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_1574446
_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         'C7 H8 O2, C12 H8 N2, C2 H4 O'
_chemical_formula_sum            'C21 H20 N2 O3'
_chemical_formula_weight         348.39
_chemical_name_systematic        orcino_phenazine
_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.cc2kmc3p
_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                83.084(4)
_cell_angle_beta                 78.243(5)
_cell_angle_gamma                68.600(5)
_cell_formula_units_Z            2
_cell_length_a                   7.4821(4)
_cell_length_b                   9.4572(4)
_cell_length_c                   13.6078(7)
_cell_measurement_reflns_used    3574
_cell_measurement_temperature    150.11(10)
_cell_measurement_theta_max      74.1700
_cell_measurement_theta_min      3.3150
_cell_volume                     876.57(8)
_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      150.11(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 0.994
_diffrn_measured_fraction_theta_max 0.939
_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    -21.00  27.00   0.50    0.16    --   38.44 -19.00 -60.00   96
  2  \w    -53.00  27.00   0.50    0.16    --   38.44 -19.00  30.00  160
  3  \w    -44.00  -2.00   0.50    0.16    --   38.44 -38.00 120.00   84
  4  \w      4.00  43.00   0.50    0.16    --   38.44 -38.00 120.00   78
  5  \w     45.00  70.00   0.50    0.16    --   38.44-140.00 -36.00   50
  6  \w     57.00 112.00   0.50    0.16    --  110.26-130.00 137.00  110
  7  \w     63.00  88.00   0.50    0.16    --   38.44-130.00 137.00   50
  8  \w     62.00 119.00   0.50    0.16    --  110.26-140.00 -36.00  114
  9  \w     80.00 105.00   0.50    0.16    --  110.26 -77.00 -60.00   50
 10  \w     75.00 101.00   0.50    0.16    --  110.26 -77.00 -90.00   52
 11  \w     39.00  64.00   0.50    0.16    --  110.26 -77.00 -60.00   50
 12  \w     28.00  69.00   0.50    0.16    --  110.26 -61.00-180.00   82
 13  \w     39.00  67.00   0.50    0.16    --  102.48 -61.00 -30.00   56
 14  \w     26.00  51.00   0.50    0.16    --  110.26 -45.00 -90.00   50
 15  \w     44.00  69.00   0.50    0.16    --  110.26 -61.00   0.00   50
 16  \w     25.00  50.00   0.50    0.16    --  110.26 -45.00  60.00   50
 17  \w     38.00  64.00   0.50    0.16    --  102.48 -61.00  90.00   52
 18  \w     30.00  64.00   0.50    0.16    --  110.26 -61.00 120.00   68
 19  \w     16.00  41.00   0.50    0.16    --  102.48 -45.00  90.00   50
 20  \w     25.00  50.00   0.50    0.16    --  110.26 -45.00-150.00   50
 21  \w     71.00 178.00   0.50    0.16    --  102.48  30.00  30.00  214
 22  \w     83.00 169.00   0.50    0.16    --  110.26  45.00 -60.00  172
 23  \w     68.00  93.00   0.50    0.16    --   38.44 140.00  22.00   50
 24  \w     60.00 123.00   0.50    0.16    --   38.44 178.00-120.00  126
 25  \w     71.00  96.00   0.50    0.16    --   38.44 130.00-151.00   50
 26  \w    116.00 141.00   0.50    0.16    --  102.48 178.00 -90.00   50
 27  \w     87.00 125.00   0.50    0.16    --  110.26 130.00-151.00   76
 28  \w     70.00 111.00   0.50    0.16    --  102.48 178.00 -90.00   82
 29  \w     94.00 119.00   0.50    0.16    --  102.48 140.00  22.00   50
 30  \w     94.00 119.00   0.50    0.16    --  110.26 140.00  22.00   50
 31  \w     97.00 175.00   0.50    0.16    --  102.48 111.00  90.00  156
 32  \w    145.00 178.00   0.50    0.16    --  102.48 111.00 -30.00   66
 33  \w    117.00 175.00   0.50    0.16    --  102.48 111.00-180.00  116
 34  \w      1.00  39.00   0.50    0.16    --  -39.19  57.00 -60.00   76
 35  \w    -65.00 -16.00   0.50    0.16    --  -39.19  57.00 -60.00   98
 36  \w    -35.00  -9.00   0.50    0.16    --  -95.69  30.00 -90.00   52
 37  \w    -51.00 -13.00   0.50    0.16    --  -95.69  45.00  30.00   76
 38  \w    -35.00  -9.00   0.50    0.16    --  -95.69  30.00  60.00   52
 39  \w    -35.00 -10.00   0.50    0.16    --  -95.69  30.00  90.00   50
