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_1574435
_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_absolute_configuration unk
_chemical_formula_moiety
'2(C8 H8 O5), 3(C10 H8 N2), 2(C H3 N O2), 2(H2 O)'
_chemical_formula_sum            'C48 H50 N8 O16'
_chemical_formula_weight         994.96
_chemical_name_systematic        4,4'-bipyridine_methyl_gallate_MeNO2
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_block_doi                 10.5517/ccdc.csd.cc2kmbsb
_audit_creation_date             2025-02-24
_audit_creation_method
;
Olex2 1.5
(compiled 2021.12.09 svn.r5202d8cf for OlexSys, GUI svn.r6439)
;
_audit_update_record
;
2025-03-04 deposited with the CCDC.	2025-04-22 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 99.9370(10)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   9.68930(10)
_cell_length_b                   16.7367(2)
_cell_length_c                   15.0094(2)
_cell_measurement_reflns_used    13312
_cell_measurement_temperature    150.00(10)
_cell_measurement_theta_max      74.4730
_cell_measurement_theta_min      2.9840
_cell_volume                     2397.51(5)
_computing_cell_refinement       'CrysAlisPro 1.171.43.126a (Rigaku OD, 2024)'
_computing_data_collection
'CrysAlisPro system (CCD 43.126a 64-bit (release 11-06-2024))'
_computing_data_reduction        'CrysAlisPro 1.171.43.126a (Rigaku OD, 2024)'
_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      150.00(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 1.000
_diffrn_measured_fraction_theta_max 0.946
_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     13.00  76.00   0.50   12.00    --   46.11 -75.00  94.00  126
  2  \w     21.00 111.00   0.50   12.00    --   46.11  75.00-138.00  180
  3  \w    -51.00 -26.00   0.50   12.00    --  -47.61  75.00-138.00   50
  4  \w    -69.00 -44.00   0.50   12.00    --  -47.61 -75.00  94.00   50
  5  \w    -98.00 -36.00   0.50   48.00    --  -92.22  75.00-138.00  124
  6  \w   -154.00 -64.00   0.50   48.00    --  -92.22 -75.00  94.00  180
  7  \w     29.00  62.00   0.50   48.00    --   95.82 -75.00  94.00   66
  8  \w     92.00 117.00   0.50   48.00    --   95.82  75.00-138.00   50
  9  \w    119.00 151.00   0.50   48.00    --  107.32  75.00-138.00   64
 10  \w     60.00  85.00   0.50   48.00    --  107.32 -75.00  94.00   50
 11  \w     74.00 119.00   0.50   12.00    --   46.11 125.00  60.00   90
 12  \w      0.00  26.00   0.50   12.00    --   46.11 -19.00  90.00   52
 13  \w     74.00 120.00   0.50   12.00    --   46.11 125.00-180.00   92
 14  \w    -36.00  -4.00   0.50   12.00    --   46.11 -19.00  90.00   64
 15  \w    -11.00  35.00   0.50   12.00    --  -47.61  19.00-150.00   92
 16  \w   -116.00 -72.00   0.50   48.00    --  -92.22 -45.00   0.00   88
 17  \w    -35.00 -10.00   0.50   48.00    --  -92.22  30.00-150.00   50
 18  \w    -35.00 -10.00   0.50   48.00    --  -92.22  30.00  30.00   50
 19  \w   -169.00 -78.00   0.50   48.00    --  -92.22 -61.00 -30.00  182
 20  \w    -51.00 -12.00   0.50   48.00    --  -92.22  45.00-120.00   78
 21  \w   -164.00-108.00   0.50   48.00    --  -92.22 -95.00-180.00  112
 22  \w    -35.00 -10.00   0.50   48.00    --  -92.22  30.00  90.00   50
 23  \w   -132.00 -74.00   0.50   48.00    --  -92.22 -45.00 -90.00  116
 24  \w    -35.00  -9.00   0.50   48.00    --  -92.22  30.00 -60.00   52
 25  \w   -165.00-139.00   0.50   48.00    --  -92.22 -45.00   0.00   52
 26  \w    -34.00  -9.00   0.50   48.00    --  -92.22  30.00   0.00   50
 27  \w     65.00 123.00   0.50   48.00    --   95.82  30.00 -30.00  116
 28  \w    135.00 168.00   0.50   48.00    --   95.82  45.00 150.00   66
 29  \w     17.00  51.00   0.50   48.00    --   95.82 -45.00 120.00   68
 30  \w     76.00 107.00   0.50   48.00    --   95.82  45.00 150.00   62
 31  \w    142.00 167.00   0.50   48.00    --   95.82  77.00 150.00   50
 32  \w     69.00 100.00   0.50   48.00    --   95.82 -77.00-180.00   62
 33  \w     25.00  56.00   0.50   48.00    --   95.82 -77.00-180.00   62
 34  \w     70.00 122.00   0.50   48.00    --   95.82  77.00 150.00  104
 35  \w     20.00  66.00   0.50   48.00    --   95.82 -61.00  30.00   92
 36  \w    136.00 175.00   0.50   48.00    --   95.82  30.00 -30.00   78
 37  \w    126.00 175.00   0.50   48.00    --  107.32  30.00   0.00   98
