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_1574454
_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, C5 H4 N'
_chemical_formula_sum            'C16 H12 N O3'
_chemical_formula_weight         266.27
_chemical_name_systematic        '4,4'-bipyridine_3-hydoxy-2-naphthoic 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.cc2kmbbw
_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                 98.270(4)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.9136(4)
_cell_length_b                   11.3523(5)
_cell_length_c                   12.4921(5)
_cell_measurement_reflns_used    8413
_cell_measurement_temperature    149.99(10)
_cell_measurement_theta_max      76.6860
_cell_measurement_theta_min      4.9730
_cell_volume                     1250.93(9)
_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 0.996
_diffrn_measured_fraction_theta_max 0.938
_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    -46.00 -12.00   0.50    0.29    --  -85.06  61.00  60.00   68
  2  \w     -9.00  32.00   0.50    0.29    --  -45.07  38.00  30.00   82
  3  \w      0.00  28.00   0.50    0.29    --  -45.07  38.00   0.00   56
  4  \w    -44.00 -14.00   0.50    0.29    --  -85.06  61.00 150.00   60
  5  \w      9.00  34.00   0.50    0.29    --  -45.07  27.00-128.00   50
  6  \w    -43.00 -12.00   0.50    0.29    --  -85.06  61.00-180.00   62
  7  \w    -42.00 -11.00   0.50    0.29    --  -85.06  61.00-150.00   62
  8  \w    -64.00 -22.00   0.50    0.29    --  -85.06 125.00 -60.00   84
  9  \w   -110.00 -76.00   0.50    0.29    --  -85.06 -27.00  69.00   68
 10  \w   -156.00-115.00   0.50    0.29    --  -85.06 -27.00  69.00   82
 11  \w   -124.00 -65.00   0.50    0.29    --  -45.07 -27.00  69.00  118
 12  \w    -60.00 -31.00   0.50    0.29    --  -45.07 -27.00  69.00   58
 13  \w    103.00 129.00   0.50    0.29    --  100.39  27.00-128.00   52
 14  \w     98.00 162.00   0.50    0.29    --  109.83  30.00 -90.00  128
 15  \w    106.00 140.00   0.50    0.29    --  109.83  27.00-128.00   68
 16  \w    116.00 160.00   0.50    0.29    --  109.83  30.00-180.00   88
 17  \w     51.00  77.00   0.50    0.29    --   46.07  27.00-128.00   52
 18  \w    -33.00  -8.00   0.50    0.29    --   46.07 -27.00  69.00   50
 19  \w     33.00  64.00   0.50    0.29    --  100.39 -77.00 150.00   62
 20  \w     52.00  80.00   0.50    0.29    --  109.83 -77.00  90.00   56
 21  \w     46.00  78.00   0.50    0.29    --  109.83 -77.00  30.00   64
 22  \w     26.00  56.00   0.50    0.29    --  100.39 -61.00   0.00   60
 23  \w     26.00  51.00   0.50    0.29    --  100.39 -61.00  60.00   50
 24  \w     26.00  51.00   0.50    0.29    --  100.39 -61.00 -60.00   50
 25  \w     45.00  70.00   0.50    0.29    --  109.83 -77.00 -90.00   50
 26  \w     30.00  56.00   0.50    0.29    --  100.39 -61.00 -90.00   52
 27  \w     49.00  74.00   0.50    0.29    --  109.83 -77.00 -60.00   50
 28  \w     39.00  64.00   0.50    0.29    --  100.39-125.00  30.00   50
 29  \w     66.00  99.00   0.50    0.29    --  100.39-125.00  30.00   66
 30  \w     29.00  56.00   0.50    0.29    --   46.07 -99.00  60.00   54
 31  \w    100.00 126.00   0.50    0.29    --  109.83  27.00-128.00   52
 32  \w     17.00  42.00   0.50    0.29    --   32.00  65.00   5.04   50
 33  \w    -60.00 -32.00   0.50    0.29    --  -44.00 -52.00-100.67   56
 34  \w     36.00  62.00   0.50    0.29    --   46.32  49.00   4.14   52
 35  \w     41.00  67.00   0.50    0.29    --   46.32  51.00  33.21   52
 36  \w     36.00  77.00   0.50    0.29    --   46.32  38.00 -60.00   82
 37  \w    -63.00 -37.00   0.50    0.29    --  -48.32 -52.00 -33.19   52
 38  \w    -68.00 -42.00   0.50    0.29    --  -52.00 -48.00 -58.00   52
 39  \w    -69.00 -44.00   0.50    0.29    --  -56.00 -52.00 -85.69   50
 40  \w    -70.00 -44.00   0.50    0.29    --  -56.00 -50.00 -81.89   52
 41  \w    -69.00 -44.00   0.50    0.29    --  -56.00 -51.00 -33.24   50
 42  \w    -76.00 -50.00   0.50    0.29    --  -60.00 -52.00-115.67   52
 43  \w   -137.00-111.00   0.50    0.29    --  -64.00 -48.00 -95.76   52
 44  \w    -79.00 -54.00   0.50    0.29    --  -64.00 -48.00 -95.76   50
 45  \w    -83.00 -57.00   0.50    0.29    --  -68.00 -49.00 -55.17   52
 46  \w    -86.00 -61.00   0.50    0.29    --  -72.00 -48.00 -28.76   50
 47  \w    -85.00 -60.00   0.50    0.29    --  -72.00 -51.00-134.72   50
 48  \w    -93.00 -68.00   0.50    0.29    --  -80.00 -52.00 -46.30   50
 49  \w    -93.00 -68.00   0.50    0.29    --  -80.00 -52.00 -67.09   50
 50  \w   -100.00 -72.00   0.50    0.29    --  -84.00 -50.00 -56.01   56
 51  \w    -98.00 -72.00   0.50    0.29    --  -84.00 -52.00 -88.80   52
 52  \w    -46.00 -21.00   0.50    0.29    --  -85.06  61.00 -30.00   50
