Emphasis on pharmaceutically acceptable solvates: linking solubility with isostructurality for better drug design
Mudda, Ramesh Reddy; Devarapalli, Ramesh; Bollineni, Manjunath; Das, Arijit; Chennuru, Ramanaiah; CrystEngComm 27 (2025) 7562–7574; doi:10.1039/D5CE00633C

data_7251046
_publ_section_title
;
 Emphasis on pharmaceutically acceptable solvates: linking solubility with
 isostructurality for better drug design
;
_journal_issue                   46
_journal_name_full               CrystEngComm
_journal_page_first              7562
_journal_page_last               7574
_journal_paper_doi               10.1039/D5CE00633C
_journal_volume                  27
_journal_year                    2025
_chemical_absolute_configuration ad
_chemical_formula_moiety         '2(C26 H24 N7 O2), 2(C4 H3 O4), C2 H6 O, H2 O'
_chemical_formula_sum            'C62 H62 N14 O14'
_chemical_formula_weight         1227.26
_chemical_name_systematic        'Acalabrutinib maleate'
_space_group_crystal_system      triclinic
_space_group_IT_number           1
_space_group_name_Hall           'P 1'
_space_group_name_H-M_alt        'P 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_date             2023-06-16
_audit_creation_method
;
Olex2 1.2-ac21
(compiled 2015.09.16 svn.r134, GUI svn.r4998)
;
_audit_update_record
;
2023-06-26 deposited with the CCDC.	2025-10-16 downloaded from the CCDC.
;
_cell_angle_alpha                78.0108(13)
_cell_angle_beta                 81.7049(12)
_cell_angle_gamma                70.9622(14)
_cell_formula_units_Z            1
_cell_length_a                   9.49588(14)
_cell_length_b                   9.79722(17)
_cell_length_c                   17.0733(2)
_cell_measurement_reflns_used    23073
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      68.0690
_cell_measurement_theta_min      2.6200
_cell_volume                     1463.72(4)
_computing_cell_refinement       'CrysAlisPro 1.171.42.58a (Rigaku OD, 2022)'
_computing_data_collection       'CrysAlisPro 1.171.42.58a (Rigaku OD, 2022)'
_computing_data_reduction        'CrysAlisPro 1.171.42.58a (Rigaku OD, 2022)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2008)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.00(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix3000
_diffrn_measured_fraction_theta_full 0.992
_diffrn_measured_fraction_theta_max 0.992
_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    -22.00  70.00   0.50    0.50    --   41.33 -81.00 -47.00  184
  2  \w   -152.00 -78.00   0.50    2.00    --  -82.50 -81.00 -47.00  148
  3  \w   -111.00 -13.00   0.50    2.00    --  -82.50  81.00  74.00  196
  4  \w     28.00 125.00   0.50    2.00    --   96.67 -81.00 -47.00  194
  5  \w    100.00 166.00   0.50    2.00    --   96.67  81.00  74.00  132
  6  \w    -24.00  35.00   0.50    0.50    --  -41.33  11.00-150.00  118
  7  \w    -28.00  30.00   0.50    0.50    --  -41.33  21.00 150.00  116
  8  \w   -109.00 -18.00   0.50    0.50    --  -41.33 -65.00 -60.00  182
  9  \w    -37.00  27.00   0.50    0.50    --  -41.33  32.00 -90.00  128
 10  \w    -69.00  28.00   0.50    0.50    --  -41.33  81.00  74.00  194
 11  \w    -48.00  26.00   0.50    0.50    --  -41.33  43.00-150.00  148
 12  \w    -48.00  26.00   0.50    0.50    --  -41.33  43.00  60.00  148
 13  \w    -30.00  28.00   0.50    0.50    --   41.33 -21.00 150.00  116
 14  \w     41.00 100.00   0.50    0.50    --   41.33-138.00 -30.00  118
 15  \w    -27.00  68.00   0.50    0.50    --   41.33 -77.00  30.00  190
 16  \w    -26.00  37.00   0.50    0.50    --   41.33 -32.00   0.00  126
 17  \w    -34.00  24.00   0.50    0.50    --   41.33 -11.00 -90.00  116
