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_1574451
_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         'C5 H8 O4, C10 H8 N2'
_chemical_formula_sum            'C15 H16 N2 O4'
_chemical_formula_weight         288.30
_chemical_name_systematic        '4,4'-bipyridine_glutaric acid'
_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_block_doi                 10.5517/ccdc.csd.cc2kmb9v
_audit_creation_date             2025-03-31
_audit_creation_method
;
Olex2 1.5
(compiled 2025.03.04 svn.red2d20d0 for OlexSys, GUI svn.r7188)
;
_audit_update_record
;
2025-04-01 deposited with the CCDC.	2025-04-22 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 92.693(2)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   5.55880(10)
_cell_length_b                   9.9773(3)
_cell_length_c                   50.1061(16)
_cell_measurement_reflns_used    9616
_cell_measurement_temperature    149.99(10)
_cell_measurement_theta_max      72.2760
_cell_measurement_theta_min      4.4890
_cell_volume                     2775.91(13)
_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      149.99(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 1.000
_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   -123.00   8.00   0.50    1.82    --  -33.08 -43.00 -32.00  262
  2  \w    -21.00  52.00   0.50    1.82    --  -33.08  43.00 118.00  146
  3  \w   -158.00 -27.00   0.50    7.28    --  -68.48 -43.00 -32.00  262
  4  \w    -21.00  31.00   0.50    7.28    --   69.09 -43.00 -32.00  104
  5  \w     28.00 154.00   0.50    7.28    --   69.09  43.00 118.00  252
  6  \w   -165.00 -33.00   0.50    7.28    --  -74.71 -43.00 -32.00  264
  7  \w     34.00 160.00   0.50    7.28    --   75.10  43.00 118.00  252
  8  \w   -172.00 -55.00   0.50    7.28    --  -96.82 -43.00 -32.00  234
  9  \w     67.00 178.00   0.50    7.28    --  107.25  43.00 118.00  222
 10  \w     24.00  52.00   0.50    1.82    --  -33.08  19.00  60.00   56
 11  \w     24.00  52.00   0.50    1.82    --  -33.08  19.00 -60.00   56
 12  \w     24.00  52.00   0.50    1.82    --  -33.08  19.00 -90.00   56
 13  \w    -14.00  52.00   0.50    1.82    --  -33.08  38.00   0.00  132
 14  \w     -3.00  60.00   0.50    1.82    --   34.08  57.00-150.00  126
 15  \w   -153.00-102.00   0.50    7.28    --  -68.48 -77.00  60.00  102
 16  \w    -24.00  11.00   0.50    7.28    --  -74.71  45.00 -90.00   70
 17  \w    -18.00  11.00   0.50    7.28    --   75.10 -30.00 150.00   58
 18  \w    -18.00  11.00   0.50    7.28    --   75.10 -30.00-180.00   58
 19  \w    -50.00 -14.00   0.50    7.28    --  -96.82  64.00-180.00   72
 20  \w   -153.00 -97.00   0.50    7.28    --  -96.82-112.00  90.00  112
 21  \w    -50.00 -14.00   0.50    7.28    --  -96.82  64.00 150.00   72
 22  \w    -67.00 -12.00   0.50    7.28    --  -96.82  77.00  60.00  110
 23  \w     25.00  60.00   0.50    7.28    --  107.25 -64.00-120.00   70
 24  \w    119.00 178.00   0.50    7.28    --  107.25 112.00 -30.00  118
 25  \w     23.00  80.00   0.50    7.28    --  107.25 -77.00 -30.00  114
 26  \w     73.00 178.00   0.50    7.28    --  107.25  50.00  60.00  210
 27  \w     29.00  80.00   0.50    7.28    --  112.96 -77.00 -60.00  102
 28  \w    124.00 178.00   0.50    7.28    --  112.96  77.00   0.00  108
 29  \w     31.00  60.00   0.50    7.28    --  112.96 -64.00 -30.00   58
 30  \w     31.00  60.00   0.50    7.28    --  112.96 -64.00  60.00   58
 31  \w     78.00 178.00   0.50    7.28    --  112.96  50.00  30.00  200
 32  \w     31.00  60.00   0.50    7.28    --  112.96 -64.00 150.00   58
 33  \w     72.00 178.00   0.50    7.28    --  112.96  43.00 118.00  212
