Quantum chemistry calculation-aided structural optimization of combretastatin A-4-like tubulin polymerization inhibitors: improved stability and biological activity.
Jiang, Junhang; Zheng, Canhui; Zhu, Kongkai; Liu, Jia; Sun, Nannan; Wang, Chongqing; Jiang, Hualiang; Zhu, Ju; Luo, Cheng; Zhou, Youjun; Journal of medicinal chemistry 58 (2015) 2538–2546; doi:10.1021/acs.jmedchem.5b00118

data_1553249
_publ_section_title
;
 Quantum chemistry calculation-aided structural optimization of
 combretastatin A-4-like tubulin polymerization inhibitors: improved
 stability and biological activity.
;
_journal_issue                   5
_journal_name_full               'Journal of medicinal chemistry'
_journal_page_first              2538
_journal_page_last               2546
_journal_paper_doi               10.1021/acs.jmedchem.5b00118
_journal_volume                  58
_journal_year                    2015
_chemical_formula_sum            'C21 H24 O5'
_chemical_formula_weight         356.40
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_atom_sites_solution_hydrogens   mixed
_audit_creation_method           SHELXL-2013
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   4.96530(10)
_cell_length_b                   10.6228(2)
_cell_length_c                   34.2129(6)
_cell_measurement_reflns_used    5368
_cell_measurement_temperature    173(2)
_cell_measurement_theta_max      68.79
_cell_measurement_theta_min      2.58
_cell_volume                     1804.57(6)
_computing_cell_refinement       'Bruker SAINT'
_computing_data_collection       'Bruker APEX2'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-2013 (Sheldrick, 2013)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 2008)'
_diffrn_ambient_temperature      173(2)
_diffrn_measured_fraction_theta_full 0.975
_diffrn_measured_fraction_theta_max 0.976
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0522
_diffrn_reflns_av_unetI/netI     0.0545
_diffrn_reflns_Laue_measured_fraction_full 0.975
_diffrn_reflns_Laue_measured_fraction_max 0.976
_diffrn_reflns_limit_h_max       5
_diffrn_reflns_limit_h_min       -4
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       37
_diffrn_reflns_limit_l_min       -41
_diffrn_reflns_number            9057
_diffrn_reflns_point_group_measured_fraction_full 0.972
_diffrn_reflns_point_group_measured_fraction_max 0.972
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         67.972
_diffrn_reflns_theta_min         2.583
_exptl_absorpt_coefficient_mu    0.759
_exptl_absorpt_correction_T_max  0.753
_exptl_absorpt_correction_T_min  0.376
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   sadabs
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.312
_exptl_crystal_description       prism
_exptl_crystal_F_000             760
_exptl_crystal_size_max          0.230
_exptl_crystal_size_mid          0.090
_exptl_crystal_size_min          0.080
_refine_diff_density_max         0.244
_refine_diff_density_min         -0.314
_refine_diff_density_rms         0.063
_refine_ls_abs_structure_details
; 
 Flack x determined using 1207 quotients [(I+)-(I-)]/[(I+)+(I-)] 
 (Parsons and Flack (2004), Acta Cryst. A60, s61). 
;
_refine_ls_abs_structure_Flack   0.27(11)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.103
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     243
_refine_ls_number_reflns         3167
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.103
_refine_ls_R_factor_all          0.0462
_refine_ls_R_factor_gt           0.0446
_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^)+(0.0728P)^2^+0.1800P] 
 where P=(Fo^2^+2Fc^2^)/3 
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1147
_refine_ls_wR_factor_ref         0.1163
_reflns_Friedel_coverage         0.669
_reflns_Friedel_fraction_full    0.966
_reflns_Friedel_fraction_max     0.967
_reflns_number_gt                3051
_reflns_number_total             3167
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jm5b00118_si_002.cif
_cod_data_source_block           cu30524a
_cod_database_code               1553249
_shelx_estimated_absorpt_t_min   0.845
_shelx_estimated_absorpt_t_max   0.942
_shelxl_version_number           2013-2
_shelx_res_checksum              18982
_shelx_hkl_checksum              26081