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_7217307
_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, 0.25(H2 O)'
_chemical_formula_sum            'C45 H57.5 N O14.25'
_chemical_formula_weight         840.42
_chemical_name_systematic        'Cabazitaxel 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             2014-03-01
_audit_creation_method
;
Olex2 1.2
(compiled 2014.02.28 svn.r2899 for OlexSys, GUI svn.r4781)
;
_cell_angle_alpha                90
_cell_angle_beta                 98.362(4)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.506(5)
_cell_length_b                   45.16(2)
_cell_length_c                   11.675(6)
_cell_measurement_reflns_used    9906
_cell_measurement_temperature    120.15
_cell_measurement_theta_max      24.356
_cell_measurement_theta_min      2.833
_cell_volume                     4437(4)
_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 0.817
_diffrn_measured_fraction_theta_max 0.843
_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  0.0698
_diffrn_reflns_av_unetI/netI     0.1116
_diffrn_reflns_Laue_measured_fraction_full 0.817
_diffrn_reflns_Laue_measured_fraction_max 0.843
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       53
_diffrn_reflns_limit_k_min       -47
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -9
_diffrn_reflns_number            20627
_diffrn_reflns_point_group_measured_fraction_full 0.649
_diffrn_reflns_point_group_measured_fraction_max 0.670
_diffrn_reflns_theta_full        25.000
_diffrn_reflns_theta_max         24.722
_diffrn_reflns_theta_min         2.623
_diffrn_source                   Synchrotron
_diffrn_source_type              'Undulator, I19, DLS, RAL'
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.088
_exptl_absorpt_correction_T_max  1.0000
_exptl_absorpt_correction_T_min  0.5944
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2008/1 (Bruker,2008) was used for absorption correction.
wR2(int) was 0.1377 before and 0.1001 after correction.
The Ratio of minimum to maximum transmission is 0.5944.
The \l/2 correction factor is Not present.
;
_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    1.258
_exptl_crystal_description       plate
_exptl_crystal_F_000             1794
_exptl_crystal_size_max          0.12
_exptl_crystal_size_mid          0.09
_exptl_crystal_size_min          0.02
_refine_diff_density_max         0.413
_refine_diff_density_min         -0.273
_refine_diff_density_rms         0.068
_refine_ls_abs_structure_details
;
 Flack x determined using 2246 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   0.4(8)
_refine_ls_extinction_coef       0.028(5)
_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   1.034
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     1118
_refine_ls_number_reflns         11168
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.034
_refine_ls_R_factor_all          0.1349
_refine_ls_R_factor_gt           0.1002
_refine_ls_shift/su_max          0.014
_refine_ls_shift/su_mean         0.002
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
;
 w=1/[\s^2^(Fo^2^)+(0.1261P)^2^+8.4207P]
 where P=(Fo^2^+2Fc^2^)/3
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2622
_refine_ls_wR_factor_ref         0.2838
_reflns_Friedel_coverage         0.568
_reflns_Friedel_fraction_full    0.477
_reflns_Friedel_fraction_max     0.492
_reflns_number_gt                7801
