisPro 1.171.40.53 (Rigaku OD, 2019)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (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      150
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix3000
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.994
_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   -101.00 -63.00   0.50    0.50    --  -38.50 -60.00 165.00   76
  2  \w    -49.00 -22.00   0.50    0.50    --  -38.50 -60.00 165.00   54
  3  \w    -13.00  44.00   0.50    0.50    --   42.60 -60.00 165.00  114
  4  \w     25.00 100.00   0.50    0.50    --   42.60  60.00 -55.00  150
  5  \w     37.00  86.00   0.50    2.02    --  100.00 -60.00 165.00   98
  6  \w     82.00 164.00   0.50    2.02    --  100.00  60.00 -55.00  164
  7  \w    -57.00 -19.00   0.50    0.50    --  -38.50 -65.00 120.00   76
  8  \w      4.00  29.00   0.50    0.50    --  -38.50  21.00 150.00   50
  9  \w    -42.00 -17.00   0.50    0.50    --  -38.50  32.00-120.00   50
 10  \w    -72.00 -32.00   0.50    0.50    --  -38.50 104.00  60.00   80
 11  \w    -25.00   9.00   0.50    0.50    --  -38.50 104.00  60.00   68
 12  \w    -18.00  25.00   0.50    0.50    --  -38.50  65.00  30.00   86
 13  \w    -56.00 -20.00   0.50    0.50    --  -38.50  65.00  30.00   72
 14  \w    -45.00 -20.00   0.50    0.50    --  -38.50  21.00 -90.00   50
 15  \w      0.00  25.00   0.50    0.50    --  -38.50  32.00-120.00   50
 16  \w     -2.00  30.00   0.50    0.50    --  -38.50  21.00 -90.00   64
 17  \w    -45.00 -20.00   0.50    0.50    --  -38.50  21.00 150.00   50
 18  \w    -96.00 -27.00   0.50    0.50    --  -38.50 -65.00 -90.00  138
 19  \w    -35.00  -7.00   0.50    0.50    --  -38.50  60.00 -55.00   56
 20  \w    -99.00 -61.00   0.50    0.50    --  -38.50 -65.00 120.00   76
 21  \w     23.00  83.00   0.50    0.50    --   42.60  65.00  90.00  120
 22  \w     35.00  61.00   0.50    0.50    --   42.60  32.00   0.00   52
 23  \w     50.00  95.00   0.50    0.50    --   42.60-138.00 150.00   90
 24  \w    -23.00  35.00   0.50    0.50    --   42.60 -32.00 -30.00  116
 25  \w     52.00  94.00   0.50    0.50    --   42.60-138.00  60.00   84
 26  \w     70.00  96.00   0.50    0.50    --   42.60-138.00 -60.00   52
 27  \w      8.00  73.00   0.50    0.50    --   42.60-104.00-180.00  130
 28  \w     79.00 104.00   0.50    0.50    --   42.60  32.00   0.00   50
 29  \w     13.00  38.00   0.50    0.50    --   42.60-104.00  30.00   50
 30  \w     54.00 101.00   0.50    0.50    --   42.60  54.00-120.00   94
 31  \w     40.00  65.00   0.50    0.50    --   42.60-138.00 -60.00   50
 32  \w    137.00 163.00   0.50    2.02    --  100.00 145.00-150.00   52
 33  \w    104.00 163.00   0.50    2.02    --  100.00  77.00-180.00  118
 34  \w     91.00 120.00   0.50    2.02    --  100.00  25.00-150.00   58
 35  \w     53.00  79.00   0.50    2.02    --  100.00 -77.00  30.00   52
 36  \w     40.00 102.00   0.50    2.02    --  100.00 -42.00-150.00  124
 37  \w     76.00 126.00   0.50    2.02    --  100.00-145.00-180.00  100
 38  \w     38.00  95.00   0.50    2.02    --  100.00 -42.00 -60.00  114
 39  \w     94.00 124.00   0.50    2.02    --  100.00 -77.00 150.00   60
 40  \w     44.00  69.00   0.50    2.02    --  100.00 -77.00 150.00   50
 41  \w     48.00 109.00   0.50    2.02    --  100.00-117.00  60.00  122
 42  \w    117.00 143.00   0.50    2.02    --  100.00  77.00  30.00   52
 43  \w     57.00  84.00   0.50    2.02    --  100.00-145.00-150.00   54
 44  \w     97.00 122.00   0.50    2.02    --  100.00 -87.00-180.00   50
