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_1574441
_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, C11 H8 O3'
_chemical_formula_sum            'C19 H18 N4 O5'
_chemical_formula_weight         382.37
_chemical_name_systematic        'caffeine_3-hydroxy-2-naphthoic 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.cc2kmbg0
_audit_creation_date             2025-03-31
_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                 116.710(7)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   9.0412(5)
_cell_length_b                   24.4254(10)
_cell_length_c                   8.6209(5)
_cell_measurement_reflns_used    7219
_cell_measurement_temperature    150
_cell_measurement_theta_max      75.4670
_cell_measurement_theta_min      3.5450
_cell_volume                     1700.65(19)
_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 0.998
_diffrn_measured_fraction_theta_max 0.935
_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   0.00   0.50    1.74    --  -45.36  55.00  81.00   84
  2  \w      1.00  28.00   0.50    1.74    --  -45.36  55.00  81.00   54
  3  \w     12.00  40.00   0.50    1.74    --   46.36 -55.00 -61.00   56
  4  \w    -26.00   4.00   0.50    1.74    --   46.36 -55.00 -61.00   60
  5  \w    -41.00 -11.00   0.50    6.95    --  -85.06  55.00  81.00   60
  6  \w    146.00 173.00   0.50    6.95    --  109.83  55.00  81.00   54
  7  \w    -17.00  34.00   0.50    1.74    --  -45.36  38.00 150.00  102
  8  \w    -13.00  34.00   0.50    1.74    --  -45.36  38.00   0.00   94
  9  \w    -66.00 -15.00   0.50    1.74    --  -45.36 125.00-180.00  102
 10  \w    -51.00 -25.00   0.50    6.95    --  -85.06  61.00 120.00   52
 11  \w   -144.00-102.00   0.50    6.95    --  -85.06 -77.00  60.00   84
 12  \w   -155.00 -86.00   0.50    6.95    --  -85.06 -55.00 -61.00  138
 13  \w    -49.00 -11.00   0.50    6.95    --  -85.06  61.00  30.00   76
 14  \w    -65.00 -39.00   0.50    6.95    --  -85.06  77.00   0.00   52
 15  \w    -39.00 -11.00   0.50    6.95    --  -85.06  61.00 -90.00   56
 16  \w    109.00 167.00   0.50    6.95    --  100.32  61.00 -30.00  116
 17  \w     32.00  74.00   0.50    6.95    --  100.32 -77.00 -90.00   84
 18  \w    151.00 176.00   0.50    6.95    --  100.32  55.00  81.00   50
 19  \w     33.00  74.00   0.50    6.95    --  100.32 -77.00-150.00   82
 20  \w     41.00  69.00   0.50    6.95    --  100.32 -77.00  60.00   56
 21  \w    144.00 171.00   0.50    6.95    --  100.32  61.00   0.00   54
 22  \w    113.00 142.00   0.50    6.95    --  100.32  61.00   0.00   58
 23  \w    110.00 143.00   0.50    6.95    --  100.32  55.00  81.00   66
 24  \w     39.00  66.00   0.50    6.95    --  100.32 -77.00   0.00   54
 25  \w     45.00  92.00   0.50    6.95    --  109.83 -95.00 150.00   94
 26  \w     45.00  87.00   0.50    6.95    --  109.83 -95.00 -30.00   84
 27  \w     43.00  72.00   0.50    6.95    --  109.83 -77.00  30.00   58
 28  \w     44.00  71.00   0.50    6.95    --  109.83 -77.00-120.00   54
 29  \w     43.00  70.00   0.50    6.95    --  109.83 -77.00  90.00   54
 30  \w     42.00  68.00   0.50    6.95    --  109.83 -77.00-180.00   52
 31  \w    140.00 174.00   0.50    6.95    --  109.83  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      -0.0073732000
_diffrn_orient_matrix_UB_12      -0.0410691000
_diffrn_orient_matrix_UB_13      -0.1388659000
_diffrn_orient_matrix_UB_21      -0.1878214000
_diffrn_orient_matrix_UB_22      -0.0066959000
_diffrn_orient_matrix_UB_23      -0.0631678000
_diffrn_orient_matrix_UB_31      -0.0330378000
_diffrn_orient_matrix_UB_32      0.0473406000
_diffrn_orient_matrix_UB_33      -0.1294595000
_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  0.0310
_diffrn_reflns_av_unetI/netI     0.0256
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.935
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       30
_diffrn_reflns_limit_k_min       -19
_diffrn_reflns_limit_l_max       10
_diffrn_reflns_limit_l_min       -10
_diffrn_reflns_number            11468
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.935
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.581
_diffrn_reflns_theta_min         3.619
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_target            Cu
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.925
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.60107
_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    1.493
_exptl_crystal_description       block
_exptl_crystal_F_000             800
_exptl_crystal_preparation
;
Crystallised from a saturated solution of caffeine
and 3-hydroxy-2-naphthoic acid (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          0.15
_exptl_crystal_size_mid          0.11
_exptl_crystal_size_min          0.079
_refine_diff_density_max         0.287
_refine_diff_density_min         -0.191
_refine_diff_density_rms         0.045
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.059
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     262
_refine_ls_number_reflns         3384
_refine_ls_number_restraints     222
_refine_ls_restrained_S_all      1.024
_refine_ls_R_factor_all          0.0427
_refine_ls_R_factor_gt           0.0395
_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^)+(0.0623P)^2^+0.3694P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1090
_refine_ls_wR_factor_ref         0.1116
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3060
_reflns_number_total             3384
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc07556k2.cif
_cod_data_source_block           caffeine_3-hydroxy-2-naphthoicacid
_cod_depositor_comments
'Adding full bibliography for 1574434--1574463.cif.'
_cod_original_cell_volume        1700.65(18)
_cod_database_code               1574441
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C19 H18 N4 O5'
_shelx_estimated_absorpt_t_max   0.931
_shelx_estimated_absorpt_t_min   0.874
_diffrn_oxdiff_digest_hkl
;
010adda4700e9651aa64bec2fafbb833f77aa1
;
_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:
 C4B(H4B), C6B(H6B), C7A(H7A), C7B(H7B), C8B(H8B), C9B(H9B), C11B(H11B)
3.b Idealised Me refined as rotating group:
 C2A(H2AA,H2AB,H2AC), C6A(H6AA,H6AB,H6AC), C8A(H8AA,H8AB,H8AC)
;
_shelx_res_checksum              59271
_shelx_hkl_checksum              90310
_olex2_exptl_crystal_mounting_method
'Crystal mounted using inert oil from the encapsulation crystallisation technique onto a MiTeGen Kapton micromount.'
_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 1.757
_oxdiff_exptl_absorpt_empirical_full_min 0.632