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_7247100
_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         'C14 H11 N O5 S'
_chemical_formula_sum            'C14 H11 N O5 S'
_chemical_formula_weight         305.30
_space_group_crystal_system      orthorhombic
_space_group_IT_number           60
_space_group_name_Hall           '-P 2n 2ab'
_space_group_name_H-M_alt        'P b c n'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     iterative
_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                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   23.240(4)
_cell_length_b                   13.0799(9)
_cell_length_c                   13.2996(13)
_cell_measurement_reflns_used    2032
_cell_measurement_temperature    150
_cell_measurement_theta_max      70.5630
_cell_measurement_theta_min      3.8920
_cell_volume                     4042.8(8)
_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    'olex2.solve 1.5 (Bourhis et al., 2015)'
_diffrn_ambient_environment      air
_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 0.999
_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    -88.00 -60.00   0.50    2.27    --  -38.50 -63.00  17.00   56
  2  \w    -22.00  24.00   0.50    2.27    --  -38.50  63.00 154.00   92
  3  \w    -74.00   5.00   0.50    2.27    --  -38.50 105.00-118.00  158
  4  \w    -13.00  13.00   0.50    2.27    --  -38.50  62.00   4.00   52
  5  \w     24.00  93.00   0.50    2.27    --   42.60  62.00   4.00  138
  6  \w     59.00  84.00   0.50    2.27    --   42.60  63.00 154.00   50
  7  \w     14.00  76.00   0.50    2.27    --   42.60-105.00 140.00  124
  8  \w      8.00  43.00   0.50    2.27    --   42.60 -63.00  17.00   70
  9  \w     -4.00  21.00   0.50    2.27    --   42.60 -62.00-133.00   50
 10  \w    100.00 125.00   0.50    9.07    --  100.00  62.00   4.00   50
 11  \w    113.00 138.00   0.50    9.07    --  100.00 105.00-118.00   50
 12  \w     68.00  94.00   0.50    9.07    --  100.00 -63.00  17.00   52
 13  \w     98.00 123.00   0.50    9.07    --  100.00  63.00 154.00   50
 14  \w    139.00 164.00   0.50    9.07    --  100.00  62.00   4.00   50
 15  \w     58.00  83.00   0.50    9.07    --  100.00-105.00 140.00   50
 16  \w     46.00  72.00   0.50    9.07    --  100.00 -62.00-133.00   52
 17  \w    -71.00 -46.00   0.50    2.27    --  -38.50 -62.00-133.00   50
 18  \w    -56.00 -16.00   0.50    2.27    --  -38.50 104.00  60.00   80
 19  \w    -82.00 -29.00   0.50    2.27    --  -38.50 -65.00-180.00  106
 20  \w     28.00 114.00   0.50    2.27    --   42.60  11.00 -60.00  172
 21  \w      8.00  48.00   0.50    2.27    --   42.60-104.00-150.00   80
 22  \w    103.00 163.00   0.50    9.07    --  100.00 117.00-180.00  120
 23  \w     39.00 127.00   0.50    9.07    --  100.00 -87.00-120.00  176
 24  \w    105.00 165.00   0.50    9.07    --  100.00  77.00-150.00  120
 25  \w     30.00  70.00   0.50    9.07    --  100.00 -96.00 -60.00   80
 26  \w     87.00 171.00   0.50    9.07    --  100.00  17.00 -60.00  168
 27  \w     89.00 162.00   0.50    9.07    --  100.00  42.00 120.00  146
 28  \w     94.00 165.00   0.50    9.07    --  100.00  33.00   0.00  142
 29  \w     41.00  67.00   0.50    9.07    --  100.00 -42.00   0.00   52
 30  \w     72.00 106.00   0.50    9.07    --  100.00 -42.00   0.00   68
 31  \w    124.00 149.00   0.50    9.07    --  100.00  50.00  90.00   50
 32  \w     89.00 159.00   0.50    9.07    --  100.00 145.00   0.00  140
 33  \w    113.00 158.00   0.50    9.07    --  100.00  77.00-180.00   90
 34  \w     91.00 118.00   0.50    9.07    --  100.00  -8.00-180.00   54
 35  \w     56.00  81.00   0.50    9.07    --  100.00 -25.00   0.00   50
