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_1574452
_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         '2(C7 H8 O2), 3(C10 H8 N2)'
_chemical_formula_sum            'C44 H40 N6 O4'
_chemical_formula_weight         716.82
_chemical_name_systematic        4,4'-bipyridine_orcinol
_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.cc2kmc2n
_audit_creation_date             2024-07-15
_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                67.885(9)
_cell_angle_beta                 77.744(7)
_cell_angle_gamma                69.420(9)
_cell_formula_units_Z            1
_cell_length_a                   8.7799(8)
_cell_length_b                   10.0344(10)
_cell_length_c                   11.9985(10)
_cell_measurement_reflns_used    3959
_cell_measurement_temperature    150.10(10)
_cell_measurement_theta_max      73.9160
_cell_measurement_theta_min      3.9650
_cell_volume                     912.91(16)
_computing_cell_refinement       'CrysAlisPro 1.171.42.73a (Rigaku OD, 2022)'
_computing_data_collection       'CrysAlisPro 1.171.42.73a (Rigaku OD, 2022)'
_computing_data_reduction        'CrysAlisPro 1.171.42.73a (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_environment      N~2~
_diffrn_ambient_temperature      150.10(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 0.987
_diffrn_measured_fraction_theta_max 0.935
_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    -53.00  24.00   0.50    0.09    --   38.19 -19.00-150.00  154
  2  \w    -43.00  26.00   0.50    0.09    --   38.19 -19.00 -90.00  138
  3  \w     40.00  66.00   0.50    0.09    --   38.19 -65.00  20.00   52
  4  \w    -36.00  65.00   0.50    0.09    --   38.19 -57.00 120.00  202
  5  \w     51.00 105.00   0.50    0.09    --  102.48 -95.00 150.00  108
  6  \w     19.00 106.00   0.50    0.09    --  102.48-111.00  90.00  174
  7  \w     28.00 105.00   0.50    0.09    --  110.26-111.00  30.00  154
  8  \w     18.00  43.00   0.50    0.09    --  102.48 -95.00 150.00   50
  9  \w     39.00  77.00   0.50    0.09    --   38.19-178.00 -90.00   76
 10  \w     70.00 107.00   0.50    0.09    --  102.48-111.00-120.00   74
 11  \w     24.00  53.00   0.50    0.09    --  102.48-111.00-120.00   58
 12  \w     33.00 103.00   0.50    0.09    --  102.48 -77.00 -90.00  140
 13  \w     48.00 103.00   0.50    0.09    --  110.26 -77.00-180.00  110
 14  \w     34.00  66.00   0.50    0.09    --  102.48 -61.00 -60.00   64
 15  \w     25.00  51.00   0.50    0.09    --  110.26 -45.00-150.00   52
 16  \w     30.00  55.00   0.50    0.09    --  110.26 -65.00  20.00   50
 17  \w     22.00  54.00   0.50    0.09    --  102.48 -65.00  20.00   64
 18  \w     23.00  48.00   0.50    0.09    --  110.26 -45.00  60.00   50
 19  \w     46.00  95.00   0.50    0.09    --  110.26 -77.00  90.00   98
 20  \w     23.00  48.00   0.50    0.09    --  110.26 -45.00 150.00   50
 21  \w     87.00 172.00   0.50    0.09    --  110.26  45.00  60.00  170
 22  \w    122.00 160.00   0.50    0.09    --  102.48  65.00 155.00   76
 23  \w    102.00 127.00   0.50    0.09    --  110.26  65.00 155.00   50
 24  \w     70.00  97.00   0.50    0.09    --  102.48  65.00 155.00   54
 25  \w     60.00 109.00   0.50    0.09    --   38.19  65.00 155.00   98
 26  \w    146.00 178.00   0.50    0.09    --  102.48  45.00-120.00   64
 27  \w     75.00 132.00   0.50    0.09    --  102.48  45.00-120.00  114
 28  \w     44.00  85.00   0.50    0.09    --  110.26 178.00  60.00   82
 29  \w     94.00 146.00   0.50    0.09    --  110.26 178.00  60.00  104
 30  \w     61.00 124.00   0.50    0.09    --   38.19 178.00  30.00  126
 31  \w    -20.00   7.00   0.50    0.09    --  -39.01  65.00 155.00   54
 32  \w    -74.00 -44.00   0.50    0.09    --  -95.69  65.00 155.00   60
 33  \w    -37.00  -9.00   0.50    0.09    --  -95.69  45.00 150.00   56
 34  \w    -35.00 -10.00   0.50    0.09    --  -95.69  30.00 120.00   50
 35  \w    -35.00 -10.00   0.50    0.09    --  -95.69  30.00  60.00   50
