Molecular bowls for inclusion complexation of toxic anticancer drug methotrexate
Karmakar, Pratik; Finnegan, Tyler J.; Rostam, Darian C.; Taneja, Sagarika; Uçar, Sefa; Hansen, Alexandar L.; Moore, Curtis E.; Hadad, Christopher M.; Pratumyot, Kornkanya; Parquette, Jon R.; Badjić, Jovica D.; Chemical Science 15 (2024) 10155–10163; doi:10.1039/D3SC05627A

data_1571738
_publ_section_title
;
 Molecular bowls for inclusion complexation of toxic anticancer drug
 methotrexate
;
_journal_issue                   26
_journal_name_full               'Chemical Science'
_journal_page_first              10155
_journal_page_last               10163
_journal_paper_doi               10.1039/D3SC05627A
_journal_volume                  15
_journal_year                    2024
_chemical_formula_moiety         'C92 H64 N6, 6(C2 F3 O2), 3[C2H3N]'
_chemical_formula_sum            'C110 H73 F17 N9 O12'
_chemical_formula_weight         2035.77
_space_group_crystal_system      trigonal
_space_group_IT_number           159
_space_group_name_Hall           'P 3 -2c'
_space_group_name_H-M_alt        'P 3 1 c'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2023-08-15
_audit_creation_method
;
Olex2 1.5-alpha
(compiled 2023.03.06 svn.rbb2c1857 for OlexSys, GUI svn.r6813)
;
_audit_update_record
;
2023-08-15 deposited with the CCDC.	2024-05-16 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                120
_cell_formula_units_Z            2
_cell_length_a                   25.2070(12)
_cell_length_b                   25.2070(12)
_cell_length_c                   14.9840(10)
_cell_measurement_reflns_used    9043
_cell_measurement_temperature    100.0
_cell_measurement_theta_max      20.826
_cell_measurement_theta_min      2.308
_cell_volume                     8245.2(8)
_computing_cell_refinement       'SAINT v8.40B (Bruker, 2021)'
_computing_data_collection       'APEX3 v2022.10-0 (Bruker, 2022)'
_computing_data_reduction        'SAINT v8.40B (Bruker, 2021)'
_computing_molecular_graphics    'Olex2 1.5-alpha (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5-alpha (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL  (Sheldrick, 2008)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      100.0
_diffrn_detector                 'Bruker Photon III area detector'
_diffrn_detector_area_resol_mean 10.5
_diffrn_detector_type            'CMOS area detector'
_diffrn_measured_fraction_theta_full 0.996
_diffrn_measured_fraction_theta_max 0.996
_diffrn_measurement_device       'Kappa Four-Circle Diffractometer'
_diffrn_measurement_device_type  'Bruker Kappa Photon III  MoTXS'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  'Double Bounce Multilayer Mirrors'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_radiation_xray_symbol    K-L~3~
_diffrn_reflns_av_R_equivalents  0.1244
_diffrn_reflns_av_unetI/netI     0.0702
_diffrn_reflns_Laue_measured_fraction_full 0.996
_diffrn_reflns_Laue_measured_fraction_max 0.996
_diffrn_reflns_limit_h_max       25
_diffrn_reflns_limit_h_min       -25
_diffrn_reflns_limit_k_max       25
_diffrn_reflns_limit_k_min       -25
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            41774
_diffrn_reflns_point_group_measured_fraction_full 0.991
_diffrn_reflns_point_group_measured_fraction_max 0.991
_diffrn_reflns_theta_full        20.868
_diffrn_reflns_theta_max         20.868
_diffrn_reflns_theta_min         1.866
_diffrn_source                   'Micro Focus Rotating Anode'
_diffrn_source_current           50.0
_diffrn_source_power             2.5
_diffrn_source_type              'Bruker TXS'
_diffrn_source_voltage           50.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.067
_exptl_absorpt_correction_T_max  0.0847
_exptl_absorpt_correction_T_min  0.0626
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2016/2 (Bruker,2016/2) was used for absorption correction.
wR2(int) was 0.1333 before and 0.0750 after correction.
