New melphalan derivatives for the treatment of retinoblastoma in combination with thermotherapy
Zebret, Soumaila; Hadiji, Mouna; Romano-deGea, Jan; Bornet, Aurélien; Ortiz, Daniel; Fadaei Tirani, Farzaneh; Stathopoulos, Christina; Nowak-Sliwinska, Patrycja; Munier, Francis; Dyson, Paul Joseph; RSC Medicinal Chemistry  (2024) –; doi:10.1039/D4MD00211C

data_7248683
_publ_section_title
;
 New melphalan derivatives for the treatment of retinoblastoma in
 combination with thermotherapy
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D4MD00211C
_journal_year                    2024
_chemical_formula_moiety         'C28 H29 Cl2 F17 N2 O4'
_chemical_formula_sum            'C28 H29 Cl2 F17 N2 O4'
_chemical_formula_weight         851.43
_space_group_crystal_system      orthorhombic
_space_group_IT_number           29
_space_group_name_Hall           'P 2c -2ac'
_space_group_name_H-M_alt        'P c a 21'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_atom_sites_solution_secondary   difmap
_audit_creation_date             2018-12-10
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2024-02-26 deposited with the CCDC.	2024-05-21 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   11.0351(3)
_cell_length_b                   32.0681(9)
_cell_length_c                   9.7587(2)
_cell_measurement_reflns_used    7854
_cell_measurement_temperature    140.00(10)
_cell_measurement_theta_max      74.7110
_cell_measurement_theta_min      4.1040
_cell_volume                     3453.36(15)
_computing_cell_refinement       'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_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    'SHelXT (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      140.00(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.2665
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.987
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
  1  \w    -71.00  27.00   1.00   25.00    --  -43.01  57.00 -30.00   98
  2  \w    -67.00  30.00   1.00   25.00    --  -43.01  37.00-150.00   97
  3  \w   -116.00 -19.00   1.00   25.00    --  -43.01 -37.00  30.00   97
  4  \w     21.00  68.00   1.00   25.00    --   43.01 -99.00  60.00   47
  5  \w     43.00  78.00   1.00   25.00    --   43.01-125.00-120.00   35
  6  \w    110.00 160.00   1.00  100.00    --  109.26  30.00   0.00   50
  7  \w    107.00 133.00   1.00  100.00    --  109.26 -61.00   0.00   26
  8  \w    105.00 131.00   1.00  100.00    --  109.26 -77.00 150.00   26
  9  \w     42.00 132.00   1.00  100.00    --  109.26 -45.00 -30.00   90
 10  \w     29.00 102.00   1.00  100.00    --  109.26 -94.00 150.00   73
 11  \w     36.00 135.00   1.00  100.00    --  109.26 -45.00 120.00   99
 12  \w     51.00 127.00   1.00  100.00    --  109.26 -45.00-150.00   76
 13  \w     65.00 105.00   1.00  100.00    --  109.26 -94.00  60.00   40
 14  \w     82.00 109.00   1.00  100.00    --  109.26 -94.00-180.00   27
 15  \w     63.00 107.00   1.00  100.00    --  109.26-111.00 -30.00   44
 16  \w     33.00  99.00   1.00  100.00    --  109.26-111.00  30.00   66
 17  \w     24.00 170.00   1.00  100.00    --  109.26   0.00 -30.00  146
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0703983000
_diffrn_orient_matrix_UB_12      0.0414681000
_diffrn_orient_matrix_UB_13      -0.0029801000
_diffrn_orient_matrix_UB_21      0.1200291000
_diffrn_orient_matrix_UB_22      0.0240055000
_diffrn_orient_matrix_UB_23      -0.0171555000
_diffrn_orient_matrix_UB_31      -0.0118845000
_diffrn_orient_matrix_UB_32      -0.0034379000
_diffrn_orient_matrix_UB_33      -0.1568512000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0463
_diffrn_reflns_av_unetI/netI     0.0341
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.987
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       40
_diffrn_reflns_limit_k_min       -38
_diffrn_reflns_limit_l_max       7
_diffrn_reflns_limit_l_min       -11
_diffrn_reflns_number            23896
_diffrn_reflns_point_group_measured_fraction_full 0.793
_diffrn_reflns_point_group_measured_fraction_max 0.763
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.428
_diffrn_reflns_theta_min         4.136
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.901
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.454
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.46 (Rigaku Oxford Diffraction, 2018).
 Numerical absorption correction based on Gaussian integration over
 a multifaceted crystal model/Empirical absorption correction using
 spherical harmonics as implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.638
_exptl_crystal_description       plate
_exptl_crystal_F_000             1720
_exptl_crystal_size_max          0.504
_exptl_crystal_size_mid          0.134
_exptl_crystal_size_min          0.03
_refine_diff_density_max         0.543
_refine_diff_density_min         -0.279
_refine_diff_density_rms         0.048
_refine_ls_abs_structure_details
;
 Flack x determined using 1413 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.01(2)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.040
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     485
_refine_ls_number_reflns         5468
_refine_ls_number_restraints     4
_refine_ls_restrained_S_all      1.041
_refine_ls_R_factor_all          0.0443
_refine_ls_R_factor_gt           0.0391
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0585P)^2^+0.9413P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1015
_refine_ls_wR_factor_ref         0.1062
_reflns_Friedel_coverage         0.454
_reflns_Friedel_fraction_full    0.557
_reflns_Friedel_fraction_max     0.509
_reflns_number_gt                5000
_reflns_number_total             5468
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4md00211c2.cif
_cod_data_source_block           sz01
_cod_depositor_comments
;
The following automatic conversions were performed:

data item '_exptl_absorpt_correction_type' value 'Gaussian' was
changed to 'gaussian' in accordance with the
/home/data/users/saulius/crontab/automatic-downloads/rss-feeds/RSC/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 last updated on
2011-04-26.

Automatic conversion script
Id: cif_fix_values 8170 2020-07-09 18:12:32Z antanas 
;
_cod_original_cell_volume        3453.38(16)
_cod_database_code               7248683
_shelx_shelxl_version_number     2018/3
_audit_contact_author            'Farzaneh Fadaei Tirani'
_chemical_oxdiff_formula         'C28 H29 N2 O4 F17 Cl2'
_reflns_odcompleteness_completeness 99.94
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     68.13
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 Cl2-C28
 1.78 with sigma of 0.01
 C26-C25 \\sim C28-C27
 with sigma of 0.02
 N2-C25 \\sim N2-C27
 with sigma of 0.02
3.a Ternary CH refined with riding coordinates:
 C1(H1A)
3.b Secondary CH2 refined with riding coordinates:
 C3(H3A,H3B), C4(H4A,H4B), C18(H18A,H18B), C25(H25A,H25B), C26(H26A,H26B),
 C27(H27A,H27B), C28(H28A,H28B)
3.c Aromatic/amide H refined with riding coordinates:
 C20(H20), C21(H21), C23(H23), C24(H24)
3.d Idealised Me refined as rotating group:
 C15(H15A,H15B,H15C), C16(H16A,H16B,H16C), C17(H17A,H17B,H17C)
;
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
- Detector area scaling
- B-factor correction
;
_oxdiff_exptl_absorpt_empirical_full_max 1.630
_oxdiff_exptl_absorpt_empirical_full_min 0.655