_reflns_number_total             11168
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c4ce01279h2.cif
_cod_data_source_block           940084_hemi
_cod_depositor_comments
'Adding full bibliography for 7217306--7217310.cif.'
_cod_original_cell_volume        4438(4)
_cod_original_formula_sum        'C45 H57.50 N O14.25'
_cod_database_code               7217307
_shelxl_version_number           2013-2
_shelx_estimated_absorpt_t_max   0.998
_shelx_estimated_absorpt_t_min   0.990
_olex2_refinement_description
;
1. Others
 Fixed Sof: O90(0.5) H90A(0.5) H90B(0.5)
 Fixed Uiso: H146(0.094) H122(0.081) H22(0.111) H54(0.084) H154(0.063)
 H103(0.061) H11A(0.056) H11B(0.056) H13A(0.086) H13B(0.086) H13C(0.086)
 H145(0.072) H11C(0.111) H11D(0.111) H11E(0.111) H113(0.064) H102(0.055)
 H153(0.086) H105(0.068) H38A(0.098) H38B(0.098) H38C(0.098) H147(0.06)
 H14A(0.07) H14B(0.07) H11F(0.094) H11G(0.094) H11H(0.094) H46(0.144)
 H12A(0.08) H12B(0.08) H149(0.072) H151(0.103) H47(0.079) H31(0.094) H13(0.066)
 H16G(0.115) H16H(0.115) H16I(0.115) H10(0.074) H11I(0.105) H11J(0.105)
 H11K(0.105) H110(0.065) H17A(0.141) H17B(0.141) H17C(0.141) H10A(0.094)
 H10B(0.094) H11L(0.126) H11M(0.126) H11N(0.126) H133(0.09) H20A(0.104)
 H20B(0.104) H15A(0.096) H15B(0.096) H15C(0.096) H150(0.1) H7(0.099) H3(0.074)
 H29(0.092) H33(0.084) H32(0.092) H45(0.088) H18A(0.121) H18B(0.121)
 H18C(0.121) H37A(0.122) H37B(0.122) H37C(0.122) H152(0.1) H19A(0.138)
 H19B(0.138) H19C(0.138) H129(0.101) H6A(0.103) H6B(0.103) H53(0.108)
 H61A(0.128) H61B(0.128) H61C(0.128) H107(0.071) H49(0.099) H16A(0.119)
 H16B(0.119) H16C(0.119) H2(0.091) H130(0.102) H30(0.118) H5(0.099) H16D(0.113)
 H16E(0.113) H16F(0.113) H90A(0.161) H90B(0.161) H131(0.115) H132(0.111)
 H50(0.122) H52(0.109) H51(0.122) H59A(0.16) H59B(0.16) H59C(0.16) H60A(0.217)
 H60B(0.217) H60C(0.217) H12C(0.18) H12D(0.18) H12E(0.18) H23A(0.191)
 H23B(0.191) H23C(0.191) H13D(0.148) H13E(0.148) H13F(0.148)
 Fixed X: H146(-0.9385) H122(-0.0698) H22(-1.2729) H54(-0.4924) H154(-0.7446)
 H103(-0.5839) H11A(-0.3353) H11B(-0.4662) H13A(-0.8008) H13B(-0.7038) H13C(-
 0.8923) H145(-0.9263) H11C(-0.2112) H11D(-0.1898) H11E(-0.0682) H113(-0.4723)
 H102(-0.2687) H153(-1.0517) H105(-0.8413) H38A(-0.8376) H38B(-0.9206) H38C(-
 0.7485) H147(-0.7094) H14A(-0.9792) H14B(-0.876) H11F(-0.8193) H11G(-0.7742)
 H11H(-0.7643) H46(-0.2203) H12A(-0.5068) H12B(-0.42) H149(-0.8069) H151(-1.21)
 H47(-0.6358) H31(-1.3015) H13(-0.8207) H16G(-1.1706) H16H(-1.2907) H16I(-
 1.1722) H10(-0.7366) H11I(-0.1108) H11J(-0.2113) H11K(-0.2853) H110(-0.6385)
 H17A(-1.0204) H17B(-1.2037) H17C(-1.0928) H10A(-0.778) H10B(-0.9207) H11L(-
 0.5074) H11M(-0.4779) H11N(-0.3479) H133(-0.0922) H20A(-0.9123) H20B(-1.0137)
 H15A(-0.2053) H15B(-0.1078) H15C(-0.2304) H150(-0.9865) H7(-0.6242) H3(-
 0.7881) H29(-1.3595) H33(-1.0681) H32(-1.1235) H45(-0.4116) H18A(-0.5381)
 H18B(-0.5757) H18C(-0.5211) H37A(-0.6415) H37B(-0.4579) H37C(-0.5339) H152(-
 1.2403) H19A(-1.0885) H19B(-0.9479) H19C(-0.9616) H129(-0.3354) H6A(-0.6759)
 H6B(-0.5153) H53(-0.5484) H61A(-0.7782) H61B(-0.9589) H61C(-0.9028) H107(-
 0.7786) H49(-0.3191) H16A(-0.3578) H16B(-0.2523) H16C(-0.4419) H2(-1.1193)
 H130(-0.326) H30(-1.4222) H5(-0.5828) H16D(-0.4345) H16E(-0.2467) H16F(-
 0.3155) H90A(-0.8503) H90B(-0.8843) H131(-0.2092) H132(-0.0819) H50(-0.1992)
 H52(-0.4234) H51(-0.2683) H59A(-0.7183) H59B(-0.8431) H59C(-0.6739) H60A(-
