The modulatory role of sulfated and non-sulfated small molecule heparan sulfate-glycomimetics in endothelial dysfunction: absolute structural clarification, molecular docking and simulated dynamics, SAR analyses and ADMET studies
Gill, Daniel M.; R. Povinelli, Ana Paula; Zazeri, Gabriel; Shamir, Sabrina A.; Mahmoud, Ayman M.; Wilkinson, Fiona L.; Alexander, M. Yvonne; L. Cornelio, Marinonio; Jones, Alan M.; RSC Medicinal Chemistry  (2021) –; doi:10.1039/D0MD00366B

data_7242697
_publ_section_title
;
 The modulatory role of sulfated and non-sulfated small molecule heparan
 sulfate-glycomimetics in endothelial dysfunction: absolute structural
 clarification, molecular docking and simulated dynamics, SAR analyses and
 ADMET studies
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D0MD00366B
_journal_year                    2021
_chemical_formula_moiety         'C8 H7 N O6'
_chemical_formula_sum            'C8 H7 N O6'
_chemical_formula_weight         213.15
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2ybc'
_space_group_name_H-M_alt        'P 1 21/c 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2019-09-10
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2020-10-14 deposited with the CCDC.	2021-03-25 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 110.056(9)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.9555(7)
_cell_length_b                   10.1597(6)
_cell_length_c                   9.9607(8)
_cell_measurement_reflns_used    1703
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      74.6780
_cell_measurement_theta_min      4.7750
_cell_volume                     851.32(12)
_computing_cell_refinement       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.00(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.1768
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.961
_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   -113.00 -11.00   1.00    1.00    --  -42.06 -77.00 -90.00  102
  2  \w      1.00  28.00   1.00    1.00    --  -42.06  57.00 150.00   27
  3  \w    -20.00  67.00   1.00    1.00    --   42.06 -57.00  60.00   87
  4  \w     56.00 118.00   1.00    1.00    --  107.88-125.00-180.00   62
  5  \w     35.00 127.00   1.00    1.00    --  107.88 -30.00-180.00   92
  6  \w    118.00 159.00   1.00    1.00    --  107.88  45.00-150.00   41
  7  \w     28.00  92.00   1.00    1.00    --  107.88 -94.00  90.00   64
  8  \w     33.00 127.00   1.00    1.00    --  107.88 -30.00 -90.00   94
  9  \w     34.00  88.00   1.00    1.00    --  107.88 -77.00-180.00   54
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0072451000
_diffrn_orient_matrix_UB_12      0.1229835000
_diffrn_orient_matrix_UB_13      -0.0925241000
_diffrn_orient_matrix_UB_21      -0.0230349000
_diffrn_orient_matrix_UB_22      -0.0886528000
_diffrn_orient_matrix_UB_23      -0.1310083000
_diffrn_orient_matrix_UB_31      -0.1815670000
_diffrn_orient_matrix_UB_32      0.0061328000
_diffrn_orient_matrix_UB_33      -0.0365710000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0197
_diffrn_reflns_av_unetI/netI     0.0263
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.961
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       12
_diffrn_reflns_limit_l_min       -12
_diffrn_reflns_number            3177
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.961
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.979
_diffrn_reflns_theta_min         5.258
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.278
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.787
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46 (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            yellow
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.663
_exptl_crystal_description       block
_exptl_crystal_F_000             440
_exptl_crystal_size_max          0.149
_exptl_crystal_size_mid          0.146
_exptl_crystal_size_min          0.119
_refine_diff_density_max         0.297
_refine_diff_density_min         -0.230
_refine_diff_density_rms         0.049
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.045
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     145
_refine_ls_number_reflns         1687
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.045
_refine_ls_R_factor_all          0.0427
_refine_ls_R_factor_gt           0.0356
_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^)+(0.0452P)^2^+0.3825P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0884
_refine_ls_wR_factor_ref         0.0944
_reflns_Friedel_coverage         0.000
_reflns_number_gt                1441
_reflns_number_total             1687
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d0md00366b2.cif
_cod_data_source_block           29
_cod_database_code               7242697
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C8 H7 N1 O6'
_reflns_odcompleteness_completeness 99.81
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2.a Aromatic/amide H refined with riding coordinates:
 C3(H3), C4(H4)
2.b Idealised Me refined as rotating group:
 C8(H8A,H8B,H8C)
;
_shelx_res_checksum              1475
_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 1.545
_oxdiff_exptl_absorpt_empirical_full_min 0.742