 18  \w    -25.00  48.00   0.50    0.50    --   41.33 -43.00-150.00  146
 19  \w    -47.00 -15.00   0.50    2.00    --  -82.50  42.00 -60.00   64
 20  \w    -80.00  -9.00   0.50    2.00    --  -82.50  96.00-180.00  142
 21  \w   -149.00 -78.00   0.50    2.00    --  -82.50-117.00 120.00  142
 22  \w    -47.00 -15.00   0.50    2.00    --  -82.50  42.00   0.00   64
 23  \w    -47.00 -15.00   0.50    2.00    --  -82.50  42.00-180.00   64
 24  \w   -150.00 -69.00   0.50    2.00    --  -82.50 -33.00   0.00  162
 25  \w     22.00 106.00   0.50    2.00    --   96.67 -96.00-150.00  168
 26  \w     30.00  57.00   0.50    2.00    --   96.67 -50.00   0.00   54
 27  \w     99.00 164.00   0.50    2.00    --   96.67 117.00   0.00  130
 28  \w    105.00 170.00   0.50    2.00    --   96.67  96.00-150.00  130
 29  \w     73.00 165.00   0.50    2.00    --   96.67  68.00 -60.00  184
 30  \w     44.00 127.00   0.50    2.00    --   96.67-145.00 -90.00  166
 31  \w     78.00 163.00   0.50    2.00    --   96.67  50.00 120.00  170
 32  \w     22.00 106.00   0.50    2.00    --   96.67 -96.00  60.00  168
 33  \w    105.00 170.00   0.50    2.00    --   96.67  96.00 150.00  130
 34  \w     27.00 127.00   0.50    2.00    --   96.67 -87.00 -90.00  200
 35  \w     30.00 109.00   0.50    2.00    --   96.67-117.00-180.00  158
 36  \w     99.00 164.00   0.50    2.00    --   96.67 117.00  30.00  130
 37  \w     81.00 164.00   0.50    2.00    --   96.67 145.00 150.00  166
 38  \w     99.00 164.00   0.50    2.00    --   96.67 117.00 120.00  130
 39  \w     30.00  57.00   0.50    2.00    --   96.67 -50.00 -60.00   54
 40  \w     29.00  83.00   0.50    2.00    --   96.67 -68.00  60.00  108
 41  \w     83.00 164.00   0.50    2.00    --   96.67  33.00-150.00  162
 42  \w     29.00  83.00   0.50    2.00    --   96.67 -68.00-150.00  108
 43  \w     28.00 105.00   0.50    2.00    --   96.67 -77.00 150.00  154
 44  \w     44.00 127.00   0.50    2.00    --   96.67-145.00 120.00  166
 45  \w     30.00  57.00   0.50    2.00    --   96.67 -50.00 150.00   54
 46  \w     44.00 127.00   0.50    2.00    --   96.67-145.00-180.00  166
 47  \w     80.00 163.00   0.50    2.00    --   96.67  42.00 -90.00  166
 48  \w     83.00 164.00   0.50    2.00    --   96.67  33.00  90.00  162
 49  \w     30.00 109.00   0.50    2.00    --   96.67-117.00 -30.00  158
 50  \w     44.00 127.00   0.50    2.00    --   96.67-145.00 -60.00  166
 51  \w     30.00  57.00   0.50    2.00    --   96.67 -50.00 -30.00   54
 52  \w   -109.00 -18.00   0.50    0.50    --  -41.33 -65.00-180.00  182
 53  \w   -109.00 -18.00   0.50    0.50    --  -41.33 -65.00-150.00  182
 54  \w   -110.00 -14.00   0.50    0.50    --  -41.33 -77.00 120.00  192
 55  \w   -109.00 -18.00   0.50    0.50    --  -41.33 -65.00  60.00  182
 56  \w   -110.00 -14.00   0.50    0.50    --  -41.33 -77.00 150.00  192
 57  \w   -109.00 -18.00   0.50    0.50    --  -41.33 -65.00-120.00  182
 58  \w   -110.00 -14.00   0.50    0.50    --  -41.33 -77.00  60.00  192
 59  \w   -110.00 -14.00   0.50    0.50    --  -41.33 -77.00 -60.00  192
 60  \w   -110.00 -14.00   0.50    0.50    --  -41.33 -77.00   0.00  192
 61  \w   -110.00 -14.00   0.50    0.50    --  -41.33 -77.00 -90.00  192
 62  \w   -110.00 -14.00   0.50    0.50    --  -41.33 -77.00-180.00  192
 63  \w   -110.00 -14.00   0.50    0.50    --  -41.33 -77.00  90.00  192
 64  \w     15.00 110.00   0.50    0.50    --   41.33  77.00 -30.00  190
 65  \w     15.00 110.00   0.50    0.50    --   41.33  77.00  30.00  190
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix3000'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0371718000
