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_1574458
_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         'C7 H6 O4, C10 H8 N2'
_chemical_formula_sum            'C17 H14 N2 O4'
_chemical_formula_weight         310.30
_chemical_name_systematic        '4,4'-bipyridine_2,4-dihydroxybenzoic 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.cc2kmb7s
_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                 97.076(6)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.5495(4)
_cell_length_b                   10.7984(7)
_cell_length_c                   20.6573(13)
_cell_measurement_reflns_used    2761
_cell_measurement_temperature    150
_cell_measurement_theta_max      69.3260
_cell_measurement_theta_min      4.3110
_cell_volume                     1449.84(16)
_computing_cell_refinement       'CrysAlisPro 1.171.42.63a (Rigaku OD, 2022)'
_computing_data_collection       'CrysAlisPro 1.171.42.63a (Rigaku OD, 2022)'
_computing_data_reduction        'CrysAlisPro 1.171.42.63a (Rigaku OD, 2022)'
_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_temperature      150.00
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            'HyPix-Arc 100'
_diffrn_measured_fraction_theta_full 0.995
_diffrn_measured_fraction_theta_max 0.966
_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      4.00  30.00   0.50    5.32    --   28.47  68.00 169.00   52
  2  \w     15.00  43.00   0.50    5.32    --   28.47 -68.00  36.00   56
  3  \w    -57.00 -23.00   0.50    5.32    --  -30.47  68.00 169.00   68
  4  \w    -18.00  25.00   0.50    5.32    --  -30.47  68.00 169.00   86
  5  \w    -11.00  51.00   0.50   21.28    --   68.09 -68.00  36.00  124
  6  \w     11.00  52.00   0.50   21.28    --   73.34 -68.00  36.00   82
  7  \w    -60.00  -8.00   0.50   21.28    --  -74.54  68.00 169.00  104
  8  \w   -129.00-103.00   0.50   21.28    --  -74.54 -68.00  36.00   52
  9  \w    -51.00 -26.00   0.50   21.28    --  -99.50  68.00 169.00   50
 10  \w   -159.00-109.00   0.50   21.28    --  -99.50 -68.00  36.00  100
 11  \w    130.00 155.00   0.50   21.28    --  110.67  68.00 169.00   50
 12  \w    130.00 155.00   0.50   21.28    --  115.27  68.00 169.00   50
 13  \w     24.00  56.00   0.50   21.28    --  115.27 -68.00  36.00   64
 14  \w    -66.00 -30.00   0.50    5.32    --   28.47 -19.00  60.00   72
 15  \w    -28.00   2.00   0.50    5.32    --   28.47 -57.00 -60.00   60
 16  \w     12.00  42.00   0.50    5.32    --   28.47 -57.00 -60.00   60
 17  \w     25.00  53.00   0.50    5.32    --  -30.47  19.00-150.00   56
 18  \w    -24.00   7.00   0.50    5.32    --  -30.47 -57.00-180.00   62
 19  \w     21.00  46.00   0.50    5.32    --  -30.47  19.00  60.00   50
 20  \w     19.00  44.00   0.50    5.32    --  -30.47  19.00-120.00   50
 21  \w    -25.00   0.00   0.50   21.28    --   68.09 -30.00 -30.00   50
 22  \w    -31.00   5.00   0.50   21.28    --   68.09 -30.00-120.00   72
 23  \w    -25.00   5.00   0.50   21.28    --   73.34 -30.00 -90.00   60
 24  \w    -25.00   4.00   0.50   21.28    --   73.34 -30.00 -60.00   58
 25  \w    -25.00   1.00   0.50   21.28    --   73.34 -30.00-150.00   52
 26  \w    -23.00   2.00   0.50   21.28    --   73.34 -30.00  90.00   50
 27  \w    -25.00   0.00   0.50   21.28    --   73.34 -30.00  60.00   50
 28  \w    115.00 158.00   0.50   21.28    --   73.34  61.00 150.00   86
