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_1574445
_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, C6 H6 N'
_chemical_formula_sum            'C17 H14 N O3'
_chemical_formula_weight         280.29
_chemical_name_systematic
'3-hydroxy-2-naphthoic acid_1,2-bis(4-pyridyl)ethane'
_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.cc2kmc5r
_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                 107.861(4)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   10.6221(4)
_cell_length_b                   11.3226(3)
_cell_length_c                   11.5995(5)
_cell_measurement_reflns_used    4911
_cell_measurement_temperature    149.99(10)
_cell_measurement_theta_max      75.1390
_cell_measurement_theta_min      4.3690
_cell_volume                     1327.83(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 0.999
_diffrn_measured_fraction_theta_max 0.945
_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    -32.00  35.00   0.50    4.20    --  -43.37  52.00  78.00  134
  2  \w   -104.00 -75.00   0.50    4.20    --  -43.37 -52.00 -66.00   58
  3  \w     67.00  94.00   0.50    4.20    --   44.56  52.00  78.00   54
  4  \w     -1.00  39.00   0.50    4.20    --   44.56 -52.00 -66.00   80
  5  \w   -157.00-130.00   0.50    4.20    --  -88.13 -52.00 -66.00   54
  6  \w     94.00 173.00   0.50    4.20    --  100.88  52.00  78.00  158
  7  \w      3.00  37.00   0.50    4.20    --  -43.37  38.00-150.00   68
  8  \w    -74.00 -48.00   0.50    4.20    --  -43.37 -52.00 -66.00   52
  9  \w    -66.00 -39.00   0.50    4.20    --  -43.37 125.00-150.00   54
 10  \w    -49.00 -13.00   0.50    4.20    --  -43.37 125.00-180.00   72
 11  \w     33.00  60.00   0.50    4.20    --   44.56  38.00-120.00   54
 12  \w     35.00 125.00   0.50    4.20    --   50.00  40.00 -81.10  180
 13  \w     37.00  86.00   0.50    4.20    --   50.00  50.00 172.90   98
 14  \w     61.00 112.00   0.50    4.20    --   74.00  48.00-154.21  102
 15  \w   -160.00-131.00   0.50    4.20    --  -86.00 -52.00 107.95   58
 16  \w   -100.00 -74.00   0.50    4.20    --  -88.13 -45.00-180.00   52
 17  \w   -113.00 -76.00   0.50    4.20    --  -88.13 -45.00 150.00   74
 18  \w   -164.00 -88.00   0.50    4.20    --  -88.13 -61.00  30.00  152
 19  \w   -107.00 -74.00   0.50    4.20    --  -88.13 -45.00-150.00   66
 20  \w    -40.00 -15.00   0.50    4.20    --  -88.13  61.00-120.00   50
 21  \w   -141.00 -76.00   0.50    4.20    --  -88.13 -45.00 120.00  130
 22  \w    -41.00 -12.00   0.50    4.20    --  -88.13  61.00 150.00   58
 23  \w    -44.00 -15.00   0.50    4.20    --  -88.13  61.00  60.00   58
 24  \w   -109.00 -83.00   0.50    4.20    --  -94.50 -57.00 179.40   52
 25  \w   -108.00 -83.00   0.50    4.20    --  -94.50 -56.00 154.33   50
 26  \w   -113.00 -86.00   0.50    4.20    --  -94.50 -53.00-175.40   54
 27  \w   -109.00 -80.00   0.50    4.20    --  -94.50 -48.00-152.13   58
 28  \w   -131.00 -80.00   0.50    4.20    --  -94.50 -52.00 139.85  102
 29  \w   -118.00 -81.00   0.50    4.20    --  -94.50 -46.00 143.85   74
 30  \w   -171.00 -83.00   0.50    4.20    --  -94.50 -54.00-156.01  176
 31  \w     90.00 115.00   0.50    4.20    --  100.88  45.00-150.00   50
 32  \w     26.00  55.00   0.50    4.20    --  100.88 -61.00 -60.00   58
 33  \w    109.00 145.00   0.50    4.20    --  100.88  61.00 -30.00   72
 34  \w    126.00 165.00   0.50    4.20    --  100.88  45.00-150.00   78
 35  \w    128.00 169.00   0.50    4.20    --  100.88  77.00   0.00   82
 36  \w     25.00  50.00   0.50    4.20    --  100.88 -61.00   0.00   50
 37  \w     25.00  50.00   0.50    4.20    --  100.88 -61.00-180.00   50
 38  \w     25.00  50.00   0.50    4.20    --  100.88 -61.00  90.00   50
