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_7248684
_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         'C30 H29 Cl2 F21 N2 O4'
_chemical_formula_sum            'C30 H29 Cl2 F21 N2 O4'
_chemical_formula_weight         951.45
_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   geom
_atom_sites_solution_primary     dual
_atom_sites_solution_secondary   difmap
_audit_creation_date             2018-12-12
_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                   10.9654(12)
_cell_length_b                   34.582(6)
_cell_length_c                   9.7715(13)
_cell_measurement_reflns_used    2938
_cell_measurement_temperature    140.00(10)
_cell_measurement_theta_max      65.0440
_cell_measurement_theta_min      3.7730
_cell_volume                     3705.4(9)
_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 0.996
_diffrn_measured_fraction_theta_max 0.978
_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    7.50    --   42.00  89.00 143.30   25
  2  \w    -77.00 -14.00   1.00    7.50    --  -42.51 -57.00  90.00   63
  3  \w   -116.00 -19.00   1.00    7.50    --  -42.51 -37.00-180.00   97
  4  \w    -96.00  -3.00   1.00    7.50    --  -42.51 125.00 120.00   93
  5  \w   -118.00 -10.00   1.00    7.50    --  -42.51 -77.00  60.00  108
  6  \w   -117.00 -18.00   1.00    7.50    --  -42.51 -37.00 -90.00   99
  7  \w     23.00  99.00   1.00    7.50    --   42.51-125.00  60.00   76
  8  \w     11.00  36.00   1.00    7.50    --   46.00  84.00 -76.92   25
  9  \w     12.00  37.00   1.00    7.50    --   46.00  81.00-155.96   25
 10  \w     11.00  36.00   1.00    7.50    --   46.00  84.00  49.73   25
 11  \w     17.00  44.00   1.00    7.50    --   50.00  80.00  23.79   27
 12  \w     20.00  45.00   1.00    7.50    --   54.00  81.00 -41.78   25
 13  \w     21.00  46.00   1.00    7.50    --   54.00  78.00 -77.26   25
 14  \w     20.00  45.00   1.00    7.50    --   54.00  81.00-134.94   25
 15  \w     29.00  56.00   1.00    7.50    --   62.00  77.00 108.55   27
 16  \w     29.00  56.00   1.00    7.50    --   62.00  77.00 145.84   27
 17  \w     80.00 124.00   1.00    7.50    --   62.00  77.00 145.84   44
 18  \w     29.00  59.00   1.00    7.50    --   62.00  77.00  63.48   30
 19  \w     34.00  60.00   1.00    7.50    --   66.00  75.00-179.88   26
 20  \w    107.00 134.00   1.00    7.50    --   70.00  77.00 -87.33   27
 21  \w     38.00  64.00   1.00    7.50    --   70.00  73.00-153.85   26
 22  \w     37.00  64.00   1.00    7.50    --   70.00  77.00 -29.35   27
 23  \w     37.00  64.00   1.00    7.50    --   70.00  77.00 -87.33   27
 24  \w     70.00  98.00   1.00    7.50    --   74.00  74.00  -0.86   28
 25  \w     41.00  67.00   1.00    7.50    --   74.00  77.00-119.08   26
 26  \w    122.00 147.00   1.00    7.50    --   74.00  74.00  -0.86   25
 27  \w     42.00  68.00   1.00    7.50    --   74.00  74.00  -0.86   26
 28  \w     41.00  67.00   1.00    7.50    --   74.00  77.00 -50.53   26
 29  \w    108.00 135.00   1.00    7.50    --   74.00  63.00 122.98   27
 30  \w     42.00  69.00   1.00    7.50    --   74.00  76.00-140.88   27
 31  \w     45.00  71.00   1.00    7.50    --   74.00  63.00 122.98   26
 32  \w     45.00  71.00   1.00   30.00    --   78.00  77.00 119.50   26
 33  \w     46.00  72.00   1.00   30.00    --   78.00  74.00  22.60   26
 34  \w     54.00  81.00   1.00   30.00    --   82.00  62.00 -90.98   27
 35  \w     95.00 158.00   1.00   30.00    --   82.00  77.00  58.03   63
 36  \w     49.00  75.00   1.00   30.00    --   82.00  77.00  58.03   26
 37  \w     49.00  77.00   1.00   30.00    --   82.00  77.00 151.65   28
 38  \w    122.00 152.00   1.00   30.00    --   86.00  70.00  35.87   30
 39  \w     55.00  82.00   1.00   30.00    --   86.00  70.00  35.87   27
 40  \w     57.00  84.00   1.00   30.00    --   86.00  66.00  77.02   27
