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_1574462
_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         'C5 H8 O4, C6 H6 N2 O'
_chemical_formula_sum            'C11 H14 N2 O5'
_chemical_formula_weight         254.24
_chemical_name_systematic        'nicotinamide_glutaric 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.cc2kmbl4
_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                99.538(5)
_cell_angle_beta                 94.453(4)
_cell_angle_gamma                104.740(4)
_cell_formula_units_Z            2
_cell_length_a                   5.4572(2)
_cell_length_b                   7.3636(3)
_cell_length_c                   15.1899(11)
_cell_measurement_reflns_used    3024
_cell_measurement_temperature    150
_cell_measurement_theta_max      75.5070
_cell_measurement_theta_min      3.0010
_cell_volume                     577.54(5)
_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  (Sheldrick, 2015)'
_diffrn_ambient_temperature      150
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            'HyPix-Arc 100'
_diffrn_measured_fraction_theta_full 0.978
_diffrn_measured_fraction_theta_max 0.923
_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    -63.00  -3.00   0.50    2.99    --  -45.36  80.00 166.00  120
  2  \w      7.00  52.00   0.50    2.99    --   46.24 -80.00  43.00   90
  3  \w    -45.00 -20.00   0.50   11.95    --  -85.06  80.00 166.00   50
  4  \w   -150.00-125.00   0.50   11.95    --  -85.06 -80.00  43.00   50
  5  \w     33.00  58.00   0.50   11.95    --  100.32 -80.00  43.00   50
  6  \w    123.00 169.00   0.50   11.95    --  109.83  80.00 166.00   92
  7  \w     43.00  68.00   0.50   11.95    --  109.83 -80.00  43.00   50
  8  \w     -8.00  31.00   0.50    2.99    --  -45.36  38.00-120.00   78
  9  \w    -17.00  25.00   0.50    2.99    --  -45.36  38.00-150.00   84
 10  \w    -18.00  26.00   0.50    2.99    --  -45.36  38.00   0.00   88
 11  \w    -19.00  32.00   0.50    2.99    --  -45.36  38.00 -60.00  102
 12  \w    -16.00  11.00   0.50    2.99    --   46.24 -38.00   0.00   54
 13  \w   -140.00-111.00   0.50   11.95    --  -85.06 -77.00 -60.00   58
 14  \w    -51.00 -14.00   0.50   11.95    --  -85.06  61.00   0.00   74
 15  \w    -50.00 -12.00   0.50   11.95    --  -85.06  61.00 -90.00   76
 16  \w    -37.00 -11.00   0.50   11.95    --  -85.06  61.00 150.00   52
 17  \w   -147.00-111.00   0.50   11.95    --  -85.06 -77.00 -90.00   72
 18  \w   -152.00-108.00   0.50   11.95    --  -85.06 -77.00 150.00   88
 19  \w     49.00 100.00   0.50   11.95    --  100.32-125.00-150.00  102
 20  \w    125.00 155.00   0.50   11.95    --  100.32  30.00-120.00   60
 21  \w     42.00  92.00   0.50   11.95    --  100.32 -95.00-120.00  100
 22  \w     88.00 118.00   0.50   11.95    --  100.32  30.00-120.00   60
 23  \w     95.00 165.00   0.50   11.95    --  100.32  30.00 120.00  140
 24  \w    119.00 171.00   0.50   11.95    --  100.32 125.00  90.00  104
 25  \w     62.00  92.00   0.50   11.95    --  100.32 -95.00  90.00   60
 26  \w     32.00  57.00   0.50   11.95    --  100.32 -95.00  90.00   50
 27  \w    120.00 169.00   0.50   11.95    --  100.32  61.00 150.00   98
 28  \w     67.00  92.00   0.50   11.95    --  100.32 -95.00  60.00   50
 29  \w     49.00  92.00   0.50   11.95    --  109.83 -95.00-150.00   86
 30  \w    115.00 177.00   0.50   11.95    --  109.83  61.00 -30.00  124
 31  \w     44.00  69.00   0.50   11.95    --  109.83 -77.00 -90.00   50
 32  \w     46.00  93.00   0.50   11.95    --  109.83-125.00-180.00   94
 33  \w     64.00  92.00   0.50   11.95    --  109.83 -95.00 -90.00   56
 34  \w     42.00  67.00   0.50   11.95    --  109.83 -77.00 -60.00   50
 35  \w    101.00 144.00   0.50   11.95    --  109.83  30.00 -60.00   86
 36  \w     50.00  91.00   0.50   11.95    --  109.83 -95.00  30.00   82
