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_1574434
_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         'C6 H6 N2 O, C11 H8 O3'
_chemical_formula_sum            'C17 H14 N2 O4'
_chemical_formula_weight         310.30
_chemical_name_systematic        'nicotinamide_3-hydroxy-2-napthoic acid'
_space_group_crystal_system      monoclinic
_space_group_IT_number           15
_space_group_name_Hall           '-C 2yc'
_space_group_name_H-M_alt        'C 1 2/c 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_block_doi                 10.5517/ccdc.csd.cc2kmbm5
_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                90
_cell_angle_beta                 107.608(4)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   25.4599(10)
_cell_length_b                   4.8787(2)
_cell_length_c                   23.7344(9)
_cell_measurement_reflns_used    5118
_cell_measurement_temperature    150
_cell_measurement_theta_max      77.1030
_cell_measurement_theta_min      3.5970
_cell_volume                     2810.0(2)
_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 0.999
_diffrn_measured_fraction_theta_max 0.943
_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    -67.00 -42.00   0.50    9.31    --  -45.11 127.00  90.00   50
  2  \w     43.00  68.00   0.50    9.31    --   46.11-127.00  15.00   50
  3  \w   -140.00-115.00   0.50   37.23    --  -85.06-127.00  15.00   50
  4  \w    -69.00 -44.00   0.50   37.23    --  -85.06 127.00  90.00   50
  5  \w     68.00 101.00   0.50   37.23    --  100.32-127.00  15.00   66
  6  \w    118.00 146.00   0.50   37.23    --  100.32 127.00  90.00   56
  7  \w     44.00  69.00   0.50   37.23    --  109.83-127.00  15.00   50
  8  \w    -10.00  19.00   0.50    9.31    --  -45.11  38.00-120.00   58
  9  \w    -16.00  15.00   0.50    9.31    --  -45.11  38.00  90.00   62
 10  \w    -18.00  26.00   0.50    9.31    --  -45.11  38.00  30.00   88
 11  \w   -118.00 -33.00   0.50    9.31    --  -45.11 -38.00  90.00  170
 12  \w    -18.00   7.00   0.50    9.31    --   46.11 -38.00 -90.00   50
 13  \w   -162.00 -73.00   0.50   37.23    --  -85.06 -30.00   0.00  178
 14  \w   -153.00-105.00   0.50   37.23    --  -85.06 -77.00 -90.00   96
 15  \w   -152.00-119.00   0.50   37.23    --  -85.06 -77.00-180.00   66
 16  \w   -153.00 -87.00   0.50   37.23    --  -85.06 -61.00 -60.00  132
 17  \w     64.00  92.00   0.50   37.23    --  100.32 -95.00  30.00   56
 18  \w     42.00  92.00   0.50   37.23    --  100.32 -95.00 -90.00  100
 19  \w     31.00  59.00   0.50   37.23    --  100.32 -95.00  30.00   56
 20  \w     45.00  70.00   0.50   37.23    --  100.32 -77.00   0.00   50
 21  \w    113.00 160.00   0.50   37.23    --  100.32  61.00-150.00   94
 22  \w     43.00  75.00   0.50   37.23    --  109.83 -77.00 -30.00   64
 23  \w     44.00  72.00   0.50   37.23    --  109.83 -77.00  30.00   56
 24  \w     67.00 135.00   0.50   37.23    --  109.83  15.00 -30.00  136
 25  \w     40.00  78.00   0.50   37.23    --  109.83 -95.00 120.00   76
 26  \w     82.00 120.00   0.50   37.23    --  109.83  15.00-120.00   76
 27  \w    125.00 165.00   0.50   37.23    --  109.83  77.00 -60.00   80
 28  \w     46.00  71.00   0.50   37.23    --  109.83 -77.00  60.00   50
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix-Arc 100'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0176
_diffrn_reflns_av_unetI/netI     0.0194
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.943
_diffrn_reflns_limit_h_max       31
_diffrn_reflns_limit_h_min       -29
_diffrn_reflns_limit_k_max       3
_diffrn_reflns_limit_k_min       -5
_diffrn_reflns_limit_l_max       29
_diffrn_reflns_limit_l_min       -29
_diffrn_reflns_number            9127
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.943
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.203
_diffrn_reflns_theta_min         3.643
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.882
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.80235
_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    1.467
_exptl_crystal_description       block
_exptl_crystal_F_000             1296
_exptl_crystal_preparation
;
Crystallised from a saturated solution of nicotinamide
and 3-hydroxy-2-napthoic acid (1:1) in MeOH.
;
_exptl_crystal_recrystallization_method
;
High-throughput screening via the ENaCt co-
crystallisation protocol using SPT Labtech mosquito.
;
_exptl_crystal_size_max          0.12
_exptl_crystal_size_mid          0.042
_exptl_crystal_size_min          0.033
_refine_diff_density_max         0.240
_refine_diff_density_min         -0.219
_refine_diff_density_rms         0.037
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.047
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     220
_refine_ls_number_reflns         2808
_refine_ls_number_restraints     169
_refine_ls_restrained_S_all      1.019
_refine_ls_R_factor_all          0.0359
_refine_ls_R_factor_gt           0.0316
_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^)+(0.0411P)^2^+2.0500P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0825
_refine_ls_wR_factor_ref         0.0851
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2522
_reflns_number_total             2808
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           nicotinamide_3-hydroxy-2-naphthoicacid
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574434
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.971
_shelx_estimated_absorpt_t_min   0.902
_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. Restrained distances
 O2B-H2B
 0.84 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:
 C1B(H1B), C3A(H3A), C4A(H4A), C4B(H4B), C5A(H5A), C6A(H6A), C6B(H6B),
 C7B(H7B), C8B(H8B), C9B(H9B)
;
_shelx_res_checksum              251
_shelx_hkl_checksum              83014
_olex2_exptl_crystal_mounting_method
'Crystal mounted using inert oil from the encapsulation crystallisation technique onto a MiTeGen Kapton micromount.'
_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
;