The Ratio of minimum to maximum transmission is 0.7391.
The \l/2 correction factor is Not present.
;
_exptl_crystal_colour            yellow
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    0.820
_exptl_crystal_description       block
_exptl_crystal_F_000             2090
_exptl_crystal_size_max          0.452
_exptl_crystal_size_mid          0.232
_exptl_crystal_size_min          0.228
_refine_diff_density_max         0.603
_refine_diff_density_min         -0.389
_refine_diff_density_rms         0.093
_refine_ls_abs_structure_details
;
 Flack x determined using 878 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.9(6)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.396
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     334
_refine_ls_number_reflns         5758
_refine_ls_number_restraints     760
_refine_ls_restrained_S_all      1.380
_refine_ls_R_factor_all          0.2652
_refine_ls_R_factor_gt           0.1611
_refine_ls_shift/su_max          0.001
_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          0.3690
_refine_ls_wR_factor_ref         0.4500
_reflns_Friedel_coverage         0.983
_reflns_Friedel_fraction_full    0.987
_reflns_Friedel_fraction_max     0.987
_reflns_number_gt                2539
_reflns_number_total             5758
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3sc05627a2.cif
_cod_data_source_block           Badjic_PK20230327
_cod_depositor_comments
;
The following automatic conversions were performed:

data item '_diffrn_radiation_probe' value 'X-ray' was changed to
'x-ray' 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 

 Adding full bibliography for 1571738.cif.
;
_cod_original_cell_volume        8245.2(10)
_cod_database_code               1571738
_shelx_shelxl_version_number     2019/1
_olex2_refinement_description
;
1. Twinned data refinement
 Scales: 0.539(18)
 0.461(18)
2. 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
3. Restrained distances
 C6-C5 = C10-C5 = C10-C9 = C8-C9 = C8-C7 = C6-C7 = C13-C15 = C16-C15 = C17-C16
 = N1-C14 = N1-C17 = C13-C14 = C20-C21 = C20-C22 = C23-C22 = C24-C23 = N2-C24 =
 N2-C21 = C28-C27 = C31-C30 = C31-C26 = C26-C27 = C29-C28 = C29-C30
 1.39 with sigma of 0.005
 C29-C32 = N2-C32 = C26-C25 = N1-C25
 1.45 with sigma of 0.02
 C11-C12 = C19-C18
 1.1 with sigma of 0.02
 C14-C25
 2.5 with sigma of 0.02
 C17-C25
 2.5 with sigma of 0.02
 C21-C32
 2.5 with sigma of 0.02
 C24-C32
 2.5 with sigma of 0.02
 C30-C32
 2.5 with sigma of 0.02
 C32-C28
 2.5 with sigma of 0.02
 C27-C25
 2.5 with sigma of 0.02
 C31-C25
 2.5 with sigma of 0.02
 F7A-C6A = F8A-C6A
 1.34 with sigma of 0.02
 F9A-C6A
 1.33 with sigma of 0.02
 O5A-C5A
 1.25 with sigma of 0.02
 O6A-C5A
 1.24 with sigma of 0.02
 C5A-C6A
 1.55 with sigma of 0.02
 F1A-C2A = F3A-C2A