 45  \w     94.00 163.00   0.50    2.02    --  100.00  33.00 -90.00  138
 46  \w     91.00 126.00   0.50    2.02    --  100.00  25.00  30.00   70
 47  \w     75.00 120.00   0.50    2.02    --  100.00 -68.00-120.00   90
 48  \w     39.00  64.00   0.50    2.02    --  100.00 -68.00-120.00   50
 49  \w     44.00 109.00   0.50    2.02    --  100.00 -33.00 120.00  130
 50  \w    110.00 154.00   0.50    2.02    --  100.00  77.00   0.00   88
 51  \w     95.00 174.00   0.50    2.02    --  100.00   8.00-180.00  158
 52  \w     81.00 107.00   0.50    2.02    --  100.00 -50.00  30.00   52
 53  \w     70.00 106.00   0.50    2.02    --  100.00 -96.00 -30.00   72
 54  \w     89.00 115.00   0.50    2.02    --  100.00-145.00-150.00   52
 55  \w     99.00 128.00   0.50    2.02    --  100.00  42.00  60.00   58
 56  \w     45.00 102.00   0.50    2.02    --  100.00 -50.00   0.00  114
 57  \w     74.00 105.00   0.50    2.02    --  100.00 -42.00   0.00   62
 58  \w     82.00 107.00   0.50    2.02    --  100.00 -33.00  30.00   50
 59  \w     81.00 106.00   0.50    2.02    --  100.00-117.00-180.00   50
 60  \w     58.00 109.00   0.50    2.02    --  100.00-112.00-149.84  102
 61  \w     75.00 108.00   0.50    2.02    --  100.00-117.00-120.00   66
 62  \w    128.00 165.00   0.50    2.02    --  100.00  25.00-150.00   74
 63  \w    118.00 163.00   0.50    2.02    --  100.00  96.00-120.00   90
 64  \w     65.00 109.00   0.50    2.02    --  100.00-117.00 -30.00   88
 65  \w     39.00  64.00   0.50    2.02    --  100.00 -50.00 -30.00   50
 66  \w     79.00 104.00   0.50    2.02    --  100.00 -77.00 -90.00   50
 67  \w     91.00 122.00   0.50    2.02    --  100.00  59.00 -30.00   62
 68  \w    135.00 160.00   0.50    2.02    --  100.00  68.00 150.00   50
 69  \w     49.00  75.00   0.50    2.02    --  100.00 -33.00  30.00   52
 70  \w     34.00  59.00   0.50    2.02    --  100.00 -96.00-180.00   50
 71  \w     78.00 118.00   0.50    2.02    --  100.00 -59.00-150.00   80
 72  \w     45.00  71.00   0.50    2.02    --  100.00 -59.00-150.00   52
 73  \w     82.00 163.00   0.50    2.02    --  100.00  68.00  60.00  162
 74  \w    115.00 141.00   0.50    2.02    --  100.00  42.00  90.00   52
 75  \w     55.00  81.00   0.50    2.02    --  100.00-145.00   0.00   52
 76  \w    101.00 126.00   0.50    2.02    --  100.00-145.00   0.00   50
 77  \w     94.00 120.00   0.50    2.02    --  100.00  42.00  30.00   52
 78  \w     45.00  70.00   0.50    2.02    --  100.00 -87.00   0.00   50
 79  \w     80.00 105.00   0.50    2.02    --  100.00 -87.00   0.00   50
 80  \w    110.00 144.00   0.50    2.02    --  100.00  77.00-150.00   68
 81  \w    109.00 152.00   0.50    2.02    --  100.00  77.00 -90.00   86
 82  \w    112.00 137.00   0.50    2.02    --  100.00 117.00  30.00   50
 83  \w     92.00 123.00   0.50    2.02    --  100.00 -77.00  60.00   62
 84  \w     64.00  89.00   0.50    2.02    --  100.00 -42.00 -30.00   50
 85  \w    101.00 140.00   0.50    2.02    --  100.00 145.00  90.00   78
 86  \w     39.00  74.00   0.50    2.02    --  100.00-117.00-180.00   70
 87  \w     98.00 123.00   0.50    2.02    --  100.00  -8.00 -60.00   50
 88  \w    100.00 125.00   0.50    2.02    --  100.00 -77.00 -30.00   50
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, HyPix3000'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0791356000
_diffrn_orient_matrix_UB_12      0.0697882000
_diffrn_orient_matrix_UB_13      -0.0372451000
_diffrn_orient_matrix_UB_21      0.0521267000
_diffrn_orient_matrix_UB_22      -0.0618106000
_diffrn_orient_matrix_UB_23      -0.0527708000
