Synthesis and evaluation of antiproliferative microtubule-destabilising combretastatin A-4 piperazine conjugates.
O'Boyle, Niamh M; Ana, Gloria; Kelly, Patrick M.; Nathwani, Seema M.; Noorani, Sara; Fayne, Darren; Bright, Sandra A.; Twamley, Brendan; Zisterer, Daniela M.; Meegan, Mary J.; Organic & biomolecular chemistry 17 (2019) 6184–6200; doi:10.1039/c9ob00558g

data_7156882
_publ_section_title
;
 Synthesis and evaluation of antiproliferative microtubule-destabilising
 combretastatin A-4 piperazine conjugates.
;
_journal_issue                   25
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              6184
_journal_page_last               6200
_journal_paper_doi               10.1039/c9ob00558g
_journal_volume                  17
_journal_year                    2019
_chemical_formula_moiety         'C19 H20 O6'
_chemical_formula_sum            'C19 H20 O6'
_chemical_formula_weight         344.35
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_symmetry_space_group_name_Hall  '-P 1'
_symmetry_space_group_name_H-M   'P -1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2017-10-23
_audit_creation_method
;
Olex2 1.2
(compiled 2017.08.10 svn.r3458 for OlexSys, GUI svn.r5381)
;
_audit_update_record
;
2018-11-09 deposited with the CCDC.    2019-05-28 downloaded from the CCDC.
;
_cell_angle_alpha                99.235(2)
_cell_angle_beta                 90.839(2)
_cell_angle_gamma                93.211(2)
_cell_formula_units_Z            2
_cell_length_a                   7.7673(2)
_cell_length_b                   8.9291(3)
_cell_length_c                   12.6819(4)
_cell_measurement_reflns_used    3820
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      69.81
_cell_measurement_theta_min      5.03
_cell_volume                     866.54(5)
_computing_cell_refinement       'SAINT v8.37A (Bruker, 2015)'
_computing_data_collection       'APEX 3 (Bruker, 2016) '
_computing_data_reduction        'SAINT v8.37A (Bruker, 2015)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL (Sheldrick, 2008)'
_computing_structure_solution    'XT (Sheldrick, 2015)'
_diffrn_ambient_temperature      100(2)
_diffrn_detector                 'CCD area detector'
_diffrn_detector_area_resol_mean 7.9
_diffrn_detector_type            APEX2
_diffrn_measured_fraction_theta_full 0.993
_diffrn_measured_fraction_theta_max 0.979
_diffrn_measurement_device       'Kappa diffractometer'
_diffrn_measurement_device_type  'Bruker APEX2 Kappa Duo'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_detector       APEX2
_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  0.0415
_diffrn_reflns_av_unetI/netI     0.0450
_diffrn_reflns_Laue_measured_fraction_full 0.993
_diffrn_reflns_Laue_measured_fraction_max 0.979
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -10
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            9343
_diffrn_reflns_point_group_measured_fraction_full 0.993
_diffrn_reflns_point_group_measured_fraction_max 0.979
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         70.133
_diffrn_reflns_theta_min         3.532
_diffrn_source                   'microfocus sealed X-ray tube'
_diffrn_source_type              'Incoatec I\ms'
_exptl_absorpt_coefficient_mu    0.818
_exptl_absorpt_correction_T_max  0.7533
_exptl_absorpt_correction_T_min  0.6412
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.0655 before and 0.0533 after correction. The Ratio of minimum to maximum transmission is 0.8512. The \l/2 correction factor is Not present.'
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.320
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       plate
_exptl_crystal_F_000             364
_exptl_crystal_size_max          0.17
_exptl_crystal_size_mid          0.07
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.249
_refine_diff_density_min         -0.236
_refine_diff_density_rms         0.054
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.060
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     228
_refine_ls_number_reflns         3226
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.060
_refine_ls_R_factor_all          0.0686
_refine_ls_R_factor_gt           0.0518
_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^)+(0.0838P)^2^+0.1648P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1380
_refine_ls_wR_factor_ref         0.1501
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2438
_reflns_number_total             3226
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c9ob00558g3.cif
_cod_data_source_block           tcd910
_cod_depositor_comments          'Adding full bibliography for 7156882.cif.'
_cod_database_code               7156882
_shelx_shelxl_version_number     2014/7
_shelx_estimated_absorpt_t_max   0.960
_shelx_estimated_absorpt_t_min   0.873
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 O12-H12
 0.84 with sigma of 0.01
3. Uiso/Uaniso restraints and constraints
Uanis(C14) = Uanis(C15)
4.a Aromatic/amide H refined with riding coordinates:
 C4(H4), C5(H5), C7(H7), C8(H8), C9(H9), C15(H15), C19(H19)
4.b Idealised Me refined as rotating group:
 C1(H1A,H1B,H1C), C21(H21A,H21B,H21C), C23(H23A,H23B,H23C), C25(H25A,H25B,H25C)
;
_shelx_res_checksum              15017
_olex2_exptl_crystal_mounting_method 'mounted in oil on a MiTeGen holder'
_olex2_submission_original_sample_id SarahFitzpatrickSS
_olex2_submission_special_instructions 'No special instructions were received'