 53  \w   -101.00 -76.00   0.50    0.29    --  -88.00 -51.00 -72.06   50
 54  \w   -155.00-124.00   0.50    0.29    --  -88.00 -52.00  15.29   62
 55  \w   -106.00 -76.00   0.50    0.29    --  -88.00 -51.00 -22.89   60
 56  \w   -104.00 -78.00   0.50    0.29    --  -88.00 -50.00 -64.32   52
 57  \w   -107.00 -81.00   0.50    0.29    --  -88.00 -52.00-108.26   52
 58  \w   -154.00-128.00   0.50    0.29    --  -88.00 -52.00-108.26   52
 59  \w   -165.00-139.00   0.50    0.29    --  -88.00 -51.00 -22.89   52
 60  \w   -107.00 -76.00   0.50    0.29    --  -88.00 -52.00  15.29   62
 61  \w   -106.00 -80.00   0.50    0.29    --  -92.00 -49.00   5.36   52
 62  \w   -118.00 -84.00   0.50    0.29    --  -92.25 -58.00 -15.11   68
 63  \w   -109.00 -84.00   0.50    0.29    --  -92.25 -59.00 -86.83   50
 64  \w   -167.00 -84.00   0.50    0.29    --  -92.25 -58.00 -36.14  166
 65  \w   -166.00-141.00   0.50    0.29    --  -92.25 -59.00 -52.24   50
 66  \w   -161.00 -83.00   0.50    0.29    --  -92.25 -54.00  -1.02  156
 67  \w   -106.00 -81.00   0.50    0.29    --  -92.25 -52.00  -0.17   50
 68  \w   -108.00 -83.00   0.50    0.29    --  -92.25 -56.00 -25.86   50
 69  \w   -108.00 -83.00   0.50    0.29    --  -92.25 -54.00 -88.33   50
 70  \w   -109.00 -84.00   0.50    0.29    --  -92.25 -58.00 -68.32   50
 71  \w     31.00  56.00   0.50    0.29    --  100.39 -61.00-150.00   50
 72  \w     26.00  51.00   0.50    0.29    --  100.39 -61.00  90.00   50
 73  \w    100.00 125.00   0.50    0.29    --  109.83  45.00  30.00   50
;
_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      0.1352296000
_diffrn_orient_matrix_UB_12      0.0414936000
_diffrn_orient_matrix_UB_13      0.0822566000
_diffrn_orient_matrix_UB_21      0.1079022000
_diffrn_orient_matrix_UB_22      -0.0234002000
_diffrn_orient_matrix_UB_23      -0.0835183000
_diffrn_orient_matrix_UB_31      -0.0241169000
_diffrn_orient_matrix_UB_32      0.1270706000
_diffrn_orient_matrix_UB_33      -0.0422281000
_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  0.0361
_diffrn_reflns_av_unetI/netI     0.0241
_diffrn_reflns_Laue_measured_fraction_full 0.996
_diffrn_reflns_Laue_measured_fraction_max 0.938
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            15848
_diffrn_reflns_point_group_measured_fraction_full 0.996
_diffrn_reflns_point_group_measured_fraction_max 0.938
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.969
_diffrn_reflns_theta_min         5.014
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.809
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.50617
_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    1.414
_exptl_crystal_description       plate
_exptl_crystal_F_000             556
_exptl_crystal_preparation
;
Crystallised from a saturated solution of 4,4'-bipyridine
and 3-hydroxy-2-naphthoic acid (1:2) in MeOH.
;
_exptl_crystal_recrystallization_method
;
High-throughput screening via the ENaCt co-
crystallisation protocol using SPT Labtech mosquito.
;
_exptl_crystal_size_max          0.12
_exptl_crystal_size_mid          0.086
_exptl_crystal_size_min          0.03
_refine_diff_density_max         0.264
_refine_diff_density_min         -0.241
_refine_diff_density_rms         0.041
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.069
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     187
_refine_ls_number_reflns         2481
_refine_ls_number_restraints     145
_refine_ls_restrained_S_all      1.042
_refine_ls_R_factor_all          0.0561
_refine_ls_R_factor_gt           0.0448
_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^)+(0.0588P)^2^+0.4577P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1163
_refine_ls_wR_factor_ref         0.1249
_reflns_Friedel_coverage         0.000
_reflns_number_gt                1983
_reflns_number_total             2481
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           44-bipyridine_3-hydroxy-2-naphthoicacid_k
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574454
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C H N O'
_shelx_estimated_absorpt_t_max   0.976
_shelx_estimated_absorpt_t_min   0.909
_diffrn_oxdiff_digest_hkl
;
0156645b1aedf1e2e28c9682783832afd24055
;
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All O(H) groups
2. Restrained distances
 O1B-H1B
 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:
 C2A(H2A), C3A(H3A), C4A(H4A), C4B(H4B), C5A(H5A), C6B(H6B), C7B(H7B),
 C8B(H8B), C9B(H9B), C11B(H11B)
;
_shelx_res_checksum              43472
_shelx_hkl_checksum              81633
_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_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 1.609
_oxdiff_exptl_absorpt_empirical_full_min 0.605