Fluorine-18 incorporation and radiometal coordination in macropa ligands for PET imaging and targeted alpha therapy.
Kanagasundaram, Thines; Sun, Yang; Lee, Kevin K.; MacMillan, Samantha N.; Brugarolas, Pedro; Wilson, Justin J.; Chemical communications (Cambridge, England) 60 (2024) 11940–11943; doi:10.1039/d4cc04165h

data_7133790
_publ_section_title
;
 Fluorine-18 incorporation and radiometal coordination in macropa ligands
 for PET imaging and targeted alpha therapy.
;
_journal_issue                   83
_journal_name_full               'Chemical communications (Cambridge, England)'
_journal_page_first              11940
_journal_page_last               11943
_journal_paper_doi               10.1039/d4cc04165h
_journal_volume                  60
_journal_year                    2024
_chemical_formula_moiety         'C27 H37 Bi F N6 Na O15, 1[CH4O]'
_chemical_formula_sum            'C27 H36 Bi F N6 Na O15'
_chemical_formula_weight         935.59
_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   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2024-01-30
_audit_creation_method
;
Olex2 1.5-ac5-024
(compiled 2022.04.12 svn.rca3783a0 for Rigaku Oxford Diffraction, GUI svn.r6498)
;
_audit_update_record
;
2024-08-15 deposited with the CCDC.	2024-09-20 downloaded from the CCDC.
;
_cell_angle_alpha                68.9380(10)
_cell_angle_beta                 85.2210(10)
_cell_angle_gamma                79.1070(10)
_cell_formula_units_Z            2
_cell_length_a                   10.17370(10)
_cell_length_b                   12.42250(10)
_cell_length_c                   15.0689(2)
_cell_measurement_reflns_used    57061
_cell_measurement_temperature    108.29(10)
_cell_measurement_theta_max      31.6570
_cell_measurement_theta_min      2.4530
_cell_volume                     1744.95(3)
_computing_cell_refinement       'CrysAlisPro 1.171.42.89a (Rigaku OD, 2023)'
_computing_data_collection       'CrysAlisPro 1.171.42.89a (Rigaku OD, 2023)'
_computing_data_reduction        'CrysAlisPro 1.171.42.89a (Rigaku OD, 2023)'
_computing_molecular_graphics    'Olex2 1.5-ac5-024 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5-ac5-024 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2016/6 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      108.29(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.999
_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    -67.00  17.00   0.50    1.47    --    5.46 -32.00   6.26  168
  2  \w    -67.00  17.00   0.50    1.47    --    5.46 -32.00  89.04  168
  3  \w    -16.00  68.00   0.50    1.47    --   -6.00  34.00 139.25  168
  4  \w    -16.00  69.00   0.50    1.47    --   -6.00  25.00  32.30  170
  5  \w    -23.00  25.00   0.50    1.47    --   -6.00 -99.00 -30.00   96
  6  \w    -17.00  68.00   0.50    1.47    --   -6.00  29.00-121.29  170
  7  \w    -23.00  25.00   0.50    1.47    --   -6.00 -99.00 120.00   96
  8  \w    -17.00  67.00   0.50    1.47    --   -6.00  30.00 112.49  168
  9  \w    -23.00  25.00   0.50    1.47    --   -6.00 -99.00-180.00   96
 10  \w    -23.00  25.00   0.50    1.47    --   -6.00 -99.00  60.00   96
 11  \w    -16.00  67.00   0.50    1.47    --   -6.00  37.00-180.00  166
 12  \w    -23.00  25.00   0.50    1.47    --   -6.00 -99.00-120.00   96
 13  \w    -16.00  67.00   0.50    1.47    --   -6.00  37.00 -90.00  166
 14  \w    -16.00  68.00   0.50    1.47    --   -6.00  31.00 -36.97  168
 15  \w    -23.00  37.00   0.50    1.47    --    5.46 -99.00 -60.00  120
 16  \w    -23.00  25.00   0.50    1.47    --   -6.00 -99.00   0.00   96
 17  \w    -16.00  66.00   0.50    1.47    --   -6.00  34.00 -60.83  164
 18  \w    -16.00  68.00   0.50    1.47    --   -6.00  34.00  57.46  168
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0169396000
_diffrn_orient_matrix_UB_12      0.0062079000
_diffrn_orient_matrix_UB_13      0.0447376000
_diffrn_orient_matrix_UB_21      0.0121897000
_diffrn_orient_matrix_UB_22      -0.0617704000
_diffrn_orient_matrix_UB_23      0.0224606000
