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_2312375
_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         'C2 H6 O S, C21 H26 N2 O7'
_chemical_formula_sum            'C23 H32 N2 O8 S'
_chemical_formula_weight         496.56
_chemical_name_common            'nimodipine DMSO'
_chemical_name_systematic
;          
(rac)-3-isopropyl 5-(2-methoxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)- 
1,4-dihydropyridine-3,5-dicarboxylate
;
_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_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                63.606(2)
_cell_angle_beta                 77.493(2)
_cell_angle_gamma                89.029(2)
_cell_formula_units_Z            2
_cell_length_a                   9.5050(8)
_cell_length_b                   11.8650(10)
_cell_length_c                   12.7533(10)
_cell_measurement_reflns_used    9949
_cell_measurement_temperature    150.01
_cell_measurement_theta_max      66.46
_cell_measurement_theta_min      6.00
_cell_volume                     1252.59(18)
_computing_cell_refinement       'APEX3 v2017.3-0 (Bruker AXS Inc., 2017)'
_computing_data_collection       'Bruker Instrument Service v6.2.6'
_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      150.01
_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 0.987
_diffrn_measured_fraction_theta_max 0.987
_diffrn_measurement_device       'three-circle diffractometer'
_diffrn_measurement_device_type  'Bruker D8 Venture'
_diffrn_measurement_method       '\w and \f 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  0.0333
_diffrn_reflns_av_unetI/netI     0.0287
_diffrn_reflns_Laue_measured_fraction_full 0.987
_diffrn_reflns_Laue_measured_fraction_max 0.987
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            19742
_diffrn_reflns_point_group_measured_fraction_full 0.987
_diffrn_reflns_point_group_measured_fraction_max 0.987
_diffrn_reflns_theta_full        66.683
_diffrn_reflns_theta_max         66.682
_diffrn_reflns_theta_min         3.979
_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    1.571
_exptl_absorpt_correction_T_max  0.7528
_exptl_absorpt_correction_T_min  0.6351
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
; 
SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. 
wR2(int) was 0.0786 before and 0.0589 after correction. 
The Ratio of minimum to maximum transmission is 0.8437. 
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    1.317
_exptl_crystal_description       plate
_exptl_crystal_F_000             528
_exptl_crystal_preparation
'Crystallised from a saturated solution of nimodipine in DMSO.'
_exptl_crystal_recrystallization_method
'High-throughput screening via the ENaCt protocol using SPT Labtech mosquito.'
_exptl_crystal_size_max          0.45
_exptl_crystal_size_mid          0.34
_exptl_crystal_size_min          0.088
_refine_diff_density_max         0.445
_refine_diff_density_min         -0.316
_refine_diff_density_rms         0.046
_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     394
_refine_ls_number_reflns         4381
_refine_ls_number_restraints     375
_refine_ls_restrained_S_all      1.006
_refine_ls_R_factor_all          0.0517
_refine_ls_R_factor_gt           0.0499
_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^)+(0.0608P)^2^+0.8920P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1303
_refine_ls_wR_factor_ref         0.1317
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4128
_reflns_number_total             4381
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            rm5073sup1.cif
_cod_data_source_block           nimodipine-dmso
_cod_depositor_comments
'Adding full bibliography for 2312368--2312375.cif.'
_cod_database_code               2312375
_cod_database_fobs_code          2312375
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.874
_shelx_estimated_absorpt_t_min   0.538
_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. Restrained distances 
 O1S-C1S \\sim C1R-O1R \\sim C1T-O1T \\sim O1S-C2S \\sim C2R-O1R \\sim C2T-O1T 
 with sigma of 0.02 
 C1S-C2S \\sim C2T-C1T \\sim C1R-C2R 
 with sigma of 0.02 
 S1R-O1R \\sim S1T-O1T \\sim S1S-O1S 
 with sigma of 0.02 
 S1S-C2S \\sim S1S-C1S \\sim S1R-C1R \\sim S1R-C2R \\sim S1T-C1T \\sim S1T-C2T 
 with sigma of 0.02 
 C2S-C1S \\sim C1R-C2R \\sim C2T-C1T 
 with sigma of 0.02 
3. Uiso/Uaniso restraints and constraints 
C1R \\sim C2T \\sim C2S \\sim C2R \\sim C1T \\sim C1S: within 2A with sigma of 
0.02 and sigma for terminal atoms of 0.04 within 2A 
O1S \\sim O1T \\sim O1R: within 2A with sigma of 0.02 and sigma for terminal 
atoms of 0.04 within 2A 
S1R \\sim S1S \\sim S1T: within 2A with sigma of 0.02 and sigma for terminal 
atoms of 0.04 within 2A 
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. Others 
 Fixed Sof: S1R(0.80603) O1R(0.80603) C1R(0.80603) H1RA(0.80603) H1RB(0.80603) 
 H1RC(0.80603) C2R(0.80603) H2RA(0.80603) H2RB(0.80603) H2RC(0.80603) 
 S1S(0.12188) O1S(0.12188) C1S(0.12188) H1SA(0.12188) H1SB(0.12188) 
 H1SC(0.12188) C2S(0.12188) H2SA(0.12188) H2SB(0.12188) H2SC(0.12188) 
 S1T(0.07209) C1T(0.07209) H1TA(0.07209) H1TB(0.07209) H1TC(0.07209) 
 C2T(0.07209) H2TA(0.07209) H2TB(0.07209) H2TC(0.07209) O1T(0.07209) 
6.a Ternary CH refined with riding coordinates: 
 C11(H11), C19(H19) 
6.b Secondary CH2 refined with riding coordinates: 
 C3(H3A,H3B), C2(H2A,H2B) 
6.c Aromatic/amide H refined with riding coordinates: 
 C13(H13), C17(H17), C15(H15), C16(H16) 
6.d Idealised Me refined as rotating group: 
 C9(H9A,H9B,H9C), C7(H7A,H7B,H7C), C20(H20A,H20B,H20C), C21(H21A,H21B,H21C), 
 C1(H1A,H1B,H1C), C1R(H1RA,H1RB,H1RC), C2R(H2RA,H2RB,H2RC), C1S(H1SA,H1SB,H1SC), 
  C2S(H2SA,H2SB,H2SC), C1T(H1TA,H1TB,H1TC), C2T(H2TA,H2TB,H2TC) 
;
_shelx_res_checksum              68769
_shelx_hkl_checksum              56028
_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 'Nimodipine DMSO solvate'
_olex2_submission_special_instructions 'No special instructions were received'