Inspiration for revival of old drugs: improving solubility and avoiding hygroscopicity of pipemidic acid by forming two pharmaceutical salts based on charge-assisted hydrogen bond recognitions
Zhang, Yunan; Duan, Yu; Su, Jin; Liu, Lixin; Feng, Yanru; Wu, Lili; Zhang, Lei; Zhang, Yunjie; Zou, Dongyu; Liu, Yingli; New Journal of Chemistry 45 (2021) 19704–19713; doi:10.1039/D1NJ03314J

data_7060969
_publ_section_title
;
 Inspiration for revival of old drugs: improving solubility and avoiding
 hygroscopicity of pipemidic acid by forming two pharmaceutical salts
 based on charge-assisted hydrogen bond recognitions
;
_journal_issue                   42
_journal_name_full               'New Journal of Chemistry'
_journal_page_first              19704
_journal_page_last               19713
_journal_paper_doi               10.1039/D1NJ03314J
_journal_volume                  45
_journal_year                    2021
_chemical_formula_moiety         'C14 H18 N5 O3, C7 H5 O3, C7 H6 O3, 2(H2 O)'
_chemical_formula_sum            'C28 H33 N5 O11'
_chemical_formula_weight         615.59
_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     direct
_audit_creation_date             2021-06-16
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2021-09-20 deposited with the CCDC.	2021-09-21 downloaded from the CCDC.
;
_cell_angle_alpha                106.133(8)
_cell_angle_beta                 103.719(7)
_cell_angle_gamma                96.363(7)
_cell_formula_units_Z            2
_cell_length_a                   8.0857(7)
_cell_length_b                   12.8969(12)
_cell_length_c                   15.2536(13)
_cell_measurement_reflns_used    2789
_cell_measurement_temperature    298(2)
_cell_measurement_theta_max      27.1420
_cell_measurement_theta_min      4.1350
_cell_volume                     1457.6(2)
_computing_data_collection       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXS (Sheldrick, 2008)'
_diffrn_ambient_temperature      298.15
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.819
_diffrn_measurement_device_type  'multiwire proportional'
_diffrn_measurement_method       'phi and omega scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0254
_diffrn_reflns_av_unetI/netI     0.0608
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.819
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            11385
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.819
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         29.533
_diffrn_reflns_theta_min         3.535
_exptl_absorpt_coefficient_mu    0.110
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.70914
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.41 (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.403
_exptl_crystal_description       block
_exptl_crystal_F_000             648
_exptl_crystal_size_max          0.14
_exptl_crystal_size_mid          0.13
_exptl_crystal_size_min          0.11
_refine_diff_density_max         0.239
_refine_diff_density_min         -0.227
_refine_diff_density_rms         0.044
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.028
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     418
_refine_ls_number_reflns         6655
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.028
_refine_ls_R_factor_all          0.1090
_refine_ls_R_factor_gt           0.0610
_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^)+(0.0456P)^2^+0.2682P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1135
_refine_ls_wR_factor_ref         0.1351
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4165
_reflns_number_total             6655
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d1nj03314j2.cif
_cod_data_source_block           1
_cod_depositor_comments
'Adding full bibliography for 7060968--7060969.cif.'
_cod_database_code               7060969
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.988
_shelx_estimated_absorpt_t_min   0.985
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups, All O(H,H) groups
2.a Free rotating group:
 O10(H10A,H10B), O11(H11A,H11B)
2.b Secondary CH2 refined with riding coordinates:
 N1(H1A,H1B), C1(H1C,H1D), C2(H2A,H2B), C3(H3A,H3B), C4(H4A,H4B), C13(H13A,H13B)
2.c Aromatic/amide H refined with riding coordinates:
 C6(H6), C9(H9), C17(H17), C18(H18), C19(H19), C24(H24), C26(H26), C27(H27),
 C28(H28)
2.d Idealised Me refined as rotating group:
 C14(H14A,H14B,H14C)
2.e Idealised tetrahedral OH refined as rotating group:
 O2(H2), O4(H4)
;
_shelx_res_checksum              13904
_olex2_submission_special_instructions 'No special instructions were received'