 1.34 with sigma of 0.02
 F2A-C2A
 1.33 with sigma of 0.02
 O1A-C1A
 1.25 with sigma of 0.02
 O2A-C1A
 1.24 with sigma of 0.02
 C1A-C2A
 1.55 with sigma of 0.02
 F5A-C4A = F4A-C4A
 1.34 with sigma of 0.02
 F6A-C4A
 1.33 with sigma of 0.02
 O3A-C3A
 1.25 with sigma of 0.02
 O4A-C3A
 1.24 with sigma of 0.02
 C3A-C4A
 1.55 with sigma of 0.02
 F12A-C8A = F10A-C8A
 1.34 with sigma of 0.02
 F11A-C8A
 1.33 with sigma of 0.02
 O8A-C7A
 1.25 with sigma of 0.02
 O7A-C7A
 1.24 with sigma of 0.02
 C7A-C8A
 1.55 with sigma of 0.02
 F7A-F9A = F9A-F8A
 2.16 with sigma of 0.04
 F7A-F8A
 2.15 with sigma of 0.04
 F7A-C5A
 2.37 with sigma of 0.04
 F9A-C5A
 2.42 with sigma of 0.04
 F8A-C5A
 2.39 with sigma of 0.04
 O5A-O6A
 2.25 with sigma of 0.04
 O5A-C6A
 2.38 with sigma of 0.04
 O6A-C6A
 2.35 with sigma of 0.04
 F1A-F2A = F2A-F3A
 2.16 with sigma of 0.04
 F1A-F3A
 2.15 with sigma of 0.04
 F1A-C1A
 2.37 with sigma of 0.04
 F2A-C1A
 2.42 with sigma of 0.04
 F3A-C1A
 2.39 with sigma of 0.04
 O1A-O2A
 2.25 with sigma of 0.04
 O1A-C2A
 2.38 with sigma of 0.04
 O2A-C2A
 2.35 with sigma of 0.04
 F5A-F6A = F6A-F4A
 2.16 with sigma of 0.04
 F5A-F4A
 2.15 with sigma of 0.04
 F5A-C3A
 2.37 with sigma of 0.04
 F6A-C3A
 2.42 with sigma of 0.04
 F4A-C3A
 2.39 with sigma of 0.04
 O3A-O4A
 2.25 with sigma of 0.04
 O3A-C4A
 2.38 with sigma of 0.04
 O4A-C4A
 2.35 with sigma of 0.04
 F12A-F11A = F11A-F10A
 2.16 with sigma of 0.04
 F12A-F10A
 2.15 with sigma of 0.04
 F12A-C7A
 2.37 with sigma of 0.04
 F11A-C7A
 2.42 with sigma of 0.04
 F10A-C7A
 2.39 with sigma of 0.04
 O8A-O7A
 2.25 with sigma of 0.04
 O8A-C8A
 2.38 with sigma of 0.04
 O7A-C8A
 2.35 with sigma of 0.04
 C6A-F7A \\sim C6A-F9A \\sim C6A-F8A
 with sigma of 0.02
 C5A-F7A \\sim C5A-F9A \\sim C5A-F8A
 with sigma of 0.04
 F7A-F9A \\sim F9A-F8A \\sim F8A-F7A
 with sigma of 0.04
 C5A-O6A \\sim C5A-O5A
 with sigma of 0.02
 C2A-F1A \\sim C2A-F2A \\sim C2A-F3A
 with sigma of 0.02
 C1A-F1A \\sim C1A-F2A \\sim C1A-F3A
 with sigma of 0.04
 F1A-F2A \\sim F2A-F3A \\sim F3A-F1A
 with sigma of 0.04
 C1A-O2A \\sim C1A-O1A
 with sigma of 0.02
 C4A-F5A \\sim C4A-F6A \\sim C4A-F4A
 with sigma of 0.02
 C3A-F5A \\sim C3A-F6A \\sim C3A-F4A
 with sigma of 0.04
 F5A-F6A \\sim F6A-F4A \\sim F4A-F5A
 with sigma of 0.04
 C3A-O4A \\sim C3A-O3A
 with sigma of 0.02
 C8A-F12A \\sim C8A-F11A \\sim C8A-F10A
 with sigma of 0.02
 C7A-F12A \\sim C7A-F11A \\sim C7A-F10A
 with sigma of 0.04
 F12A-F11A \\sim F11A-F10A \\sim F10A-F12A
 with sigma of 0.04
 C7A-O7A \\sim C7A-O8A
 with sigma of 0.02
4. Restrained planarity
 C11, C12, C13, C14, N1, C17, C16, C15, C25
 with sigma of 0.005
 C32, C25, C26, C27, C28, C29, C30, C31
 with sigma of 0.005
 C18, C19, C20, C22, C23, C24, N2, C21, C32
 with sigma of 0.005
 C5A, C6A, O5A, O6A
 with sigma of 0.1
