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_1574437
_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         '3(C3 H3 O), C8 H10 N4 O2'
_chemical_formula_sum            'C17 H19 N4 O5'
_chemical_formula_weight         359.36
_chemical_name_systematic        caffeine_quinol
_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.cc2kmbvd
_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                109.346(5)
_cell_angle_beta                 104.319(6)
_cell_angle_gamma                92.860(5)
_cell_formula_units_Z            2
_cell_length_a                   8.2386(6)
_cell_length_b                   9.1933(6)
_cell_length_c                   12.2557(7)
_cell_measurement_reflns_used    4946
_cell_measurement_temperature    150.15
_cell_measurement_theta_max      73.3250
_cell_measurement_theta_min      3.9670
_cell_volume                     839.76(10)
_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_temperature      150.15
_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 0.897
_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    -17.00  59.00   0.50    1.52    --   48.51-101.00-168.00  152
  2  \w    -56.00  17.00   0.50    1.52    --  -49.38 101.00 -64.00  146
  3  \w   -148.00-123.00   0.50    1.52    --  -92.01-101.00-168.00   50
  4  \w    -64.00 -39.00   0.50    1.52    --  -92.01 101.00 -64.00   50
  5  \w     59.00  85.00   0.50    1.52    --   96.11-101.00-168.00   52
  6  \w    112.00 145.00   0.50    1.52    --   96.11 101.00 -64.00   66
  7  \w    100.00 143.00   0.50    1.52    --  108.00 101.00 -64.00   86
  8  \w     38.00 100.00   0.50    1.52    --  108.00-101.00-168.00  124
  9  \w    -18.00  27.00   0.50    1.52    --   48.51 -19.00-180.00   90
 10  \w     78.00 120.00   0.50    1.52    --   48.51 125.00-120.00   84
 11  \w    -30.00  27.00   0.50    1.52    --   48.51 -19.00-120.00  114
 12  \w   -119.00 -73.00   0.50    1.52    --  -49.38-125.00 -90.00   92
 13  \w   -103.00 -76.00   0.50    1.52    --  -49.38-125.00 -60.00   54
 14  \w   -155.00 -83.00   0.50    1.52    --  -92.01 -95.00 -30.00  144
 15  \w    -87.00 -39.00   0.50    1.52    --  -92.01 125.00 -30.00   96
 16  \w    -51.00 -16.00   0.50    1.52    --  -92.01  45.00-120.00   70
 17  \w   -152.00 -71.00   0.50    1.52    --  -92.01 -30.00  30.00  162
 18  \w   -159.00 -85.00   0.50    1.52    --  -92.01 -95.00-150.00  148
 19  \w    -50.00 -14.00   0.50    1.52    --  -92.01  45.00 150.00   72
 20  \w   -167.00-115.00   0.50    1.52    --  -92.01 -45.00  90.00  104
 21  \w     18.00  48.00   0.50    1.52    --   96.11 -45.00 -30.00   60
 22  \w    114.00 168.00   0.50    1.52    --   96.11 125.00  30.00  108
 23  \w    -55.00 -29.00   0.50    1.52    --  -99.00 103.00  20.38   52
 24  \w   -107.00 -76.00   0.50    1.52    --  -99.00 103.00  20.38   62
 25  \w   -107.00 -33.00   0.50    1.52    --  -99.00 109.00 101.67  148
 26  \w     34.00 106.00   0.50    1.52    --  102.05-105.00 -45.89  144
 27  \w     42.00  70.00   0.50    1.52    --  108.00 -61.00-150.00   56
 28  \w     44.00  69.00   0.50    1.52    --  108.00 -61.00 -60.00   50
 29  \w     45.00 103.00   0.50    1.52    --  108.00 -77.00  30.00  116
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix-Arc 100'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0240
_diffrn_reflns_av_unetI/netI     0.0299
_diffrn_reflns_Laue_measured_fraction_full 0.990
_diffrn_reflns_Laue_measured_fraction_max 0.897
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            7978
_diffrn_reflns_point_group_measured_fraction_full 0.990
_diffrn_reflns_point_group_measured_fraction_max 0.897
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         79.153
_diffrn_reflns_theta_min         3.982
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.894
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.60527
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'CrysAlisPro 1.171.42.63a (Rigaku Oxford Diffraction, 2022)'
_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    1.421
_exptl_crystal_description       plate
_exptl_crystal_F_000             378
_exptl_crystal_preparation
;
Crystallised from a saturated solution of caffeine and 
quinol (1:2) in 1,4-dioxane.
