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_1574440
_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         'C11 H8 O3, 1.5(C10 H8 N2)'
_chemical_formula_sum            'C26 H20 N3 O3'
_chemical_formula_weight         422.45
_chemical_name_systematic        '4,4'-bipyridine_3-hydroxy-2-naphthoic acid'
_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.cc2kmbp7
_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                77.280(5)
_cell_angle_beta                 86.238(5)
_cell_angle_gamma                72.443(5)
_cell_formula_units_Z            2
_cell_length_a                   9.7342(6)
_cell_length_b                   10.4465(5)
_cell_length_c                   10.8557(7)
_cell_measurement_reflns_used    2581
_cell_measurement_temperature    150
_cell_measurement_theta_max      70.7420
_cell_measurement_theta_min      4.5250
_cell_volume                     1026.64(11)
_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 0.986
_diffrn_measured_fraction_theta_max 0.954
_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    -36.00 -10.00   0.50    5.89    --   28.72 -56.00 121.00   52
  2  \w     13.00  42.00   0.50    5.89    --   28.72 -56.00 121.00   58
  3  \w     25.00  55.00   0.50    5.89    --  -30.47  56.00 -96.00   60
  4  \w    -42.00  19.00   0.50    5.89    --  -30.47  56.00 -96.00  122
  5  \w    -17.00   9.00   0.50   23.56    --   68.21 -56.00 121.00   52
  6  \w   -143.00 -86.00   0.50   23.56    --  -74.54 -56.00 121.00  114
  7  \w    -37.00 -11.00   0.50   23.56    --  -74.54  56.00 -96.00   52
  8  \w   -155.00-130.00   0.50   23.56    --  -99.50 -56.00 121.00   50
  9  \w    -44.00 -14.00   0.50   23.56    --  -99.50  56.00 -96.00   60
 10  \w   -125.00 -92.00   0.50   23.56    --  -99.50 -56.00 121.00   66
 11  \w    141.00 166.00   0.50   23.56    --  115.27  56.00 -96.00   50
 12  \w      1.00  26.00   0.50    5.89    --   28.72  56.00 -96.00   50
 13  \w    -37.00   9.00   0.50    5.89    --   28.72 -57.00  30.00   92
 14  \w     37.00  63.00   0.50    5.89    --   28.72 -77.00 -60.00   52
 15  \w      5.00  33.00   0.50    5.89    --   28.72 -77.00 -60.00   56
 16  \w     19.00  45.00   0.50    5.89    --   28.72 -57.00  30.00   52
 17  \w     24.00  55.00   0.50    5.89    --  -30.47  19.00 -60.00   62
 18  \w     21.00  51.00   0.50    5.89    --  -30.47  19.00   0.00   60
 19  \w    -29.00   6.00   0.50    5.89    --  -30.47 -57.00  60.00   70
 20  \w     29.00  92.00   0.50   23.56    --   68.21-112.00  30.00  126
 21  \w    -30.00   5.00   0.50   23.56    --   68.21 -30.00 -30.00   70
 22  \w   -131.00-105.00   0.50   23.56    --  -68.90-112.00 -30.00   52
 23  \w    -25.00   4.00   0.50   23.56    --   73.48 -30.00   0.00   58
 24  \w    -12.00  26.00   0.50   23.56    --   73.48 -45.00 150.00   76
 25  \w     15.00  41.00   0.50   23.56    --   73.48 -95.00  60.00   52
 26  \w    -25.00   6.00   0.50   23.56    --   73.48 -30.00  30.00   62
 27  \w     57.00  92.00   0.50   23.56    --   73.48 -95.00  60.00   70
 28  \w    -20.00   6.00   0.50   23.56    --   73.48 -30.00  60.00   52
 29  \w    -25.00   0.00   0.50   23.56    --   73.48 -30.00 -60.00   50
 30  \w     -1.00  44.00   0.50   23.56    --   73.48 -56.00 121.00   90
 31  \w     28.00  75.00   0.50   23.56    --   73.48-112.00 -30.00   94
 32  \w    -25.00   3.00   0.50   23.56    --   73.48 -30.00-150.00   56
 33  \w   -147.00 -99.00   0.50   23.56    --  -74.54-112.00 150.00   96
 34  \w    -27.00  11.00   0.50   23.56    --  -74.54  45.00   0.00   76
 35  \w   -152.00 -97.00   0.50   23.56    --  -74.54-112.00  90.00  110
 36  \w    -51.00 -14.00   0.50   23.56    --  -99.50  64.00 150.00   74
 37  \w    -71.00 -34.00   0.50   23.56    --  -99.50 139.00   0.00   74
 38  \w    -67.00 -42.00   0.50   23.56    --  -99.50  77.00 -90.00   50
 39  \w   -136.00-110.00   0.50   23.56    --  -99.50-104.00  60.00   52
 40  \w    -53.00 -27.00   0.50   23.56    --  -99.50  64.00 120.00   52
 41  \w    -66.00 -35.00   0.50   23.56    --  -99.50 104.00-180.00   62
 42  \w   -158.00-102.00   0.50   23.56    --  -99.50-104.00-180.00  112
 43  \w   -157.00 -63.00   0.50   23.56    --  -99.50 -12.00  30.00  188
 44  \w   -154.00-102.00   0.50   23.56    --  -99.50-104.00  30.00  104
 45  \w    -44.00 -18.00   0.50   23.56    --  -99.50  77.00  30.00   52
 46  \w     20.00  48.00   0.50   23.56    --  110.67 -64.00-180.00   56
 47  \w     25.00  92.00   0.50   23.56    --  110.67-104.00 120.00  134
 48  \w     23.00  55.00   0.50   23.56    --  110.67 -64.00 -30.00   64
 49  \w    117.00 142.00   0.50   23.56    --  110.67  56.00 -96.00   50
 50  \w     23.00  91.00   0.50   23.56    --  110.67-104.00  60.00  136
 51  \w     48.00  92.00   0.50   23.56    --  110.67 -92.00-180.00   88
