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_1574460
_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 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.cc2kmc4q
_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                 97.939(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   7.24400(10)
_cell_length_b                   11.3576(2)
_cell_length_c                   17.2682(3)
_cell_measurement_reflns_used    7064
_cell_measurement_temperature    149.99(10)
_cell_measurement_theta_max      75.7930
_cell_measurement_theta_min      4.6360
_cell_volume                     1407.11(4)
_computing_cell_refinement       'CrysAlisPro 1.171.42.90a (Rigaku OD, 2023)'
_computing_data_collection       'CrysAlisPro 1.171.42.90a (Rigaku OD, 2023)'
_computing_data_reduction        'CrysAlisPro 1.171.42.90a (Rigaku OD, 2023)'
_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      149.99(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 0.999
_diffrn_measured_fraction_theta_max 0.956
_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    -76.00 -35.00   0.50    6.35    --  -45.54 130.00-158.00   82
  2  \w     52.00  92.00   0.50    6.35    --   46.41-130.00 129.00   80
  3  \w   -143.00-118.00   0.50    6.35    --  -85.10-130.00 129.00   50
  4  \w    -69.00 -44.00   0.50    6.35    --  -85.10 130.00-158.00   50
  5  \w     46.00  71.00   0.50    6.35    --  100.29-130.00 129.00   50
  6  \w    126.00 151.00   0.50    6.35    --  100.29 130.00-158.00   50
  7  \w     70.00 102.00   0.50    6.35    --  109.76-130.00 129.00   64
  8  \w    114.00 139.00   0.50    6.35    --  109.76 130.00-158.00   50
  9  \w    -11.00  19.00   0.50    6.35    --  -45.54  38.00 -90.00   60
 10  \w     -5.00  30.00   0.50    6.35    --  -45.54  38.00  60.00   70
 11  \w     -8.00  22.00   0.50    6.35    --  -45.54  38.00 -60.00   60
 12  \w   -123.00 -50.00   0.50    6.35    --  -45.54 -38.00   0.00  146
 13  \w     -4.00  29.00   0.50    6.35    --  -45.54  38.00 120.00   66
 14  \w    -11.00  29.00   0.50    6.35    --  -45.54  38.00 150.00   80
 15  \w    -40.00 -15.00   0.50    6.35    --  -85.10  61.00  30.00   50
 16  \w   -142.00-105.00   0.50    6.35    --  -85.10 -77.00-120.00   74
 17  \w   -151.00-108.00   0.50    6.35    --  -85.10 -77.00  90.00   86
 18  \w    -46.00 -13.00   0.50    6.35    --  -85.10  61.00 150.00   66
 19  \w   -130.00-104.00   0.50    6.35    --  -85.10 -77.00 -30.00   52
 20  \w   -145.00-119.00   0.50    6.35    --  -85.10 -77.00   0.00   52
 21  \w   -131.00 -62.00   0.50    6.35    --  -85.10 -15.00 -30.00  138
 22  \w    -46.00 -20.00   0.50    6.35    --  -85.10  61.00   0.00   52
 23  \w    -45.00 -19.00   0.50    6.35    --  -85.10  61.00 -60.00   52
 24  \w   -151.00-107.00   0.50    6.35    --  -85.10 -77.00 -60.00   88
 25  \w     34.00  97.00   0.50    6.35    --  100.29-125.00 -30.00  126
 26  \w     66.00  92.00   0.50    6.35    --  100.29 -95.00   0.00   52
 27  \w     28.00  56.00   0.50    6.35    --  100.29 -61.00   0.00   56
 28  \w    142.00 176.00   0.50    6.35    --  100.29  45.00 -30.00   68
 29  \w    100.00 128.00   0.50    6.35    --  100.29  45.00 -30.00   56
 30  \w    115.00 170.00   0.50    6.35    --  100.29 125.00 -30.00  110
 31  \w     27.00  52.00   0.50    6.35    --  100.29 -61.00 150.00   50
 32  \w     31.00  56.00   0.50    6.35    --  100.29 -61.00 -60.00   50
 33  \w     27.00  53.00   0.50    6.35    --  100.29 -61.00-120.00   52
 34  \w     29.00  54.00   0.50    6.35    --  100.29 -61.00  30.00   50
 35  \w     28.00  54.00   0.50    6.35    --  100.29 -61.00 -30.00   52
 36  \w     82.00 140.00   0.50    6.35    --  100.29  15.00-120.00  116
 37  \w     34.00  91.00   0.50    6.35    --  100.29 -95.00 120.00  114
 38  \w     46.00  91.00   0.50    6.35    --  109.76 -95.00-180.00   90
 39  \w     44.00  71.00   0.50    6.35    --  109.76 -77.00 120.00   54
 40  \w     87.00 132.00   0.50    6.35    --  109.76  15.00 150.00   90
 41  \w    124.00 152.00   0.50    6.35    --  109.76  77.00-150.00   56
 42  \w     67.00  92.00   0.50    6.35    --  109.76 -95.00 150.00   50
 43  \w    148.00 174.00   0.50    6.35    --  109.76 125.00  30.00   52
 44  \w    127.00 171.00   0.50    6.35    --  109.76  77.00-120.00   88
 45  \w     62.00  92.00   0.50    6.35    --  109.76 -95.00 -30.00   60
 46  \w     67.00  92.00   0.50    6.35    --  109.76 -95.00-150.00   50
 47  \w     67.00  92.00   0.50    6.35    --  109.76 -95.00  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      -0.0286233000
_diffrn_orient_matrix_UB_12      -0.0353684000
_diffrn_orient_matrix_UB_13      -0.0869767000
_diffrn_orient_matrix_UB_21      -0.0220280000
_diffrn_orient_matrix_UB_22      -0.1296765000
_diffrn_orient_matrix_UB_23      0.0232407000
_diffrn_orient_matrix_UB_31      -0.2116273000
_diffrn_orient_matrix_UB_32      0.0183324000
_diffrn_orient_matrix_UB_33      -0.0033283000
_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  0.0294
_diffrn_reflns_av_unetI/netI     0.0231
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.956
_diffrn_reflns_limit_h_max       5
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            14707
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.956
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.194
_diffrn_reflns_theta_min         4.674
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.842
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.66046
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.90a (Rigaku Oxford Diffraction, 2023)
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    1.413
_exptl_crystal_description       needle
_exptl_crystal_F_000             628
_exptl_crystal_preparation
;
Crystallised from a saturated solution of nicotinamide,
quinol and nicotinic acid (1:1:1) in 1,4-dioxane.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.33
_exptl_crystal_size_mid          0.18
_exptl_crystal_size_min          0.03
_refine_diff_density_max         0.208
_refine_diff_density_min         -0.199
_refine_diff_density_rms         0.036
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.043
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     214
_refine_ls_number_reflns         2841
_refine_ls_number_restraints     138
_refine_ls_restrained_S_all      1.017
_refine_ls_R_factor_all          0.0374
_refine_ls_R_factor_gt           0.0336
_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^)+(0.0455P)^2^+0.4191P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0908
_refine_ls_wR_factor_ref         0.0932
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2575
_reflns_number_total             2841
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           nicotinamide_quinol_n
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574460
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C N H O'
_chemical_oxdiff_usercomment     1,4-dioxane
_shelx_estimated_absorpt_t_max   0.975
_shelx_estimated_absorpt_t_min   0.693
_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              337
_shelx_hkl_checksum              71066
_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 1.557
_oxdiff_exptl_absorpt_empirical_full_min 0.687