_diffrn_orient_matrix_UB_12      0.0328758000
_diffrn_orient_matrix_UB_13      0.0776663000
_diffrn_orient_matrix_UB_21      0.1040298000
_diffrn_orient_matrix_UB_22      -0.1584615000
_diffrn_orient_matrix_UB_23      0.0188615000
_diffrn_orient_matrix_UB_31      0.1321105000
_diffrn_orient_matrix_UB_32      0.0481700000
_diffrn_orient_matrix_UB_33      -0.0466892000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0635
_diffrn_reflns_av_unetI/netI     0.0468
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -20
_diffrn_reflns_number            25082
_diffrn_reflns_theta_full        68.25
_diffrn_reflns_theta_max         68.25
_diffrn_reflns_theta_min         2.65
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.840
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.80730
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.58a (Rigaku Oxford Diffraction, 2022)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.392
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       block
_exptl_crystal_F_000             644
_exptl_crystal_size_max          0.3
_exptl_crystal_size_mid          0.21
_exptl_crystal_size_min          0.13
_refine_diff_density_max         0.306
_refine_diff_density_min         -0.288
_refine_diff_density_rms         0.046
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0.05(13)
_refine_ls_extinction_coef       0.0012(3)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     SHELXL
_refine_ls_goodness_of_fit_ref   1.053
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     821
_refine_ls_number_reflns         8266
_refine_ls_number_restraints     3
_refine_ls_restrained_S_all      1.053
_refine_ls_R_factor_all          0.0437
_refine_ls_R_factor_gt           0.0429
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0826P)^2^+0.1131P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1139
_refine_ls_wR_factor_ref         0.1151
_reflns_number_gt                8028
_reflns_number_total             8266
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            d5ce00633c2.cif
_cod_data_source_block           am-ii
_cod_depositor_comments
'Adding full bibliography for 7251045--7251046.cif.'
_cod_database_code               7251046
_chemical_oxdiff_formula         'C H N O'
_chemical_oxdiff_usercomment     '100 K'
_diffrn_oxdiff_digest_frames
;
01d02f49bcf251b4e60a8c84ae5db62a67000328eff
;
_diffrn_oxdiff_digest_hkl
;
01f33aedfa1e278a8baa9c7226001bbc3fc09d
;
_reflns_odcompleteness_completeness 99.96
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups, All N(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups, All O(H,H) groups
2.a Free rotating group:
 O14(H14a,H14b)
2.b Ternary CH refined with riding coordinates:
 C19(H19), C49(H49)
2.c Secondary CH2 refined with riding coordinates:
 C20(H20a,H20b), C21(H21a,H21b), C22(H22a,H22b), C50(H50a,H50b), C51(H51a,
 H51b), C52(H52a,H52b), C61(H61a,H61b)
2.d Aromatic/amide H refined with riding coordinates:
 N2(H2), N5(H5), C1(H1), C2(H2a), C4(H4), C5(H5a), C8(H8), C9(H9), C11(H11),
 C12(H12), C17(H17), C18(H18), N9(H9a), N12(H12a), C31(H31), C32(H32), C34(H34),
  C35(H35), C38(H38), C39(H39), C41(H41), C42(H42), C47(H47), C48(H48),
 C28(H28), C29(H29), C58(H58), C59(H59)
2.e X=CH2 refined with riding coordinates:
 N6(H6a,H6b), N13(H13a,H13b)
2.f Idealised Me refined as rotating group:
 C26(H26a,H26b,H26c), C56(H56a,H56b,H56c), C62(H62a,H62b,H62c)
2.g Idealised tetrahedral OH refined as rotating group:
 O3(H3), O9(H9b), O13(H13)
;
_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 1.539
_oxdiff_exptl_absorpt_empirical_full_min 0.735