_diffrn_orient_matrix_UB_31      0.0678723000
_diffrn_orient_matrix_UB_32      0.0015323000
_diffrn_orient_matrix_UB_33      0.0062450000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Mo K\a'
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0488
_diffrn_reflns_av_unetI/netI     0.0214
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            74691
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.999
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         27.103
_diffrn_reflns_theta_min         2.469
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    5.147
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.402
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.89a (Rigaku Oxford Diffraction, 2023)
Numerical absorption correction based on gaussian integration over
a multifaceted crystal model
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear colourless'
_exptl_crystal_density_diffrn    1.781
_exptl_crystal_description       plate
_exptl_crystal_F_000             926
_exptl_crystal_size_max          0.277
_exptl_crystal_size_mid          0.084
_exptl_crystal_size_min          0.066
_refine_diff_density_max         0.982
_refine_diff_density_min         -0.663
_refine_diff_density_rms         0.094
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.048
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     516
_refine_ls_number_reflns         7683
_refine_ls_number_restraints     47
_refine_ls_restrained_S_all      1.047
_refine_ls_R_factor_all          0.0218
_refine_ls_R_factor_gt           0.0192
_refine_ls_shift/su_max          0.003
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0233P)^2^+1.4736P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0442
_refine_ls_wR_factor_ref         0.0450
_reflns_Friedel_coverage         0.000
_reflns_number_gt                7212
_reflns_number_total             7683
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4cc04165h2.cif
_cod_data_source_block           rtk4_abs2
_cod_depositor_comments          'Adding full bibliography for 7133790.cif.'
_cod_database_code               7133790
_shelx_shelxl_version_number     2016/6
_chemical_oxdiff_formula         C27H41BiFN6O16
_chemical_oxdiff_usercomment     'Crystallized from MeOH/Et2O.'
_shelx_estimated_absorpt_t_max   0.728
_shelx_estimated_absorpt_t_min   0.330
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All O(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 O15-H15
 0.88 with sigma of 0.02
 O15B-H15C
 0.88 with sigma of 0.02
 C27-H15
 1.8746 with sigma of 0.02
 Na-H15
 2.780237 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
O15 \\sim O15B \\sim C28 \\sim C27: within 2A with sigma of 0.04 and sigma for
terminal atoms of 0.08 within 2A
4. Rigid body (RIGU) restrains
 O15, O15B, C28, C27
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
5. Same fragment restrains
{O15B, C28} sigma for 1-2: 0.02, 1-3: 0.02
as in
{O15, C27}
6. Others
 Sof(O12B)=Sof(O13B)=1-FVAR(1)
 Sof(O12)=Sof(O13)=FVAR(1)
 Sof(F1B)=Sof(H4)=1-FVAR(2)
 Sof(F1)=Sof(H23)=FVAR(2)
 Sof(O15B)=Sof(H15C)=Sof(C28)=Sof(H28A)=Sof(H28B)=Sof(H28C)=1-FVAR(3)
 Sof(O15)=Sof(H15)=Sof(C27)=Sof(H27A)=Sof(H27B)=Sof(H27C)=FVAR(3)
7.a Secondary CH2 refined with riding coordinates:
 C7(H7A,H7B), C8(H8A,H8B), C9(H9A,H9B), C10(H10A,H10B), C11(H11A,H11B),
 C12(H12A,H12B), C13(H13A,H13B), C14(H14A,H14B), C15(H15A,H15B), C16(H16A,H16B),
  C17(H17A,H17B), C18(H18A,H18B), C19(H19A,H19B), C20(H20A,H20B)
7.b Aromatic/amide H refined with riding coordinates:
 C3(H3), C4(H4), C5(H5), C22(H22), C23(H23), C24(H24)
7.c Idealised Me refined as rotating group:
 C27(H27A,H27B,H27C), C28(H28A,H28B,H28C)
;
_smtbx_masks_void_probe_radius   1.2
_smtbx_masks_void_truncation_radius 1.2
_shelx_res_checksum              1879
_shelx_hkl_checksum              23439
_shelx_fab_checksum              5157
_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 1.258
_oxdiff_exptl_absorpt_empirical_full_min 0.809