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_1574436
_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         'C8 H8 O5, C6 H6 N2 O'
_chemical_formula_sum            'C14 H14 N2 O6'
_chemical_formula_weight         306.27
_chemical_name_systematic        'nicotinamide_methyl gallate'
_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.cc2kmbxg
_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                85.429(4)
_cell_angle_beta                 88.957(4)
_cell_angle_gamma                83.901(4)
_cell_formula_units_Z            2
_cell_length_a                   5.1980(3)
_cell_length_b                   7.7142(4)
_cell_length_c                   16.8659(8)
_cell_measurement_reflns_used    2966
_cell_measurement_temperature    149.99(10)
_cell_measurement_theta_max      76.9670
_cell_measurement_theta_min      5.2470
_cell_volume                     670.30(6)
_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      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 0.984
_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    -63.00  17.00   0.50    0.54    --  -45.09  80.00 -70.00  160
  2  \w    -13.00  15.00   0.50    0.54    --  -45.09  38.00-180.00   56
  3  \w    -37.00  12.00   0.50    0.54    --  -45.09  57.00 -90.00   98
  4  \w    -14.00  19.00   0.50    0.54    --  -45.09  38.00 -30.00   66
  5  \w     -1.00  34.00   0.50    0.54    --  -45.09  38.00  90.00   70
  6  \w    -41.00 -16.00   0.50    0.54    --  -85.06  61.00  60.00   50
  7  \w    -45.00 -19.00   0.50    0.54    --  -85.06  61.00  30.00   52
  8  \w    -58.00 -19.00   0.50    0.54    --  -85.06  80.00 -70.00   78
  9  \w    -46.00 -14.00   0.50    0.54    --  -85.06  61.00 150.00   64
 10  \w    -98.00 -34.00   0.50    0.54    --  -45.09 -38.00 150.00  128
 11  \w   -147.00-122.00   0.50    0.54    --  -85.06 -80.00 166.00   50
 12  \w   -149.00-103.00   0.50    0.54    --  -85.06 -77.00  90.00   92
 13  \w   -150.00-103.00   0.50    0.54    --  -85.06 -77.00  60.00   94
 14  \w   -139.00-103.00   0.50    0.54    --  -85.06 -77.00   0.00   72
 15  \w   -152.00-107.00   0.50    0.54    --  -85.06 -77.00-180.00   90
 16  \w   -152.00-110.00   0.50    0.54    --  -85.06 -95.00 -60.00   84
 17  \w     93.00 133.00   0.50    0.54    --  100.34  45.00   0.00   80
 18  \w     96.00 166.00   0.50    0.54    --  109.85  30.00 120.00  140
 19  \w     68.00 140.00   0.50    0.54    --  109.85  15.00-120.00  144
 20  \w    106.00 149.00   0.50    0.54    --  100.34  30.00 -90.00   86
 21  \w    131.00 157.00   0.50    0.54    --  109.85  80.00 -70.00   52
 22  \w    153.00 178.00   0.50    0.54    --  109.85 125.00 -60.00   50
 23  \w     53.00  78.00   0.50    0.54    --  109.85 -80.00 166.00   50
 24  \w     41.00  79.00   0.50    0.54    --  100.34 -80.00 166.00   76
 25  \w     11.00  36.00   0.50    0.54    --   46.09 -80.00 166.00   50
 26  \w     46.00  75.00   0.50    0.54    --  109.85 -77.00  60.00   58
 27  \w     44.00  84.00   0.50    0.54    --  109.85 -95.00 -30.00   80
 28  \w     42.00  89.00   0.50    0.54    --  100.34 -95.00 -60.00   94
 29  \w     32.00  92.00   0.50    0.54    --  100.34 -95.00-120.00  120
 30  \w     63.00  88.00   0.50    0.54    --  109.85 -95.00-150.00   50
 31  \w     32.00  58.00   0.50    0.54    --  100.34 -95.00  30.00   52
 32  \w     66.00  92.00   0.50    0.54    --  109.85 -95.00   0.00   52
 33  \w     42.00  91.00   0.50    0.54    --  100.34 -95.00  60.00   98
 34  \w     35.00  90.00   0.50    0.54    --  100.34 -95.00 120.00  110
 35  \w     40.00  90.00   0.50    0.54    --  109.85 -95.00 150.00  100
;
_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      0.0503809000
_diffrn_orient_matrix_UB_12      0.1475581000
_diffrn_orient_matrix_UB_13      0.0522745000
_diffrn_orient_matrix_UB_21      -0.2128427000
_diffrn_orient_matrix_UB_22      -0.0549659000
_diffrn_orient_matrix_UB_23      0.0585883000
_diffrn_orient_matrix_UB_31      0.2025084000
_diffrn_orient_matrix_UB_32      -0.1256623000
_diffrn_orient_matrix_UB_33      0.0472473000
_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     0.0469
_diffrn_reflns_Laue_measured_fraction_full 0.984
_diffrn_reflns_Laue_measured_fraction_max 0.917
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -5
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            6082
_diffrn_reflns_point_group_measured_fraction_full 0.984
_diffrn_reflns_point_group_measured_fraction_max 0.917
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.914
_diffrn_reflns_theta_min         2.628
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.026
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.53789
_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    1.517
_exptl_crystal_description       plate
_exptl_crystal_F_000             320
_exptl_crystal_preparation
;
Crystallised from a saturated solution of nicotinamide
and methyl gallate (1:1) in MeNO2.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt co-crystallisation protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.33
_exptl_crystal_size_mid          0.26
_exptl_crystal_size_min          0.12
_refine_diff_density_max         0.352
_refine_diff_density_min         -0.259
_refine_diff_density_rms         0.058
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.050
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     215
_refine_ls_number_reflns         2606
_refine_ls_number_restraints     153
_refine_ls_restrained_S_all      1.019
_refine_ls_R_factor_all          0.0537
_refine_ls_R_factor_gt           0.0449
_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^)+(0.0882P)^2^+0.0096P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1245
_refine_ls_wR_factor_ref         0.1323
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2152
_reflns_number_total             2606
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           nicotinamide_methyl_gallate
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574436
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C10 H12 O7 N2'
_shelx_estimated_absorpt_t_max   0.887
_shelx_estimated_absorpt_t_min   0.639
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All N(H,H) groups, All O(H) groups
 At 1.5 times of:
  All C(H,H,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(H2AA), C2B(H2B), C3B(H3B), C4B(H4B), C5B(H5B), C6A(H6A)
3.b Idealised Me refined as rotating group:
 C8A(H8AA,H8AB,H8AC)
;
_shelx_res_checksum              80360
_shelx_hkl_checksum              18027
_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_methyl gallate'
_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 1.476
_oxdiff_exptl_absorpt_empirical_full_min 0.572