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_1574438
_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 H6 O4, C6 H6 N2 O'
_chemical_formula_sum            'C13 H12 N2 O5'
_chemical_formula_weight         276.25
_chemical_name_systematic        'nicotinamide_2,4-dihydroxybenzoic acid'
_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.cc2kmbk3
_audit_creation_date             2025-03-31
_audit_creation_method
;
Olex2 1.5
(compiled 2025.03.04 svn.red2d20d0 for OlexSys, GUI svn.r7188)
;
_audit_update_record
;
2025-04-01 deposited with the CCDC.	2025-04-22 downloaded from the CCDC.
;
_cell_angle_alpha                96.039(3)
_cell_angle_beta                 91.946(3)
_cell_angle_gamma                94.003(3)
_cell_formula_units_Z            2
_cell_length_a                   5.7882(2)
_cell_length_b                   8.0510(3)
_cell_length_c                   13.3821(5)
_cell_measurement_reflns_used    2854
_cell_measurement_temperature    150
_cell_measurement_theta_max      75.9920
_cell_measurement_theta_min      3.2930
_cell_volume                     618.11(4)
_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 0.988
_diffrn_measured_fraction_theta_max 0.924
_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    -51.00 -15.00   0.50    1.28    --  -45.36  92.00  91.00   72
  2  \w     44.00  71.00   0.50    1.28    --   46.24 -92.00 -20.00   54
  3  \w   -151.00-126.00   0.50    5.10    --  -85.06 -92.00 -20.00   50
  4  \w    -66.00 -41.00   0.50    5.10    --  -85.06  92.00  91.00   50
  5  \w     35.00  61.00   0.50    5.10    --  100.32 -92.00 -20.00   52
  6  \w     62.00  89.00   0.50    5.10    --  100.32 -92.00 -20.00   54
  7  \w    124.00 149.00   0.50    5.10    --  109.83  92.00  91.00   50
  8  \w    -19.00  21.00   0.50    1.28    --  -45.36  38.00 -60.00   80
  9  \w    -19.00  32.00   0.50    1.28    --  -45.36  38.00 150.00  102
 10  \w      7.00  33.00   0.50    1.28    --  -45.36  38.00-120.00   52
 11  \w   -115.00 -34.00   0.50    1.28    --  -45.36 -38.00 -30.00  162
 12  \w    -44.00 -13.00   0.50    5.10    --  -85.06  61.00  90.00   62
 13  \w    -42.00 -12.00   0.50    5.10    --  -85.06  61.00-150.00   60
 14  \w   -153.00-104.00   0.50    5.10    --  -85.06 -77.00  90.00   98
 15  \w   -143.00-105.00   0.50    5.10    --  -85.06 -77.00-150.00   76
 16  \w   -164.00 -72.00   0.50    5.10    --  -85.06 -30.00 120.00  184
 17  \w   -143.00-110.00   0.50    5.10    --  -85.06 -77.00-120.00   66
 18  \w     43.00  92.00   0.50    5.10    --  100.32 -95.00-180.00   98
 19  \w     89.00 136.00   0.50    5.10    --  100.32  15.00  90.00   94
 20  \w    131.00 162.00   0.50    5.10    --  100.32  61.00-120.00   62
 21  \w     33.00  73.00   0.50    5.10    --  100.32 -77.00  30.00   80
 22  \w     61.00  87.00   0.50    5.10    --  100.32 -95.00 -60.00   52
 23  \w     31.00  60.00   0.50    5.10    --  100.32 -95.00 -60.00   58
 24  \w     57.00  98.00   0.50    5.10    --  100.32-125.00-180.00   82
 25  \w     33.00  72.00   0.50    5.10    --  100.32 -77.00-120.00   78
 26  \w    138.00 172.00   0.50    5.10    --  100.32  61.00 -90.00   68
 27  \w    125.00 178.00   0.50    5.10    --  109.83  77.00 120.00  106
 28  \w     76.00 101.00   0.50    5.10    --  109.83-125.00-150.00   50
 29  \w     38.00  74.00   0.50    5.10    --  109.83-125.00-120.00   72
 30  \w     47.00  73.00   0.50    5.10    --  109.83-125.00-150.00   52
 31  \w     40.00  90.00   0.50    5.10    --  109.83 -95.00  30.00  100
 32  \w    112.00 178.00   0.50    5.10    --  109.83 125.00  30.00  132
