High-throughput nanoscale crystallization of dihydropyridine active pharmaceutical ingredients.
Metherall, Jessica P.; Corner, Philip A.; McCabe, James F.; Hall, Michael J.; Probert, Michael R.; Acta crystallographica Section B, Structural science, crystal engineering and materials 80 (2024) 4–12; doi:10.1107/S2052520623010053

data_2312371
_publ_section_title
;
 High-throughput nanoscale crystallization of dihydropyridine active
 pharmaceutical ingredients.
;
_journal_coeditor_code           RM5073SUP1
_journal_issue                   1
_journal_name_full
'Acta crystallographica Section B, Structural science, crystal engineering and materials'
_journal_page_first              4
_journal_page_last               12
_journal_paper_doi               10.1107/S2052520623010053
_journal_volume                  80
_journal_year                    2024
_chemical_formula_moiety         'C20 H24 N2 O6'
_chemical_formula_sum            'C20 H24 N2 O6'
_chemical_formula_weight         388.41
_chemical_name_common            nisoldipine
_chemical_name_systematic
;          
 (rac)-3-isobutyl 5-methyl 2,6-dimethyl-4-(2-nitrophenyl) 
-1,4-dihydropyridine-3,5-dicarboxylate
;
_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_creation_date             2023-12-07
_audit_creation_method
; 
Olex2 1.5 
(compiled 2023.08.24 svn.re1ec1418 for OlexSys, GUI svn.r6817) 
;
_cell_angle_alpha                90
_cell_angle_beta                 102.5280(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   10.78620(10)
_cell_length_b                   15.63200(10)
_cell_length_c                   11.92410(10)
_cell_measurement_reflns_used    9651
_cell_measurement_temperature    100
_cell_measurement_theta_max      39.538
_cell_measurement_theta_min      2.560
_cell_volume                     1962.65(3)
_computing_cell_refinement       'APEX3 v2017.3-0 (Bruker AXS Inc., 2017)'
_computing_data_collection       'GDA 8.44; generic data acquisition software'
_computing_data_reduction        'SAINT V8.38A (Bruker AXS Inc., 2017)'
_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      100
_diffrn_detector                 'Photon counting pixel array'
_diffrn_detector_area_resol_mean 0.0350
_diffrn_detector_type            'Dectris Pilatus 2M'
_diffrn_measured_fraction_theta_full 0.994
_diffrn_measured_fraction_theta_max 0.963
_diffrn_measurement_device       'Fixed \c 3-circle diffractometer'
_diffrn_measurement_device_type  'Fluid Film Devices'
_diffrn_measurement_method       '\f and \w rotation with 0.1 degree frames'
_diffrn_measurement_specimen_support 'MiTeGen MicroMount'
_diffrn_radiation_collimation    '0.3 x 1.5 Double Pinhole'
_diffrn_radiation_monochromator  'Silicon 111'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           Synchrotron
_diffrn_radiation_wavelength     1.0402
_diffrn_reflns_av_R_equivalents  0.0312
_diffrn_reflns_av_unetI/netI     0.0201
_diffrn_reflns_Laue_measured_fraction_full 0.994
_diffrn_reflns_Laue_measured_fraction_max 0.963
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       19
_diffrn_reflns_limit_k_min       -19
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            15426
_diffrn_reflns_point_group_measured_fraction_full 0.994
_diffrn_reflns_point_group_measured_fraction_max 0.963
_diffrn_reflns_theta_full        38.618
_diffrn_reflns_theta_max         40.045
_diffrn_reflns_theta_min         3.194
_diffrn_source                   Synchrotron
_diffrn_source_type              'Undulator, I19, DLS, RAL'
_exptl_absorpt_coefficient_mu    0.251
_exptl_absorpt_correction_T_max  0.7528
_exptl_absorpt_correction_T_min  0.6634
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction.'
_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    1.314
_exptl_crystal_description       needle
_exptl_crystal_F_000             824
_exptl_crystal_preparation
'Crystallised from a saturated solution of nisoldipine in MIBK.'
_exptl_crystal_recrystallization_method
'High-throughput screeining via ENaCt protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.21
_exptl_crystal_size_mid          0.03
_exptl_crystal_size_min          0.02
_refine_diff_density_max         0.689
_refine_diff_density_min         -0.213
_refine_diff_density_rms         0.052
_refine_ls_extinction_coef       0.0066(8)
_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   1.045
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     263
_refine_ls_number_reflns         3749
_refine_ls_number_restraints     210
_refine_ls_restrained_S_all      1.016
_refine_ls_R_factor_all          0.0464
_refine_ls_R_factor_gt           0.0451
_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^)+(0.0654P)^2^+1.0715P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1248
_refine_ls_wR_factor_ref         0.1258
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3554
_reflns_number_total             3749
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            rm5073sup1.cif
_cod_data_source_block           nisoldipine
_cod_depositor_comments
'Adding full bibliography for 2312368--2312375.cif.'
_cod_database_code               2312371
_cod_database_fobs_code          2312371
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.994
_shelx_estimated_absorpt_t_min   0.943
_olex2_refinement_description
; 
1. Fixed Uiso 
 At 1.2 times of: 
  All C(H) groups, All C(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 Ternary CH refined with riding coordinates: 
 C9(H9), C18(H18) 
3.b Secondary CH2 refined with riding coordinates: 
 C17(H17A,H17B) 
3.c Aromatic/amide H refined with riding coordinates: 
 C12(H12), C13(H13), C14(H14), C15(H15) 
3.d Idealised Me refined as rotating group: 
 C1(H1A,H1B,H1C), C7(H7A,H7B,H7C), C5(H5A,H5B,H5C), C19(H19A,H19B,H19C), 
 C20(H20A,H20B,H20C) 
;
_shelx_res_checksum              3490
_shelx_hkl_checksum              87649
_olex2_exptl_crystal_mounting_method
; 
 'Crystals mounted using inert oils following encapsulation  
using MiTeGen kapton micomounts.' 
;
_olex2_submission_original_sample_id nisoldipine
_olex2_submission_special_instructions 'No special instructions were received'