 38  \w     79.00 107.00   0.50   48.00    --  107.32  30.00   0.00   56
 39  \w     48.00 103.00   0.50   48.00    --  107.32 -95.00  30.00  110
 40  \w     36.00  86.00   0.50   48.00    --  107.32 -95.00 -90.00  100
 41  \w     39.00  65.00   0.50   48.00    --  107.32 -61.00 -60.00   52
 42  \w     93.00 134.00   0.50   48.00    --  107.32  61.00 -90.00   82
 43  \w     37.00 105.00   0.50   48.00    --  107.32 -77.00 120.00  136
;
_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      0.0990291000
_diffrn_orient_matrix_UB_12      0.0706435000
_diffrn_orient_matrix_UB_13      0.0302739000
_diffrn_orient_matrix_UB_21      0.0989508000
_diffrn_orient_matrix_UB_22      -0.0287939000
_diffrn_orient_matrix_UB_23      -0.0634206000
_diffrn_orient_matrix_UB_31      -0.0802979000
_diffrn_orient_matrix_UB_32      0.0515331000
_diffrn_orient_matrix_UB_33      -0.0769415000
_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  0.0367
_diffrn_reflns_av_unetI/netI     0.0365
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.946
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       20
_diffrn_reflns_limit_k_min       -20
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            29451
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.925
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.183
_diffrn_reflns_theta_min         2.989
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.884
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.945
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.43.126a (Rigaku Oxford Diffraction, 2024)
Numerical absorption correction based on gaussian integration over
a multifaceted crystal model
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    1.378
_exptl_crystal_description       block
_exptl_crystal_F_000             1044
_exptl_crystal_preparation
;
Crystallised from a saturated solution of 4,4'-bipyridine, 
and methyl gallate (2:1) in MeNO2,
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.06
_exptl_crystal_size_mid          0.048
_exptl_crystal_size_min          0.038
_refine_diff_density_max         0.322
_refine_diff_density_min         -0.255
_refine_diff_density_rms         0.048
_refine_ls_abs_structure_details
;
 Flack x determined using 3634 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.46(7)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.040
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     665
_refine_ls_number_reflns         9408
_refine_ls_number_restraints     484
_refine_ls_restrained_S_all      1.014
_refine_ls_R_factor_all          0.0481
_refine_ls_R_factor_gt           0.0428
_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^)+(0.0739P)^2^+0.4269P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1164
_refine_ls_wR_factor_ref         0.1200
_reflns_Friedel_coverage         0.888
_reflns_Friedel_fraction_full    0.997
_reflns_Friedel_fraction_max     0.902
_reflns_number_gt                8525
_reflns_number_total             9408
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           44bipyridine_methyl_gallate_meno2_h2o
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574435
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C48 H50 N8 O16'
_shelx_estimated_absorpt_t_max   0.967
_shelx_estimated_absorpt_t_min   0.949
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups, All O(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 Free rotating group:
 O1S(H1Sa,H1Sb), O2S(H2Sa,H2Sb)
3.b Aromatic/amide H refined with riding coordinates:
 C2A(H2A), C2B(H2Ba), C2C(H2C), C2D(H2Da), C2E(H2E), C3A(H3A), C3C(H3C),
 C3E(H3E), C4A(H4A), C4C(H4C), C4E(H4E), C5A(H5A), C5C(H5C), C5E(H5E), C6B(H6B),
  C6D(H6D), C7A(H7A), C7C(H7C), C7E(H7E), C8A(H8A), C8C(H8C), C8E(H8E),
 C9A(H9A), C9C(H9C), C9E(H9E), C10A(H10A), C10C(H10C), C10E(H10E)
3.c Idealised Me refined as rotating group:
 C1F(H1Fa,H1Fb,H1Fc), C1G(H1Ga,H1Gb,H1Gc), C8B(H8Ba,H8Bb,H8Bc), C8D(H8Da,H8Db,
 H8Dc)
3.d Idealised tetrahedral OH refined as rotating group:
 O1B(H1B), O1D(H1D), O2B(H2B), O2D(H2D), O3B(H3B), O3D(H3D)
;
_shelx_res_checksum              69681
_shelx_hkl_checksum              41215
_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_methyl_gallate_MeNO2
_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 2.213
_oxdiff_exptl_absorpt_empirical_full_min 0.443