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_2312372
_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         'C18 H20 N2 O6'
_chemical_formula_sum            'C18 H20 N2 O6'
_chemical_formula_weight         360.36
_chemical_name_common            nitrendipine
_chemical_name_systematic
;       
 (rac)-3-ethyl 5-methyl 2,6-dimethyl-4-(3-nitrophenyl) 
-1,4-dihydropyridine-3,5-dicarboxylate
;
_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_creation_date             2023-05-11
_audit_creation_method
; 
Olex2 1.5 
(compiled 2023.03.06 svn.rbb2c1857 for OlexSys, GUI svn.r6748) 
;
_cell_angle_alpha                90
_cell_angle_beta                 93.615(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.8143(5)
_cell_length_b                   15.3632(8)
_cell_length_c                   12.9602(7)
_cell_measurement_reflns_used    9981
_cell_measurement_temperature    150.00
_cell_measurement_theta_max      66.73
_cell_measurement_theta_min      4.47
_cell_volume                     1751.52(16)
_computing_cell_refinement       'SAINT V8.40B (?, 2016)'
_computing_data_collection       'Bruker Instrument Service v6.2.6'
_computing_data_reduction        'SAINT V8.40B (?, 2016)'
_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      150.0
_diffrn_detector                 'Bruker Photon II area detector'
_diffrn_detector_area_resol_mean 7.3910
_diffrn_detector_type            'Hybrid area detector'
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 1.000
_diffrn_measurement_device       'three-circle diffractometer'
_diffrn_measurement_device_type  'Bruker D8 Venture'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_orient_matrix_type       'Bruker AXS Inc. convention APEX3'
_diffrn_radiation_collimation    'focussed source'
_diffrn_radiation_monochromator  'mirror optics'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0427
_diffrn_reflns_av_unetI/netI     0.0254
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 1.000
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -18
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            21238
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 1.000
_diffrn_reflns_theta_full        66.732
_diffrn_reflns_theta_max         66.731
_diffrn_reflns_theta_min         4.468
_diffrn_source                   'microfocus sealed X-ray tube'
_diffrn_source_current           1.0
_diffrn_source_power             0.05
_diffrn_source_target            Cu
_diffrn_source_type
; 
'Incoatec microfocus 3.0 (cu) X-ray Source' 
;
_diffrn_source_voltage           50.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.868
_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. 
wR2(int) was 0.1443 before and 0.0747 after correction. 
The Ratio of minimum to maximum transmission is 0.8812. 
The \l/2 correction factor is Not present. 
;
_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    1.367
_exptl_crystal_description       plate
_exptl_crystal_F_000             760
_exptl_crystal_preparation
'Crystallised from a saturated solution of nitrendipine in DMF.'
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.56
_exptl_crystal_size_mid          0.43
_exptl_crystal_size_min          0.12
_refine_diff_density_max         0.394
_refine_diff_density_min         -0.267
_refine_diff_density_rms         0.048
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.052
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     243
_refine_ls_number_reflns         3107
_refine_ls_number_restraints     195
_refine_ls_restrained_S_all      1.022
_refine_ls_R_factor_all          0.0611
_refine_ls_R_factor_gt           0.0569
_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^)+(0.0750P)^2^+1.0941P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1517
_refine_ls_wR_factor_ref         0.1557
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2820
_reflns_number_total             3107
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            rm5073sup1.cif
_cod_data_source_block           nitrendipine
_cod_depositor_comments
'Adding full bibliography for 2312368--2312375.cif.'
_cod_database_code               2312372
_cod_database_fobs_code          2312372
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.903
_shelx_estimated_absorpt_t_min   0.642
_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: 
 C10(H10) 
3.b Secondary CH2 refined with riding coordinates: 
 C2(H2A,H2B) 
3.c Aromatic/amide H refined with riding coordinates: 
 C16(H16), C12(H12), C14(H14), C15(H15) 
3.d Idealised Me refined as rotating group: 
 C6(H6A,H6B,H6C), C8(H8A,H8B,H8C), C1A(H1AA,H1AB,H1AC), C18A(H18A,H18B,H18C) 
;
_shelx_res_checksum              52999
_shelx_hkl_checksum              80907
_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 Nitrendipine
_olex2_submission_special_instructions 'No special instructions were received'