Structural flexibility of favipiravir and its structural analogues in solutions: experimental and computational insight.
Gerasimova, Tatiana P.; Zagidullin, Almaz A.; Nikolaeva, Anastasiia N.; Fayzullin, Robert R.; Saitova, Aliya M.; Miluykov, Vasili A.; Grimme, Stefan; Katsyuba, Sergey A.; Organic & biomolecular chemistry 22 (2024) 3668–3683; doi:10.1039/d4ob00404c

data_7159894
_publ_section_title
;
 Structural flexibility of favipiravir and its structural analogues in
 solutions: experimental and computational insight.
;
_journal_issue                   18
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              3668
_journal_page_last               3683
_journal_paper_doi               10.1039/d4ob00404c
_journal_volume                  22
_journal_year                    2024
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C7 H8 N4 O4'
_chemical_formula_sum            'C7 H8 N4 O4'
_chemical_formula_weight         212.17
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_atom_sites_solution_hydrogens   mixed
_audit_creation_method           SHELXL-2018/3
_audit_update_record
;
2024-02-18 deposited with the CCDC.	2024-04-09 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 102.0641(10)
_cell_angle_gamma                90
_cell_formula_units_Z            12
_cell_length_a                   11.6092(5)
_cell_length_b                   15.2706(7)
_cell_length_c                   15.2983(7)
_cell_measurement_reflns_used    52924
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      34.95
_cell_measurement_theta_min      2.41
_cell_volume                     2652.2(2)
_computing_cell_refinement       'APEX4 v2021.10-0 (Bruker AXS)'
_computing_data_collection       'APEX4 v2021.10-0 (Bruker AXS)'
_computing_data_reduction        'APEX4 v2021.10-0 (Bruker AXS)'
_computing_molecular_graphics
;
WinGX (Farrugia, 2012); ORTEP-3 (Farrugia, 2012);
PLATON (Spek, 2009); Olex2 (Dolomanov et al., 2009)
;
_computing_publication_material
;
WinGX (Farrugia, 2012); ORTEP-3 (Farrugia, 2012);
PLATON (Spek, 2009); Olex2 (Dolomanov et al., 2009)
;
_computing_structure_refinement  'SHELXL-2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT-2018/2 (Sheldrick, 2015)'
_diffrn_ambient_temperature      100(2)
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.997
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_unetI/netI     0.0396
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.997
_diffrn_reflns_limit_h_max       18
_diffrn_reflns_limit_h_min       -18
_diffrn_reflns_limit_k_max       24
_diffrn_reflns_limit_k_min       -24
_diffrn_reflns_limit_l_max       24
_diffrn_reflns_limit_l_min       -24
_diffrn_reflns_number            23264
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.996
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         35.022
_diffrn_reflns_theta_min         1.361
_diffrn_source                   'sealed tube'
_exptl_absorpt_coefficient_mu    0.133
_exptl_absorpt_correction_T_max  0.841176
_exptl_absorpt_correction_T_min  0.504965
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2016/2 (Stalke et al., 2015)

 Equivalent reflections defined according to point group 2
 Mean and maximum errors in direction cosine check function =   0.000   0.002
 Restraint esd for equal adjacent scale factors =  0.0090
 Maximum odd and even orders for spherical harmonics =   1   4

 Parameter refinement for twin component  1
 ------------------------------------------
   63575 single and      0 composite reflections used for parameter fitting
 Effective data to parameter ratio =   18.43
 wR2(int) =  0.1535 (selected reflections only, before parameter refinement)
 wR2(int) =  0.0776 (selected reflections only, after parameter refinement)

 Parameter refinement for twin component  2
 ------------------------------------------
   53895 single and      0 composite reflections used for parameter fitting
 Effective data to parameter ratio =   15.45
 wR2(int) =  0.1906 (selected reflections only, before parameter refinement)
 wR2(int) =  0.0842 (selected reflections only, after parameter refinement)

 ------------------------------------------

  219897 total and  39794 unique reflections after rejecting pathological cases

 Reflections rejected for which |I-<I>|/su >   3.00
 Where:  su^2 = sigma(I)^2 + (  0.04000 <I>)^2  (sigma(I) from SAINT)
  216765 total and  39779 unique reflections left after |I-<I>|/su test

 g = 0.0364 gave best error model; g set to 0.0364 for further calculations

 Statistics for singles of twin component  1
 -------------------------------------------
 Scan 2-theta  R(int)  Incid. factors  Diffr. factors    K     Total I>2sig(I)
    1   33.6  0.1103   0.107 - 0.171   1.139 - 1.237   0.977   13307    9237
    2   33.6  0.1332   0.063 - 0.176   1.139 - 1.229   1.008   13099    8420
    3   33.6  0.0999   0.088 - 0.166   1.139 - 1.233   0.964   13394    9487
    4   33.6  0.1159   0.078 - 0.149   1.139 - 1.239   0.983   13006    8922
    5   33.6  0.1410   0.067 - 0.183   1.139 - 1.235   0.995   12879    8248
    6   33.6  0.1195   0.090 - 0.156   1.139 - 1.229   1.015   13437    8855
    7    0.0  0.2070   0.123 - 0.370   1.139 - 1.239   1.074    9691    5131
   All scans  0.1330   0.063 - 0.370   1.139 - 1.239   1.002   88813   58300