 41  \w     60.00  86.00   1.00   30.00    --   90.00  68.00 -92.73   26
 42  \w     60.00  89.00   1.00   30.00    --   90.00  67.00 173.48   29
 43  \w     60.00  92.00   1.00   30.00    --   90.00  67.00 -34.46   32
 44  \w     62.00  91.00   1.00   30.00    --   94.00  73.00-140.69   29
 45  \w    110.00 169.00   1.00   30.00    --   98.00  67.00-154.16   59
 46  \w     68.00 102.00   1.00   30.00    --   98.00  67.00-154.16   34
 47  \w     66.00  93.00   1.00   30.00    --   98.00  74.00 -71.33   27
 48  \w     67.00  98.00   1.00   30.00    --   98.00  70.00 110.83   31
 49  \w     78.00 178.00   1.00   30.00    --  110.51  77.00 120.00  100
 50  \w    113.00 172.00   1.00   30.00    --  110.51  61.00  90.00   59
 51  \w     82.00 109.00   1.00   30.00    --  110.51  61.00  90.00   27
 52  \w     81.00 174.00   1.00   30.00    --  110.51  61.00-120.00   93
 53  \w     79.00 177.00   1.00   30.00    --  110.51  77.00 -60.00   98
 54  \w     78.00 143.00   1.00   30.00    --  110.51  77.00  30.00   65
 55  \w    110.00 138.00   1.00   30.00    --  110.51 -61.00  30.00   28
 56  \w     39.00 108.00   1.00   30.00    --  110.51 -61.00  30.00   69
 57  \w     97.00 125.00   1.00   30.00    --  110.51 -45.00-150.00   28
 58  \w     38.00  66.00   1.00   30.00    --  110.51 -45.00-150.00   28
 59  \w     82.00 172.00   1.00   30.00    --  110.51  61.00-180.00   90
 60  \w     78.00 152.00   1.00   30.00    --  110.51  77.00 -30.00   74
 61  \w    112.00 153.00   1.00   30.00    --  110.51  77.00  60.00   41
 62  \w     78.00 104.00   1.00   30.00    --  110.51  77.00  60.00   26
 63  \w     58.00 107.00   1.00   30.00    --  110.51 -94.00 120.00   49
 64  \w     32.00 107.00   1.00   30.00    --  110.51 -94.00 -60.00   75
 65  \w     29.00 109.00   1.00   30.00    --  110.51 -94.00  30.00   80
 66  \w     31.00 109.00   1.00   30.00    --  110.51 -94.00-150.00   78
 67  \w     78.00 172.00   1.00   30.00    --  110.51  77.00   0.00   94
 68  \w     83.00 172.00   1.00   30.00    --  110.51  61.00 -90.00   89
 69  \w    120.00 145.00   1.00   30.00    --  110.51  77.00 150.00   25
 70  \w     78.00 105.00   1.00   30.00    --  110.51  77.00 150.00   27
;
_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      0.0454535000
_diffrn_orient_matrix_UB_12      -0.0421125000
_diffrn_orient_matrix_UB_13      -0.0025657000
_diffrn_orient_matrix_UB_21      0.1315543000
_diffrn_orient_matrix_UB_22      0.0142009000
_diffrn_orient_matrix_UB_23      0.0233615000
_diffrn_orient_matrix_UB_31      -0.0189130000
_diffrn_orient_matrix_UB_32      -0.0027099000
_diffrn_orient_matrix_UB_33      0.1560226000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_unetI/netI     0.1664
_diffrn_reflns_Laue_measured_fraction_full 0.996
_diffrn_reflns_Laue_measured_fraction_max 0.978
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       43
_diffrn_reflns_limit_k_min       -43
_diffrn_reflns_limit_l_max       12
_diffrn_reflns_limit_l_min       -11
_diffrn_reflns_number            19475
_diffrn_reflns_point_group_measured_fraction_full 0.973
_diffrn_reflns_point_group_measured_fraction_max 0.942
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.510
_diffrn_reflns_theta_min         3.835
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.938
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.332
_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    1.706
_exptl_crystal_description       plate
_exptl_crystal_F_000             1912
_exptl_crystal_size_max          0.393
_exptl_crystal_size_mid          0.129
_exptl_crystal_size_min          0.036
_refine_diff_density_max         1.447
_refine_diff_density_min         -0.823
_refine_diff_density_rms         0.213
_refine_ls_abs_structure_details
;
 Classical Flack method preferred over Parsons because s.u. lower.