 52  \w     66.00  92.00   0.50   23.56    --  110.67-104.00-120.00   52
 53  \w    125.00 160.00   0.50   23.56    --  110.67  64.00  30.00   70
 54  \w     21.00  92.00   0.50   23.56    --  110.67-104.00 -30.00  142
 55  \w     14.00  65.00   0.50   23.56    --  110.67 -77.00-120.00  102
 56  \w     54.00  90.00   0.50   23.56    --  115.27-104.00   0.00   72
 57  \w     62.00  88.00   0.50   23.56    --  115.27 -92.00-120.00   52
 58  \w     22.00  48.00   0.50   23.56    --  115.27-104.00   0.00   52
 59  \w     39.00  91.00   0.50   23.56    --  115.27-104.00  30.00  104
 60  \w    124.00 149.00   0.50   23.56    --  115.27  64.00-120.00   50
 61  \w     17.00  43.00   0.50   23.56    --  115.27 -92.00-120.00   52
 62  \w     23.00  91.00   0.50   23.56    --  115.27-104.00  90.00  136
 63  \w     34.00  92.00   0.50   23.56    --  115.27-104.00 -60.00  116
 64  \w     28.00  90.00   0.50   23.56    --  115.27-104.00-120.00  124
 65  \w    153.00 178.00   0.50   23.56    --  115.27  12.00   0.00   50
 66  \w     94.00 130.00   0.50   23.56    --  115.27  12.00   0.00   72
 67  \w     64.00  89.00   0.50   23.56    --  115.27  12.00   0.00   50
 68  \w     66.00  92.00   0.50   23.56    --  115.27-104.00-180.00   52
 69  \w    114.00 150.00   0.50   23.56    --  115.27 139.00-120.00   72
 70  \w     21.00  63.00   0.50   23.56    --  115.27-104.00-180.00   84
 71  \w    116.00 159.00   0.50   23.56    --  115.27  64.00 150.00   86
;
_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      0.0106342000
_diffrn_orient_matrix_UB_12      0.1294603000
_diffrn_orient_matrix_UB_13      -0.0958698000
_diffrn_orient_matrix_UB_21      0.1603479000
_diffrn_orient_matrix_UB_22      -0.0715074000
_diffrn_orient_matrix_UB_23      -0.0213500000
_diffrn_orient_matrix_UB_31      -0.0415941000
_diffrn_orient_matrix_UB_32      -0.0562378000
_diffrn_orient_matrix_UB_33      -0.1073240000
_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  0.0231
_diffrn_reflns_av_unetI/netI     0.0320
_diffrn_reflns_Laue_measured_fraction_full 0.986
_diffrn_reflns_Laue_measured_fraction_max 0.954
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       8
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            8392
_diffrn_reflns_point_group_measured_fraction_full 0.986
_diffrn_reflns_point_group_measured_fraction_max 0.954
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         71.331
_diffrn_reflns_theta_min         4.175
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.737
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.81750
_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    1.367
_exptl_crystal_description       plate
_exptl_crystal_F_000             442
_exptl_crystal_preparation
;
Crystallised from a saturated solution of 4,4'-bipyridine
and 3-hydroxy-2-naphthoic acid (1:2) in MeNO2.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.12
_exptl_crystal_size_mid          0.062
_exptl_crystal_size_min          0.034
_refine_diff_density_max         0.194
_refine_diff_density_min         -0.176
_refine_diff_density_rms         0.036
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.062
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     295
_refine_ls_number_reflns         3810
_refine_ls_number_restraints     232
_refine_ls_restrained_S_all      1.033
_refine_ls_R_factor_all          0.0579
_refine_ls_R_factor_gt           0.0457
_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^)+(0.0561P)^2^+0.2545P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1133
_refine_ls_wR_factor_ref         0.1201
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3178
_reflns_number_total             3810
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           44-bipyridine_3-hydroxy-2-naphthoicacid
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_original_cell_volume        1026.65(11)
_cod_database_code               1574440
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.975
_shelx_estimated_absorpt_t_min   0.917
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All O(H) groups
2. Restrained distances
 O2A-H2A
 0.9 with sigma of 0.02
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.a Aromatic/amide H refined with riding coordinates:
 C1A(H1AA), C2(H2), C2B(H2B), C2C(H2C), C3(H3), C3B(H3B), C3C(H3C), C4(H4),
 C4A(H4A), C4B(H4B), C4C(H4C), C5(H5), C5B(H5B), C5C(H5C), C6A(H6A), C7A(H7A),
 C8A(H8A), C9A(H9A)
;
_shelx_res_checksum              66722
_shelx_hkl_checksum              12850
_olex2_exptl_crystal_mounting_method
'Crystal mounted using inert oil from the encapsulation crystallisation technique onto a Mitegan Kapton micromount.'
_olex2_submission_original_sample_id
'4,4'-bipyridine_3-hydroxy-2-naphthoic 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 1.675
_oxdiff_exptl_absorpt_empirical_full_min 0.628