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_1574448
_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         'C6 H6 O2, C8 H12 N2'
_chemical_formula_sum            'C14 H18 N2 O2'
_chemical_formula_weight         246.30
_chemical_name_systematic        tetramethylpyrazine_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.cc2kmc0l
_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                 111.011(6)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   7.6282(4)
_cell_length_b                   9.2277(4)
_cell_length_c                   10.0237(5)
_cell_measurement_reflns_used    2435
_cell_measurement_temperature    149.99(10)
_cell_measurement_theta_max      76.7580
_cell_measurement_theta_min      6.1850
_cell_volume                     658.66(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 0.997
_diffrn_measured_fraction_theta_max 0.924
_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    109.00 153.00   0.50    0.38    --  100.34  61.00 150.00   88
  2  \w     98.00 123.00   0.50    0.38    --  109.84  30.00  60.00   50
  3  \w    138.00 168.00   0.50    0.38    --  109.84  30.00  60.00   60
  4  \w    127.00 159.00   0.50    0.38    --  100.34 126.00 -50.00   64
  5  \w    102.00 157.00   0.50    0.38    --  109.84  45.00 -60.00  110
  6  \w    -23.00  24.00   0.50    0.38    --   46.35 -38.00-120.00   94
  7  \w     30.00  55.00   0.50    0.38    --  100.34 -61.00-180.00   50
  8  \w     42.00  67.00   0.50    0.38    --  109.84 -77.00-150.00   50
  9  \w     26.00  51.00   0.50    0.38    --  100.34 -61.00 -90.00   50
 10  \w     29.00  55.00   0.50    0.38    --  100.34 -61.00 -60.00   52
 11  \w     45.00  77.00   0.50    0.38    --  109.84 -77.00 120.00   64
 12  \w     27.00  53.00   0.50    0.38    --  100.34 -61.00  60.00   52
 13  \w     51.00  90.00   0.50    0.38    --  109.84 -95.00 -90.00   78
 14  \w     63.00  91.00   0.50    0.38    --  109.84 -95.00-150.00   56
 15  \w     64.00 100.00   0.50    0.38    --  109.84-126.00-127.00   72
 16  \w     44.00  69.00   0.50    0.38    --   46.35-126.00-127.00   50
 17  \w      6.00  32.00   0.50    0.38    --  -45.35  38.00-180.00   52
 18  \w     -2.00  30.00   0.50    0.38    --  -45.35  38.00-150.00   64
 19  \w      1.00  27.00   0.50    0.38    --  -45.35  38.00-120.00   52
 20  \w     -2.00  34.00   0.50    0.38    --  -45.35  38.00 -90.00   72
 21  \w     -9.00  31.00   0.50    0.38    --  -45.35  38.00 -30.00   80
 22  \w    -42.00 -17.00   0.50    0.38    --  -45.35 126.00 -50.00   50
 23  \w    -66.00 -20.00   0.50    0.38    --  -85.07  77.00 -90.00   92
 24  \w   -121.00 -76.00   0.50    0.38    --  -85.07 -45.00   0.00   90
 25  \w   -152.00-105.00   0.50    0.38    --  -85.07 -77.00 -30.00   94
 26  \w   -153.00-102.00   0.50    0.38    --  -85.07 -77.00 -90.00  102
 27  \w   -146.00-121.00   0.50    0.38    --  -85.07-126.00-127.00   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      -0.2003102000
_diffrn_orient_matrix_UB_12      0.0104523000
_diffrn_orient_matrix_UB_13      0.0024893000
_diffrn_orient_matrix_UB_21      -0.0793857000
_diffrn_orient_matrix_UB_22      0.0124365000
_diffrn_orient_matrix_UB_23      -0.1641336000
_diffrn_orient_matrix_UB_31      -0.0185357000
_diffrn_orient_matrix_UB_32      -0.1662403000
_diffrn_orient_matrix_UB_33      -0.0121747000
_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  0.0195
_diffrn_reflns_av_unetI/netI     0.0199
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.924
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       7
_diffrn_reflns_limit_k_min       -10
_diffrn_reflns_limit_l_max       11
_diffrn_reflns_limit_l_min       -12
_diffrn_reflns_number            3804
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.924
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.406
_diffrn_reflns_theta_min         6.215
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.675
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.87659
_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    1.242
_exptl_crystal_description       plate
_exptl_crystal_F_000             264
_exptl_crystal_preparation
;
Crystallised from a saturated solution of caffeine, quinol
and tetramethylpyrazine (1:2:2) in MeOH.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.32
_exptl_crystal_size_mid          0.28
_exptl_crystal_size_min          0.09
_refine_diff_density_max         0.139
_refine_diff_density_min         -0.165
_refine_diff_density_rms         0.039
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.075
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     87
_refine_ls_number_reflns         1299
_refine_ls_number_restraints     36
_refine_ls_restrained_S_all      1.060
_refine_ls_R_factor_all          0.0363
_refine_ls_R_factor_gt           0.0338
_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^)+(0.0452P)^2^+0.1412P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0906
_refine_ls_wR_factor_ref         0.0922
_reflns_Friedel_coverage         0.000
_reflns_number_gt                1182
_reflns_number_total             1299
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           tetramethylpyrazine_quinol
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574448
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C H N O'
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(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(H2A), C3A(H3A)
3.b Idealised Me refined as rotating group:
 C1B(H1Ba,H1Bb,H1Bc), C4B(H4Ba,H4Bb,H4Bc)
;
_shelx_res_checksum              76253
_shelx_hkl_checksum              42827
_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 tetramethylpyrazine_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 1.219
_oxdiff_exptl_absorpt_empirical_full_min 0.733