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_7217306
_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'
_chemical_formula_sum            'C45 H57 N O14'
_chemical_formula_weight         835.91
_chemical_name_systematic        Cabazitaxel
_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   geom
_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                 98.532(5)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.351(3)
_cell_length_b                   44.438(17)
_cell_length_c                   11.410(4)
_cell_measurement_reflns_used    9983
_cell_measurement_temperature    120.15
_cell_measurement_theta_max      23.948
_cell_measurement_theta_min      2.666
_cell_volume                     4187(3)
_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 0.902
_diffrn_measured_fraction_theta_max 0.985
_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  0.0938
_diffrn_reflns_av_unetI/netI     0.1219
_diffrn_reflns_Laue_measured_fraction_full 0.902
_diffrn_reflns_Laue_measured_fraction_max 0.985
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       52
_diffrn_reflns_limit_k_min       -52
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            30848
_diffrn_reflns_point_group_measured_fraction_full 0.872
_diffrn_reflns_point_group_measured_fraction_max 0.953
_diffrn_reflns_theta_full        25.000
_diffrn_reflns_theta_max         24.221
_diffrn_reflns_theta_min         0.888
_diffrn_source                   Synchrotron
_diffrn_source_type              'Undulator, I19, DLS, RAL'
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.092
_exptl_absorpt_correction_T_max  1.0000
_exptl_absorpt_correction_T_min  0.5460
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2008/1 (Bruker,2008) was used for absorption correction.
wR2(int) was 0.1307 before and 0.0962 after correction.
The Ratio of minimum to maximum transmission is 0.5460.
The \l/2 correction factor is Not present.
;
_exptl_crystal_colour            'clear light orange'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    orange
_exptl_crystal_density_diffrn    1.326
_exptl_crystal_description       lath
_exptl_crystal_F_000             1784
_exptl_crystal_size_max          0.1
_exptl_crystal_size_mid          0.03
_exptl_crystal_size_min          0.001
_refine_diff_density_max         0.530
_refine_diff_density_min         -0.384
_refine_diff_density_rms         0.086
_refine_ls_abs_structure_details
;
 Flack x determined using 3680 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   0.2(6)
_refine_ls_extinction_coef       0.039(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   1.051
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     1106
_refine_ls_number_reflns         14114
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.051
_refine_ls_R_factor_all          0.1306
_refine_ls_R_factor_gt           0.0989
_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^)+(0.1173P)^2^+8.2975P]
 where P=(Fo^2^+2Fc^2^)/3
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2557
_refine_ls_wR_factor_ref         0.2760
_reflns_Friedel_coverage         0.908
_reflns_Friedel_fraction_full    0.842
