Impact of aliphatic acyl and aromatic thioamide substituents on the anticancer activity of Ru(II)-p-cymene complexes carrying acylthiourea ligands – In vitro and in vivo studies
Swaminathan, Srividya; Haribabu, Jebiti; Mohamed Kasim, Mohamed Subarkhan; dasararaju, gayathri; Balakrishnan, Nithya; Bhuvanesh, Nattamai; Echeverria, Cesar; Karvembu, R.; Dalton Transactions  (2021) –; doi:10.1039/D1DT02611A

data_7708570
_publ_section_title
;
 Impact of aliphatic acyl and aromatic thioamide substituents on the
 anticancer activity of Ru(II)-p-cymene complexes carrying acylthiourea
 ligands -- In vitro and in vivo studies
;
_journal_name_full               'Dalton Transactions'
_journal_paper_doi               10.1039/D1DT02611A
_journal_year                    2021
_chemical_formula_moiety         'C30 H40 Cl2 N2 O Ru S'
_chemical_formula_sum            'C30 H40 Cl2 N2 O Ru S'
_chemical_formula_weight         648.67
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_audit_creation_date             2020-01-13
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2021-09-18 deposited with the CCDC.	2021-10-15 downloaded from the CCDC.
;
_cell_angle_alpha                112.455(3)
_cell_angle_beta                 95.919(3)
_cell_angle_gamma                91.536(3)
_cell_formula_units_Z            4
_cell_length_a                   10.4538(10)
_cell_length_b                   16.6161(15)
_cell_length_c                   18.7518(17)
_cell_measurement_reflns_used    9794
_cell_measurement_temperature    110.0
_cell_measurement_theta_max      33.056
_cell_measurement_theta_min      2.223
_cell_volume                     2986.4(5)
_computing_cell_refinement
'SAINT V8.38 Bruker AXS Inc., Madison, WI, USA.'
_computing_data_collection       'APEX 3 (Bruker AXS)'
_computing_data_reduction
'SAINT V8.38 Bruker AXS Inc., Madison, WI, USA.'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL (Sheldrick, 2008)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      110.0
_diffrn_detector                 'Bruker APEX2 area detector'
_diffrn_detector_area_resol_mean 7.9
_diffrn_detector_type            'CCD area detector'
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_device       'three-circle diffractometer'
_diffrn_measurement_device_type  'Bruker PHOTON II'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  'mirror optics'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0399
_diffrn_reflns_av_unetI/netI     0.0141
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       21
_diffrn_reflns_limit_k_min       -21
_diffrn_reflns_limit_l_max       24
_diffrn_reflns_limit_l_min       -24
_diffrn_reflns_number            223947
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.999
_diffrn_reflns_theta_full        26.000
_diffrn_reflns_theta_max         27.500
_diffrn_reflns_theta_min         2.095
_diffrn_source                   'microfocus sealed X-ray tube'
_diffrn_source_type              'Incoatec I\ms'
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.800
_exptl_absorpt_correction_T_max  0.4353
_exptl_absorpt_correction_T_min  0.3959
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.1017 before and 0.0651 after correction. The Ratio of minimum to maximum transmission is 0.9095. The \l/2 correction factor is Not present.'