 36  \w    -50.00 -10.00   0.50    0.09    --  -95.69  45.00  60.00   80
 37  \w    -35.00 -10.00   0.50    0.09    --  -95.69  30.00   0.00   50
 38  \w    -34.00  -9.00   0.50    0.09    --  -95.69  30.00 -30.00   50
 39  \w    -35.00 -10.00   0.50    0.09    --  -95.69  30.00 -90.00   50
 40  \w    -35.00  -9.00   0.50    0.09    --  -95.69  30.00-120.00   52
 41  \w   -163.00 -91.00   0.50    0.09    --  -95.69 -65.00  20.00  144
 42  \w   -114.00 -60.00   0.50    0.09    --  -39.01-178.00 120.00  108
 43  \w   -142.00 -98.00   0.50    0.09    --  -95.69-111.00 150.00   88
 44  \w   -104.00 -79.00   0.50    0.09    --  -39.01 -65.00  20.00   50
 45  \w    -75.00  -4.00   0.50    0.09    --  -39.01 -65.00  20.00  142
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type
'XtaLAB Synergy, Single source at home/near, HyPix-Arc 100'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0361992000
_diffrn_orient_matrix_UB_12      0.1374220000
_diffrn_orient_matrix_UB_13      0.0042698000
_diffrn_orient_matrix_UB_21      0.1083383000
_diffrn_orient_matrix_UB_22      -0.1035723000
_diffrn_orient_matrix_UB_23      0.1039536000
_diffrn_orient_matrix_UB_31      0.1496072000
_diffrn_orient_matrix_UB_32      -0.0238205000
_diffrn_orient_matrix_UB_33      -0.0924542000
_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  0.0253
_diffrn_reflns_av_unetI/netI     0.0326
_diffrn_reflns_Laue_measured_fraction_full 0.987
_diffrn_reflns_Laue_measured_fraction_max 0.935
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            8435
_diffrn_reflns_point_group_measured_fraction_full 0.987
_diffrn_reflns_point_group_measured_fraction_max 0.935
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.517
_diffrn_reflns_theta_min         3.994
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.683
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.74167
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.73a (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    1.304
_exptl_crystal_description       block
_exptl_crystal_F_000             378
_exptl_crystal_preparation
;
Crystallised from a saturated solution of 4,4'-bipyridine
and orcinol: phenazine (1:2:1) in DMF.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.29
_exptl_crystal_size_mid          0.25
_exptl_crystal_size_min          0.08
_refine_diff_density_max         0.389
_refine_diff_density_min         -0.263
_refine_diff_density_rms         0.070
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.076
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     251
_refine_ls_number_reflns         3491
_refine_ls_number_restraints     186
_refine_ls_restrained_S_all      1.047
_refine_ls_R_factor_all          0.0576
_refine_ls_R_factor_gt           0.0517
_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^)+(0.0962P)^2^+0.0899P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1416
_refine_ls_wR_factor_ref         0.1476
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2987
_reflns_number_total             3491
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           44-bipyridine_orcinol
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574452
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C H N O'
_shelx_estimated_absorpt_t_max   0.956
_shelx_estimated_absorpt_t_min   0.735
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All O(H) groups
 At 1.5 times of:
  All C(H,H,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 Aromatic/amide H refined with riding coordinates:
 C2A(H2Aa), C2B(H2B), C2C(H2C), C3B(H3B), C3C(H3C), C4A(H4A), C4B(H4B),
 C4C(H4C), C5B(H5B), C5C(H5C), C6A(H6A), C7B(H7B), C8B(H8B), C9B(H9B),
 C10B(H10B)
3.b Idealised Me refined as rotating group:
 C7A(H7Aa,H7Ab,H7Ac)
;
_shelx_res_checksum              44299
_shelx_hkl_checksum              11900
_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_orcinol
_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 1.436
_oxdiff_exptl_absorpt_empirical_full_min 0.741