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_7247099
_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, 2(C4 H10 O)'
_chemical_formula_sum            'C35 H42 N2 O12 S2'
_chemical_formula_weight         746.82
_space_group_crystal_system      orthorhombic
_space_group_IT_number           41
_space_group_name_Hall           'A 2 -2ab'
_space_group_name_H-M_alt        'A e a 2'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     iterative
_audit_creation_date             2023-01-08
_audit_creation_method
;
Olex2 1.5
(compiled 2021.07.19 svn.r715e62df for OlexSys, GUI svn.r6380)
;
_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            4
_cell_length_a                   13.1496(5)
_cell_length_b                   21.1566(8)
_cell_length_c                   13.3584(4)
_cell_measurement_reflns_used    2275
_cell_measurement_temperature    150
_cell_measurement_theta_max      70.2360
_cell_measurement_theta_min      4.1730
_cell_volume                     3716.3(2)
_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      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 0.997
_diffrn_measured_fraction_theta_max 0.992
_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    -66.00 -39.00   0.50    2.56    --  -38.50 109.00  33.00   54
  2  \w    -58.00   2.00   0.50    2.56    --  -38.50  75.00 -50.00  120
  3  \w    -33.00  -7.00   0.50    2.56    --  -38.50  50.00 165.00   52
  4  \w    -62.00 -25.00   0.50    2.56    --  -38.50 -50.00  19.00   74
  5  \w     48.00  73.00   0.50    2.56    --   42.60-109.00 -63.00   50
  6  \w     53.00  79.00   0.50    2.56    --   42.60  50.00 165.00   52
  7  \w      2.00  27.00   0.50    2.56    --   42.60 -75.00-178.00   50
  8  \w      8.00  33.00   0.50    2.56    --   42.60 -50.00  19.00   50
  9  \w    103.00 163.00   0.50   10.26    --  100.00  75.00 -50.00  120
 10  \w    127.00 153.00   0.50   10.26    --  100.00 109.00  33.00   52
 11  \w    117.00 155.00   0.50   10.26    --  100.00  50.00 165.00   76
 12  \w     80.00 107.00   0.50   10.26    --  100.00 -75.00-178.00   54
 13  \w     47.00 116.00   0.50   10.26    --  100.00 -50.00  19.00  138
 14  \w     53.00  78.00   0.50   10.26    --  100.00-109.00 -63.00   50
 15  \w    -37.00  35.00   0.50    2.56    --  -38.50  11.00  60.00  144
 16  \w    -89.00 -56.00   0.50    2.56    --  -38.50 -54.00-150.00   66
 17  \w     -4.00  54.00   0.50    2.56    --   42.60 -43.00-180.00  116
 18  \w    105.00 153.00   0.50   10.26    --  100.00  77.00-180.00   96
 19  \w     35.00 117.00   0.50   10.26    --  100.00 -87.00 -60.00  164
 20  \w    109.00 157.00   0.50   10.26    --  100.00  77.00  90.00   96
 21  \w     48.00 103.00   0.50   10.26    --  100.00-117.00-120.00  110
 22  \w     70.00 122.00   0.50   10.26    --  100.00 -68.00 -60.00  104
 23  \w     98.00 123.00   0.50   10.26    --  100.00  42.00  60.00   50
 24  \w    131.00 156.00   0.50   10.26    --  100.00 145.00-180.00   50
 25  \w    106.00 145.00   0.50   10.26    --  100.00 117.00 120.00   78
;
_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      -0.1103857000
_diffrn_orient_matrix_UB_12      0.0043167000
_diffrn_orient_matrix_UB_13      0.0380559000
_diffrn_orient_matrix_UB_21      0.0265669000
_diffrn_orient_matrix_UB_22      -0.0446677000
_diffrn_orient_matrix_UB_23      0.0872367000
_diffrn_orient_matrix_UB_31      0.0289371000
_diffrn_orient_matrix_UB_32      0.0573385000
_diffrn_orient_matrix_UB_33      0.0651205000
_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  0.0434
_diffrn_reflns_av_unetI/netI     0.0582
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.992
_diffrn_reflns_limit_h_max       16
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       25
_diffrn_reflns_limit_k_min       -18
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            7099
_diffrn_reflns_point_group_measured_fraction_full 0.819
_diffrn_reflns_point_group_measured_fraction_max 0.805
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         71.110
_diffrn_reflns_theta_min         4.179
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.841
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.68373
_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 colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.335
_exptl_crystal_description       needle
_exptl_crystal_F_000             1576
_exptl_crystal_size_max          0.4
_exptl_crystal_size_mid          0.2
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.209
_refine_diff_density_min         -0.209
_refine_diff_density_rms         0.048
_refine_ls_abs_structure_details
;
 Flack x determined using 749 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.02(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.079
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     235
_refine_ls_number_reflns         2902
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.078
_refine_ls_R_factor_all          0.0540
_refine_ls_R_factor_gt           0.0441
_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^)+(0.0666P)^2^+0.2768P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1173
_refine_ls_wR_factor_ref         0.1251
_reflns_Friedel_coverage         0.550
_reflns_Friedel_fraction_full    0.622
_reflns_Friedel_fraction_max     0.599
_reflns_number_gt                2464
_reflns_number_total             2902
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3md00044c2.cif
_cod_data_source_block           5a
_cod_original_sg_symbol_Hall     'A 2 -2ac'
_cod_database_code               7247099
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C21H20N4S2O8
_shelx_estimated_absorpt_t_max   0.837
_shelx_estimated_absorpt_t_min   0.526
_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. Others
 Fixed Sof: H2A(0.5) H2B(0.5)
3.a Ternary CH refined with riding coordinates:
 C1(H1)
3.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C16(H16A,H16B), C17(H17A,H17B)
3.c Aromatic/amide H refined with riding coordinates:
 C13(H13), C10(H10), C7(H7), C9(H9), C12(H12)
3.d Idealised Me refined as rotating group:
 C14(H14A,H14B,H14C), C15(H15A,H15B,H15C), C18(H18A,H18B,H18C)
3.e Idealised tetrahedral OH refined as rotating group:
 O2(H2)
;
_shelx_res_checksum              32794
_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 1.550
_oxdiff_exptl_absorpt_empirical_full_min 0.743