_reflns_Friedel_fraction_max     0.920
_reflns_number_gt                10130
_reflns_number_total             14114
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c4ce01279h2.cif
_cod_data_source_block           940083_Anh
_cod_depositor_comments
'Adding full bibliography for 7217306--7217310.cif.'
_cod_database_code               7217306
_shelxl_version_number           2013-2
_shelx_estimated_absorpt_t_max   1.000
_shelx_estimated_absorpt_t_min   0.991
_olex2_refinement_description
;
1. Others
 Fixed Uiso: H146(0.077) H22(0.084) H122(0.065) H54(0.069) H46(0.104)
 H154(0.055) H11A(0.045) H11B(0.045) H10(0.056) H147(0.056) H151(0.078)
 H149(0.059) H145(0.052) H13A(0.071) H13B(0.071) H13C(0.071) H103(0.052)
 H16G(0.08) H16H(0.08) H16I(0.08) H113(0.064) H102(0.048) H13(0.053)
 H105(0.056) H17A(0.088) H17B(0.088) H17C(0.088) H12A(0.069) H12B(0.069)
 H110(0.056) H11C(0.08) H11D(0.08) H11E(0.08) H11F(0.07) H11G(0.07) H11H(0.07)
 H14A(0.056) H14B(0.056) H153(0.064) H38A(0.078) H38B(0.078) H38C(0.078)
 H11I(0.087) H11J(0.087) H11K(0.087) H11L(0.082) H11M(0.082) H11N(0.082)
 H10A(0.074) H10B(0.074) H31(0.081) H3(0.061) H33(0.074) H29(0.08) H7(0.067)
 H32(0.075) H150(0.069) H20A(0.086) H20B(0.086) H152(0.068) H53(0.084)
 H37A(0.091) H37B(0.091) H37C(0.091) H107(0.055) H23A(0.118) H23B(0.118)
 H23C(0.118) H18A(0.091) H18B(0.091) H18C(0.091) H49(0.069) H2(0.061)
 H129(0.063) H47(0.069) H51(0.099) H45(0.066) H19A(0.108) H19B(0.108)
 H19C(0.108) H133(0.072) H59A(0.118) H59B(0.118) H59C(0.118) H50(0.091)
 H61A(0.106) H61B(0.106) H61C(0.106) H16A(0.09) H16B(0.09) H16C(0.09)
 H130(0.091) H30(0.076) H16D(0.083) H16E(0.083) H16F(0.083) H132(0.094)
 H131(0.085) H15A(0.098) H15B(0.098) H15C(0.098) H5(0.076) H52(0.088)
 H60A(0.129) H60B(0.129) H60C(0.129) H6A(0.081) H6B(0.081) H12C(0.121)
 H12D(0.121) H12E(0.121) H13D(0.107) H13E(0.107) H13F(0.107)
 Fixed X: H146(0.0766) H22(-0.2683) H122(0.9346) H54(0.5158) H46(0.7102)
 H154(0.2608) H11A(0.5331) H11B(0.6691) H10(0.2726) H147(0.3011) H151(-0.1976)
 H149(0.2084) H145(0.0782) H13A(0.112) H13B(0.2041) H13C(0.3035) H103(0.4231)
 H16G(-0.1573) H16H(-0.2819) H16I(-0.1748) H113(0.5358) H102(0.7356)
 H13(0.1944) H105(0.165) H17A(-0.0991) H17B(-0.1898) H17C(-0.0019) H12A(0.5809)
 H12B(0.4915) H110(0.3645) H11C(0.2359) H11D(0.2295) H11E(0.1824) H11F(0.9414)
 H11G(0.8128) H11H(0.8052) H14A(0.0277) H14B(0.133) H153(-0.0453) H38A(0.0943)
 H38B(0.1609) H38C(0.2672) H11I(0.7228) H11J(0.7948) H11K(0.8991) H11L(0.5176)
 H11M(0.4838) H11N(0.6505) H10A(0.2169) H10B(0.0766) H31(-0.3005) H3(0.2185)
 H33(-0.0573) H29(-0.374) H7(0.3888) H32(-0.1125) H150(0.0223) H20A(-0.007)
 H20B(0.098) H152(-0.2349) H53(0.4635) H37A(0.3773) H37B(0.4434) H37C(0.5634)
 H107(0.2229) H23A(0.5503) H23B(0.5452) H23C(0.4948) H18A(0.4342) H18B(0.4693)
 H18C(0.4911) H49(0.6976) H2(-0.1117) H129(0.6793) H47(0.3776) H51(0.7381)
 H45(0.6162) H19A(-0.0859) H19B(0.037) H19C(0.0582) H133(0.9005) H59A(0.0565)
 H59B(-0.0624) H59C(-0.017) H50(0.8172) H61A(0.0947) H61B(0.0444) H61C(0.2282)
 H16A(0.6795) H16B(0.763) H16C(0.5699) H130(0.6876) H30(-0.4289) H16D(0.7836)
 H16E(0.9022) H16F(0.8) H132(0.9098) H131(0.7974) H15A(0.5644) H15B(0.7576)
