A Safe and Efficacious Pt(II) Anticancer Prodrug: Design, Synthesis, In-vitro Efficacy, Role of Carrier Ligand and In-vivo Tumour Growth Inhibition
Dutta, Pradip; Sharma, Rupali; Kumari, Smita; Dubey, Ravindra Dhar; Sarkar, Sujit; Jhonpeter, Justin; vijaykumar, gonela; Pandey, Manoj; Sravanti, L.; Samarla, M.; Das, Hari Sankar; S, Yashpal; B, Heeralal; Goyal, Ravinder; Gupta, Nimish; Mandal, Swadhin K.; Sengupta, Aniruddha; Sarkar, Arindam; Chemical Communications  (2018) –; doi:10.1039/C8CC06586A

data_7122756
_publ_section_title
;
 A Safe and Efficacious Pt(II) Anticancer Prodrug: Design, Synthesis,
 In-vitro Efficacy, Role of Carrier Ligand and In-vivo Tumour Growth
 Inhibition
;
_journal_name_full               'Chemical Communications'
_journal_paper_doi               10.1039/C8CC06586A
_journal_year                    2018
_chemical_absolute_configuration ad
_chemical_formula_moiety         '2(C19 H21 N2 O2 Pt), 2(N O3)'
_chemical_formula_sum            'C38 H42 N6 O10 Pt2'
_chemical_formula_weight         1132.96
_chemical_name_systematic
;
 ? 
;
_space_group_crystal_system      triclinic
_space_group_IT_number           1
_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   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_date             2017-05-05
_audit_creation_method
;
Olex2 1.2
(compiled 2017.03.28 svn.r3405 for OlexSys, GUI svn.r5335)
;
_audit_update_record
;
2018-06-16 deposited with the CCDC.
2018-12-19 downloaded from the CCDC.
;
_cell_angle_alpha                110.339(5)
_cell_angle_beta                 97.169(4)
_cell_angle_gamma                98.871(5)
_cell_formula_units_Z            1
_cell_length_a                   8.5488(5)
_cell_length_b                   9.3389(6)
_cell_length_c                   12.6348(6)
_cell_measurement_reflns_used    4744
_cell_measurement_temperature    100.01(10)
_cell_measurement_theta_max      27.7520
_cell_measurement_theta_min      2.3550
_cell_volume                     917.02(10)
_computing_cell_refinement
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.33c (release 11-04-2014 CrysAlis171 .NET)
(compiled Apr 11 2014,15:12:41)
;
_computing_data_collection
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.33c (release 11-04-2014 CrysAlis171 .NET)
(compiled Apr 11 2014,15:12:41)
;
_computing_data_reduction
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.33c (release 11-04-2014 CrysAlis171 .NET)
(compiled Apr 11 2014,15:12:41)
;
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXS (Sheldrick, 2008)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.01(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 7.9580
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.900
_diffrn_measurement_details
;
  1 omega  -12.00   15.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -        0.7031  -57.0000    0.0000 27

  2 omega   19.00   45.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -        0.7031  -57.0000    0.0000 26

  3 omega   -5.00   38.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -        0.7031   57.0000 -180.0000 43

  4 omega  -51.00   66.00   1.0000    3.6200
omega____ theta____ kappa____ phi______ frames
    -       30.9779  -38.0000 -180.0000 117

  5 omega  -54.00   70.00   1.0000    3.6200
omega____ theta____ kappa____ phi______ frames
    -       30.9779  -38.0000   60.0000 124

  6 omega  -56.00   68.00   1.0000    3.6200
omega____ theta____ kappa____ phi______ frames
    -       30.9779  -38.0000  -60.0000 124

  7 omega  -64.00  -37.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -        0.7031  -57.0000    0.0000 27

  8 omega -117.00  -70.00   1.0000    3.6200
omega____ theta____ kappa____ phi______ frames
    -      -29.5717  178.0000  -60.0000 47

  9 omega -111.00  -68.00   1.0000    3.6200
omega____ theta____ kappa____ phi______ frames
    -      -29.5717  178.0000 -180.0000 43

