Design, modular synthesis and screening of 58 shape-diverse 3-D fragments.
Downes, Thomas D.; Jones, S. Paul; Firth, James D.; Darby, John F.; Gilio, Amelia K.; Klein, Hanna F.; Wang, Xinyu; Blakemore, David C.; De Fusco, Claudia; Roughley, Stephen D.; Vidler, Lewis R.; Whatton, Maria Ann; Woolford, Alison J.-A.; Wrigley, Gail L.; Hubbard, Roderick E.; Wu, Liang; Davies, Gideon J.; O'Brien, Peter; Chemical science 16 (2025) 20030–20041; doi:10.1039/d5sc05819h

data_1575834
_publ_section_title
;
 Design, modular synthesis and screening of 58 shape-diverse 3-D
 fragments.
;
_journal_issue                   42
_journal_name_full               'Chemical science'
_journal_page_first              20030
_journal_page_last               20041
_journal_paper_doi               10.1039/d5sc05819h
_journal_volume                  16
_journal_year                    2025
_chemical_formula_moiety         'C11 H11 F O3'
_chemical_formula_sum            'C11 H11 F O3'
_chemical_formula_weight         210.20
_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   mixed
_atom_sites_solution_primary     dual
_audit_block_doi                 10.5517/ccdc.csd.cc28crn2
_audit_creation_date             2019-12-20
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2021-07-15 deposited with the CCDC.	2025-09-19 downloaded from the CCDC.
;
_cell_angle_alpha                68.397(7)
_cell_angle_beta                 86.839(7)
_cell_angle_gamma                87.855(6)
_cell_formula_units_Z            4
_cell_length_a                   5.6368(5)
_cell_length_b                   11.7599(8)
_cell_length_c                   15.6467(12)
_cell_measurement_reflns_used    2187
_cell_measurement_temperature    110.00(10)
_cell_measurement_theta_max      70.3690
_cell_measurement_theta_min      4.0830
_cell_volume                     962.71(14)
_computing_cell_refinement       'CrysAlisPro 1.171.40.63a (Rigaku OD, 2019)'
_computing_data_collection       'CrysAlisPro 1.171.40.63a (Rigaku OD, 2019)'
_computing_data_reduction        'CrysAlisPro 1.171.40.63a (Rigaku OD, 2019)'
_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      110.00(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 16.1450
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.972
_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     -6.00  20.00   1.00    1.00    --    0.00 -77.00-120.00   26
  2  \w     -6.00  39.00   1.00    1.00    --    0.00  77.00  30.00   45
  3  \w    -19.00  31.00   1.00    1.00    --    0.00  77.00-180.00   50
  4  \w    -20.00  13.00   1.00    1.00    --    0.00 -77.00-150.00   33
  5  \w     27.00 106.00   1.00    1.00    --   54.00-125.00 150.00   79
  6  \w     22.00  49.00   1.00    1.00    --   54.00 -57.00 150.00   27
  7  \w    -15.00  72.00   1.00    1.00    --   54.00 -57.00 -60.00   87
  8  \w     52.00  78.00   1.00    1.00    --   54.00-127.00 -38.00   26
  9  \w     48.00  82.00   1.00    1.00    --   54.00  57.00  60.00   34
 10  \w     -5.00  69.00   1.00    1.00    --   54.00 -37.00-180.00   74
 11  \w     58.00 123.00   1.00    1.00    --   54.00  57.00  90.00   65
 12  \w     54.00 121.00   1.00    1.00    --   54.00  37.00-180.00   67
 13  \w     54.00 130.00   1.00    2.00    --  108.00 -63.00 120.00   76
 14  \w     39.00  69.00   1.00    2.00    --  108.00 -91.00  60.00   30
 15  \w    107.00 155.00   1.00    2.00    --  108.00  77.00 -60.00   48
 16  \w     72.00 109.00   1.00    2.00    --  108.00-111.00 -30.00   37
 17  \w     84.00 174.00   1.00    2.00    --  108.00  37.00-150.00   90
 18  \w    119.00 173.00   1.00    2.00    --  108.00  63.00 150.00   54
 19  \w     59.00 127.00   1.00    2.00    --  108.00 -63.00   0.00   68
 20  \w    125.00 174.00   1.00    2.00    --  108.00 111.00 120.00   49
 21  \w     73.00 121.00   1.00    2.00    --  108.00 -50.00-150.00   48
 22  \w     45.00 101.00   1.00    2.00    --  108.00-111.00 150.00   56
 23  \w     80.00 106.00   1.00    2.00    --  108.00-111.00  60.00   26
 24  \w     74.00 105.00   1.00    2.00    --  108.00-111.00-120.00   31
 25  \w     37.00  63.00   1.00    2.00    --  108.00-111.00  60.00   26
 26  \w     89.00 155.00   1.00    2.00    --  108.00  63.00  90.00   66
 27  \w    104.00 175.00   1.00    2.00    --  108.00 111.00  30.00   71
 28  \w     78.00 104.00   1.00    2.00    --  108.00 178.00-120.00   26
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, Eos'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0119975000
_diffrn_orient_matrix_UB_12      0.0435039000
_diffrn_orient_matrix_UB_13      -0.1057999000
_diffrn_orient_matrix_UB_21      0.2663807000
_diffrn_orient_matrix_UB_22      -0.0347639000
_diffrn_orient_matrix_UB_23      0.0014069000
_diffrn_orient_matrix_UB_31      -0.0620065000
_diffrn_orient_matrix_UB_32      -0.1294526000
_diffrn_orient_matrix_UB_33      0.0064091000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0221
_diffrn_reflns_av_unetI/netI     0.0383
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.972
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       17
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            6094
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.972
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         71.053
_diffrn_reflns_theta_min         4.044
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.000
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.91049
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.63a (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    1.450
_exptl_crystal_description       needle
_exptl_crystal_F_000             440
_exptl_crystal_recrystallization_method Chloroform/Pentane
_exptl_crystal_size_max          0.189
_exptl_crystal_size_mid          0.146
_exptl_crystal_size_min          0.096
_refine_diff_density_max         0.239
_refine_diff_density_min         -0.233
_refine_diff_density_rms         0.047
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.035
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     279
_refine_ls_number_reflns         3610
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.035
_refine_ls_R_factor_all          0.0517
_refine_ls_R_factor_gt           0.0400
_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^)+(0.0473P)^2^+0.2470P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0969
_refine_ls_wR_factor_ref         0.1047
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2936
_reflns_number_total             3610
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5sc05819h2.cif
_cod_data_source_block           paob1927
_cod_depositor_comments
'Adding full bibliography for 1575833--1575834.cif.'
_cod_original_cell_volume        962.71(13)
_cod_database_code               1575834
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C11 H11 O3 F'
_chemical_oxdiff_usercomment     'Tom Downes TD 5/52'
_reflns_odcompleteness_completeness 99.85
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
2.a Ternary CH refined with riding coordinates:
 C15(H15), C14(H14), C10(H10), C7(H7)
2.b Secondary CH2 refined with riding coordinates:
 C12(H12A,H12B), C13(H13A,H13B), C9(H9A,H9B), C8(H8A,H8B)
2.c Aromatic/amide H refined with riding coordinates:
 C22(H22), C18(H18), C4(H4), C21(H21), C5(H5A), C19(H19), C3(H3A), C2(H2)
;
_shelx_res_checksum              58317
_olex2_date_sample_data_collection 2019-12-20
_olex2_date_sample_submission    2019-12-13
_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 1.488
_oxdiff_exptl_absorpt_empirical_full_min 0.748