;
_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          0.22
_exptl_crystal_size_min          0.069
_refine_diff_density_max         0.190
_refine_diff_density_min         -0.331
_refine_diff_density_rms         0.063
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.060
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     322
_refine_ls_number_reflns         3272
_refine_ls_number_restraints     336
_refine_ls_restrained_S_all      1.012
_refine_ls_R_factor_all          0.0678
_refine_ls_R_factor_gt           0.0550
_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^)+(0.0870P)^2^+0.4740P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1525
_refine_ls_wR_factor_ref         0.1658
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2610
_reflns_number_total             3272
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           caffeine_quinol
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_original_cell_volume        839.75(10)
_cod_database_code               1574437
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.941
_shelx_estimated_absorpt_t_min   0.689
_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. Restrained distances
 H1B-O1B
 0.82 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
Uanis(C2C) = Uanis(C3D)
Uanis(C5C) = Uanis(C6D)
Uanis(C6C) = Uanis(C2D)
Uanis(O1) = Uanis(O1C)
Uanis(C3C) = Uanis(C5D)
Uanis(C1C) = Uanis(C1D)
Uanis(C8C) = Uanis(C7D)
Uanis(N4C) = Uanis(N4D)
Uanis(N1D) = Uanis(N1C)
4. 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
5. Same fragment restrains
{N4D, C1D, N1D, C3D, N2D, C2D, O1C, C6D, O1D, C5D, N3D, C4D, C8D, C7D} sigma
for 1-2: 0.02, 1-3: 0.02
as in
{N1C, C1C, N4C, C5C, N3C, C8C, O1, C2C, O2C, C3C, N2C, C4C, C7C, C6C}
6. Others
 Fixed Sof: N4D(0.78561) C1D(0.78561) N1D(0.78561) C3D(0.78561) N2D(0.78561)
 C2D(0.78561) H2DA(0.78561) H2DB(0.78561) H2DC(0.78561) O1C(0.78561)
 C6D(0.78561) O1D(0.78561) C5D(0.78561) N3D(0.78561) C4D(0.78561) H4D(0.78561)
 C8D(0.78561) H8DA(0.78561) H8DB(0.78561) H8DC(0.78561) C7D(0.78561)
 H7DA(0.78561) H7DB(0.78561) H7DC(0.78561) N1C(0.21439) C1C(0.21439)
 N4C(0.21439) C5C(0.21439) N3C(0.21439) C8C(0.21439) H8CA(0.21439)
 H8CB(0.21439) H8CC(0.21439) O1(0.21439) C2C(0.21439) O2C(0.21439) C3C(0.21439)
 N2C(0.21439) C4C(0.21439) H4C(0.21439) C7C(0.21439) H7CA(0.21439)
 H7CB(0.21439) H7CC(0.21439) C6C(0.21439) H6CA(0.21439) H6CB(0.21439)
 H6CC(0.21439)
7.a Aromatic/amide H refined with riding coordinates:
 C4D(H4D), C4C(H4C), C1A(H1AA), C2A(H2A), C2B(H2BA), C3B(H3B), C5B(H5B),
 C6B(H6B)
7.b Idealised Me refined as rotating group:
 C2D(H2DA,H2DB,H2DC), C8D(H8DA,H8DB,H8DC), C7D(H7DA,H7DB,H7DC), C8C(H8CA,H8CB,
 H8CC), C7C(H7CA,H7CB,H7CC), C6C(H6CA,H6CB,H6CC)
;
_shelx_res_checksum              951
_shelx_hkl_checksum              63831
_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_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
;