 39  \w     30.00  55.00   0.50    4.20    --  100.88 -61.00-120.00   50
 40  \w     42.00  68.00   0.50    4.20    --  109.87 -77.00   0.00   52
 41  \w     66.00  93.00   0.50    4.20    --  109.87  15.00-180.00   54
 42  \w     61.00 141.00   0.50    4.20    --  109.87  15.00  60.00  160
 43  \w     41.00  73.00   0.50    4.20    --  109.87 -77.00-120.00   64
 44  \w     44.00  75.00   0.50    4.20    --  109.87 -77.00 150.00   62
 45  \w    128.00 175.00   0.50    4.20    --  109.87  77.00 120.00   94
 46  \w    116.00 178.00   0.50    4.20    --  109.87  45.00-180.00  124
 47  \w     41.00  76.00   0.50    4.20    --  109.87 -77.00 -90.00   70
;
_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      0.0693846000
_diffrn_orient_matrix_UB_12      -0.0849708000
_diffrn_orient_matrix_UB_13      -0.0646938000
_diffrn_orient_matrix_UB_21      -0.1284581000
_diffrn_orient_matrix_UB_22      -0.0100420000
_diffrn_orient_matrix_UB_23      -0.1069072000
_diffrn_orient_matrix_UB_31      0.0436350000
_diffrn_orient_matrix_UB_32      0.1056949000
_diffrn_orient_matrix_UB_33      -0.0622750000
_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  0.0350
_diffrn_reflns_av_unetI/netI     0.0247
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.945
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            13885
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.945
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.377
_diffrn_reflns_theta_min         5.597
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.790
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.59822
_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    1.402
_exptl_crystal_description       block
_exptl_crystal_F_000             588
_exptl_crystal_preparation
;
Crystallised from a saturated solution of 3-hydroxy-2-
naphthoic acid, 4,4'-bipyridne and 1,2-bis(4-
pyridyl)ethane (2:1:2) in DMF and mineral oil.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.48
_exptl_crystal_size_mid          0.23
_exptl_crystal_size_min          0.11
_refine_diff_density_max         0.449
_refine_diff_density_min         -0.280
_refine_diff_density_rms         0.042
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.147
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     196
_refine_ls_number_reflns         2640
_refine_ls_number_restraints     154
_refine_ls_restrained_S_all      1.125
_refine_ls_R_factor_all          0.0641
_refine_ls_R_factor_gt           0.0551
_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^)+(0.0573P)^2^+0.6308P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1318
_refine_ls_wR_factor_ref         0.1366
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2348
_reflns_number_total             2640
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           3-hydroxy-2-naphthoicacid_12-bis4-pyridylethane
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574445
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C H N O'
_chemical_oxdiff_usercomment     DMF
_shelx_estimated_absorpt_t_max   0.918
_shelx_estimated_absorpt_t_min   0.703
_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. Restrained distances
 O2B-H2B
 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 Secondary CH2 refined with riding coordinates:
 C6A(H6AA,H6AB)
4.b Aromatic/amide H refined with riding coordinates:
 C1B(H1BA), C2A(H2A), C3A(H3A), C4A(H4A), C4B(H4B), C5A(H5A), C6B(H6B),
 C7B(H7B), C8B(H8B), C9B(H9B)
;
_shelx_res_checksum              7094
_shelx_hkl_checksum              81989
_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
'3-hydroxy-2-naphthoic acid_1,2-bis(4-pyridyl)ethane'
_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 1.758
_oxdiff_exptl_absorpt_empirical_full_min 0.639