 H15C(0.6491) H5(0.4236) H52(0.5878) H60A(0.3305) H60B(0.1572) H60C(0.2784)
 H6A(0.4935) H6B(0.3299) H12C(0.0065) H12D(0.0681) H12E(0.0863) H13D(0.3504)
 H13E(0.4657) H13F(0.5149)
 Fixed Y: H146(1.0072) H22(1.137) H122(0.898) H54(1.2547) H46(1.1958)
 H154(1.0087) H11A(0.9059) H11B(0.9311) H10(1.0625) H147(0.95) H151(0.9428)
 H149(0.9852) H145(0.9499) H13A(0.8727) H13B(0.9037) H13C(0.8751) H103(0.8833)
 H16G(1.0766) H16H(1.0977) H16I(1.0738) H113(0.9646) H102(0.8609) H13(1.16)
 H105(0.8226) H17A(1.1141) H17B(1.1392) H17C(1.143) H12A(0.8089) H12B(0.8064)
 H110(0.9119) H11C(0.9392) H11D(0.9647) H11E(0.9307) H11F(0.9076) H11G(0.9122)
 H11H(0.8826) H14A(1.1767) H14B(1.1627) H153(0.9334) H38A(1.0526) H38B(1.0826)
 H38C(1.0525) H11I(0.9642) H11J(0.9617) H11K(0.9502) H11L(0.8206) H11M(0.8083)
 H11N(0.8251) H10A(0.8093) H10B(0.8305) H31(1.2505) H3(1.1076) H33(1.1958)
 H29(1.1618) H7(1.0683) H32(1.2433) H150(0.9747) H20A(1.0976) H20B(1.1232)
 H152(0.9226) H53(1.2384) H37A(1.1874) H37B(1.1804) H37C(1.1787) H107(0.8729)
 H23A(1.0332) H23B(1.0113) H23C(0.999) H18A(1.0876) H18B(1.1191) H18C(1.116)
 H49(1.2751) H2(1.1019) H129(0.8568) H47(1.2252) H51(1.3111) H45(1.1938)
 H19A(1.0545) H19B(1.0267) H19C(1.0537) H133(0.785) H59A(1.2768) H59B(1.2553)
 H59C(1.2474) H50(1.3102) H61A(1.1983) H61B(1.2019) H61C(1.1946) H16A(1.0084)
 H16B(1.0404) H16C(1.0375) H130(0.8337) H30(1.2096) H16D(1.0235) H16E(1.03)
 H16F(0.9994) H132(0.7624) H131(0.7872) H15A(1.0777) H15B(1.0783) H15C(1.0722)
 H5(1.0967) H52(1.2731) H60A(1.2359) H60B(1.2482) H60C(1.2697) H6A(1.0564)
 H6B(1.0407) H12C(0.8543) H12D(0.8633) H12E(0.8866) H13D(0.9271) H13E(0.8989)
 H13F(0.9315)
 Fixed Z: H146(0.5203) H22(0.2007) H122(0.443) H54(0.5104) H46(0.5278)
 H154(0.7733) H11A(0.527) H11B(0.5562) H10(0.3883) H147(0.7121) H151(0.9897)
 H149(0.9274) H145(0.5517) H13A(0.6488) H13B(0.6327) H13C(0.689) H103(0.3435)
 H16G(0.2444) H16H(0.2998) H16I(0.3818) H113(0.4343) H102(0.3463) H13(0.4502)
 H105(0.3958) H17A(0.517) H17B(0.4309) H17C(0.4821) H12A(0.4055) H12B(0.5223)
 H110(0.1079) H11C(0.164) H11D(0.2624) H11E(0.2888) H11F(0.261) H11G(0.1436)
 H11H(0.223) H14A(0.2924) H14B(0.2002) H153(0.6749) H38A(0.6372) H38B(0.5832)
 H38C(0.5925) H11I(0.3638) H11J(0.2418) H11K(0.3625) H11L(0.0944) H11M(0.2203)
 H11N(0.2094) H10A(0.1726) H10B(0.2075) H31(-0.2032) H3(0.189) H33(0.0419) H29(-
 0.2267) H7(0.199) H32(-0.0288) H150(1.0553) H20A(-0.1105) H20B(-0.1675)
 H152(0.8034) H53(0.1284) H37A(0.1066) H37B(-0.0152) H37C(0.1078) H107(0.1942)
 H23A(0.2611) H23B(0.1494) H23C(0.2705) H18A(0.4335) H18B(0.5004) H18C(0.3639)
 H49(0.4241) H2(0.1025) H129(0.7252) H47(0.3079) H51(0.1071) H45(0.31)
 H19A(0.0358) H19B(0.047) H19C(-0.0422) H133(0.6154) H59A(0.6126) H59B(0.672)
 H59C(0.5441) H50(0.3095) H61A(0.6009) H61B(0.7301) H61C(0.716) H16A(0.5572)
 H16B(0.5462) H16C(0.5229) H130(0.9153) H30(-0.2937) H16D(0.8615) H16E(0.7664)
 H16F(0.7595) H132(0.7997) H131(0.9423) H15A(0.6737) H15B(0.7052) H15C(0.8072)
 H5(-0.0641) H52(0.0148) H60A(0.8351) H60B(0.8563) H60C(0.7987) H6A(0.032) H6B(-
 0.0282) H12C(0.0315) H12D(-0.0902) H12E(0.0176) H13D(-0.0859) H13E(-0.0983)
 H13F(-0.1402)
;
_olex2_computing_structure_refinement_long 'ShelXL (Sheldrick, 2008)'