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_1574457
_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_absolute_configuration unk
_chemical_formula_moiety         'C8 H10 N4 O2, C7 H4 N2 O6'
_chemical_formula_sum            'C15 H14 N6 O8'
_chemical_formula_weight         406.32
_chemical_name_systematic        'caffeine_3,5-dinitrobenzoic acid'
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_block_doi                 10.5517/ccdc.csd.cc2kmbtc
_audit_creation_date             2024-07-18
_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                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   9.0637(2)
_cell_length_b                   29.4253(8)
_cell_length_c                   12.6604(4)
_cell_measurement_reflns_used    6292
_cell_measurement_temperature    149.99(10)
_cell_measurement_theta_max      67.9950
_cell_measurement_theta_min      3.0070
_cell_volume                     3376.56(16)
_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      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 0.999
_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    -56.00 -19.00   0.50   20.00    --  -88.07 116.00 128.00   74
  2  \w    -71.00 -40.00   0.50   20.00    --  -88.07 129.00  30.00   62
  3  \w     61.00 127.00   0.50   20.00    --  100.90  12.00 -26.00  132
  4  \w    132.00 171.00   0.50   20.00    --  100.90  12.00 -26.00   78
  5  \w     37.00  97.00   0.50   20.00    --  109.94-116.00  40.00  120
  6  \w    -12.00  32.00   0.50    5.00    --  -43.89  38.00-150.00   88
  7  \w    -89.00  -3.00   0.50    5.00    --  -43.89 -12.00 161.00  172
  8  \w    -39.00   1.00   0.50    5.00    --  -43.89  57.00  30.00   80
  9  \w      4.00  36.00   0.50    5.00    --  -43.89  38.00 120.00   64
 10  \w    -26.00  23.00   0.50    5.00    --   44.76 -38.00  90.00   98
 11  \w   -149.00-104.00   0.50   20.00    --  -88.07 -77.00   0.00   90
 12  \w   -164.00 -87.00   0.50   20.00    --  -88.07 -61.00 150.00  154
 13  \w    -43.00 -13.00   0.50   20.00    --  -88.07  61.00  60.00   60
 14  \w    -46.00 -14.00   0.50   20.00    --  -88.07  61.00 -90.00   64
 15  \w     35.00  93.00   0.50   20.00    --  100.90 -95.00  60.00  116
 16  \w     26.00  51.00   0.50   20.00    --  100.90 -61.00 -90.00   50
 17  \w    133.00 164.00   0.50   20.00    --  100.90  77.00-150.00   62
 18  \w     25.00  50.00   0.50   20.00    --  100.90 -61.00 -60.00   50
 19  \w     45.00  78.00   0.50   20.00    --  100.90 -77.00 120.00   66
 20  \w    125.00 161.00   0.50   20.00    --  100.90  77.00-180.00   72
 21  \w     29.00  56.00   0.50   20.00    --  100.90 -61.00 120.00   54
 22  \w     43.00  80.00   0.50   20.00    --  109.94 -77.00  90.00   74
;
_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      0.0097404000
_diffrn_orient_matrix_UB_12      0.0520425000
_diffrn_orient_matrix_UB_13      0.0111537000
_diffrn_orient_matrix_UB_21      0.0259759000
_diffrn_orient_matrix_UB_22      -0.0052012000
_diffrn_orient_matrix_UB_23      0.1196808000
_diffrn_orient_matrix_UB_31      0.1676619000
_diffrn_orient_matrix_UB_32      -0.0022353000
_diffrn_orient_matrix_UB_33      -0.0191546000
_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  0.0387
_diffrn_reflns_av_unetI/netI     0.0419
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.939
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       36
_diffrn_reflns_limit_k_min       -36
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            18418
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.922
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.543
_diffrn_reflns_theta_min         3.004
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.144
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.86435
_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    1.599
_exptl_crystal_description       plate
_exptl_crystal_F_000             1680
_exptl_crystal_preparation
;
Crystallised from a saturated solution of caffeine and 
3,5-dinitrobenzoic acid (1:1) in DMF.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.34
_exptl_crystal_size_mid          0.23
_exptl_crystal_size_min          0.045
_refine_diff_density_max         0.468
_refine_diff_density_min         -0.242
_refine_diff_density_rms         0.062
_refine_ls_abs_structure_details
;
 Flack x determined using 2081 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.50(12)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.123
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     531
_refine_ls_number_reflns         6539
_refine_ls_number_restraints     444
_refine_ls_restrained_S_all      1.089
_refine_ls_R_factor_all          0.0669
_refine_ls_R_factor_gt           0.0597
_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^)+(0.0674P)^2^+2.1269P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1455
_refine_ls_wR_factor_ref         0.1494
_reflns_Friedel_coverage         0.742
_reflns_Friedel_fraction_full    0.995
_reflns_Friedel_fraction_max     0.901
_reflns_number_gt                5936
_reflns_number_total             6539
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           caffeine_35-dinitrobenzoic_acid
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574457
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C H N O'
_shelx_estimated_absorpt_t_max   0.950
_shelx_estimated_absorpt_t_min   0.651
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(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:
 C2B(H2B), C2D(H2D), C4B(H4B), C4D(H4D), C6B(H6BA), C6D(H6DA), C7A(H7A),
 C7C(H7C)
3.b Idealised Me refined as rotating group:
 C3A(H3AA,H3AB,H3AC), C3C(H3CA,H3CB,H3CC), C5A(H5AA,H5AB,H5AC), C5C(H5CA,H5CB,
 H5CC), C8A(H8AA,H8AB,H8AC), C8C(H8CA,H8CB,H8CC)
3.c Idealised tetrahedral OH refined as rotating group:
 O6D(H6D), O6B(H6B)
;
_shelx_res_checksum              25266
_shelx_hkl_checksum              97756
_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_3,5-dinitrobenzoic 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 1.299
_oxdiff_exptl_absorpt_empirical_full_min 0.796