 10 omega   71.00  118.00   1.0000    3.6200
omega____ theta____ kappa____ phi______ frames
    -       30.9779  178.0000  -60.0000 47
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, Eos'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      -0.0114362000
_diffrn_orient_matrix_UB_12      -0.0826226000
_diffrn_orient_matrix_UB_13      -0.0216102000
_diffrn_orient_matrix_UB_21      0.0642469000
_diffrn_orient_matrix_UB_22      0.0044646000
_diffrn_orient_matrix_UB_23      -0.0300128000
_diffrn_orient_matrix_UB_31      0.0553613000
_diffrn_orient_matrix_UB_32      0.0049652000
_diffrn_orient_matrix_UB_33      0.0485272000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0420
_diffrn_reflns_av_unetI/netI     0.0726
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -12
_diffrn_reflns_number            6777
_diffrn_reflns_theta_full        25.00
_diffrn_reflns_theta_max         27.94
_diffrn_reflns_theta_min         2.37
_diffrn_source                   'SuperNova (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    7.689
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.50282
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.33c (release 11-04-2014 CrysAlis171 .NET)
(compiled Apr 11 2014,15:12:41)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear reddish red'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   reddish
_exptl_crystal_colour_primary    red
_exptl_crystal_density_diffrn    2.052
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       block
_exptl_crystal_F_000             548
_exptl_crystal_size_max          0.56
_exptl_crystal_size_mid          0.38
_exptl_crystal_size_min          0.21
_refine_diff_density_max         2.810
_refine_diff_density_min         -2.731
_refine_diff_density_rms         0.265
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0.06(2)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.042
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     217
_refine_ls_number_reflns         4935
_refine_ls_number_restraints     3
_refine_ls_restrained_S_all      1.041
_refine_ls_R_factor_all          0.0487
_refine_ls_R_factor_gt           0.0456
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0534P)^2^+4.1161P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1113
_refine_ls_wR_factor_ref         0.1164
_reflns_number_gt                4601
_reflns_number_total             4935
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            c8cc06586a2.cif
_cod_data_source_block           mr4
_cod_original_cell_volume        917.03(8)
_cod_database_code               7122756
_chemical_oxdiff_formula         'C H O N Pt'
_reflns_odcompleteness_completeness 99.97
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     26.32
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H,H) groups
2. Uiso/Uaniso restraints and constraints
Uanis(C10) = Uanis(C9) = Uanis(C8) = Uanis(C7) = Uanis(C6) = Uanis(C11) =
Uanis(C4) = Uanis(C12) = Uanis(C5) = Uanis(C3) = Uanis(C2) = Uanis(C13) =
Uanis(C1)
Uanis(C30) = Uanis(C31) = Uanis(C23) = Uanis(C20) = Uanis(C27) = Uanis(C32) =
Uanis(C28) = Uanis(C29) = Uanis(C24) = Uanis(C25) = Uanis(C26) = Uanis(C21) =
Uanis(C22)
Uanis(O1) = Uanis(O2) = Uanis(O3) = Uanis(O5) = Uanis(O4) = Uanis(O7) =
Uanis(O6) = Uanis(O9) = Uanis(O10) = Uanis(O8)
Uanis(N6) = Uanis(N5) = Uanis(N4) = Uanis(N2) = Uanis(N1) = Uanis(N3)
Uanis(C35) = Uanis(C36) = Uanis(C37) = Uanis(C38) = Uanis(C33) = Uanis(C34)
Uanis(C18) = Uanis(C17) = Uanis(C16) = Uanis(C15) = Uanis(C14) = Uanis(C19)
3.a Ternary CH refined with riding coordinates:
 C33(H33), C34(H34), C15(H15), C14(H14)
3.b Secondary CH2 refined with riding coordinates:
 N2(H2A,H2B), N4(H4A,H4B), N1(H1A,H1B), N5(H5A,H5B), C35(H35A,H35B), C38(H38A,
 H38B), C19(H19A,H19B), C17(H17A,H17B), C36(H36A,H36B), C37(H37A,H37B),
 C18(H18A,H18B), C16(H16A,H16B)
3.c Aromatic/amide H refined with riding coordinates:
 C28(H28), C29(H29), C10(H10), C9(H9), C24(H24), C5(H5), C6(H6), C3(H3),
 C25(H25), C26(H26), C7(H7), C21(H21), C2(H2), C22(H22)
;
_olex2_date_sample_data_collection 2015-09-11
_olex2_submission_special_instructions 'No special instructions were received'