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_1574453
_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         '2(C6 H6 N2 O), C3 H3 O'
_chemical_formula_sum            'C15 H15 N4 O3'
_chemical_formula_weight         299.31
_chemical_name_systematic        nicotinamide_quinol
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2yn'
_space_group_name_H-M_alt        'P 1 21/n 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_block_doi                 10.5517/ccdc.csd.cc2kmbyh
_audit_creation_date             2024-07-15
_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                 102.312(3)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   5.2125(2)
_cell_length_b                   27.0087(10)
_cell_length_c                   10.3421(3)
_cell_measurement_reflns_used    3934
_cell_measurement_temperature    150.01(10)
_cell_measurement_theta_max      75.4230
_cell_measurement_theta_min      3.2640
_cell_volume                     1422.50(9)
_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 0.917
_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     40.00  86.00   0.50    4.81    --   48.76-130.00 169.00   92
  2  \w     64.00 115.00   0.50    4.81    --   48.76 140.00  54.00  102
  3  \w    -86.00 -61.00   0.50    4.81    --  -49.57 130.00-119.00   50
  4  \w    -99.00 -73.00   0.50    4.81    --  -49.57-140.00  -4.00   52
  5  \w    -96.00 -71.00   0.50    4.81    --  -92.01 140.00  54.00   50
  6  \w    -67.00 -20.00   0.50    4.81    --  -92.01 130.00-119.00   94
  7  \w   -164.00 -79.00   0.50    4.81    --  -92.01-140.00  -4.00  170
  8  \w     92.00 117.00   0.50    4.81    --   96.11 140.00  54.00   50
  9  \w     94.00 119.00   0.50    4.81    --  108.00 140.00  54.00   50
 10  \w     84.00 112.00   0.50    4.81    --  108.00-130.00 169.00   56
 11  \w     79.00 117.00   0.50    4.81    --  108.00-140.00  -4.00   76
 12  \w    -28.00  25.00   0.50    4.81    --   48.76 -19.00 -30.00  106
 13  \w     90.00 120.00   0.50    4.81    --   48.76 125.00-150.00   60
 14  \w    -30.00  27.00   0.50    4.81    --   48.76 -19.00-150.00  114
 15  \w    -51.00 -18.00   0.50    4.81    --  -92.01  45.00  90.00   66
 16  \w   -171.00 -85.00   0.50    4.81    --  -92.01 -30.00   0.00  172
 17  \w     77.00 125.00   0.50    4.81    --   96.11 125.00-180.00   96
 18  \w     29.00  72.00   0.50    4.81    --   96.11 -95.00   0.00   86
 19  \w     19.00  49.00   0.50    4.81    --   96.11 -45.00 120.00   60
 20  \w    139.00 168.00   0.50    4.81    --   96.11 125.00-180.00   58
 21  \w     76.00 103.00   0.50    4.81    --   96.11 -95.00   0.00   54
 22  \w     18.00  43.00   0.50    4.81    --   96.11 -45.00 -60.00   50
 23  \w     40.00 102.00   0.50    4.81    --  108.00 -77.00-180.00  124
;
_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      0.0185062000
_diffrn_orient_matrix_UB_12      0.0517783000
_diffrn_orient_matrix_UB_13      -0.0598007000
_diffrn_orient_matrix_UB_21      -0.0642511000
_diffrn_orient_matrix_UB_22      0.0238333000
_diffrn_orient_matrix_UB_23      0.1247177000
_diffrn_orient_matrix_UB_31      0.2949725000
_diffrn_orient_matrix_UB_32      0.0019686000
_diffrn_orient_matrix_UB_33      0.0642318000
_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  0.0371
_diffrn_reflns_av_unetI/netI     0.0357
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.917
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -4
_diffrn_reflns_limit_k_max       31
_diffrn_reflns_limit_k_min       -32
_diffrn_reflns_limit_l_max       12
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            9492
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.917
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.761
_diffrn_reflns_theta_min         3.273
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.833
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.55665
_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    1.398
_exptl_crystal_description       plate
_exptl_crystal_F_000             628
_exptl_crystal_preparation
;
Crystallised from a saturated solution of nicotinamide
and quinol (2:1) in MeOH.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt co-crystallisation protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.22
_exptl_crystal_size_mid          0.19
_exptl_crystal_size_min          0.049
_refine_diff_density_max         0.357
_refine_diff_density_min         -0.354
_refine_diff_density_rms         0.070
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.036
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     214
_refine_ls_number_reflns         2788
_refine_ls_number_restraints     135
_refine_ls_restrained_S_all      1.011
_refine_ls_R_factor_all          0.0648
_refine_ls_R_factor_gt           0.0553
_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^)+(0.1010P)^2^+0.3587P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1485
_refine_ls_wR_factor_ref         0.1551
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2367
_reflns_number_total             2788
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           nicotinamide_quinol
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574453
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.960
_shelx_estimated_absorpt_t_min   0.691
_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:
 C2A(H2A), C2B(H2B), C2C(H2C), C3A(H3A), C3B(H3B), C3C(H3C), C4A(H4A),
 C4B(H4B), C5A(H5A), C5B(H5B)
;
_shelx_res_checksum              47500
_shelx_hkl_checksum              2369
_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_quinol
_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 1.566
_oxdiff_exptl_absorpt_empirical_full_min 0.637