_exptl_crystal_colour            brown
_exptl_crystal_colour_primary    brown
_exptl_crystal_density_diffrn    1.443
_exptl_crystal_description       block
_exptl_crystal_F_000             1344
_exptl_crystal_size_max          0.325
_exptl_crystal_size_mid          0.221
_exptl_crystal_size_min          0.153
_refine_diff_density_max         1.186
_refine_diff_density_min         -0.712
_refine_diff_density_rms         0.074
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.057
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     724
_refine_ls_number_reflns         13730
_refine_ls_number_restraints     393
_refine_ls_restrained_S_all      1.074
_refine_ls_R_factor_all          0.0348
_refine_ls_R_factor_gt           0.0302
_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^)+(0.0249P)^2^+5.3126P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0698
_refine_ls_wR_factor_ref         0.0746
_reflns_Friedel_coverage         0.000
_reflns_number_gt                12502
_reflns_number_total             13730
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d1dt02611a2.cif
_cod_data_source_block           svpncnap
_cod_database_code               7708570
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.887
_shelx_estimated_absorpt_t_min   0.781
_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,
  All N(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 C13B-C15B = C14B-C16B = C15B-C17B = C16B-C18B = C17B-C19B = C18B-C20B = C19B-
 C21B = C13C-C15C = C14C-C16C = C15C-C17C = C16C-C18C = C17C-C19C = C18C-C20C =
 C19C-C21C
 2.5 with sigma of 0.005
 C15-C17 = C16-C18 = C17-C19 = C18-C20 = C19-C21 = C15A-C17A = C16A-C18A =
 C17A-C19A = C18A-C20A = C19A-C21A
 2.5 with sigma of 0.005
 C13B-O1B \\sim C13C-O1C
 with sigma of 0.005
 C13B-C14B \\sim C14B-C15B \\sim C15B-C16B \\sim C16B-C17B \\sim C17B-C18B
\\sim C18B-C19B \\sim C19B-
 C20B \\sim C20B-C21B \\sim C13C-C14C \\sim C14C-C15C \\sim C15C-C16C \\sim
C16C-C17C \\sim C17C-C18C ~
 C18C-C19C \\sim C19C-C20C \\sim C20C-C21C
 with sigma of 0.005
 C15-C16 \\sim C16-C17 \\sim C17-C18 \\sim C18-C19 \\sim C19-C20 \\sim C20-C21
\\sim C15A-C16A \\sim C16A-
 C17A \\sim C17A-C18A \\sim C18A-C19A \\sim C19A-C20A \\sim C20A-C21A
 with sigma of 0.005
3. Uiso/Uaniso restraints and constraints
O1B \\sim C13B \\sim C14B \\sim C15B \\sim C16B \\sim C17B \\sim C18B \\sim
C19B \\sim C20B \\sim C21B: within 2A with sigma of 0.005 and sigma for
terminal atoms of 0.01
C15 \\sim C16 \\sim C17 \\sim C18 \\sim C19 \\sim C20 \\sim C21: within 2A with
sigma of 0.005 and sigma for terminal atoms of 0.01
Uanis(O1B) = Uanis(O1C)
Uanis(C13B) = Uanis(C13C)
Uanis(C15C) = Uanis(C15B)
Uanis(C16C) = Uanis(C16B)
Uanis(C17C) = Uanis(C17B)
Uanis(C18C) = Uanis(C18B)
Uanis(C19B) = Uanis(C19C)
Uanis(C20B) = Uanis(C20C)
Uanis(C21C) = Uanis(C21B)
Uanis(C21) = Uanis(C21A)
Uanis(C20) = Uanis(C20A)
Uanis(C19) = Uanis(C19A)
Uanis(C18) = Uanis(C18A)
Uanis(C17) = Uanis(C17A)
Uanis(C16) = Uanis(C16A)
Uanis(C15) = Uanis(C15A)
Uanis(C14C) = Uanis(C14B)
4. Rigid body (RIGU) restrains
