High-throughput encapsulated nanodroplet screening for accelerated co-crystal discovery
Metherall, Jessica P.; Corner, Philip A.; McCabe, James F.; Probert, Michael R.; Hall, Michael J.; Chemical Science 16 (2025) 9843–9853; doi:10.1039/D4SC07556K

data_1574461
_publ_section_title
;
 High-throughput encapsulated nanodroplet screening for accelerated
 co-crystal discovery
;
_journal_issue                   22
_journal_name_full               'Chemical Science'
_journal_page_first              9843
_journal_page_last               9853
_journal_paper_doi               10.1039/D4SC07556K
_journal_volume                  16
_journal_year                    2025
_chemical_formula_moiety         'C6 H10 O4 S, C10 H8 N2'
_chemical_formula_sum            'C16 H18 N2 O4 S'
_chemical_formula_weight         334.38
_chemical_name_systematic        '4,4'-bipyridine_thiodipropinoic acid'
_space_group_crystal_system      monoclinic
_space_group_IT_number           13
_space_group_name_Hall           '-P 2yac'
_space_group_name_H-M_alt        'P 1 2/n 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_block_doi                 10.5517/ccdc.csd.cc2kmbzj
_audit_creation_date             2024-07-16
_audit_creation_method
;
Olex2 1.5
(compiled 2024.02.16 svn.r378c4104 for OlexSys, GUI svn.r6928)
;
_audit_update_record
;
2024-07-18 deposited with the CCDC.	2025-04-22 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 110.000(4)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   11.3891(4)
_cell_length_b                   4.84020(10)
_cell_length_c                   15.7088(5)
_cell_measurement_reflns_used    2191
_cell_measurement_temperature    150.00(10)
_cell_measurement_theta_max      74.3630
_cell_measurement_theta_min      4.1980
_cell_volume                     813.73(5)
_computing_cell_refinement       'CrysAlisPro 1.171.42.90a (Rigaku OD, 2023)'
_computing_data_collection       'CrysAlisPro 1.171.42.90a (Rigaku OD, 2023)'
_computing_data_reduction        'CrysAlisPro 1.171.42.90a (Rigaku OD, 2023)'
_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    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      150.00(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            'HyPix-Arc 100'
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.932
_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    -29.00  19.00   0.50    0.11    --   44.81 -38.00-150.00   96
  2  \w    -21.00   6.00   0.50    0.11    --   44.81 -38.00-180.00   54
  3  \w     19.00  61.00   0.50    0.11    --   44.81 -77.00-120.00   84
  4  \w     35.00  61.00   0.50    0.11    --  100.88-125.00-120.00   52
  5  \w     75.00 100.00   0.50    0.11    --  100.88-125.00-120.00   50
  6  \w     -9.00  36.00   0.50    0.11    --  -43.81  38.00-180.00   90
  7  \w      0.00  36.00   0.50    0.11    --  -43.81  38.00 -60.00   72
  8  \w     26.00  54.00   0.50    0.11    --  100.88 -61.00 -60.00   56
  9  \w     41.00  67.00   0.50    0.11    --  109.87 -77.00-120.00   52
 10  \w     43.00  68.00   0.50    0.11    --  109.87 -77.00 -90.00   50
 11  \w     44.00  80.00   0.50    0.11    --  109.87 -77.00 -30.00   72
 12  \w     21.00  62.00   0.50    0.11    --   44.81  23.00 149.00   82
 13  \w     80.00 118.00   0.50    0.11    --  100.88  23.00 149.00   76
 14  \w    124.00 149.00   0.50    0.11    --  100.88  77.00 150.00   50
 15  \w     86.00 152.00   0.50    0.11    --  109.87  23.00 149.00  132
 16  \w    125.00 166.00   0.50    0.11    --  100.88  77.00  60.00   82
 17  \w    110.00 177.00   0.50    0.11    --  100.88  61.00-150.00  134
 18  \w    128.00 157.00   0.50    0.11    --  109.87  77.00-180.00   58
 19  \w    -39.00 -13.00   0.50    0.11    --  -88.13  61.00 -30.00   52
 20  \w    -46.00 -14.00   0.50    0.11    --  -88.13  61.00-120.00   64
 21  \w    -43.00 -17.00   0.50    0.11    --  -88.13  61.00 -60.00   52
 22  \w    -43.00 -18.00   0.50    0.11    --  -88.13  61.00   0.00   50
 23  \w    -65.00 -32.00   0.50    0.11    --  -88.13  77.00  90.00   66
 24  \w    -45.00 -13.00   0.50    0.11    --  -88.13  61.00 120.00   64
 25  \w    -91.00 -29.00   0.50    0.11    --  -43.81 -23.00 -16.00  124
 26  \w   -152.00 -65.00   0.50    0.11    --  -88.13 -23.00 -16.00  174
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix-Arc 100'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0812305000
_diffrn_orient_matrix_UB_12      -0.0378692000
_diffrn_orient_matrix_UB_13      0.1002703000
_diffrn_orient_matrix_UB_21      0.1110906000
_diffrn_orient_matrix_UB_22      -0.0876396000
_diffrn_orient_matrix_UB_23      -0.0286629000
_diffrn_orient_matrix_UB_31      0.0422507000
_diffrn_orient_matrix_UB_32      0.3035908000
_diffrn_orient_matrix_UB_33      0.0042924000
_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  0.0323
_diffrn_reflns_av_unetI/netI     0.0343
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.932
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       5
_diffrn_reflns_limit_k_min       -4
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            4321
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.932
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.747
_diffrn_reflns_theta_min         4.192
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.962
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.84316
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.90a (Rigaku Oxford Diffraction, 2023)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.365
_exptl_crystal_description       plate
_exptl_crystal_F_000             352
_exptl_crystal_preparation
;
Crystallised from a saturated solution of 4,4'-bipyridine, 
glutaric acid and 3,3'-thiodipropinoic acid (1:1:1) in DMF.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.32
_exptl_crystal_size_mid          0.28
_exptl_crystal_size_min          0.09
_refine_diff_density_max         0.171
_refine_diff_density_min         -0.217
_refine_diff_density_rms         0.045
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.071
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     108
_refine_ls_number_reflns         1577
_refine_ls_number_restraints     64
_refine_ls_restrained_S_all      1.049
_refine_ls_R_factor_all          0.0397
_refine_ls_R_factor_gt           0.0353
_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^)+(0.0432P)^2^+0.2295P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0911
_refine_ls_wR_factor_ref         0.0943
_reflns_Friedel_coverage         0.000
_reflns_number_gt                1394
_reflns_number_total             1577
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           44-bipyridine_thiodipropinoicacid
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574461
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C H N O S'
_shelx_estimated_absorpt_t_max   0.828
_shelx_estimated_absorpt_t_min   0.440
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All O(H) groups
2. Rigid body (RIGU) restrains
 All non-hydrogen atoms
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
3.a Secondary CH2 refined with riding coordinates:
 C1B(H1BA,H1BB), C2B(H2BA,H2BB)
3.b Aromatic/amide H refined with riding coordinates:
 C2A(H2A), C3A(H3A), C4A(H4A), C5A(H5A)
;
_shelx_res_checksum              63826
_shelx_hkl_checksum              18728
_olex2_exptl_crystal_mounting_method
'Crystal mounted using inert oil from the encapsulation crystallisation technique onto a MiTeGen Kapton micromount.'
_olex2_submission_original_sample_id '4,4'-bipyridine_thiodipropinoic acid'
_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 1.232
_oxdiff_exptl_absorpt_empirical_full_min 0.676