Design, synthesis and evaluation of multi-pharmacophore-containing spiropolycyclic harmaline-based hybrids as anticancer agents
Chen, Shuang; Yu, Ze-Hua; Wang, Wei-Na; Chen, Zi-Yue; Pan, Bo-Wen; Chen, Lin; Zhou, Ying; Liu, Xiong-Wei; Liu, Xiong-Li; New Journal of Chemistry 47 (2023) 6073–6085; doi:10.1039/D2NJ05987H

data_7062296
_publ_section_title
;
 Design, synthesis and evaluation of multi-pharmacophore-containing
 spiropolycyclic harmaline-based hybrids as anticancer agents
;
_journal_issue                   13
_journal_name_full               'New Journal of Chemistry'
_journal_page_first              6073
_journal_page_last               6085
_journal_paper_doi               10.1039/D2NJ05987H
_journal_volume                  47
_journal_year                    2023
_chemical_formula_moiety         'C25 H26 N4 O S'
_chemical_formula_sum            'C25 H26 N4 O S'
_chemical_formula_weight         430.56
_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   geom
_atom_sites_solution_primary     direct
_audit_creation_date             2022-06-02
_audit_creation_method
;
Olex2 1.5-beta
(compiled 2021.12.09 svn.r5202d8cf for OlexSys, GUI svn.r6439)
;
_audit_update_record
;
2022-08-02 deposited with the CCDC.	2023-02-16 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 98.5160(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   13.01620(10)
_cell_length_b                   15.4077(2)
_cell_length_c                   11.23150(10)
_cell_measurement_reflns_used    12596
_cell_measurement_temperature    295.55(10)
_cell_measurement_theta_max      75.6130
_cell_measurement_theta_min      2.8950
_cell_volume                     2227.64(4)
_computing_cell_refinement       'CrysAlisPro 1.171.40.84a (Rigaku OD, 2020)'
_computing_data_collection       'CrysAlisPro 1.171.40.84a (Rigaku OD, 2020)'
_computing_data_reduction        'CrysAlisPro 1.171.40.84a (Rigaku OD, 2020)'
_computing_molecular_graphics    'Olex2 1.5-beta (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5-beta (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2017/1 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXS  (Sheldrick, 2008)'
_diffrn_ambient_environment      air
_diffrn_ambient_temperature      295.55(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.961
_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     -4.00  21.00   0.50    0.34    --  -43.18 100.00 172.00   50
  2  \w    -70.00 -44.00   0.50    0.34    --  -43.18 100.00 172.00   52
  3  \w      2.00  76.00   0.50    0.34    --   43.18-100.00  67.00  148
  4  \w    -72.00 -47.00   0.50    0.70    --  -90.25 100.00 172.00   50
  5  \w     45.00  99.00   0.50    0.70    --  109.26-100.00  67.00  108
  6  \w    108.00 134.00   0.50    0.70    --  109.26 100.00 172.00   52
  7  \w    -20.00  31.00   0.50    0.34    --  -43.18  19.00 -90.00  102
  8  \w    -26.00  17.00   0.50    0.34    --  -43.18  19.00-120.00   86
  9  \w    -72.00  27.00   0.50    0.34    --  -43.18  77.00 -30.00  198
 10  \w    -45.00 -14.00   0.50    0.70    --  -90.25  45.00  30.00   62
 11  \w    -48.00 -19.00   0.50    0.70    --  -90.25  61.00   0.00   58
 12  \w   -142.00 -92.00   0.50    0.70    --  -90.25-100.00  67.00  100
 13  \w   -162.00-137.00   0.50    0.70    --  -90.25 -94.00  30.00   50
 14  \w   -131.00-105.00   0.50    0.70    --  -90.25 -94.00  30.00   52
 15  \w    -50.00 -14.00   0.50    0.70    --  -90.25  45.00 120.00   72
 16  \w    -48.00 -17.00   0.50    0.70    --  -90.25  45.00-150.00   62
 17  \w     37.00  77.00   0.50    0.70    --  109.26-125.00 -60.00   80
 18  \w     35.00  96.00   0.50    0.70    --  109.26 -77.00 120.00  122
 19  \w     87.00 173.00   0.50    0.70    --  109.26  45.00  90.00  172
 20  \w     36.00  65.00   0.50    0.70    --  109.26 -61.00-150.00   58
