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_7248682
_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_absolute_configuration rmad
_chemical_formula_moiety         'C23 H22 Cl2 F17 N2 O2, Cl, C2 H3 N'
_chemical_formula_sum            'C25 H25 Cl3 F17 N3 O2'
_chemical_formula_weight         828.83
_space_group_crystal_system      monoclinic
_space_group_IT_number           5
_space_group_name_Hall           'I 2y'
_space_group_name_H-M_alt        'I 1 2 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_atom_sites_solution_secondary   difmap
_audit_creation_date             2018-12-14
_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                 96.882(6)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   22.4357(14)
_cell_length_b                   5.2436(3)
_cell_length_c                   27.9895(18)
_cell_measurement_reflns_used    2123
_cell_measurement_temperature    99.99(10)
_cell_measurement_theta_max      73.0650
_cell_measurement_theta_min      4.8010
_cell_volume                     3269.1(3)
_computing_cell_refinement       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_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      99.99(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.2665
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 0.958
_diffrn_measured_fraction_theta_max 0.958
_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   -116.00 -10.00   1.00    7.50    --  -42.76 -77.00 120.00  106
  2  \w    -71.00  23.00   1.00    7.50    --  -42.76  57.00 -90.00   94
  3  \w   -124.00 -88.00   1.00    7.50    --  -42.76 -99.00 -90.00   36
  4  \w     36.00 117.00   1.00    7.50    --   42.76  37.00   0.00   81
  5  \w     39.00 105.00   1.00    7.50    --   42.76-145.00  78.00   66
  6  \w     89.00 133.00   1.00   50.00    --  109.26  61.00  60.00   44
  7  \w     82.00 137.00   1.00   50.00    --  109.26 -61.00  60.00   55
  8  \w     39.00 129.00   1.00   50.00    --  109.26 -77.00-150.00   90
  9  \w     78.00 108.00   1.00   50.00    --  109.26-126.00-113.00   30
 10  \w     37.00  64.00   1.00   50.00    --  109.26-126.00-113.00   27
 11  \w     80.00 108.00   1.00   50.00    --  109.26  61.00  30.00   28
 12  \w    135.00 176.00   1.00   50.00    --  109.26  61.00  30.00   41
 13  \w     45.00 131.00   1.00   50.00    --  109.26 -45.00-120.00   86
 14  \w     45.00 133.00   1.00   50.00    --  109.26 -45.00  30.00   88
 15  \w     34.00  62.00   1.00   50.00    --  109.26-111.00 -60.00   28
 16  \w     78.00 113.00   1.00   50.00    --  109.26-111.00-180.00   35
 17  \w     60.00 107.00   1.00   50.00    --  109.26-111.00  30.00   47
 18  \w     84.00 109.00   1.00   50.00    --  109.26-111.00 -60.00   25
 19  \w     27.00 108.00   1.00   50.00    --  109.26 -94.00  60.00   81
 20  \w     21.00 178.00   1.00   50.00    --  109.26   0.00  30.00  157
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0576980000
_diffrn_orient_matrix_UB_12      -0.0013221000
_diffrn_orient_matrix_UB_13      -0.0358729000
_diffrn_orient_matrix_UB_21      0.0379969000
_diffrn_orient_matrix_UB_22      0.0226519000
_diffrn_orient_matrix_UB_23      -0.0421608000
_diffrn_orient_matrix_UB_31      0.0032660000
_diffrn_orient_matrix_UB_32      -0.2928850000
_diffrn_orient_matrix_UB_33      -0.0031142000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_unetI/netI     0.0621
_diffrn_reflns_Laue_measured_fraction_full 0.958
_diffrn_reflns_Laue_measured_fraction_max 0.958
_diffrn_reflns_limit_h_max       26
_diffrn_reflns_limit_h_min       -22
_diffrn_reflns_limit_k_max       4
_diffrn_reflns_limit_k_min       -6
_diffrn_reflns_limit_l_max       32
_diffrn_reflns_limit_l_min       -32
_diffrn_reflns_number            5297
_diffrn_reflns_point_group_measured_fraction_full 0.744
_diffrn_reflns_point_group_measured_fraction_max 0.744
_diffrn_reflns_theta_full        65.070
_diffrn_reflns_theta_max         65.070
_diffrn_reflns_theta_min         4.946
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    3.741
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.289
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46 (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_density_diffrn    1.684
_exptl_crystal_description       needle
_exptl_crystal_F_000             1664
_exptl_crystal_size_max          0.717
_exptl_crystal_size_mid          0.069
_exptl_crystal_size_min          0.03
_refine_diff_density_max         1.630
_refine_diff_density_min         -1.471
_refine_diff_density_rms         0.223
_refine_ls_abs_structure_details
;
 Classical Flack method preferred over Parsons because s.u. lower.