 O1B, C13B, C14B, C15B, C16B, C17B, C18B, C19B, C20B, C21B
 with sigma for 1-2 distances of 0.005 and sigma for 1-3 distances of 0.005
 C15, C16, C17, C18, C19, C20, C21
 with sigma for 1-2 distances of 0.005 and sigma for 1-3 distances of 0.005
5. Same fragment restrains
{O1B, C13B, C14B, C15B, C16B, C17B, C18B, C19B, C20B, C21B} sigma for 1-2:
0.005, 1-3: 0.04
as
{O1C, C13C, C14C, C15C, C16C, C17C, C18C, C19C, C20C, C21C}
6. Others
 Sof(H2BA)=Sof(O1C)=Sof(C13C)=Sof(C14C)=Sof(H14C)=Sof(H14D)=Sof(C15C)=
 Sof(H15C)=Sof(H15D)=Sof(C16C)=Sof(H16C)=Sof(H16D)=Sof(C17C)=Sof(H17C)=
 Sof(H17D)=Sof(C18C)=Sof(H18C)=Sof(H18D)=Sof(C19C)=Sof(H19C)=Sof(H19D)=
 Sof(C20C)=Sof(H20C)=Sof(H20D)=Sof(C21C)=Sof(H21D)=Sof(H21E)=Sof(H21F)=1-FVAR(1)
 Sof(H2B)=Sof(O1B)=Sof(C13B)=Sof(C14B)=Sof(H14A)=Sof(H14B)=Sof(C15B)=Sof(H15A)=
 Sof(H15B)=Sof(C16B)=Sof(H16A)=Sof(H16B)=Sof(C17B)=Sof(H17A)=Sof(H17B)=
 Sof(C18B)=Sof(H18A)=Sof(H18B)=Sof(C19B)=Sof(H19A)=Sof(H19B)=Sof(C20B)=
 Sof(H20A)=Sof(H20B)=Sof(C21B)=Sof(H21A)=Sof(H21B)=Sof(H21C)=FVAR(1)
 Sof(H14G)=Sof(H14H)=Sof(C15A)=Sof(H15G)=Sof(H15H)=Sof(C16A)=Sof(H16G)=
 Sof(H16H)=Sof(C17A)=Sof(H17G)=Sof(H17H)=Sof(C18A)=Sof(H18G)=Sof(H18H)=
 Sof(C19A)=Sof(H19G)=Sof(H19H)=Sof(C20A)=Sof(H20G)=Sof(H20H)=Sof(C21A)=
 Sof(H21J)=Sof(H21K)=Sof(H21L)=1-FVAR(2)
 Sof(H14E)=Sof(H14F)=Sof(C15)=Sof(H15E)=Sof(H15F)=Sof(C16)=Sof(H16E)=Sof(H16F)=
 Sof(C17)=Sof(H17E)=Sof(H17F)=Sof(C18)=Sof(H18E)=Sof(H18F)=Sof(C19)=Sof(H19E)=
 Sof(H19F)=Sof(C20)=Sof(H20E)=Sof(H20F)=Sof(C21)=Sof(H21G)=Sof(H21H)=Sof(H21I)=
 FVAR(2)
 Fixed U11: C14(0.051277)
 Fixed U12: C14(0.010607)
 Fixed U13: C14(0.016499)
 Fixed U22: C14(0.060761)
 Fixed U23: C14(-0.002736)
 Fixed U33: C14(0.02717)
7.a Ternary CH refined with riding coordinates:
 C28(H28), C28B(H28B)
7.b Secondary CH2 refined with riding coordinates:
 C14(H14E,H14F), C14(H14G,H14H), C15(H15E,H15F), C16(H16E,H16F), C17(H17E,
 H17F), C18(H18E,H18F), C19(H19E,H19F), C20(H20E,H20F), C15A(H15G,H15H),
 C16A(H16G,H16H), C17A(H17G,H17H), C18A(H18G,H18H), C19A(H19G,H19H), C20A(H20G,
 H20H), C14B(H14A,H14B), C15B(H15A,H15B), C16B(H16A,H16B), C17B(H17A,H17B),
 C18B(H18A,H18B), C19B(H19A,H19B), C20B(H20A,H20B), C14C(H14C,H14D), C15C(H15C,
 H15D), C16C(H16C,H16D), C17C(H17C,H17D), C18C(H18C,H18D), C19C(H19C,H19D),
 C20C(H20C,H20D)
7.c Aromatic/amide H refined with riding coordinates:
 N1(H1), N2(H2), C4(H4), C5(H5), C6(H6), C9(H9), C10(H10), C11(H11), C12(H12),
 C23(H23), C24(H24), C26(H26), C27(H27), N1B(H1B), N2B(H2B), N2B(H2BA),
 C4B(H4B), C5B(H5B), C6B(H6B), C9B(H9B), C10B(H10B), C11B(H11B), C12B(H12B),
 C23B(H23B), C24B(H24B), C26B(H26B), C27B(H27B)
7.d Idealised Me refined as rotating group:
 C21(H21G,H21H,H21I), C21A(H21J,H21K,H21L), C29(H29D,H29E,H29F), C30(H30D,H30E,
 H30F), C31(H31D,H31E,H31F), C21B(H21A,H21B,H21C), C21C(H21D,H21E,H21F),
 C29B(H29A,H29B,H29C), C30B(H30A,H30B,H30C), C31B(H31A,H31B,H31C)
;
_shelx_res_checksum              21350
_shelx_hkl_checksum              82287
_olex2_submission_special_instructions 'No special instructions were received'