Salicylate Metal-Binding Isosteres as Fragments for Metalloenzyme Inhibition
Jackl, Moritz K.; Seo, Hyeonglim; Karges, Johannes; Kalaj, Mark; Cohen, Seth M.; Chemical Science  (2022) –; doi:10.1039/D1SC06011B

data_1566094
_publ_section_title
;
 Salicylate Metal-Binding Isosteres as Fragments for Metalloenzyme
 Inhibition
;
_journal_name_full               'Chemical Science'
_journal_paper_doi               10.1039/D1SC06011B
_journal_year                    2022
_chemical_formula_moiety
'C38 H32 B N7 O4 Zn, 0.375(C5 H12), 0.249(C3 H3)'
_chemical_formula_sum            'C40.62 H37.25 B N7 O4 Zn'
_chemical_formula_weight         763.70
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2yn'
_space_group_name_H-M_alt        'P 1 21/n 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2021-04-06
_audit_creation_method
;
Olex2 1.3
(compiled 2020.11.12 svn.r5f609507 for OlexSys, GUI svn.r6272)
;
_audit_update_record
;
2021-10-22 deposited with the CCDC.	2022-01-13 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 97.912(3)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   11.6546(9)
_cell_length_b                   14.6697(11)
_cell_length_c                   21.3858(17)
_cell_measurement_reflns_used    9942
_cell_measurement_temperature    100.0
_cell_measurement_theta_max      70.459
_cell_measurement_theta_min      3.665
_cell_volume                     3621.5(5)
_computing_cell_refinement       'SAINT V8.38A (Bruker, 2018)'
_computing_data_reduction        'SAINT V8.38A (Bruker, 2018)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL  (Sheldrick, 2008)'
_computing_structure_solution    'SHELXT  (Sheldrick, 2015)'
_diffrn_ambient_temperature      100.0
_diffrn_measured_fraction_theta_full 0.993
_diffrn_measured_fraction_theta_max 0.982
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0401
_diffrn_reflns_av_unetI/netI     0.0518
_diffrn_reflns_Laue_measured_fraction_full 0.993
_diffrn_reflns_Laue_measured_fraction_max 0.982
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       26
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            22461
_diffrn_reflns_point_group_measured_fraction_full 0.993
_diffrn_reflns_point_group_measured_fraction_max 0.982
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         70.578
_diffrn_reflns_theta_min         3.665
_diffrn_source_current           30.0
_diffrn_source_power             1.35
_diffrn_source_voltage           45.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    1.373
_exptl_absorpt_correction_T_max  0.5220
_exptl_absorpt_correction_T_min  0.3756
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2016/2 (Bruker,2016/2) was used for absorption correction.
wR2(int) was 0.1101 before and 0.0621 after correction.
The Ratio of minimum to maximum transmission is 0.7195.
The \l/2 correction factor is Not present.
;
_exptl_crystal_colour            'clear pink'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    pink
_exptl_crystal_density_diffrn    1.401
_exptl_crystal_description       block
_exptl_crystal_F_000             1588
_exptl_crystal_size_max          0.24
_exptl_crystal_size_mid          0.22
_exptl_crystal_size_min          0.19
_refine_diff_density_max         0.248
_refine_diff_density_min         -0.619
_refine_diff_density_rms         0.060
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.087
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     526
_refine_ls_number_reflns         6808
_refine_ls_number_restraints     33
_refine_ls_restrained_S_all      1.085
_refine_ls_R_factor_all          0.0478
_refine_ls_R_factor_gt           0.0418
_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^)+(0.0635P)^2^+0.6944P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1122
_refine_ls_wR_factor_ref         0.1168
_reflns_Friedel_coverage         0.000
_reflns_number_gt                5929
_reflns_number_total             6808
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d1sc06011b4.cif
_cod_data_source_block           cohen_mkj214_0m_a
_cod_database_code               1566094
_shelx_shelxl_version_number     2016/6
_shelx_estimated_absorpt_t_max   0.780
_shelx_estimated_absorpt_t_min   0.734
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All B(H) groups, All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 C6S-C8S_$1 \\sim C7S_$1-C8S_$1 \\sim C6S_$1-C7S_$1 \\sim C6S_$1-C8S \\sim
C7S-C8S \\sim C6S-C7S
 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
Uanis(C2S) = Uanis(C5S)
Uanis(C3S) = Uanis(C4S)
4. Rigid body (RIGU) restrains
 C1S, C2S, C3S
 with sigma for 1-2 distances of 0.002 and sigma for 1-3 distances of 0.002
 C8S, C7S, C6S, C8S, C7S, C6S
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
5. Others
 Sof(C3S)=Sof(H3SA)=Sof(H3SB)=Sof(C2S)=Sof(H2SA)=Sof(H2SB)=Sof(C1S)=Sof(H1SA)=
 Sof(H1SB)=Sof(H1SC)=Sof(C5S)=Sof(H5SA)=Sof(H5SB)=Sof(H5SC)=Sof(C4S)=Sof(H4SA)=
 Sof(H4SB)=0.5*(1-FVAR(2))
 Sof(C8S)=Sof(H8S)=Sof(C7S)=Sof(H7S)=Sof(C6S)=Sof(H6S)=FVAR(1)
6.a Ternary CH refined with riding coordinates:
 B1(H1B)
6.b Secondary CH2 refined with riding coordinates:
 C3S(H3SA,H3SB), C2S(H2SA,H2SB), C4S(H4SA,H4SB)
6.c Aromatic/amide H refined with riding coordinates:
 N1(H1), C36(H36), C23(H23), C9(H9), C1(H1A), C16(H16), C29(H29), C30(H30),
 C13(H13), C26(H26), C19(H19), C12(H12), C22(H22), C33(H33), C11(H11), C20(H20),
  C10(H10), C31(H31), C3(H3), C21(H21), C32(H32), C2(H2), C8S(H8S), C7S(H7S),
 C6S(H6S)
6.d Idealised Me refined as rotating group:
 C18(H18A,H18B,H18C), C38(H38A,H38B,H38C), C28(H28A,H28B,H28C), C1S(H1SA,H1SB,
 H1SC), C5S(H5SA,H5SB,H5SC)
;
_shelx_res_checksum              88736
_shelx_hkl_checksum              44348
_olex2_submission_special_instructions 'No special instructions were received'