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_1574442
_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), 2(H2 O), C3 H7 N O, 3(C10 H8 N2)'
_chemical_formula_sum            'C49 H51 N7 O13'
_chemical_formula_weight         945.96
_chemical_name_systematic        '4,4'-bipyridine_methyl gallate_DMF_H2O'
_space_group_crystal_system      monoclinic
_space_group_IT_number           9
_space_group_name_Hall           'C -2yc'
_space_group_name_H-M_alt        'C 1 c 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_block_doi                 10.5517/ccdc.csd.cc2kmbr9
_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                 93.143(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   9.4553(2)
_cell_length_b                   17.6614(4)
_cell_length_c                   28.0494(5)
_cell_measurement_reflns_used    12053
_cell_measurement_temperature    150
_cell_measurement_theta_max      76.9670
_cell_measurement_theta_min      3.1190
_cell_volume                     4677.03(17)
_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 0.997
_diffrn_measured_fraction_theta_max 0.950
_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    -59.00 -34.00   0.50    8.50    --  -45.36 108.00 -61.00   50
  2  \w     31.00  61.00   0.50    8.50    --   46.36-108.00-158.00   60
  3  \w    -64.00 -39.00   0.50   34.02    --  -85.06 108.00 -61.00   50
  4  \w   -152.00-101.00   0.50   34.02    --  -85.06-108.00-158.00  102
  5  \w     36.00  61.00   0.50   34.02    --  100.32-108.00-158.00   50
  6  \w    124.00 149.00   0.50   34.02    --  100.32 108.00 -61.00   50
  7  \w    126.00 151.00   0.50   34.02    --  109.83 108.00 -61.00   50
  8  \w     54.00  82.00   0.50   34.02    --  109.83-108.00-158.00   56
  9  \w     -8.00  32.00   0.50    8.50    --  -45.36  38.00 120.00   80
 10  \w    -16.00  31.00   0.50    8.50    --  -45.36  38.00  60.00   94
 11  \w    -19.00  30.00   0.50    8.50    --  -45.36  38.00  30.00   98
 12  \w      1.00  64.00   0.50    8.50    --   46.36 -77.00 -30.00  126
 13  \w    -26.00  19.00   0.50    8.50    --   46.36 -38.00 120.00   90
 14  \w   -153.00-119.00   0.50   34.02    --  -85.06 -77.00  30.00   68
 15  \w    -50.00 -12.00   0.50   34.02    --  -85.06  61.00  60.00   76
 16  \w   -134.00-108.00   0.50   34.02    --  -85.06 -95.00-120.00   52
 17  \w    -75.00 -22.00   0.50   34.02    --  -85.06 125.00  30.00  106
 18  \w   -153.00-102.00   0.50   34.02    --  -85.06 -77.00 -30.00  102
 19  \w     32.00  89.00   0.50   34.02    --  100.32 -95.00 -90.00  114
 20  \w    109.00 175.00   0.50   34.02    --  100.32  61.00 -30.00  132
 21  \w     32.00  75.00   0.50   34.02    --  100.32 -77.00   0.00   86
 22  \w     34.00  61.00   0.50   34.02    --  100.32 -77.00-150.00   54
 23  \w     33.00  97.00   0.50   34.02    --  105.07-115.00-109.78  128
 24  \w     43.00  68.00   0.50   34.02    --  109.83 -77.00  90.00   50
 25  \w     56.00  87.00   0.50   34.02    --  109.83 -95.00 -60.00   62
 26  \w     74.00 135.00   0.50   34.02    --  109.83  15.00 150.00  122
 27  \w     64.00  92.00   0.50   34.02    --  109.83 -95.00-120.00   56
 28  \w     43.00  69.00   0.50   34.02    --  109.83 -77.00 -30.00   52
 29  \w     47.00  73.00   0.50   34.02    --  109.83 -77.00  60.00   52
 30  \w     42.00  67.00   0.50   34.02    --  109.83 -77.00  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      0.0346090000
_diffrn_orient_matrix_UB_12      0.0290612000
_diffrn_orient_matrix_UB_13      0.0511421000
_diffrn_orient_matrix_UB_21      0.0279893000
_diffrn_orient_matrix_UB_22      0.0796263000
_diffrn_orient_matrix_UB_23      -0.0198303000
_diffrn_orient_matrix_UB_31      -0.1568522000
_diffrn_orient_matrix_UB_32      0.0207119000
_diffrn_orient_matrix_UB_33      0.0045110000
_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  0.0185
_diffrn_reflns_av_unetI/netI     0.0200
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.950
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       21
_diffrn_reflns_limit_k_min       -22
_diffrn_reflns_limit_l_max       33
_diffrn_reflns_limit_l_min       -34
_diffrn_reflns_number            17067
_diffrn_reflns_point_group_measured_fraction_full 0.655
_diffrn_reflns_point_group_measured_fraction_max 0.609
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.272
_diffrn_reflns_theta_min         3.156
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.821
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.75907
_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    1.343
_exptl_crystal_description       plate
_exptl_crystal_F_000             1992
_exptl_crystal_preparation
;
Crystallised from a saturated solution of 4,4'-bipyridine
and methyl gallate (2:1) in DMF.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt co-crystallisationprotocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.44
_exptl_crystal_size_mid          0.25
_exptl_crystal_size_min          0.074
_refine_diff_density_max         0.162
_refine_diff_density_min         -0.168
_refine_diff_density_rms         0.031
_refine_ls_abs_structure_details
;
 Flack x determined using 1245 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.11(8)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.049
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     665
_refine_ls_number_reflns         6028
_refine_ls_number_restraints     475
_refine_ls_restrained_S_all      1.008
_refine_ls_R_factor_all          0.0282
_refine_ls_R_factor_gt           0.0274
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0472P)^2^+1.0286P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0749
_refine_ls_wR_factor_ref         0.0753
_reflns_Friedel_coverage         0.280
_reflns_Friedel_fraction_full    0.311
_reflns_Friedel_fraction_max     0.267
_reflns_number_gt                5875
_reflns_number_total             6028
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           44-bipyridine_methylgallate_dmf_h2o
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574442
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C18 H17 O5 N2'
_shelx_estimated_absorpt_t_max   0.942
_shelx_estimated_absorpt_t_min   0.714
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All O(H) groups, All O(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 O2S-H3D_$1
 1.8 with sigma of 0.02
 O3B-H3B
 0.82 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. Others
 Fixed Sof: O2S(0.60516) O2T(0.39484)
5.a Aromatic/amide H refined with riding coordinates:
 C1A(H1A), C1C(H1C), C1E(H1E), C2A(H2A), C2C(H2C), C2E(H2E), C3B(H3Ba),
 C3D(H3Da), C3S(H3S), C4A(H4A), C4C(H4C), C4E(H4E), C5A(H5A), C5C(H5C),
 C5E(H5E), C7A(H7A), C7B(H7B), C7C(H7C), C7D(H7D), C7E(H7E), C8A(H8A), C8C(H8C),
  C8E(H8E), C9A(H9A), C9C(H9C), C9E(H9E), C10A(H10A), C10C(H10C), C10E(H10E)
5.b Idealised Me refined as rotating group:
 C4S(H4Sa,H4Sb,H4Sc), C5S(H5Sa,H5Sb,H5Sc), C8B(H8Ba,H8Bb,H8Bc), C8D(H8Da,H8Db,
 H8Dc)
;
_shelx_res_checksum              88444
_shelx_hkl_checksum              45240
_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_DMF_H2O'
_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 1.634
_oxdiff_exptl_absorpt_empirical_full_min 0.658