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_1574447
_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         'C5 H8 O4, C8 H10 N4 O2'
_chemical_formula_sum            'C13 H18 N4 O6'
_chemical_formula_weight         326.31
_chemical_name_systematic        'caffeine_glutaric 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.cc2kmbfz
_audit_creation_date             2025-04-01
_audit_creation_method
;
Olex2 1.5
(compiled 2025.03.04 svn.red2d20d0 for OlexSys, GUI svn.r7188)
;
_audit_update_record
;
2025-04-01 deposited with the CCDC.	2025-04-22 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 97.832(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   13.0056(3)
_cell_length_b                   6.5779(2)
_cell_length_c                   17.0942(4)
_cell_measurement_reflns_used    4784
_cell_measurement_temperature    149.99(10)
_cell_measurement_theta_max      75.8880
_cell_measurement_theta_min      3.4300
_cell_volume                     1448.76(7)
_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 0.997
_diffrn_measured_fraction_theta_max 0.931
_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     42.00  79.00   0.50    0.95    --  109.94 -77.00 120.00   74
  2  \w     45.00  72.00   0.50    0.95    --  100.90 -77.00  90.00   54
  3  \w     33.00  61.00   0.50    0.95    --  100.90 -76.00  48.00   56
  4  \w     44.00  72.00   0.50    0.95    --  109.94 -76.00  48.00   56
  5  \w     41.00  80.00   0.50    0.95    --  109.94 -77.00   0.00   78
  6  \w     27.00  55.00   0.50    0.95    --  100.90 -61.00 -30.00   56
  7  \w     43.00  69.00   0.50    0.95    --  109.94 -77.00-180.00   52
  8  \w     25.00  50.00   0.50    0.95    --  100.90 -61.00 -90.00   50
  9  \w     25.00  50.00   0.50    0.95    --  100.90 -61.00 -60.00   50
 10  \w     10.00  35.00   0.50    0.95    --   44.76 -76.00  48.00   50
 11  \w     30.00  55.00   0.50    0.95    --  100.90 -61.00 120.00   50
 12  \w    125.00 152.00   0.50    0.95    --  100.90  77.00 -30.00   54
 13  \w    122.00 172.00   0.50    0.95    --  100.90  61.00-120.00  100
 14  \w    124.00 150.00   0.50    0.95    --  109.94  76.00 174.00   52
 15  \w    129.00 161.00   0.50    0.95    --  100.90  76.00 174.00   64
 16  \w     29.00  80.00   0.50    0.95    --  100.90 -95.00-120.00  102
 17  \w     46.00  92.00   0.50    0.95    --  109.94 -95.00 -90.00   92
 18  \w    -11.00  25.00   0.50    0.95    --  -43.89  38.00-120.00   72
 19  \w     -1.00  33.00   0.50    0.95    --  -43.89  38.00-150.00   68
 20  \w      5.00  33.00   0.50    0.95    --  -43.89  38.00 -90.00   56
 21  \w    -12.00  37.00   0.50    0.95    --  -43.89  38.00 -60.00   98
 22  \w    -13.00  33.00   0.50    0.95    --  -43.89  38.00  60.00   92
 23  \w    -62.00 -22.00   0.50    0.95    --  -43.89  76.00 174.00   80
 24  \w    -42.00 -15.00   0.50    0.95    --  -88.07  61.00 120.00   54
 25  \w    -68.00 -19.00   0.50    0.95    --  -43.89 125.00  60.00   98
 26  \w    -54.00 -28.00   0.50    0.95    --  -88.07  76.00 174.00   52
 27  \w   -154.00-111.00   0.50    0.95    --  -88.07 -77.00 120.00   86
 28  \w   -152.00-116.00   0.50    0.95    --  -88.07 -76.00  48.00   72
 29  \w   -157.00-104.00   0.50    0.95    --  -88.07 -77.00   0.00  106
 30  \w   -149.00-104.00   0.50    0.95    --  -88.07 -77.00-150.00   90
;
_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      -0.1099810000
_diffrn_orient_matrix_UB_12      -0.0709517000
_diffrn_orient_matrix_UB_13      0.0110506000
_diffrn_orient_matrix_UB_21      -0.0465837000
_diffrn_orient_matrix_UB_22      0.1810894000
_diffrn_orient_matrix_UB_23      -0.0499759000
_diffrn_orient_matrix_UB_31      -0.0050564000
_diffrn_orient_matrix_UB_32      -0.1305847000
_diffrn_orient_matrix_UB_33      -0.0752124000
_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  0.0269
_diffrn_reflns_av_unetI/netI     0.0292
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.931
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       7
_diffrn_reflns_limit_k_min       -8
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            8658
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.931
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.047
_diffrn_reflns_theta_min         3.430
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.021
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.95919
_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    1.496
_exptl_crystal_description       needle
_exptl_crystal_F_000             688
_exptl_crystal_preparation
;
Crystallised from a saturated solution of caffeine 
and glutaric acid (1:1) in MeNO2.
;
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.12
_exptl_crystal_size_mid          0.089
_exptl_crystal_size_min          0.031
_refine_diff_density_max         0.246
_refine_diff_density_min         -0.227
_refine_diff_density_rms         0.043
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.034
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     217
_refine_ls_number_reflns         2826
_refine_ls_number_restraints     165
_refine_ls_restrained_S_all      1.004
_refine_ls_R_factor_all          0.0472
_refine_ls_R_factor_gt           0.0377
_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^)+(0.0589P)^2^+0.4337P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1044
_refine_ls_wR_factor_ref         0.1116
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2291
_reflns_number_total             2826
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           caffeine_glutaricacid
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_database_code               1574447
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C H N O'
_cell_oxdiff_angle_alpha         89.958(3)
_cell_oxdiff_angle_beta          97.890(3)
_cell_oxdiff_angle_gamma         90.062(3)
_cell_oxdiff_length_a            13.0099(5)
_cell_oxdiff_length_b            6.5762(2)
_cell_oxdiff_length_c            17.0956(6)
_cell_oxdiff_measurement_reflns_used 4784
_cell_oxdiff_volume              1448.77(9)
_shelx_estimated_absorpt_t_max   0.969
_shelx_estimated_absorpt_t_min   0.887
_diffrn_oxdiff_digest_hkl
;
0176e99aa759eb13746726d40f807a526fadc5
;
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All C(H,H,H,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 Secondary CH2 refined with riding coordinates:
 C4B(H4BA,H4BB), C3B(H3BA,H3BB), C2B(H2BA,H2BB)
3.b Aromatic/amide H refined with riding coordinates:
 C7A(H7A)
3.c Idealised Me refined as rotating group:
 C8A(H8AA,H8AB,H8AC), C3A(H3AA,H3AB,H3AC), C5A(H5AA,H5AB,H5AC)
;
_shelx_res_checksum              95868
_shelx_hkl_checksum              12074
_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_glutaric 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 1.213
_oxdiff_exptl_absorpt_empirical_full_min 0.874