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_7122757
_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(C20 H24 N3 O Pt), 2(N O3)'
_chemical_formula_sum            'C40 H48 N8 O8 Pt2'
_chemical_formula_weight         1159.04
_chemical_name_systematic
;
 ? 
;
_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     iterative
_atom_sites_solution_secondary   difmap
_audit_creation_date             2017-05-04
_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                90.00
_cell_angle_beta                 107.246(7)
_cell_angle_gamma                90.00
_cell_formula_units_Z            2
_cell_length_a                   8.5924(5)
_cell_length_b                   17.7287(9)
_cell_length_c                   13.3203(7)
_cell_measurement_reflns_used    4861
_cell_measurement_temperature    99.98(10)
_cell_measurement_theta_max      66.3340
_cell_measurement_theta_min      3.4680
_cell_volume                     1937.9(2)
_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
;
Superflip (Palatinus & Chapuis, 2007;Palatinus & van der Lee, 2008;
Palatinus et al., 2012)
;
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      99.98(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 7.9580
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.996
_diffrn_measured_fraction_theta_max 0.996
_diffrn_measurement_details
;
  1 omega   11.00   36.00   1.0000    4.5000
omega____ theta____ kappa____ phi______ frames
    -       26.4359   57.0000  -30.0000 25

  2 omega   44.00  102.00   1.0000    4.5000
omega____ theta____ kappa____ phi______ frames
    -       26.4359   57.0000  -30.0000 58

  3 omega  100.00  125.00   1.0000   12.5000
omega____ theta____ kappa____ phi______ frames
    -       67.2180  111.0000  -60.0000 25

  4 omega  101.00  151.00   1.0000   12.5000
omega____ theta____ kappa____ phi______ frames
    -       67.2180  111.0000    0.0000 50

  5 omega  137.00  177.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  104.0000  -30.0000 40

  6 omega  124.00  150.00   1.0000   12.5000
omega____ theta____ kappa____ phi______ frames
    -       67.2180  111.0000 -150.0000 26

  7 omega  121.00  151.00   1.0000   12.5000
omega____ theta____ kappa____ phi______ frames
    -       67.2180  111.0000 -120.0000 30

  8 omega  117.00  144.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   65.0000  -60.0000 27

  9 omega  100.00  127.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   54.0000 -150.0000 27

 10 omega   80.00  116.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   65.0000 -180.0000 36

 11 omega   73.00  112.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   65.0000  -90.0000 39

 12 omega  110.00  137.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  104.0000   30.0000 27

 13 omega  115.00  147.00   1.0000   12.5000
omega____ theta____ kappa____ phi______ frames
    -       67.2180  111.0000  120.0000 32

 14 omega  149.00  176.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  104.0000  150.0000 27

 15 omega  103.00  178.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   32.0000   60.0000 75

 16 omega  101.00  129.00   1.0000   12.5000
omega____ theta____ kappa____ phi______ frames
    -       67.2180  111.0000  150.0000 28

 17 omega   87.00  160.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  138.0000   90.0000 73

 18 omega   94.00  143.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  138.0000   60.0000 49

 19 omega  101.00  128.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   44.0000  109.0000 27

 20 omega   73.00  143.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -43.0000  -30.0000 70

 21 omega   87.00  143.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -89.0000    0.0000 56

 22 omega   75.00  100.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -89.0000   60.0000 25

 23 omega   62.00   91.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000 -104.0000    0.0000 29

 24 omega   52.00   79.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -89.0000    0.0000 27

 25 omega   24.00  112.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000 -104.0000   30.0000 88

 26 omega   87.00  113.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -77.0000  150.0000 26

 27 omega   44.00  175.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000   32.0000   90.0000 131

 28 omega   78.00  106.00   1.0000    4.5000
omega____ theta____ kappa____ phi______ frames
    -       26.4359  178.0000 -120.0000 28

 29 omega   60.00  120.00   1.0000    4.5000
omega____ theta____ kappa____ phi______ frames
    -       26.4359  178.0000  -90.0000 60

 30 omega   -2.00  150.00   1.0000   12.5000
omega____ theta____ kappa____ phi______ frames
    -       67.2180   30.0000  150.0000 152

 31 omega   26.00   61.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -77.0000  150.0000 35

 32 omega   27.00  106.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000 -104.0000  -30.0000 79

 33 omega  112.00  137.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -65.0000 -150.0000 25