 40  \w    -35.00  -9.00   0.50    0.16    --  -95.69  30.00 150.00   52
 41  \w    -43.00   3.00   0.50    0.16    --  -39.19  38.00  90.00   92
 42  \w    -35.00 -10.00   0.50    0.16    --  -95.69  30.00 -30.00   50
 43  \w    -35.00  -9.00   0.50    0.16    --  -95.69  30.00-120.00   52
 44  \w    -34.00  -9.00   0.50    0.16    --  -95.69  30.00-150.00   50
 45  \w   -174.00 -86.00   0.50    0.16    --  -95.69-130.00 137.00  176
 46  \w   -116.00 -91.00   0.50    0.16    --  -39.19-140.00 -36.00   50
 47  \w   -125.00-100.00   0.50    0.16    --  -39.19-178.00-180.00   50
 48  \w    -91.00 -44.00   0.50    0.16    --  -39.19-178.00-180.00   94
 49  \w   -124.00 -99.00   0.50    0.16    --  -95.69-140.00 -36.00   50
 50  \w   -123.00 -90.00   0.50    0.16    --  -95.69 140.00  22.00   66
 51  \w    -70.00 -45.00   0.50    0.16    --  -39.19 140.00  22.00   50
;
_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      0.0583197000
_diffrn_orient_matrix_UB_12      -0.0133546000
_diffrn_orient_matrix_UB_13      -0.1147280000
_diffrn_orient_matrix_UB_21      0.0919004000
_diffrn_orient_matrix_UB_22      -0.1740071000
_diffrn_orient_matrix_UB_23      0.0150586000
_diffrn_orient_matrix_UB_31      -0.1963828000
_diffrn_orient_matrix_UB_32      -0.0152562000
_diffrn_orient_matrix_UB_33      -0.0041332000
_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  0.0228
_diffrn_reflns_av_unetI/netI     0.0288
_diffrn_reflns_Laue_measured_fraction_full 0.994
_diffrn_reflns_Laue_measured_fraction_max 0.939
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            8381
_diffrn_reflns_point_group_measured_fraction_full 0.994
_diffrn_reflns_point_group_measured_fraction_max 0.939
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.471
_diffrn_reflns_theta_min         3.322
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.721
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.73766
_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    1.320
_exptl_crystal_description       block
_exptl_crystal_F_000             368
_exptl_crystal_preparation
;
Crystallised from a saturated solution of 4,4'-bipyridine, 
orcinol, and phenazine (1:2:1) in 1,4-dioxane.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.29
_exptl_crystal_size_mid          0.25
_exptl_crystal_size_min          0.13
_refine_diff_density_max         0.318
_refine_diff_density_min         -0.250
_refine_diff_density_rms         0.050
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.072
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     242
_refine_ls_number_reflns         3365
_refine_ls_number_restraints     186
_refine_ls_restrained_S_all      1.043
_refine_ls_R_factor_all          0.0526
_refine_ls_R_factor_gt           0.0464
_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^)+(0.0767P)^2^+0.2295P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1318
_refine_ls_wR_factor_ref         0.1376
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2861
_reflns_number_total             3365
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           orcinol_phenazine_14-dioxane
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574446
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C H O N'
_shelx_estimated_absorpt_t_max   0.792
_shelx_estimated_absorpt_t_min   0.761
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(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 Secondary CH2 refined with riding coordinates:
 C1C(H1Ca,H1Cb), C2C(H2Ca,H2Cb)
3.b Aromatic/amide H refined with riding coordinates:
 C1B(H1Ba), C5B(H5B), C8A(H8A), C2A(H2A), C4A(H4A), C11A(H11A), C3B(H3B),
 C5A(H5A), C3A(H3A), C10A(H10A), C9A(H9A)
3.c Idealised Me refined as rotating group:
 C8B(H8Ba,H8Bb,H8Bc)
;
_shelx_res_checksum              80392
_shelx_hkl_checksum              9582
_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 orcino_phenazine
_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 1.485
_oxdiff_exptl_absorpt_empirical_full_min 0.689