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_1574456
_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 H10 N4 O2, C H O2'
_chemical_formula_sum            'C9 H11 N4 O4'
_chemical_formula_weight         239.22
_chemical_name_systematic        'caffeine_oxalic acid'
_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.cc2kmc1m
_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                 96.239(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   4.40790(10)
_cell_length_b                   14.7459(4)
_cell_length_c                   15.8719(4)
_cell_measurement_reflns_used    3833
_cell_measurement_temperature    150.00(10)
_cell_measurement_theta_max      76.0210
_cell_measurement_theta_min      4.0970
_cell_volume                     1025.54(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      150.00(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 0.998
_diffrn_measured_fraction_theta_max 0.953
_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    -14.00  15.00   0.50    0.70    --  -44.06  38.00-150.00   58
  2  \w     -4.00  37.00   0.50    0.70    --  -44.06  38.00-120.00   82
  3  \w     -3.00  23.00   0.50    0.70    --  -44.06  38.00 -30.00   52
  4  \w    -34.00   7.00   0.50    0.70    --  -44.06  57.00  90.00   82
  5  \w    -14.00  31.00   0.50    0.70    --  -44.06  38.00 120.00   90
  6  \w    -67.00 -42.00   0.50    0.70    --  -88.13 115.00  19.00   50
  7  \w    -63.00 -38.00   0.50    0.70    --  -44.06 115.00  19.00   50
  8  \w    -73.00 -40.00   0.50    0.70    --  -44.06 125.00 -60.00   66
  9  \w    -74.00 -14.00   0.50    0.70    --  -88.13 125.00 -90.00  120
 10  \w     35.00  60.00   0.50    0.70    --   45.06-115.00 -69.00   50
 11  \w     67.00  96.00   0.50    0.70    --  100.88-115.00 -69.00   58
 12  \w     42.00  67.00   0.50    0.70    --  109.87-115.00 -69.00   50
 13  \w     41.00  92.00   0.50    0.70    --  109.87 -95.00 -60.00  102
 14  \w     30.00  93.00   0.50    0.70    --  100.88 -95.00   0.00  126
 15  \w     38.00  90.00   0.50    0.70    --  109.87 -95.00  30.00  104
 16  \w     -7.00  23.00   0.50    0.70    --   45.06 -38.00 -60.00   60
 17  \w     43.00  78.00   0.50    0.70    --  109.87 -77.00-180.00   70
 18  \w     52.00  80.00   0.50    0.70    --  109.87 -77.00  60.00   56
 19  \w     25.00  50.00   0.50    0.70    --  100.88 -61.00 150.00   50
 20  \w    122.00 147.00   0.50    0.70    --  100.88 115.00  19.00   50
 21  \w    123.00 148.00   0.50    0.70    --  109.87 115.00  19.00   50
 22  \w    128.00 170.00   0.50    0.70    --  100.88  77.00 -90.00   84
 23  \w    139.00 176.00   0.50    0.70    --  100.88  61.00   0.00   74
 24  \w     94.00 169.00   0.50    0.70    --  109.87  30.00  60.00  150
 25  \w    109.00 135.00   0.50    0.70    --  100.88  61.00   0.00   52
 26  \w   -154.00-128.00   0.50    0.70    --  -88.13 -77.00-150.00   52
 27  \w   -152.00-114.00   0.50    0.70    --  -88.13-115.00 -69.00   76
 28  \w   -153.00-104.00   0.50    0.70    --  -88.13 -77.00  30.00   98
 29  \w   -136.00-102.00   0.50    0.70    --  -88.13 -77.00  60.00   68
;
_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      0.0344135000
_diffrn_orient_matrix_UB_12      -0.0935782000
_diffrn_orient_matrix_UB_13      -0.0411820000
_diffrn_orient_matrix_UB_21      -0.0613865000
_diffrn_orient_matrix_UB_22      0.0433219000
_diffrn_orient_matrix_UB_23      -0.0885250000
_diffrn_orient_matrix_UB_31      0.3443191000
_diffrn_orient_matrix_UB_32      0.0170619000
_diffrn_orient_matrix_UB_33      -0.0008151000
_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  0.0244
_diffrn_reflns_av_unetI/netI     0.0257
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.953
_diffrn_reflns_limit_h_max       5
_diffrn_reflns_limit_h_min       -3
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            6546
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.953
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.146
_diffrn_reflns_theta_min         4.104
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.063
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.89930
_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    1.549
_exptl_crystal_description       plate
_exptl_crystal_F_000             500
_exptl_crystal_preparation
;
Crystallised from a saturated solution of caffeine, 3,5-
dinitrobenzoic acid, 2-methylresorcinol and orcinol (1:1:1:1)
 in MeNO2.
;
_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          0.16
_exptl_crystal_size_min          0.062
_refine_diff_density_max         0.213
_refine_diff_density_min         -0.245
_refine_diff_density_rms         0.044
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.042
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     160
_refine_ls_number_reflns         2054
_refine_ls_number_restraints     123
_refine_ls_restrained_S_all      1.010
_refine_ls_R_factor_all          0.0414
_refine_ls_R_factor_gt           0.0346
_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^)+(0.0537P)^2^+0.1936P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0909
_refine_ls_wR_factor_ref         0.0952
_reflns_Friedel_coverage         0.000
_reflns_number_gt                1753
_reflns_number_total             2054
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           caffeine_oxalicacid
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574456
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C H N O'
_shelx_estimated_absorpt_t_max   0.937
_shelx_estimated_absorpt_t_min   0.721
_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:
 C1A(H1A)
3.b Idealised Me refined as rotating group:
 C6A(H6AA,H6AB,H6AC), C7A(H7AA,H7AB,H7AC), C8A(H8AA,H8AB,H8AC)
;
_shelx_res_checksum              13620
_shelx_hkl_checksum              50603
_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 'caffeine_oxalic 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 1.218
_oxdiff_exptl_absorpt_empirical_full_min 0.824