 Statistics for singles of twin component  2
 -------------------------------------------
 Scan 2-theta  R(int)  Incid. factors  Diffr. factors    K     Total I>2sig(I)
    1   33.6  0.2150   0.017 - 0.070   1.535 - 1.897   0.977   13257    6603
    2   33.6  0.1241   0.008 - 0.023   1.535 - 1.896   1.008   13013    8509
    3   33.6  0.2017   0.017 - 0.063   1.554 - 1.897   0.964   13411    6993
    4   33.6  0.1627   0.011 - 0.033   1.536 - 1.897   0.983   12857    7511
    5   33.6  0.1587   0.009 - 0.031   1.535 - 1.897   0.995   12853    7753
    6   33.6  0.2461   0.013 - 0.063   1.535 - 1.897   1.015   13351    6116
    7    0.0  0.2740   0.028 - 0.069   1.535 - 1.888   1.074    9746    4280
   All scans  0.1973   0.008 - 0.070   1.535 - 1.897   1.002   88488   47765

 Statistics for all composite reflections
 ----------------------------------------
 Scan 2-theta  R(int)  Incid. factors  Diffr. factors    K     Total I>2sig(I)
    1   33.6  0.0491   0.036 - 0.116   1.286 - 1.616   0.977    5866    5179
    2   33.6  0.0714   0.030 - 0.134   1.304 - 1.618   1.008    5566    4759
    3   33.6  0.0475   0.048 - 0.127   1.334 - 1.605   0.964    5747    5192
    4   33.6  0.0555   0.025 - 0.111   1.286 - 1.699   0.983    6100    5294
    5   33.6  0.0533   0.029 - 0.133   1.308 - 1.628   0.995    6296    5410
    6   33.6  0.0562   0.049 - 0.128   1.298 - 1.645   1.015    5640    4997
    7    0.0  0.0579   0.067 - 0.244   1.337 - 1.574   1.074    4249    3755
   All scans  0.0556   0.025 - 0.244   1.286 - 1.699   1.002   39464   34586

 Statistics for all single and composite reflections
 ---------------------------------------------------
 Scan 2-theta  R(int)  Incid. factors  Diffr. factors    K     Total I>2sig(I)
    1   33.6  0.0676   0.017 - 0.171   1.139 - 1.897   0.977   32430   21019
    2   33.6  0.0888   0.008 - 0.176   1.139 - 1.896   1.008   31678   21688
    3   33.6  0.0640   0.017 - 0.166   1.139 - 1.897   0.964   32552   21672
    4   33.6  0.0718   0.011 - 0.149   1.139 - 1.897   0.983   31963   21727
    5   33.6  0.0742   0.009 - 0.183   1.139 - 1.897   0.995   32028   21411
    6   33.6  0.0762   0.013 - 0.156   1.139 - 1.897   1.015   32428   19968
    7    0.0  0.0857   0.028 - 0.370   1.139 - 1.888   1.074   23686   13166
   All scans  0.0759   0.008 - 0.370   1.139 - 1.897   1.002  216765  140651

 su = K * Sqrt[ sigma^2(I) + (g<I>)^2 ]  where sigma(I) is estimated by SAINT

 Rint = 0.0749  for all  216672  observations and
 Rint = 0.0594  for all  110123  observations with I > 3sigma(I)

 HKLF 5 dataset constructed from all observations involving domain 1
   31990 Corrected reflections written to file hkl
 Reflections merged according to point-group 2
 Single reflections that also occur in composites omitted
 Racemic twinning not included for all components
 Second component not inverted relative to first
 Minimum and maximum apparent transmission:  0.504965  0.841176
 Additional spherical absorption correction applied with mu*r =  0.0300
;
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.594
_exptl_crystal_description       prism
_exptl_crystal_F_000             1320
_exptl_crystal_size_max          0.538
_exptl_crystal_size_mid          0.520
_exptl_crystal_size_min          0.168
_refine_diff_density_max         0.533
_refine_diff_density_min         -0.442
_refine_diff_density_rms         0.065
_refine_ls_abs_structure_details
;
 Flack x determined using 8143 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.1(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.044
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     866
_refine_ls_number_reflns         23264
_refine_ls_number_restraints     31
_refine_ls_restrained_S_all      1.043
_refine_ls_R_factor_all          0.0677
_refine_ls_R_factor_gt           0.0509
_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^)+(0.0713P)^2^+0.7419P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1269
_refine_ls_wR_factor_ref         0.1401
_reflns_Friedel_coverage         0.939
_reflns_Friedel_fraction_full    0.997
_reflns_Friedel_fraction_max     0.995
_reflns_number_gt                19754
_reflns_number_total             23264
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4ob00404c2.cif
_cod_data_source_block           zagid016
_cod_depositor_comments
'Adding full bibliography for 7159893--7159895.cif.'
_cod_original_sg_symbol_H-M      'P 21'
_cod_database_code               7159894
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_min   0.932
_shelx_estimated_absorpt_t_max   0.978
_shelx_res_checksum              1403
_shelx_hkl_checksum              70187