 33  \w    109.00 142.00   0.50    5.10    --  109.83  61.00   0.00   66
 34  \w     42.00  90.00   0.50    5.10    --  109.83 -95.00  90.00   96
 35  \w     41.00  92.00   0.50    5.10    --  109.83 -95.00-120.00  102
 36  \w     67.00  92.00   0.50    5.10    --  109.83 -95.00 -30.00   50
 37  \w     67.00  92.00   0.50    5.10    --  109.83 -95.00  60.00   50
 38  \w     43.00  68.00   0.50    5.10    --  109.83 -92.00 -20.00   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      0.0880159000
_diffrn_orient_matrix_UB_12      -0.0941618000
_diffrn_orient_matrix_UB_13      0.0865195000
_diffrn_orient_matrix_UB_21      -0.2078249000
_diffrn_orient_matrix_UB_22      0.0518564000
_diffrn_orient_matrix_UB_23      0.0619360000
_diffrn_orient_matrix_UB_31      -0.1427287000
_diffrn_orient_matrix_UB_32      -0.1602252000
_diffrn_orient_matrix_UB_33      -0.0458548000
_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  0.0217
_diffrn_reflns_av_unetI/netI     0.0285
_diffrn_reflns_Laue_measured_fraction_full 0.988
_diffrn_reflns_Laue_measured_fraction_max 0.924
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -10
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            5731
_diffrn_reflns_point_group_measured_fraction_full 0.988
_diffrn_reflns_point_group_measured_fraction_max 0.924
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.777
_diffrn_reflns_theta_min         3.324
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.984
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.76560
_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    1.484
_exptl_crystal_description       plate
_exptl_crystal_F_000             288
_exptl_crystal_preparation
;
Crystallised from a saturated solution of nicotinamide
and 2,4-dihydroxybenzoic acid (2:1) in MeNO2.
;
_exptl_crystal_recrystallization_method
;
High-throughput screening via the ENaCt co-
crystallisation protocol using SPT Labtech mosquito.
;
_exptl_crystal_size_max          0.17
_exptl_crystal_size_mid          0.11
_exptl_crystal_size_min          0.031
_refine_diff_density_max         0.201
_refine_diff_density_min         -0.203
_refine_diff_density_rms         0.038
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.072
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     196
_refine_ls_number_reflns         2403
_refine_ls_number_restraints     138
_refine_ls_restrained_S_all      1.041
_refine_ls_R_factor_all          0.0413
_refine_ls_R_factor_gt           0.0351
_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^)+(0.0554P)^2^+0.1037P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0965
_refine_ls_wR_factor_ref         0.1000
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2078
_reflns_number_total             2403
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           nicotinamide_2,4-dihydroxybenzoicacid
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574438
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C14 H12 N2 O5'
_shelx_estimated_absorpt_t_max   0.970
_shelx_estimated_absorpt_t_min   0.850
_diffrn_oxdiff_digest_hkl
;
0145518fce23390eecb063b9b424c001694cd8
;
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All N(H,H) groups, All O(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:
 C3A(H3Aa), C3B(H3B), C4B(H4B), C5A(H5A), C5B(H5B), C6A(H6A), C6B(H6B)
;
_shelx_res_checksum              74592
_shelx_hkl_checksum              80201
_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 'nicotinamide_2,4-dihydroxybenzoic acid'
_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 1.398
_oxdiff_exptl_absorpt_empirical_full_min 0.695