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_1574455
_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         'C7 H4 N2 O6, C6 H6 N2 O, C H4 O'
_chemical_formula_sum            'C14 H14 N4 O8'
_chemical_formula_weight         366.29
_chemical_name_systematic        'nicotinamide_3,5-dinitrobenzoic acid_MeOH'
_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.cc2kmbwf
_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                 92.304(3)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   7.0215(3)
_cell_length_b                   22.3185(8)
_cell_length_c                   20.2612(7)
_cell_measurement_reflns_used    10257
_cell_measurement_temperature    150.01(10)
_cell_measurement_theta_max      77.2340
_cell_measurement_theta_min      2.9300
_cell_volume                     3172.6(2)
_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      150.01(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 0.998
_diffrn_measured_fraction_theta_max 0.928
_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     75.00 121.00   0.50    1.35    --   48.76 125.00 -30.00   92
  2  \w     35.00  60.00   0.50    1.35    --  108.00 -61.00-150.00   50
  3  \w     44.00  69.00   0.50    1.35    --  108.00 -61.00   0.00   50
  4  \w     33.00  66.00   0.50    1.35    --  108.00 -58.00 -80.00   66
  5  \w    -26.00  31.00   0.50    1.35    --   48.76 -58.00 -80.00  114
  6  \w     25.00  51.00   0.50    1.35    --   96.11 -58.00 -80.00   52
  7  \w     18.00  44.00   0.50    1.35    --   96.11 -45.00   0.00   52
  8  \w     18.00  46.00   0.50    1.35    --   96.11 -45.00-120.00   56
  9  \w     39.00  67.00   0.50    1.35    --  108.00 -61.00  60.00   56
 10  \w     24.00  65.00   0.50    1.35    --   96.11 -61.00 150.00   82
 11  \w     36.00  61.00   0.50    1.35    --  108.00 -61.00 120.00   50
 12  \w     22.00  47.00   0.50    1.35    --   96.11 -45.00  60.00   50
 13  \w     18.00  43.00   0.50    1.35    --   96.11 -45.00-180.00   50
 14  \w     91.00 127.00   0.50    1.35    --  108.00  61.00 -30.00   72
 15  \w    133.00 160.00   0.50    1.35    --  108.00  61.00 -30.00   54
 16  \w    109.00 134.00   0.50    1.35    --  108.00  58.00  60.00   50
 17  \w    100.00 125.00   0.50    1.35    --   96.11  58.00  60.00   50
 18  \w     76.00 114.00   0.50    1.35    --   48.76  58.00  60.00   76
 19  \w    -71.00 -19.00   0.50    1.35    --  -92.01  61.00  30.00  104
 20  \w    -50.00 -24.00   0.50    1.35    --  -92.01  58.00  60.00   52
 21  \w    -39.00 -14.00   0.50    1.35    --  -92.01  45.00  30.00   50
 22  \w    -66.00  21.00   0.50    1.35    --  -49.76  58.00  60.00  174
 23  \w    -51.00 -15.00   0.50    1.35    --  -92.01  45.00-120.00   72
 24  \w    -48.00 -15.00   0.50    1.35    --  -92.01  45.00-180.00   66
 25  \w   -171.00 -71.00   0.50    1.35    --  -92.01 -30.00 -30.00  200
 26  \w   -167.00 -81.00   0.50    1.35    --  -92.01 -58.00 -80.00  172
 27  \w   -113.00 -84.00   0.50    1.35    --  -49.76 -58.00 -80.00   58
 28  \w    -99.00 -74.00   0.50    1.35    --  -49.76-125.00  60.00   50
;
_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      -0.1488851000
_diffrn_orient_matrix_UB_12      0.0463569000
_diffrn_orient_matrix_UB_13      -0.0247630000
_diffrn_orient_matrix_UB_21      0.0668101000
_diffrn_orient_matrix_UB_22      -0.0078028000
_diffrn_orient_matrix_UB_23      -0.0709651000
_diffrn_orient_matrix_UB_31      -0.1469902000
_diffrn_orient_matrix_UB_32      -0.0505456000
_diffrn_orient_matrix_UB_33      -0.0117655000
_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  0.0301
_diffrn_reflns_av_unetI/netI     0.0262
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.928
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -27
_diffrn_reflns_limit_l_max       25
_diffrn_reflns_limit_l_min       -25
_diffrn_reflns_number            23820
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.928
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         78.277
_diffrn_reflns_theta_min         2.947
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.107
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.81149
_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    1.534
_exptl_crystal_description       plate
_exptl_crystal_F_000             1520
_exptl_crystal_preparation
;
Crystallised from a saturated solution of nicotinamide
and 3,5-dinitrobenzoic 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          0.32
_exptl_crystal_size_mid          0.29
_exptl_crystal_size_min          0.064
_refine_diff_density_max         0.246
_refine_diff_density_min         -0.416
_refine_diff_density_rms         0.058
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.074
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     495
_refine_ls_number_reflns         6309
_refine_ls_number_restraints     347
_refine_ls_restrained_S_all      1.050
_refine_ls_R_factor_all          0.0581
_refine_ls_R_factor_gt           0.0462
_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^)+(0.0797P)^2^+1.2691P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1319
_refine_ls_wR_factor_ref         0.1440
_reflns_Friedel_coverage         0.000
_reflns_number_gt                5060
_reflns_number_total             6309
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           nicotinamide_35-dihydroxybenzoicacid
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574455
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C12 H10 N4 O3'
_shelx_estimated_absorpt_t_max   0.933
_shelx_estimated_absorpt_t_min   0.641
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All N(H,H) groups, All O(H) groups
 At 1.5 times of:
  All C(H,H) groups, All C(H,H,H) groups
2. Restrained distances
 H6C-O6C
 0.99 with sigma of 0.02
 N1D-H6C
 1.555 with sigma of 0.02
 O5A-H5A = O1E-H1E = O6C-H6C
 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.a Aromatic/amide H refined with riding coordinates:
 C2A(H2A), C2B(H2B), C2C(H2C), C2D(H2D), C3B(H3B), C3D(H3D), C4A(H4A),
 C4B(H4B), C4C(H4C), C4D(H4D), C5B(H5B), C5D(H5D), C6A(H6A), C6C(H6CA)
4.b Idealised Me refined as rotating group:
 C1E(H1EA,H1EB,H1EC), C1F(H1FA,H1FB,H1FC)
;
_shelx_res_checksum              19812
_shelx_hkl_checksum              25649
_olex2_exptl_crystal_mounting_method
'CCrystal mounted using inert oil from the encapsulation crystallisation technique onto a MiTeGen Kapton micromount.'
_olex2_submission_original_sample_id 'nicotinamide_3,5-dinitrobenzoic acid_MeOH'
_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 1.209
_oxdiff_exptl_absorpt_empirical_full_min 0.791