Towards understanding P-gp resistance: a case study of the antitumour drug cabazitaxel
Baisch, U.; Vella-Zarb, L.; CrystEngComm 16 (2014) 10161–; doi:10.1039/C4CE01279H

data_7217308
_publ_section_title
;
 Towards understanding P-gp resistance: a case study of the antitumour
 drug cabazitaxel
;
_journal_issue                   44
_journal_name_full               CrystEngComm
_journal_page_first              10161
_journal_paper_doi               10.1039/C4CE01279H
_journal_volume                  16
_journal_year                    2014
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C45 H57 N O14, C2 H5 O, 0.5(H2 O)'
_chemical_formula_sum            'C47 H63 N O15.5'
_chemical_formula_weight         889.98
_chemical_name_systematic        'Cabazitaxel ethanol solvate hemihydrate'
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2014-07-20
_audit_creation_method
;
Olex2 1.2
(compiled 2014.06.27 svn.r2953 for OlexSys, GUI svn.r4855)
;
_cell_angle_alpha                90
_cell_angle_beta                 89.987(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   12.542(2)
_cell_length_b                   8.6716(16)
_cell_length_c                   42.090(8)
_cell_measurement_reflns_used    9895
_cell_measurement_temperature    120.15
_cell_measurement_theta_max      24.858
_cell_measurement_theta_min      2.462
_cell_volume                     4577.7(14)
_computing_data_reduction        'SAINT v7.68A (Bruker, 2009)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2008)'
_computing_structure_solution    'XM (Sheldrick, 2008)'
_diffrn_ambient_temperature      120.15
_diffrn_detector                 'CCD area detector'
_diffrn_detector_area_resol_mean 0.0350
_diffrn_detector_type            'Rigaku Saturn724+'
_diffrn_measured_fraction_theta_full 0.958
_diffrn_measured_fraction_theta_max 0.972
_diffrn_measurement_device       'CrystalLogic Kappa (4 circle)'
_diffrn_measurement_device_type  'Kappa Rigaku Saturn724+'
_diffrn_measurement_method       'omega rotation'
_diffrn_radiation_collimation    '0.3 x 1.5 Double Pinhole'
_diffrn_radiation_monochromator  Synchrotron
_diffrn_radiation_probe          x-ray
_diffrn_radiation_wavelength     0.6889
_diffrn_reflns_av_R_equivalents  0.0315
_diffrn_reflns_av_unetI/netI     0.0389
_diffrn_reflns_Laue_measured_fraction_full 0.958
_diffrn_reflns_Laue_measured_fraction_max 0.972
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -8
_diffrn_reflns_limit_l_max       51
_diffrn_reflns_limit_l_min       -51
_diffrn_reflns_number            36815
_diffrn_reflns_point_group_measured_fraction_full 0.854
_diffrn_reflns_point_group_measured_fraction_max 0.867
_diffrn_reflns_theta_full        25.000
_diffrn_reflns_theta_max         24.863
_diffrn_reflns_theta_min         0.938
_diffrn_source                   Synchrotron
_diffrn_source_type              'Undulator, I19, DLS, RAL'
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.090
_exptl_absorpt_correction_T_max  0.7451
_exptl_absorpt_correction_T_min  0.6221
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2008/1 (Bruker,2008) was used for absorption correction.
wR2(int) was 0.0697 before and 0.0489 after correction.
The Ratio of minimum to maximum transmission is 0.8349.
The \l/2 correction factor is 0.0015.
;
_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    1.291
_exptl_crystal_description       plank
_exptl_crystal_F_000             1904
_exptl_crystal_recrystallization_method 'Re-crystallisation from solvent: '
_exptl_crystal_size_max          0.2
_exptl_crystal_size_mid          0.05
_exptl_crystal_size_min          0.001
_refine_diff_density_max         0.366
_refine_diff_density_min         -0.266
_refine_diff_density_rms         0.048
_refine_ls_abs_structure_details
;
 Flack x determined using 5441 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   0.35(17)
_refine_ls_extinction_coef       0.073(6)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     SHELXL
_refine_ls_goodness_of_fit_ref   1.101
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     1281
_refine_ls_number_reflns         15163
_refine_ls_number_restraints     2
_refine_ls_restrained_S_all      1.101
_refine_ls_R_factor_all          0.0575
_refine_ls_R_factor_gt           0.0549
_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^)+(0.0622P)^2^+2.9619P]
 where P=(Fo^2^+2Fc^2^)/3
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1430
_refine_ls_wR_factor_ref         0.1456
_reflns_Friedel_coverage         0.666
_reflns_Friedel_fraction_full    0.735
_reflns_Friedel_fraction_max     0.746
_reflns_number_gt                14383
_reflns_number_total             15163
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c4ce01279h2.cif
_cod_data_source_block           940085_EtW
_cod_depositor_comments
'Adding full bibliography for 7217306--7217310.cif.'