 36  \w     67.00  93.00   0.50    9.07    --  100.00 -17.00  60.00   52
 37  \w     28.00  80.00   0.50    9.07    --  100.00  -8.00-180.00  104
 38  \w     60.00 104.00   0.50    9.07    --  100.00 -33.00  30.00   88
 39  \w     80.00 105.00   0.50    9.07    --  100.00 -96.00 -60.00   50
 40  \w     49.00  74.00   0.50    9.07    --  100.00 -96.00 120.00   50
 41  \w    123.00 163.00   0.50    9.07    --  100.00  25.00 -30.00   80
 42  \w     89.00 142.00   0.50    9.07    --  100.00  50.00-120.00  106
 43  \w    105.00 130.00   0.50    9.07    --  100.00 117.00-120.00   50
 44  \w     97.00 123.00   0.50    9.07    --  100.00  33.00 120.00   52
 45  \w    100.00 125.00   0.50    9.07    --  100.00  33.00 150.00   50
 46  \w     59.00  84.00   0.50    9.07    --  100.00 -42.00-180.00   50
 47  \w     84.00 110.00   0.50    9.07    --  100.00  50.00  90.00   52
 48  \w     93.00 118.00   0.50    9.07    --  100.00  50.00  60.00   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      0.0385339000
_diffrn_orient_matrix_UB_12      -0.0032014000
_diffrn_orient_matrix_UB_13      -0.1109091000
_diffrn_orient_matrix_UB_21      -0.0733800000
_diffrn_orient_matrix_UB_22      -0.0498412000
_diffrn_orient_matrix_UB_23      -0.0219429000
_diffrn_orient_matrix_UB_31      -0.0809059000
_diffrn_orient_matrix_UB_32      0.0436210000
_diffrn_orient_matrix_UB_33      -0.0330528000
_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  0.1559
_diffrn_reflns_av_unetI/netI     0.0780
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       28
_diffrn_reflns_limit_h_min       -25
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            27673
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.999
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         68.249
_diffrn_reflns_theta_min         3.804
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.569
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.72969
_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    1.003
_exptl_crystal_description       plate
_exptl_crystal_F_000             1264
_exptl_crystal_size_max          0.2
_exptl_crystal_size_mid          0.18
_exptl_crystal_size_min          0.16
_refine_diff_density_max         0.250
_refine_diff_density_min         -0.644
_refine_diff_density_rms         0.093
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.046
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     191
_refine_ls_number_reflns         3692
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.046
_refine_ls_R_factor_all          0.1561
_refine_ls_R_factor_gt           0.1158
_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^)+(0.2000P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.3094
_refine_ls_wR_factor_ref         0.3585
_reflns_Friedel_coverage         0.000
_reflns_number_gt                1802
_reflns_number_total             3692
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3md00044c2.cif
_cod_data_source_block           11b
_cod_database_code               7247100
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C20H18N2O6S2
_shelx_estimated_absorpt_t_max   0.787
_shelx_estimated_absorpt_t_min   0.744
_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
2.a Ternary CH refined with riding coordinates:
 C007(H007)
2.b Secondary CH2 refined with riding coordinates:
 C00C(H00A,H00B)
2.c Aromatic/amide H refined with riding coordinates:
 C00E(H00E), C00F(H00F), C00G(H00G), C00J(H00J), C00K(H00K)
2.d Idealised Me refined as rotating group:
 C00L(H00C,H00D,H00H)
;
_shelx_res_checksum              16700
_shelx_fab_checksum              89588
_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 2.959
_oxdiff_exptl_absorpt_empirical_full_min 0.405