 29  \w    -24.00   6.00   0.50   21.28    --  -74.54  45.00  30.00   60
 30  \w    -19.00   9.00   0.50   21.28    --  -74.54  45.00 150.00   56
 31  \w    -27.00  -2.00   0.50   21.28    --  -74.54  45.00 -60.00   50
 32  \w   -155.00 -93.00   0.50   21.28    --  -99.50 -64.00 -60.00  124
 33  \w   -154.00-108.00   0.50   21.28    --  -99.50-104.00 -30.00   92
 34  \w    -42.00 -16.00   0.50   21.28    --  -99.50  64.00 -90.00   52
 35  \w    -55.00 -23.00   0.50   21.28    --  -99.50  64.00 -30.00   64
 36  \w    -65.00 -14.00   0.50   21.28    --  -99.50  77.00-150.00  102
 37  \w    124.00 177.00   0.50   21.28    --  110.67 104.00 150.00  106
 38  \w     43.00  68.00   0.50   21.28    --  110.67 -77.00  90.00   50
 39  \w    125.00 175.00   0.50   21.28    --  110.67 104.00 -30.00  100
 40  \w    118.00 174.00   0.50   21.28    --  110.67  64.00 -90.00  112
 41  \w     18.00  43.00   0.50   21.28    --  110.67 -68.00  36.00   50
 42  \w     22.00  48.00   0.50   21.28    --  110.67 -64.00   0.00   52
 43  \w    126.00 177.00   0.50   21.28    --  110.67 104.00 120.00  102
 44  \w    131.00 160.00   0.50   21.28    --  115.27 139.00 -90.00   58
 45  \w     24.00  53.00   0.50   21.28    --  115.27 -64.00 -30.00   58
 46  \w    133.00 162.00   0.50   21.28    --  115.27  77.00  90.00   58
 47  \w     30.00  55.00   0.50   21.28    --  115.27 -64.00  60.00   50
 48  \w    147.00 173.00   0.50   21.28    --  115.27  64.00  60.00   52
 49  \w    128.00 155.00   0.50   21.28    --  115.27 104.00  30.00   54
 50  \w     20.00  69.00   0.50   21.28    --  115.27 -92.00-150.00   98
 51  \w    116.00 142.00   0.50   21.28    --  115.27  64.00  60.00   52
 52  \w    125.00 173.00   0.50   21.28    --  115.27 104.00-120.00   96
;
_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      -0.1962267000
_diffrn_orient_matrix_UB_12      0.0249556000
_diffrn_orient_matrix_UB_13      0.0320837000
_diffrn_orient_matrix_UB_21      0.0549702000
_diffrn_orient_matrix_UB_22      -0.1078992000
_diffrn_orient_matrix_UB_23      0.0477815000
_diffrn_orient_matrix_UB_31      0.1208174000
_diffrn_orient_matrix_UB_32      0.0898089000
_diffrn_orient_matrix_UB_33      0.0484355000
_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  0.0250
_diffrn_reflns_av_unetI/netI     0.0308
_diffrn_reflns_Laue_measured_fraction_full 0.995
_diffrn_reflns_Laue_measured_fraction_max 0.966
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       25
_diffrn_reflns_limit_l_min       -22
_diffrn_reflns_number            7423
_diffrn_reflns_point_group_measured_fraction_full 0.995
_diffrn_reflns_point_group_measured_fraction_max 0.966
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         70.955
_diffrn_reflns_theta_min         4.313
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.855
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.85976
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.63a (Rigaku Oxford Diffraction, 2022)
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    1.422
_exptl_crystal_description       needle
_exptl_crystal_F_000             648
_exptl_crystal_preparation
;
Crystallised from a saturated solution of 4,4'-bipyridine
and 2,4-dihydroxybenzoic 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          0.062
_exptl_crystal_size_mid          0.035
_exptl_crystal_size_min          0.015
_refine_diff_density_max         0.220