 34 omega   67.00  109.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000 -104.0000 -180.0000 42

 35 omega   45.00   80.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -32.0000 -180.0000 35

 36 omega   31.00   88.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -65.0000 -150.0000 57

 37 omega   45.00   70.00   1.0000    5.0000
omega____ theta____ kappa____ phi______ frames
    -      108.0000 -104.0000 -150.0000 25

 38 omega   19.00  116.00   1.0000   12.5000
omega____ theta____ kappa____ phi______ frames
    -       67.2180 -111.0000  -60.0000 97

 39 omega    3.00   77.00   1.0000    4.5000
omega____ theta____ kappa____ phi______ frames
    -       26.4359  -99.0000  -60.0000 74

 40 omega  -45.00   37.00   1.0000    4.5000
omega____ theta____ kappa____ phi______ frames
    -       26.4359  -57.0000   60.0000 82
;
_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      0.0326159000
_diffrn_orient_matrix_UB_12      -0.0393911000
_diffrn_orient_matrix_UB_13      -0.0949864000
_diffrn_orient_matrix_UB_21      -0.1786734000
_diffrn_orient_matrix_UB_22      -0.0262692000
_diffrn_orient_matrix_UB_23      -0.0379314000
_diffrn_orient_matrix_UB_31      -0.0469256000
_diffrn_orient_matrix_UB_32      0.0729524000
_diffrn_orient_matrix_UB_33      -0.0647808000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0869
_diffrn_reflns_av_unetI/netI     0.0698
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       21
_diffrn_reflns_limit_k_min       -19
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            10161
_diffrn_reflns_theta_full        66.26
_diffrn_reflns_theta_max         66.26
_diffrn_reflns_theta_min         3.47
_diffrn_source                   'sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    13.855
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.28171
_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 dark red'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   dark
_exptl_crystal_colour_primary    red
_exptl_crystal_density_diffrn    1.986
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       block
_exptl_crystal_F_000             1128
_exptl_crystal_size_max          0.56
_exptl_crystal_size_mid          0.41
_exptl_crystal_size_min          0.25
_refine_diff_density_max         4.418
_refine_diff_density_min         -4.424
_refine_diff_density_rms         0.383
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0.03(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.044
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     441
_refine_ls_number_reflns         4917
_refine_ls_number_restraints     2
_refine_ls_restrained_S_all      1.043
_refine_ls_R_factor_all          0.0870
_refine_ls_R_factor_gt           0.0810
_refine_ls_shift/su_max          0.005
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.1709P)^2^+0.0000P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2074
_refine_ls_wR_factor_ref         0.2135
_reflns_number_gt                4471
_reflns_number_total             4917
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            c8cc06586a2.cif
_cod_data_source_block           plynopt
_cod_original_cell_volume        1937.87(19)
_cod_database_code               7122757
_chemical_oxdiff_formula         'C H N O Pt'
_reflns_odcompleteness_completeness 97.69
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_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
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 H30-H34B
 2.122 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
Uanis(C26) = Uanis(C27) = Uanis(C25) = Uanis(C24) = Uanis(C33) = Uanis(C28) =
Uanis(C29) = Uanis(C30) = Uanis(C31) = Uanis(C32) = Uanis(C21) = Uanis(C22) =
Uanis(C23)
Uanis(C34) = Uanis(C14)
Uanis(N5) = Uanis(N1)
4.a Ternary CH refined with riding coordinates:
 C40(H40), C35(H35), C20(H20), C15(H15)
4.b Secondary CH2 refined with riding coordinates:
 N2(H2A,H2B), N6(H6A,H6B), N3(H3A,H3B), N7(H7A,H7B), C19(H19A,H19B), C39(H39A,
 H39B), C16(H16A,H16B), C36(H36A,H36B), C37(H37A,H37B), C18(H18A,H18B),
 C38(H38A,H38B), C17(H17A,H17B)
4.c Aromatic/amide H refined with riding coordinates:
 C10(H10), C2(H2), C22(H22), C5(H5), C25(H25), C7(H7), C9(H9), C3(H3),
 C29(H29), C6(H6), C26(H26), C30(H30), C23(H23), C27(H27)
4.d Idealised Me refined as rotating group:
 C34(H34A,H34B,H34C), C14(H14A,H14B,H14C)
;
_olex2_date_sample_data_collection 2015-11-04
_olex2_submission_special_instructions 'No special instructions were received'