 37  \w     60.00 101.00   0.50   11.95    --  109.83-125.00  30.00   82
 38  \w     43.00  68.00   0.50   11.95    --  109.83 -77.00  90.00   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      0.2915387000
_diffrn_orient_matrix_UB_12      0.0820108000
_diffrn_orient_matrix_UB_13      0.0231186000
_diffrn_orient_matrix_UB_21      0.0104505000
_diffrn_orient_matrix_UB_22      0.0839608000
_diffrn_orient_matrix_UB_23      -0.0864653000
_diffrn_orient_matrix_UB_31      -0.0383326000
_diffrn_orient_matrix_UB_32      0.1866064000
_diffrn_orient_matrix_UB_33      0.0522999000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_unetI/netI     0.0181
_diffrn_reflns_Laue_measured_fraction_full 0.978
_diffrn_reflns_Laue_measured_fraction_max 0.923
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            8283
_diffrn_reflns_point_group_measured_fraction_full 0.978
_diffrn_reflns_point_group_measured_fraction_max 0.923
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.831
_diffrn_reflns_theta_min         2.974
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.992
_exptl_absorpt_correction_T_max  0.980
_exptl_absorpt_correction_T_min  0.877
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.73a (Rigaku Oxford Diffraction, 2022)
Analytical numeric absorption correction using a multifaceted crystal
model based on expressions derived by R.C. Clark & J.S. Reid.
(Clark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887-897)
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    1.462
_exptl_crystal_description       block
_exptl_crystal_F_000             268
_exptl_crystal_preparation
;
Crystallised from a saturated solution of nicotinamide
and glutaric acid (1:2) in MeOH.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt co-crystallisation protocol usingSPT Labtech mosquito.'
_exptl_crystal_size_max          0.185
_exptl_crystal_size_mid          0.116
_exptl_crystal_size_min          0.02
_refine_diff_density_max         0.261
_refine_diff_density_min         -0.185
_refine_diff_density_rms         0.044
_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     176
_refine_ls_number_reflns         8283
_refine_ls_number_restraints     111
_refine_ls_restrained_S_all      1.040
_refine_ls_R_factor_all          0.0436
_refine_ls_R_factor_gt           0.0392
_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^)+(0.0671P)^2^+0.0839P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1069
_refine_ls_wR_factor_ref         0.1096
_reflns_Friedel_coverage         0.000
_reflns_number_gt                7479
_reflns_number_total             8283
_reflns_threshold_expression     'I > 2\s(I)'
_twin_special_details
;
Component 2 rotated by -179.9901\% 
around [0.00 0.00 1.00] (reciprocal) or [0.31 0.36 0.88] (direct)
;
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           nicotinamide_glutaric_acid
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574462
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C10 H13 O5 N3 '
_shelx_estimated_absorpt_t_max   0.980
_shelx_estimated_absorpt_t_min   0.838
_olex2_refinement_description
;
1. Twinned data refinement
 Scales: 0.6008(13)
 0.3992(13)
2. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H,H) groups, All O(H) groups
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 Secondary CH2 refined with riding coordinates:
 C2A(H2Aa,H2Ab), C3A(H3Aa,H3Ab), C4A(H4Aa,H4Ab)
4.b Aromatic/amide H refined with riding coordinates:
 C2B(H2B), C3B(H3B), C4B(H4B), C5B(H5B)
;
_shelx_res_checksum              49085
_shelx_hkl_checksum              16733
_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_glutaric 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 1.427
_oxdiff_exptl_absorpt_empirical_full_min 0.724
_oxdiff_twin_integration_method  simultaneous
_oxdiff_twin_items               2