 34  \w     24.00  52.00   0.50    1.82    --  -33.08  19.00  30.00   56
 35  \w     18.00  88.00   0.50    1.82    --   34.08 -99.00 -30.00  140
 36  \w      1.00  45.00   0.50    1.82    --   34.08 -77.00  90.00   88
 37  \w     -3.00  60.00   0.50    1.82    --   34.08  57.00 -60.00  126
;
_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      0.2198837000
_diffrn_orient_matrix_UB_12      0.0611364000
_diffrn_orient_matrix_UB_13      0.0154085000
_diffrn_orient_matrix_UB_21      -0.1662827000
_diffrn_orient_matrix_UB_22      0.0567549000
_diffrn_orient_matrix_UB_23      0.0210185000
_diffrn_orient_matrix_UB_31      0.0309551000
_diffrn_orient_matrix_UB_32      -0.1298735000
_diffrn_orient_matrix_UB_33      0.0164001000
_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  0.0321
_diffrn_reflns_av_unetI/netI     0.0276
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.961
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       7
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       61
_diffrn_reflns_limit_l_min       -61
_diffrn_reflns_number            25349
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.961
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         72.988
_diffrn_reflns_theta_min         3.532
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.842
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.71869
_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    1.380
_exptl_crystal_description       plate
_exptl_crystal_F_000             1216
_exptl_crystal_preparation
;
Crystallised from a saturated solution of 4,4'-bipyridine
and glutaric acid (1:1) in MeOH.
;
_exptl_crystal_recrystallization_method
;
High-throughput screening via the ENaCt co-
crystallisation protocol using SPT Labtech mosquito.
;
_exptl_crystal_size_max          0.19
_exptl_crystal_size_mid          0.062
_exptl_crystal_size_min          0.024
_refine_diff_density_max         0.277
_refine_diff_density_min         -0.201
_refine_diff_density_rms         0.042
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.070
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     391
_refine_ls_number_reflns         5328
_refine_ls_number_restraints     276
_refine_ls_restrained_S_all      1.043
_refine_ls_R_factor_all          0.0574
_refine_ls_R_factor_gt           0.0440
_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^)+(0.0595P)^2^+0.9485P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1155
_refine_ls_wR_factor_ref         0.1242
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4247
_reflns_number_total             5328
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           4,4-bipyridine_glutaricacid
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574451
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C30 H32 N4 O8'
_shelx_estimated_absorpt_t_max   0.980
_shelx_estimated_absorpt_t_min   0.856
_diffrn_oxdiff_digest_hkl
;
01a6683631a2d4579ce157bfa9b34d8c292418
;
_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:
 C2A(H2Aa,H2Ab), C2C(H2Ca,H2Cb), C3A(H3Aa,H3Ab), C3C(H3Ca,H3Cb), C4A(H4Aa,
 H4Ab), C4C(H4Ca,H4Cb)
3.b Aromatic/amide H refined with riding coordinates:
 C2B(H2B), C2D(H2D), C3B(H3B), C3D(H3D), C4B(H4B), C4D(H4D), C5B(H5B),
 C5D(H5D), C7B(H7B), C7D(H7D), C8B(H8B), C8D(H8D), C9B(H9B), C9D(H9D),
 C10B(H10B), C10D(H10D)
;
_shelx_res_checksum              49623
_shelx_hkl_checksum              63145
_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_glutaric 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 2.725
_oxdiff_exptl_absorpt_empirical_full_min 0.782