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_1574449
_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, C8 H8 O5'
_chemical_formula_sum            'C16 H18 N4 O7'
_chemical_formula_weight         378.34
_chemical_name_systematic        'caffeine_methyl gallate'
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2yn'
_space_group_name_H-M_alt        'P 1 21/n 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_block_doi                 10.5517/ccdc.csd.cc2kmbh1
_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                 91.161(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.9229(2)
_cell_length_b                   10.1175(3)
_cell_length_c                   23.0844(7)
_cell_measurement_reflns_used    6556
_cell_measurement_temperature    150
_cell_measurement_theta_max      76.6530
_cell_measurement_theta_min      3.7950
_cell_volume                     1616.56(8)
_computing_cell_refinement       'CrysAlisPro 1.171.42.63a (Rigaku OD, 2022)'
_computing_data_collection       'CrysAlisPro 1.171.42.63a (Rigaku OD, 2022)'
_computing_data_reduction        'CrysAlisPro 1.171.42.63a (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_temperature      150.00
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            'HyPix-Arc 100'
_diffrn_measured_fraction_theta_full 0.990
_diffrn_measured_fraction_theta_max 0.990
_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    -10.00  33.00   0.50    0.14    --  -45.36  38.00  60.00   86
  2  \w    -19.00  25.00   0.50    0.14    --  -45.36  38.00  30.00   88
  3  \w    -48.00 -17.00   0.50    0.56    --  -85.06  61.00 -60.00   62
  4  \w    -19.00  13.00   0.50    0.14    --  -45.36  38.00 -30.00   64
  5  \w     62.00  87.00   0.50    0.56    --  100.32  15.00 150.00   50
  6  \w    104.00 136.00   0.50    0.56    --  100.32  15.00 150.00   64
  7  \w    119.00 157.00   0.50    0.56    --  100.32  61.00 150.00   76
  8  \w    132.00 169.00   0.50    0.56    --  109.83  77.00  30.00   74
  9  \w    121.00 178.00   0.50    0.56    --  109.83  61.00-180.00  114
 10  \w    112.00 161.00   0.50    0.56    --  100.32 125.00 -90.00   98
 11  \w    138.00 163.00   0.50    0.56    --  109.83  96.00 161.00   50
 12  \w    137.00 168.00   0.50    0.56    --  100.32  96.00 161.00   62
 13  \w     44.00  70.00   0.50    0.56    --  109.83 -77.00  90.00   52
 14  \w     42.00  77.00   0.50    0.14    --   46.36 -96.00  53.00   70
 15  \w     42.00  67.00   0.50    0.56    --  109.83 -77.00-180.00   50
 16  \w     40.00  89.00   0.50    0.56    --  109.83 -95.00 -60.00   98
 17  \w     44.00  71.00   0.50    0.56    --  109.83 -96.00  53.00   54
 18  \w     64.00  92.00   0.50    0.56    --  100.32 -96.00  53.00   56
 19  \w     64.00  89.00   0.50    0.56    --  109.83 -95.00 120.00   50
 20  \w     49.00 100.00   0.50    0.56    --  100.32-125.00 150.00  102
 21  \w    -38.00  -3.00   0.50    0.14    --  -45.36  96.00 161.00   70
 22  \w    -65.00 -39.00   0.50    0.56    --  -85.06  96.00 161.00   52
 23  \w   -149.00-107.00   0.50    0.56    --  -85.06 -96.00  53.00   84
 24  \w   -153.00-118.00   0.50    0.56    --  -85.06 -77.00 -90.00   70
 25  \w   -153.00-102.00   0.50    0.56    --  -85.06 -77.00-180.00  102
;
_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      0.0044253000
_diffrn_orient_matrix_UB_12      0.0423525000
_diffrn_orient_matrix_UB_13      -0.0640857000
_diffrn_orient_matrix_UB_21      -0.0799929000
_diffrn_orient_matrix_UB_22      -0.1361766000
_diffrn_orient_matrix_UB_23      -0.0182546000
_diffrn_orient_matrix_UB_31      -0.2075497000
_diffrn_orient_matrix_UB_32      0.0534181000
_diffrn_orient_matrix_UB_33      0.0042529000
_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  0.0145
_diffrn_reflns_av_unetI/netI     0.0158
_diffrn_reflns_Laue_measured_fraction_full 0.990
_diffrn_reflns_Laue_measured_fraction_max 0.990
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       27
_diffrn_reflns_limit_l_min       -27
_diffrn_reflns_number            8578
_diffrn_reflns_point_group_measured_fraction_full 0.990
_diffrn_reflns_point_group_measured_fraction_max 0.990
_diffrn_reflns_theta_full        66.572
_diffrn_reflns_theta_max         66.572
_diffrn_reflns_theta_min         3.831
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.057
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.87886
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.63a (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    1.555
_exptl_crystal_description       block
_exptl_crystal_F_000             792
_exptl_crystal_preparation
;
Crystallised from a saturated solution of caffeine
and methyl gallate (1:1) in MeOH.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt co-crystallisation protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.35
_exptl_crystal_size_mid          0.22
_exptl_crystal_size_min          0.19
_refine_diff_density_max         0.233
_refine_diff_density_min         -0.228
_refine_diff_density_rms         0.043
_refine_ls_extinction_coef       0.00056(11)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2018/3 (Sheldrick 2018)'
_refine_ls_goodness_of_fit_ref   1.056
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     258
_refine_ls_number_reflns         2833
_refine_ls_number_restraints     207
_refine_ls_restrained_S_all      1.017
_refine_ls_R_factor_all          0.0347
_refine_ls_R_factor_gt           0.0330
_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^)+(0.0543P)^2^+0.5547P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0946
_refine_ls_wR_factor_ref         0.0961
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2631
_reflns_number_total             2833
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           caffeine_methylgallate
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574449
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C16 H18 O7 N4'
_shelx_estimated_absorpt_t_max   0.976
_shelx_estimated_absorpt_t_min   0.620
_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:
 C3B(H3BA), C5A(H5A), C7B(H7B)
3.b Idealised Me refined as rotating group:
 C00O(H00A,H00B,H00C), C4A(H4AA,H4AB,H4AC), C7A(H7AA,H7AB,H7AC), C8B(H8BA,H8BB,
 H8BC)
;
_shelx_res_checksum              28560
_shelx_hkl_checksum              2255
_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_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 1.227
_oxdiff_exptl_absorpt_empirical_full_min 0.732