 C1A, C2A, O1A, O2A
 with sigma of 0.1
 C3A, C4A, O3A, O4A
 with sigma of 0.1
 C7A, C8A, O8A, O7A
 with sigma of 0.1
5. Uiso/Uaniso restraints and constraints
F7A \\sim F9A \\sim F8A \\sim O5A \\sim O6A \\sim C5A \\sim C6A: within 2A with
sigma of 0.04 and sigma for terminal atoms of 0.08 within 2A
F1A \\sim F2A \\sim F3A \\sim O1A \\sim O2A \\sim C1A \\sim C2A: within 2A with
sigma of 0.04 and sigma for terminal atoms of 0.08 within 2A
F5A \\sim F6A \\sim F4A \\sim O3A \\sim O4A \\sim C3A \\sim C4A: within 2A with
sigma of 0.04 and sigma for terminal atoms of 0.08 within 2A
F12A \\sim F11A \\sim F10A \\sim O8A \\sim O7A \\sim C7A \\sim C8A: within 2A
with sigma of 0.04 and sigma for terminal atoms of 0.08 within 2A
Uanis(C31) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(C11) = Uanis(C18)
Uanis(C12) = Uanis(C19)
Uanis(C13) = Uanis(C20)
Uanis(C14) = Uanis(C21)
Uanis(N1) = Uanis(N2)
Uanis(C17) = Uanis(C24)
Uanis(C16) = Uanis(C23)
Uanis(C15) = Uanis(C22)
Uanis(O5A) = Uanis(F7A) = Uanis(C6A) = Uanis(F9A) = Uanis(F8A) = Uanis(C5A) =
Uanis(O6A) = Uanis(O1A) = Uanis(F1A) = Uanis(C2A) = Uanis(F2A) = Uanis(F3A) =
Uanis(C1A) = Uanis(O2A)
Uanis(C32) = Uanis(C29) = Uanis(C28) = Uanis(C27) = Uanis(C26) = Uanis(C31) =
Uanis(C25) = Uanis(C30)
6. 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
7. Others
 Fixed Sof: H32A(0.333333) H1A(0.333333) H1B(0.333333) H1C(0.333333)
 F7A(0.333333) F9A(0.333333) F8A(0.333333) O5A(0.333333) O6A(0.333333)
 C5A(0.333333) C6A(0.333333) F1A(0.666667) F2A(0.666667) F3A(0.333333)
 O1A(0.666667) O2A(0.666667) C1A(0.666667) C2A(0.666667) F5A(0.666667)
 F6A(0.666667) F4A(0.666667) O3A(0.666667) O4A(0.666667) C3A(0.666667)
 C4A(0.666667) F12A(0.333333) F11A(0.333333) F10A(0.333333) O8A(0.333333)
 O7A(0.333333) C7A(0.333333) C8A(0.333333)
8.a Secondary CH2 refined with riding coordinates:
 C32(H32A,H32B), C25(H25A,H25B)
8.b Aromatic/amide H refined with riding coordinates:
 C10(H10), C7(H7), C22(H22), C23(H23), C24(H24), C21(H21), C15(H15), C16(H16),
 C17(H17), C14(H14), C27(H27), C28(H28), C30(H30), C31(H31)
8.c Fitted hexagon refined as free rotating group:
 C5(C10,C9,C8,C7,C6), C20(C22,C23,C24,N2,C21), C13(C15,C16,C17,N1,C14),
 C26(C27,C28,C29,C30,C31)
8.d Idealised Me refined as rotating group:
 C4(H4A,H4B,H4C), C1(H1A,H1B,H1C)
;
_smtbx_masks_special_details
;
A solvent mask was calculated and 148 electrons were 
found in a volume of 3458\%A^3^ in 1 void per unit cell. 
This is consistent with the presence of 3[C2H3N] per 
Asymmetric Unit which account for 132 electrons 
per unit cell.
;
_smtbx_masks_void_probe_radius   1.2
_smtbx_masks_void_truncation_radius 1.2
_shelx_res_checksum              16632
_shelx_fab_checksum              19111
_olex2_submission_special_instructions 'No special instructions were received'