_refine_diff_density_min         -0.171
_refine_diff_density_rms         0.042
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.178
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     318
_refine_ls_number_reflns         2703
_refine_ls_number_restraints     273
_refine_ls_restrained_S_all      1.125
_refine_ls_R_factor_all          0.0560
_refine_ls_R_factor_gt           0.0481
_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^)+(0.0478P)^2^+0.6143P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1164
_refine_ls_wR_factor_ref         0.1204
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2428
_reflns_number_total             2703
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           44-bipyridine_24-dihydroxybenzoicacid
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574458
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.987
_shelx_estimated_absorpt_t_min   0.949
_diffrn_oxdiff_digest_hkl
;
010593b0d1694ed903bc421e49e9b1f1ab8f4a
;
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All O(H) groups
2. Restrained distances
 O4C-H4C = O1C-H1C = O2C-H2C
 0.84 with sigma of 0.02
 H2B-N2A
 2.1 with sigma of 0.02
 O4C-C7C \\sim O3B-C7B
 with sigma of 0.02
 O2C-C4C \\sim O2B-C4B
 with sigma of 0.02
 O4C-O3C \\sim O3B-O4B
 with sigma of 0.04
 O2C-C3C \\sim O2B-C3B
 with sigma of 0.04
 O4C-C1C \\sim O3B-C1B
 with sigma of 0.04
 O1C-C2C \\sim O1B-C2B
 with sigma of 0.02
 O2C-C5C \\sim O2B-C5B
 with sigma of 0.04
 O1C-C3C \\sim O1B-C3B
 with sigma of 0.04
 O1C-C1C \\sim O1B-C1B
 with sigma of 0.04
 O3C-C7C \\sim O4B-C7B
 with sigma of 0.02
 C2C-C3C \\sim C2B-C3B
 with sigma of 0.02
 C2C-C1C \\sim C2B-C1B
 with sigma of 0.02
 C6C-C1C \\sim C6B-C1B
 with sigma of 0.02
 C6C-C5C \\sim C6B-C5B
 with sigma of 0.02
 C7C-C1C \\sim C7B-C1B
 with sigma of 0.02
 C3C-C4C \\sim C3B-C4B
 with sigma of 0.02
 C5C-C4C \\sim C5B-C4B
 with sigma of 0.02
 O3C-C1C \\sim O4B-C1B
 with sigma of 0.04
 C2C-C6C \\sim C2B-C6B
 with sigma of 0.04
 C2C-C7C \\sim C2B-C7B
 with sigma of 0.04
 C2C-C4C \\sim C2B-C4B
 with sigma of 0.04
 C6C-C7C \\sim C6B-C7B
 with sigma of 0.04
 C6C-C4C \\sim C6B-C4B
 with sigma of 0.04
 C3C-C1C \\sim C3B-C1B
 with sigma of 0.04
 C3C-C5C \\sim C3B-C5B
 with sigma of 0.04
 C1C-C5C \\sim C1B-C5B
 with sigma of 0.04
3. 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
4. Others
 Fixed Sof: O1B(0.09916) H1B(0.09916) O1C(0.90084) H1C(0.90084) O2B(0.09916)
 H2B(0.09916) O2C(0.90084) H2C(0.90084) O3B(0.09916) H3B(0.09916) O3C(0.90084)
 O4B(0.09916) O4C(0.90084) H4C(0.90084) C1B(0.09916) C1C(0.90084) C2B(0.09916)
 C2C(0.90084) C3B(0.09916) H3BA(0.09916) C3C(0.90084) H3C(0.90084) C4B(0.09916)
 C4C(0.90084) C5B(0.09916) H5B(0.09916) C5C(0.90084) H5C(0.90084) C6B(0.09916)
 H6B(0.09916) C6C(0.90084) H6C(0.90084) C7B(0.09916) C7C(0.90084)
5.a Aromatic/amide H refined with riding coordinates:
 C2A(H2A), C3A(H3A), C3B(H3BA), C3C(H3C), C4A(H4A), C5A(H5A), C5B(H5B),
 C5C(H5C), C6B(H6B), C6C(H6C), C7A(H7A), C8A(H8A), C9A(H9A), C10A(H10A)
5.b Tetrahedral OH refined with riding coordinates:
 O3B(H3B)
5.c Idealised tetrahedral OH refined as rotating group:
 O1B(H1B), O2B(H2B)
;
_shelx_res_checksum              60285
_shelx_hkl_checksum              38281
_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_2,4-dihydroxybenzoic 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 1.456
_oxdiff_exptl_absorpt_empirical_full_min 0.753