 21  \w     46.00  71.00   0.50    0.70    --  109.26 -61.00-120.00   50
 22  \w     42.00 103.00   0.50    0.70    --  109.26 -94.00  90.00  122
 23  \w     39.00  71.00   0.50    0.70    --  109.26 -61.00 120.00   64
 24  \w     35.00  70.00   0.50    0.70    --  109.26 -61.00   0.00   70
 25  \w     35.00  60.00   0.50    0.70    --  109.26 -61.00 -60.00   50
 26  \w     36.00  68.00   0.50    0.70    --  109.26 -61.00-180.00   64
 27  \w     72.00  98.00   0.50    0.70    --  109.26 -94.00 120.00   52
 28  \w     40.00  68.00   0.50    0.70    --  109.26 -61.00 -90.00   56
 29  \w     81.00 107.00   0.50    0.70    --  109.26-125.00 -60.00   52
 30  \w     40.00  69.00   0.50    0.70    --  109.26 -61.00  90.00   58
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.1018122000
_diffrn_orient_matrix_UB_12      -0.0477885000
_diffrn_orient_matrix_UB_13      0.0129112000
_diffrn_orient_matrix_UB_21      -0.0622954000
_diffrn_orient_matrix_UB_22      0.0824500000
_diffrn_orient_matrix_UB_23      -0.0412222000
_diffrn_orient_matrix_UB_31      -0.0089038000
_diffrn_orient_matrix_UB_32      -0.0304098000
_diffrn_orient_matrix_UB_33      -0.1316718000
_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  0.0255
_diffrn_reflns_av_unetI/netI     0.0227
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.961
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -19
_diffrn_reflns_limit_l_max       9
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            15536
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.961
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.652
_diffrn_reflns_theta_min         3.433
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.478
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.69745
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.84a (Rigaku Oxford Diffraction, 2020)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.284
_exptl_crystal_description       block
_exptl_crystal_F_000             912
_exptl_crystal_size_max          0.14
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.11
_refine_diff_density_max         0.228
_refine_diff_density_min         -0.386
_refine_diff_density_rms         0.082
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.172
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     283
_refine_ls_number_reflns         4442
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.172
_refine_ls_R_factor_all          0.0438
_refine_ls_R_factor_gt           0.0422
_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^)+(0.0526P)^2^+0.5553P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1081
_refine_ls_wR_factor_ref         0.1092
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4154
_reflns_number_total             4442
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d2nj05987h2.cif
_cod_data_source_block           mme-15_2
_cod_depositor_comments
'Adding full bibliography for 7062295--7062296.cif.'
_cod_database_code               7062296
_shelx_shelxl_version_number     2017/1
_chemical_oxdiff_formula         'C100 H96 Cl4 N16 O4 '
_shelx_estimated_absorpt_t_max   0.854
_shelx_estimated_absorpt_t_min   0.820
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2.a Secondary CH2 refined with riding coordinates:
 C10(H10A,H10B), C11(H11A,H11B), C26(H26A,H26B), C30(H30A,H30B)
2.b Aromatic/amide H refined with riding coordinates:
 N1(H1), N3(H3), C13(H13), C14(H14), C15(H15), C16(H16), C18(H18), C19(H19),
 C21(H21)
2.c Idealised Me refined as rotating group:
 C27(H27A,H27B,H27C), C28(H28A,H28B,H28C), C31(H31A,H31B,H31C)
;
_shelx_res_checksum              16342
_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 1.433
_oxdiff_exptl_absorpt_empirical_full_min 0.563