Protonation Pattern, Tautomerism, Conformerism, and Physicochemical Analysis in New Crystal Forms of the Antibiotic Doxycycline
Santos, Olímpia M. M.; Silva, Douglas M.; Martins, Felipe T.; Legendre, Alexandre O.; Azarias, Lilian C.; Rosa, Iara M. L.; Neves, Person P.; de Araujo, Magali B.; Doriguetto, Antonio C.; Crystal Growth & Design 14 (2014) 3711–; doi:10.1021/cg500877z

data_4511685
_publ_section_title
;
 Protonation Pattern, Tautomerism, Conformerism, and Physicochemical
 Analysis in New Crystal Forms of the Antibiotic Doxycycline
;
_journal_issue                   8
_journal_name_full               'Crystal Growth &amp; Design'
_journal_page_first              3711
_journal_paper_doi               10.1021/cg500877z
_journal_volume                  14
_journal_year                    2014
_chemical_absolute_configuration ad
_chemical_compound_source        'Synthetic Product'
_chemical_formula_moiety         '2(C22 H25 N2 O8) 1+, 2(N1 O3) 1-, 1(O1 H2)'
_chemical_formula_sum            'C44 H52 N6 O23'
_chemical_formula_weight         1032.92
_chemical_melting_point          397
_chemical_name_common            'doxycycline nitrate salt hemihydrate'
_chemical_name_systematic
;
2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-
octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-,
nitrate, hemihydrate, (4S,4aR,5S,5aR,6R,12aS)- (9CI)
;
_space_group_crystal_system      triclinic
_space_group_IT_number           1
_space_group_name_Hall           'P 1'
_space_group_name_H-M_alt        'P 1'
_symmetry_space_group_name_Hall  'P 1'
_symmetry_space_group_name_H-M   'P 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_date             2013-11-25T20:05:55-00:00
_audit_creation_method           'WinGX routine CIF_UPDATE'
_cell_angle_alpha                77.872(2)
_cell_angle_beta                 87.581(2)
_cell_angle_gamma                74.133(3)
_cell_formula_units_Z            1
_cell_length_a                   8.0679(2)
_cell_length_b                   8.9156(3)
_cell_length_c                   16.6791(5)
_cell_measurement_reflns_used    14756
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      66.2657
_cell_measurement_theta_min      2.7078
_cell_measurement_wavelength     1.5418
_cell_volume                     1128.11(6)
_computing_cell_refinement
;
        CrysAlisPro, Oxford Diffraction Ltd.,
        Version 1.171.33.55 (release 05-01-2010 CrysAlis171 .NET)
        (compiled Jan  5 2010,16:28:46)
;
_computing_data_collection
;
        CrysAlisPro, Oxford Diffraction Ltd.,
        Version 1.171.33.55 (release 05-01-2010 CrysAlis171 .NET)
        (compiled Jan  5 2010,16:28:46)
;
_computing_data_reduction
;
        CrysAlisPro, Oxford Diffraction Ltd.,
        Version 1.171.33.55 (release 05-01-2010 CrysAlis171 .NET)
        (compiled Jan  5 2010,16:28:46)
;
_computing_molecular_graphics
'Ortep-3 for Windows (Farrugia, 1997); Mercury (Bruno et al. 2002)'
_computing_publication_material
'WinGX publication routines (Farrugia, 1999); enCIFer (Allen et al., 2004)'
_computing_structure_refinement  'SHELXL-2013 (Sheldrick, 2013)'
_diffrn_ambient_temperature      293(2)
_diffrn_detector_area_resol_mean 10.4186
_diffrn_measured_fraction_theta_full 0.985
_diffrn_measured_fraction_theta_max 0.986
_diffrn_measurement_device_type  'Xcalibur, Atlas, Gemini ultra'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      -0.0146529
_diffrn_orient_matrix_UB_12      0.0642434
_diffrn_orient_matrix_UB_13      0.0795868
_diffrn_orient_matrix_UB_21      0.044024
_diffrn_orient_matrix_UB_22      -0.1718487
_diffrn_orient_matrix_UB_23      0.0507716
_diffrn_orient_matrix_UB_31      0.1930416
_diffrn_orient_matrix_UB_32      -0.0070718
_diffrn_orient_matrix_UB_33      -0.0039642
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.5418
_diffrn_reflns_av_R_equivalents  0.0283
_diffrn_reflns_av_unetI/netI     0.0220
_diffrn_reflns_Laue_measured_fraction_full 0.985
_diffrn_reflns_Laue_measured_fraction_max 0.986
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -10
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            21480
_diffrn_reflns_point_group_measured_fraction_max 0.952
_diffrn_reflns_theta_full        66.400
_diffrn_reflns_theta_max         66.370
_diffrn_reflns_theta_min         2.710
_exptl_absorpt_coefficient_mu    1.065
_exptl_absorpt_correction_T_max  1
_exptl_absorpt_correction_T_min  0.93821
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
        CrysAlisPro, Oxford Diffraction Ltd.,
        Version 1.171.33.55 (release 05-01-2010 CrysAlis171 .NET)
        (compiled Jan  5 2010,16:28:46)
        Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'pale yellow'
_exptl_crystal_density_diffrn    1.520
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       prism
_exptl_crystal_F_000             542
_exptl_crystal_size_max          0.30
_exptl_crystal_size_mid          0.19
_exptl_crystal_size_min          0.15
_refine_diff_density_max         0.441
_refine_diff_density_min         -0.296
_refine_diff_density_rms         0.041
_refine_ls_abs_structure_details
;
 Flack x determined using 3269 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   0.03(6)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.027
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     662
_refine_ls_number_reflns         7575
_refine_ls_number_restraints     3
_refine_ls_restrained_S_all      1.027
_refine_ls_R_factor_all          0.0369
_refine_ls_R_factor_gt           0.0332
_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^)+(0.0542P)^2^+0.2565P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0840
_refine_ls_wR_factor_ref         0.0867
_reflns_Friedel_coverage         0.931
_reflns_Friedel_fraction_full    0.918
_reflns_Friedel_fraction_max     0.918
_reflns_number_gt                7093
_reflns_number_total             7575
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            cg500877z_si_002.cif
_cod_data_source_block           doxinitrate
_cod_depositor_comments
'Adding full bibliography for 4511685--4511687.cif.'
_cod_database_code               4511685