_diffrn_orient_matrix_UB_31      -0.0723922000
_diffrn_orient_matrix_UB_32      0.0442716000
_diffrn_orient_matrix_UB_33      -0.0642735000
_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  0.0546
_diffrn_reflns_av_unetI/netI     0.0556
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.994
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -18
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            44877
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.994
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         71.369
_diffrn_reflns_theta_min         3.421
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.864
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.79065
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.53 (Rigaku Oxford Diffraction, 2019)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear yellow'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.174
_exptl_crystal_description       plate
_exptl_crystal_F_000             1238
_exptl_crystal_size_max          0.2
_exptl_crystal_size_mid          0.18
_exptl_crystal_size_min          0.14
_refine_diff_density_max         2.257
_refine_diff_density_min         -0.325
_refine_diff_density_rms         0.078
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.074
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     746
_refine_ls_number_reflns         13077
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.074
_refine_ls_R_factor_all          0.1093
_refine_ls_R_factor_gt           0.0807
_refine_ls_shift/su_max          0.002
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1616P)^2^+0.2799P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2365
_refine_ls_wR_factor_ref         0.2641
_reflns_Friedel_coverage         0.000
_reflns_number_gt                8385
_reflns_number_total             13077
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3md00044c2.cif
_cod_data_source_block           4b
_cod_depositor_comments
;

2024-10-18
Z value and formula fixed to values more according to usual
chemical conventions.                 miguel
;
_cod_original_formula_sum            'C54 H43 N4 O20 S4'
_cod_original_formula_weight         1196.16
_cod_original_formula_moiety         'C27 H22 N2 O10 S2, C27 H21 N2 O10 S2'
_cod_original_formula_units_Z            2
_cod_database_code               7247098
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C27H20N2O8S2
_shelx_estimated_absorpt_t_max   0.780
_shelx_estimated_absorpt_t_min   0.707
_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, All O(H) groups
2.a Ternary CH refined with riding coordinates:
 C00W(H00W), C00Y(H00Y), C011(H011), C01B(H01D)
2.b Secondary CH2 refined with riding coordinates:
 C00Z(H00A,H00B), C018(H01A,H01B)
2.c Aromatic/amide H refined with riding coordinates:
 C01A(H01C), C01D(H01E), C01F(H01F), C01G(H01G), C01M(H01M), C01O(H01O),
 C01P(H01P), C01R(H01R), C01T(H01T), C01U(H01U), C01V(H01V), C01W(H01W),
 C020(H020), C021(H021), C022(H022), C023(H023), C024(H024), C026(H026),
 C027(H027), C029(H029)
2.d Idealised Me refined as rotating group:
 C028(H02G,H02H,H02I), C02C(H02A,H02B,H02C), C02E(H02D,H02E,H02F), C02F(H02J,
 H02K,H02L)
2.e Idealised tetrahedral OH refined as rotating group:
 O009(H009), O2(H2), O00T(H00T)
;
_smtbx_masks_void_probe_radius   1.2
_smtbx_masks_void_truncation_radius 1.2
_shelx_res_checksum              67795
_shelx_fab_checksum              88585
_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 1.554
_oxdiff_exptl_absorpt_empirical_full_min 0.677