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_7248681
_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         'C26 H29 Cl2 F13 N2 O4'
_chemical_formula_sum            'C26 H29 Cl2 F13 N2 O4'
_chemical_formula_weight         751.41
_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             2018-12-11
_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                   10.97900(20)
_cell_length_b                   30.0354(5)
_cell_length_c                   9.7195(2)
_cell_measurement_reflns_used    18070
_cell_measurement_temperature    140.01(10)
_cell_measurement_theta_max      74.6190
_cell_measurement_theta_min      4.2380
_cell_volume                     3205.09(10)
_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      140.01(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 0.992
_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      5.00  30.00   1.00    5.00    --   42.00  89.00-103.04   25
  2  \w   -115.00 -15.00   1.00    5.00    --  -43.13 -57.00 -90.00  100
  3  \w   -112.00 -18.00   1.00    5.00    --  -43.13 -57.00-180.00   94
  4  \w   -117.00 -19.00   1.00    5.00    --  -43.13 -37.00   0.00   98
  5  \w    -70.00  29.00   1.00    5.00    --  -43.13  57.00 -30.00   99
  6  \w     69.00 104.00   1.00    5.00    --   43.13  66.00  -5.63   35
  7  \w     13.00  39.00   1.00    5.00    --   43.13  66.00  -5.63   26
  8  \w     31.00  99.00   1.00    5.00    --   43.13-125.00-150.00   68
  9  \w     11.00  36.00   1.00    5.00    --   46.00  84.00  15.80   25
 10  \w     11.00  36.00   1.00    5.00    --   46.00  84.00  89.44   25
 11  \w     17.00  42.00   1.00    5.00    --   50.00  80.00  85.85   25
 12  \w     20.00  46.00   1.00    5.00    --   54.00  81.00 -33.27   26
 13  \w     20.00  45.00   1.00    5.00    --   54.00  81.00 -92.12   25
 14  \w     20.00  45.00   1.00    5.00    --   54.00  81.00 151.51   25
 15  \w     20.00  45.00   1.00    5.00    --   54.00  81.00-149.23   25
 16  \w     30.00  57.00   1.00    5.00    --   62.00  75.00  34.10   27
 17  \w     33.00  59.00   1.00    5.00    --   66.00  77.00-101.07   26
 18  \w     33.00  62.00   1.00    5.00    --   66.00  77.00 101.96   29
 19  \w     36.00  62.00   1.00    5.00    --   66.00  65.00  79.36   26
 20  \w     38.00  65.00   1.00    5.00    --   70.00  77.00  78.24   27
 21  \w     38.00  65.00   1.00    5.00    --   70.00  75.00-167.86   27
 22  \w     91.00 144.00   1.00    5.00    --   70.00  77.00 -60.88   53
 23  \w     37.00  63.00   1.00    5.00    --   70.00  77.00 -60.88   26
 24  \w     43.00  70.00   1.00    5.00    --   74.00  77.00 -47.96   27
 25  \w     42.00  68.00   1.00    5.00    --   74.00  76.00-140.85   26
 26  \w     41.00  67.00   1.00    5.00    --   74.00  77.00 149.92   26
 27  \w    111.00 150.00   1.00    5.00    --   74.00  76.00-140.85   39
 28  \w    126.00 153.00   1.00   20.00    --   78.00  77.00 154.12   27
 29  \w     48.00  74.00   1.00   20.00    --   78.00  77.00 154.12   26
 30  \w     47.00  73.00   1.00   20.00    --   78.00  70.00  17.71   26
 31  \w     50.00  76.00   1.00   20.00    --   82.00  73.00 -24.18   26
 32  \w     55.00  82.00   1.00   20.00    --   82.00  64.00-118.70   27
 33  \w     58.00  83.00   1.00   20.00    --   86.00  59.00 -59.41   25
 34  \w     54.00  80.00   1.00   20.00    --   86.00  74.00 118.16   26
 35  \w     59.00  85.00   1.00   20.00    --   90.00  71.00-105.80   26
 36  \w     58.00  84.00   1.00   20.00    --   90.00  74.00  34.12   26
 37  \w     62.00  93.00   1.00   20.00    --   94.00  76.00  76.30   31
 38  \w     97.00 168.00   1.00   20.00    --   94.00  75.00 172.06   71
 39  \w     62.00  88.00   1.00   20.00    --   94.00  75.00 172.06   26
 40  \w     66.00 136.00   1.00   20.00    --   98.00  74.00-163.52   70
 41  \w    122.00 170.00   1.00   20.00    --   98.00  69.00 124.99   48
 42  \w     67.00  94.00   1.00   20.00    --   98.00  69.00 124.99   27
 43  \w     67.00 157.00   1.00   20.00    --   98.00  69.00  14.34   90
 44  \w    148.00 173.00   1.00   20.00    --   98.00  74.00-163.52   25
 45  \w    134.00 178.00   1.00   20.00    --  109.26 111.00   0.00   44
 46  \w     80.00 161.00   1.00   20.00    --  109.26  61.00  60.00   81
 47  \w     78.00 149.00   1.00   20.00    --  109.26  77.00-150.00   71