 1.0051) H60B(-1.0633) H60C(-0.9457) H12C(-0.9288) H12D(-0.9926) H12E(-0.9089)
 H23A(-0.4607) H23B(-0.4504) H23C(-0.5054) H13D(-0.5094) H13E(-0.5167) H13F(-
 0.6559)
 Fixed Y: H146(-0.7386) H122(-0.6369) H22(-0.8696) H54(-0.9887) H154(-0.742)
 H103(-0.617) H11A(-0.6658) H11B(-0.6404) H13A(-0.5973) H13B(-0.6272) H13C(-
 0.6265) H145(-0.6842) H11C(-0.6181) H11D(-0.6484) H11E(-0.64) H113(-0.6981)
 H102(-0.5957) H153(-0.6673) H105(-0.5569) H38A(-0.8163) H38B(-0.7892) H38C(-
 0.7851) H147(-0.684) H14A(-0.9095) H14B(-0.8952) H11F(-0.6643) H11G(-0.6982)
 H11H(-0.6742) H46(-0.9396) H12A(-0.5409) H12B(-0.5439) H149(-0.7186) H151(-
 0.6749) H47(-0.9606) H31(-0.9825) H13(-0.8934) H16G(-0.8049) H16H(-0.8291)
 H16I(-0.8119) H10(-0.7961) H11I(-0.6854) H11J(-0.6957) H11K(-0.6989) H110(-
 0.6464) H17A(-0.8781) H17B(-0.8701) H17C(-0.8484) H10A(-0.5432) H10B(-0.5633)
 H11L(-0.5426) H11M(-0.5551) H11N(-0.5604) H133(-0.5224) H20A(-0.8542) H20B(-
 0.8289) H15A(-0.7338) H15B(-0.7643) H15C(-0.7569) H150(-0.7051) H7(-0.8009)
 H3(-0.841) H29(-0.8932) H33(-0.9286) H32(-0.9757) H45(-0.9286) H18A(-0.8557)
 H18B(-0.8228) H18C(-0.8477) H37A(-0.9197) H37B(-0.9117) H37C(-0.911) H152(-
 0.6555) H19A(-0.785) H19B(-0.7855) H19C(-0.7586) H129(-0.5923) H6A(-0.7732)
 H6B(-0.7883) H53(-0.9721) H61A(-0.9288) H61B(-0.937) H61C(-0.9336) H107(-
 0.6067) H49(-1.0109) H16A(-0.8057) H16B(-0.8118) H16C(-0.8106) H2(-0.8348)
 H130(-0.5713) H30(-0.9409) H5(-0.8288) H16D(-0.7694) H16E(-0.775) H16F(-
 0.7424) H90A(-0.444) H90B(-0.4748) H131(-0.5256) H132(-0.5016) H50(-1.0445)
 H52(-1.0052) H51(-1.0427) H59A(-1.0025) H59B(-0.9818) H59C(-0.9689) H60A(-
 0.9856) H60B(-0.9883) H60C(-1.0126) H12C(-0.5947) H12D(-0.5901) H12E(-0.6206)
 H23A(-0.7412) H23B(-0.7693) H23C(-0.7379) H13D(-0.6684) H13E(-0.6341) H13F(-
 0.6559)
 Fixed Z: H146(0.0046) H122(-0.0633) H22(-0.3132) H54(0.0067) H154(0.2702)
 H103(-0.1609) H11A(0.0507) H11B(0.0252) H13A(0.1699) H13B(0.1576) H13C(0.1197)
 H145(0.052) H11C(-0.2899) H11D(-0.3571) H11E(-0.2439) H113(-0.0672) H102(-
 0.1542) H153(0.1746) H105(-0.1116) H38A(0.0774) H38B(0.1336) H38C(0.0957)
 H147(0.2091) H14A(-0.2115) H14B(-0.3009) H11F(-0.2169) H11G(-0.2368) H11H(-
 0.3366) H46(-0.0776) H12A(0.0185) H12B(-0.0964) H149(0.4213) H151(0.4787) H47(-
 0.193) H31(-0.7108) H13(-0.0587) H16G(-0.1265) H16H(-0.1895) H16I(-0.261) H10(-
 0.1155) H11I(-0.1408) H11J(-0.2608) H11K(-0.143) H110(-0.3935) H17A(-0.0322)
 H17B(-0.0709) H17C(0.0143) H10A(-0.3234) H10B(-0.2932) H11L(-0.2812) H11M(-
 0.4045) H11N(-0.2928) H133(0.1231) H20A(-0.6646) H20B(-0.6073) H15A(0.2633)
 H15B(0.2752) H15C(0.3631) H150(0.5501) H7(-0.3038) H3(-0.3145) H29(-0.7306)
 H33(-0.4655) H32(-0.5361) H45(-0.2005) H18A(-0.0074) H18B(-0.0549) H18C(-
 0.1386) H37A(-0.4169) H37B(-0.3798) H37C(-0.5135) H152(0.2947) H19A(-0.4597)
 H19B(-0.5371) H19C(-0.4497) H129(0.2164) H6A(-0.5258) H6B(-0.4646) H53(-
 0.3695) H61A(0.2165) H61B(0.2258) H61C(0.1015) H107(-0.3075) H49(-0.0888)
 H16A(0.3058) H16B(0.2053) H16C(0.1754) H2(-0.4) H130(0.4046) H30(-0.7979) H5(-
 0.5562) H16D(0.0276) H16E(0.0489) H16F(0.0627) H90A(0.2508) H90B(0.2502)
 H131(0.442) H132(0.3104) H50(-0.204) H52(-0.4922) H51(-0.404) H59A(0.3006)
 H59B(0.3529) H59C(0.3336) H60A(0.0466) H60B(0.1705) H60C(0.1305) H12C(-0.5897)
 H12D(-0.4685) H12E(-0.4952) H23A(-0.3334) H23B(-0.2491) H23C(-0.2055) H13D(-
 0.6366) H13E(-0.6038) H13F(-0.5792)
;
_olex2_computing_structure_refinement_long 'ShelXL (Sheldrick, 2008)'