_cod_original_formula_sum        'C47 H63 N O15.50'
_cod_database_code               7217308
_shelxl_version_number           2013-2
_shelx_estimated_absorpt_t_max   1.000
_shelx_estimated_absorpt_t_min   0.982
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All C(H,H,H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups, All O(H,H) groups
2. Restrained distances
 O22-H22
 0.85 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
Uanis(C81) = Uanis(C81A)
Uanis(O93) = Uanis(O93A)
Uanis(C91A) = Uanis(C91)
Uanis(O39) = Uanis(O38)
Uanis(C39) = Uanis(C38)
Uanis(O83) = Uanis(O83A)
Uanis(C13A) = Uanis(C139)
4. Others
 Sof(H10A)=Sof(C39)=Sof(H39A)=Sof(H39B)=Sof(H39C)=Sof(O38)=1-FVAR(1)
 Sof(H10)=Sof(C38)=Sof(H38A)=Sof(H38B)=Sof(H38C)=Sof(O39)=FVAR(1)
 Sof(C13A)=Sof(H13G)=Sof(H13H)=Sof(H13I)=1-FVAR(2)
 Sof(C139)=Sof(H13D)=Sof(H13E)=Sof(H13F)=FVAR(2)
 Sof(C81)=Sof(H81A)=Sof(H81B)=1-FVAR(3)
 Sof(H80)=Sof(O83A)=Sof(H83A)=0.5*(1-FVAR(4))
 Sof(H80A)=Sof(O83)=Sof(H83)=0.5*FVAR(4)
 Sof(C81A)=Sof(H81C)=Sof(H81D)=FVAR(3)
 Sof(C91)=Sof(H91A)=Sof(H91B)=1-FVAR(4)
 Sof(H90)=Sof(O93)=Sof(H92E)=0.5*(1-FVAR(5))
 Sof(H90A)=Sof(O93A)=Sof(H93A)=0.5*FVAR(5)
 Sof(C91A)=Sof(H91C)=Sof(H91D)=FVAR(4)
 Sof(H7A)=Sof(O23B)=1-FVAR(5)
 Sof(H7B)=Sof(O23A)=FVAR(5)
 Sof(C23B)=Sof(H23D)=Sof(H23E)=Sof(H23F)=1-FVAR(6)
 Sof(C23A)=Sof(H23A)=Sof(H23B)=Sof(H23C)=FVAR(6)
 Sof(H110)=Sof(O13A)=1-FVAR(7)
 Sof(H11A)=Sof(O138)=FVAR(7)
 Sof(H107)=Sof(O12A)=1-FVAR(8)
 Sof(H10D)=Sof(O123)=FVAR(8)
 Sof(C12A)=Sof(H12C)=Sof(H12D)=Sof(H12E)=1-FVAR(9)
 Sof(C123)=Sof(H12F)=Sof(H12G)=Sof(H12H)=FVAR(9)
 Fixed Sof: O80(0.5) O90(0.5) H92A(0.5) H92B(0.5) H92C(0.5) H92D(0.5)
 O100(0.5) H10E(0.5) H10F(0.5) O101(0.5) H10G(0.5) H10H(0.5)
5.a Free rotating group:
 O100(H10E,H10F), O101(H10G,H10H)
5.b Ternary CH refined with riding coordinates:
 C2(H2), C3(H3), C5(H5), C7(H7B), C7(H7A), C10(H10), C10(H10A), C13(H13),
 C45(H45), C47(H47), C102(H102), C103(H103), C105(H105), C107(H107), C107(H10D),
  C110(H11A), C110(H110), C113(H113), C145(H145), C147(H147)
5.c Secondary CH2 refined with riding coordinates:
 C6(H6A,H6B), C14(H14A,H14B), C20(H20A,H20B), C106(H10B,H10C), C114(H11B,H11C),
  C120(H12A,H12B), C81(H81A,H81B), C82(H82A,H82B), C81A(H81C,H81D), C92(H92A,
 H92B), C92(H92C,H92D), C91(H91A,H91B), C91A(H91C,H91D)
5.d Aromatic/amide H refined with riding coordinates:
 C29(H29), C30(H30), C31(H31), C32(H32), C33(H33), C49(H49), C50(H50),
 C51(H51), C52(H52), C53(H53), N54(H54), C129(H129), C130(H130), C131(H131),
 C132(H132), C133(H133), C149(H149), C150(H150), C151(H151), C152(H152),
 C153(H153), N154(H154)
5.e Tetrahedral OH refined with riding coordinates:
 O80(H80), O80(H80A), O83A(H83A), O83(H83), O90(H90), O90(H90A), O93(H92E),
 O93A(H93A)
5.f Idealised Me refined as rotating group:
 C16(H16A,H16B,H16C), C17(H17A,H17B,H17C), C18(H18A,H18B,H18C), C19(H19A,H19B,
 H19C), C23A(H23A,H23B,H23C), C37(H37A,H37B,H37C), C39(H39A,H39B,H39C),
 C38(H38A,H38B,H38C), C59(H59A,H59B,H59C), C60(H60A,H60B,H60C), C61(H61A,H61B,
 H61C), C116(H11D,H11E,H11F), C117(H11G,H11H,H11I), C118(H11J,H11K,H11L),
 C119(H11M,H11N,H11O), C12A(H12C,H12D,H12E), C137(H13A,H13B,H13C), C139(H13D,
 H13E,H13F), C13A(H13G,H13H,H13I), C159(H15A,H15B,H15C), C160(H16D,H16E,H16F),
 C161(H16G,H16H,H16I), C23B(H23D,H23E,H23F), C123(H12F,H12G,H12H)
5.g Idealised tetrahedral OH refined as rotating group:
 O22(H22), O46(H46), O122(H122), O146(H146)
;
_olex2_computing_structure_refinement_long 'ShelXL (Sheldrick, 2008)'
_olex2_submission_special_instructions 'No special instructions were received'