;
_refine_ls_abs_structure_Flack   0.27(8)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.212
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     566
_refine_ls_number_reflns         19475
_refine_ls_number_restraints     913
_refine_ls_restrained_S_all      1.220
_refine_ls_R_factor_all          0.2309
_refine_ls_R_factor_gt           0.1547
_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          0.3789
_refine_ls_wR_factor_ref         0.4328
_reflns_Friedel_coverage         0.813
_reflns_Friedel_fraction_full    0.946
_reflns_Friedel_fraction_max     0.902
_reflns_number_gt                8863
_reflns_number_total             19475
_reflns_threshold_expression     'I > 2\s(I)'
_twin_special_details
;
Component 2 rotated by 179.7469\% 
 around [-0.00 -0.09 1.00] (reciprocal) or [0.00 -0.01 1.00] (direct)
Component 3 rotated by 179.9905\% 
 around [-0.00 1.00 -0.02] (reciprocal) or [-0.01 0.98 -0.19] (direct)
Component 4 rotated by 1.6689\% 
 around [-1.00 0.08 0.04] (reciprocal) or [-1.00 0.01 0.05] (direct)
;
_cod_data_source_file            d4md00211c2.cif
_cod_data_source_block           zs3_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               7248684
_shelx_shelxl_version_number     2018/3
_audit_contact_author            'Farzaneh Fadaei Tirani'
_chemical_oxdiff_formula         'C30 H29 N2 O4 F21 Cl2'
_olex2_refinement_description
;
1. Twinned data refinement
 Scales: 0.193(15)
 0.228(8) 0.254(7) 0.325(10)
2. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
3. Restrained distances
 Cl2A-C30A = Cl2B-C30B
 1.78 with sigma of 0.01
 C28-C27 \\sim C30A-C29A
 with sigma of 0.01
 C30B-C29B \\sim C30A-C29A
 with sigma of 0.01
 C29A-Cl2A \\sim Cl2B-C29B
 with sigma of 0.01
 C27-N2 \\sim C29A-N2
 with sigma of 0.01
 C28-N2 \\sim N2-C30A
 with sigma of 0.01
 C29A-N2 \\sim N2-C29B
 with sigma of 0.01
 Cl1-C27 \\sim Cl2A-C29A
 with sigma of 0.01
4. Uiso/Uaniso restraints and constraints
All non-hydrogen atoms have similar U: 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. Others
 Sof(Cl2B)=Sof(C29B)=Sof(H29C)=Sof(H29D)=Sof(C30B)=Sof(H30C)=Sof(H30D)=1-FVAR(1)
 Sof(Cl2A)=Sof(C29A)=Sof(H29A)=Sof(H29B)=Sof(C30A)=Sof(H30A)=Sof(H30B)=FVAR(1)
7.a Ternary CH refined with riding coordinates:
 C1(H1A)
7.b Secondary CH2 refined with riding coordinates:
 C3(H3A,H3B), C4(H4A,H4B), C20(H20A,H20B), C27(H27A,H27B), C28(H28A,H28B),
 C29A(H29A,H29B), C29B(H29C,H29D), C30A(H30A,H30B), C30B(H30C,H30D)
7.c Aromatic/amide H refined with riding coordinates:
 N1(H1), C22(H22), C23(H23), C25(H25), C26(H26)
7.d Idealised Me refined as rotating group:
 C17(H17A,H17B,H17C), C18(H18A,H18B,H18C), C19(H19A,H19B,H19C)
;
_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 5.361
_oxdiff_exptl_absorpt_empirical_full_min 0.247
_oxdiff_twin_integration_method  simultaneous
_oxdiff_twin_items               4