;
_refine_ls_abs_structure_Flack   -0.01(8)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.830
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     454
_refine_ls_number_reflns         5297
_refine_ls_number_restraints     562
_refine_ls_restrained_S_all      1.803
_refine_ls_R_factor_all          0.2102
_refine_ls_R_factor_gt           0.1769
_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^)+(0.2000P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.4322
_refine_ls_wR_factor_ref         0.4649
_reflns_Friedel_coverage         0.386
_reflns_Friedel_fraction_full    0.472
_reflns_Friedel_fraction_max     0.472
_reflns_number_gt                3614
_reflns_number_total             5297
_reflns_threshold_expression     'I > 2\s(I)'
_twin_special_details
;
Component 2 rotated by 1.8999\% 
 around [0.92 0.13 0.36] (reciprocal) or [0.36 0.92 0.12] (direct)
;
_cod_data_source_file            d4md00211c2.cif
_cod_data_source_block           mf7_hklf5
_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_database_code               7248682
_shelx_shelxl_version_number     2018/3
_audit_contact_author            'Farzaneh Fadaei Tirani'
_chemical_oxdiff_formula         'C23 H22 N2 O2F17 Cl3'
_olex2_refinement_description
;
1. Twinned data refinement
 Scales: 0.528(16)
 0.472(16)
2. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H,H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
3. Restrained distances
 F2-C5 = F1-C5
 1.33 with sigma of 0.01
 F3-C6 = F4-C6
 1.33 with sigma of 0.01
 C4-C5 = C5-C6 = C7-C6 = C7-C8 = C9-C8 = C10-C9
 1.54 with sigma of 0.01
 F8-C8 = F7-C8
 1.33 with sigma of 0.01
 F11-C10 = F12-C10
 1.33 with sigma of 0.01
 F10-C9 = F9-C9 = F8-C8 = F7-C8 = F6-C7 = F5-C7 = F4-C6 = F3-C6 = F1-C5 = F2-C5
 1.33 with sigma of 0.01
 C11-C10 = C10-C9 = C9-C8 = C7-C8 = C7-C6 = C5-C6 = C4-C5
 1.54 with sigma of 0.01
 F14-C11 = F13-C11
 1.33 with sigma of 0.01
 C11-C12
 1.54 with sigma of 0.01
 F17-C12 = F16-C12 = F15-C12
 1.33 with sigma of 0.01
 F15-F16
 2.15 with sigma of 0.01
 F16-F17
 2.15 with sigma of 0.01
 F17-F15
 2.15 with sigma of 0.01
 C11-F16
 2.3 with sigma of 0.01
 F2-F1
 2.15 with sigma of 0.01
 F3-F4
 2.15 with sigma of 0.01
 F5-F6
 2.15 with sigma of 0.01
 F7-F8
 2.15 with sigma of 0.01
 F9-F10
 2.15 with sigma of 0.01
 F11-F12
 2.15 with sigma of 0.01
 F14-F13
 2.15 with sigma of 0.01
 F15-F17 \\sim F17-F16
 with sigma of 0.02
4. Uiso/Uaniso restraints and constraints
F1 \\sim F2 \\sim F3 \\sim F4 \\sim F5 \\sim F6 \\sim F7 \\sim F8 \\sim F9
\\sim F10 \\sim F11 \\sim F12 \\sim F13 \\sim F14 \\sim F15 \\sim F16 \\sim F17
\\sim C5 \\sim C6 \\sim C7 \\sim C8 \\sim C9 \\sim C10 \\sim C11 \\sim C12:
within 2A with sigma of 0.001 and sigma for terminal atoms of 0.002
5. Rigid body (RIGU) restrains
 All non-hydrogen atoms
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
6.a Ternary CH refined with riding coordinates:
 C1(H1)
6.b Secondary CH2 refined with riding coordinates:
 C3(H3A,H3B), C4(H4A,H4B), C13(H13A,H13B), C20(H20A,H20B), C21(H21A,H21B),
 C22(H22A,H22B), C23(H23A,H23B)
6.c Aromatic/amide H refined with riding coordinates:
 C15(H15), C16(H16), C18(H18), C19(H19)
6.d Idealised Me refined as rotating group:
 N1(H1A,H1B,H1C), C25(H25A,H25B,H25C)
;
_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
;
_oxdiff_exptl_absorpt_empirical_full_max 4.861
_oxdiff_exptl_absorpt_empirical_full_min 0.292
_oxdiff_twin_integration_method  simultaneous
_oxdiff_twin_items               2