 48  \w     79.00 175.00   1.00   20.00    --  109.26  77.00-120.00   96
 49  \w     78.00 162.00   1.00   20.00    --  109.26  77.00 -60.00   84
 50  \w    138.00 178.00   1.00   20.00    --  109.26  77.00  30.00   40
 51  \w     77.00 103.00   1.00   20.00    --  109.26  77.00  30.00   26
 52  \w     77.00 178.00   1.00   20.00    --  109.26  77.00 -90.00  101
 53  \w     78.00 171.00   1.00   20.00    --  109.26  77.00  90.00   93
 54  \w     81.00 174.00   1.00   20.00    --  109.26  61.00 150.00   93
 55  \w     34.00 138.00   1.00   20.00    --  109.26 -77.00  60.00  104
 56  \w    150.00 177.00   1.00   20.00    --  109.26 111.00  90.00   27
 57  \w     77.00 178.00   1.00   20.00    --  109.26  77.00 -30.00  101
 58  \w     33.00 104.00   1.00   20.00    --  109.26 -94.00 -60.00   71
 59  \w     43.00 108.00   1.00   20.00    --  109.26 -94.00  30.00   65
 60  \w     60.00 116.00   1.00   20.00    --  109.26-111.00-120.00   56
;
_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      0.1306674000
_diffrn_orient_matrix_UB_12      0.0132937000
_diffrn_orient_matrix_UB_13      -0.0403779000
_diffrn_orient_matrix_UB_21      -0.0358124000
_diffrn_orient_matrix_UB_22      0.0495100000
_diffrn_orient_matrix_UB_23      0.0077027000
_diffrn_orient_matrix_UB_31      0.0363289000
_diffrn_orient_matrix_UB_32      0.0010361000
_diffrn_orient_matrix_UB_33      0.1531951000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0538
_diffrn_reflns_av_unetI/netI     0.0239
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.992
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       37
_diffrn_reflns_limit_k_min       -37
_diffrn_reflns_limit_l_max       11
_diffrn_reflns_limit_l_min       -11
_diffrn_reflns_number            57908
_diffrn_reflns_point_group_measured_fraction_full 0.992
_diffrn_reflns_point_group_measured_fraction_max 0.973
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.376
_diffrn_reflns_theta_min         4.288
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.855
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.534
_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_density_diffrn    1.557
_exptl_crystal_description       plate
_exptl_crystal_F_000             1528
_exptl_crystal_size_max          0.678
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.027
_refine_diff_density_max         0.313
_refine_diff_density_min         -0.250
_refine_diff_density_rms         0.047
_refine_ls_abs_structure_details
;
 Flack x determined using 2483 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.003(11)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.026
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     431
_refine_ls_number_reflns         6448
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.026
_refine_ls_R_factor_all          0.0426
_refine_ls_R_factor_gt           0.0370
_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^)+(0.0550P)^2^+0.9320P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0912
_refine_ls_wR_factor_ref         0.0961
_reflns_Friedel_coverage         0.845
_reflns_Friedel_fraction_full    0.984
_reflns_Friedel_fraction_max     0.953
_reflns_number_gt                5851
_reflns_number_total             6448
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4md00211c2.cif
_cod_data_source_block           sz02
_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        3205.10(11)
_cod_database_code               7248681
_shelx_shelxl_version_number     2018/3
_audit_contact_author            'Farzaneh Fadaei Tirani'
_chemical_oxdiff_formula         'C26 H29 N2 O4 F13 Cl2'
_chemical_oxdiff_usercomment     'black crystal'
_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.a Ternary CH refined with riding coordinates:
 C1(H1A)
2.b Secondary CH2 refined with riding coordinates:
 C3(H3A,H3B), C4(H4A,H4B), C16(H16A,H16B), C23(H23A,H23B), C24(H24A,H24B),
 C25(H25A,H25B), C26(H26A,H26B)
2.c Aromatic/amide H refined with riding coordinates:
 C18(H18), C19(H19), C21(H21), C22(H22)
2.d Idealised Me refined as rotating group:
 C13(H13A,H13B,H13C), C14(H14A,H14B,H14C), C15(H15A,H15B,H15C)
;
_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 1.917
_oxdiff_exptl_absorpt_empirical_full_min 0.661