Biguanide Iridium(III) Complexes with Potent Antimicrobial Activity.
Chen, Feng; Moat, John; McFeely, Daniel; Clarkson, Guy; Hands-Portman, Ian J; Furner-Pardoe, Jessica P; Harrison, Freya; Dowson, Christopher G.; Sadler, Peter J.; Journal of medicinal chemistry 61 (2018) 7330–7344; doi:10.1021/acs.jmedchem.8b00906

data_1553262
_publ_section_title
;
 Biguanide Iridium(III) Complexes with Potent Antimicrobial Activity.
;
_journal_issue                   16
_journal_name_full               'Journal of medicinal chemistry'
_journal_page_first              7330
_journal_page_last               7344
_journal_paper_doi               10.1021/acs.jmedchem.8b00906
_journal_volume                  61
_journal_year                    2018
_chemical_formula_moiety         'C29 H31 Ir N5, Cl, 0.2(C H4 O)'
_chemical_formula_sum            'C29.2 H31.8 Cl Ir N5 O0.2'
_chemical_formula_weight         683.64
_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   geom
_atom_sites_solution_primary     direct
_audit_creation_date             2016-04-05
_audit_creation_method
;
Olex2 1.2
(compiled 2016.02.19 svn.r3266 for OlexSys, GUI svn.r5155)
;
_cell_angle_alpha                82.7271(13)
_cell_angle_beta                 86.7456(14)
_cell_angle_gamma                72.2390(14)
_cell_formula_units_Z            4
_cell_length_a                   9.80400(17)
_cell_length_b                   15.8991(2)
_cell_length_c                   18.4457(3)
_cell_measurement_reflns_used    34897
_cell_measurement_temperature    150(2)
_cell_measurement_theta_max      32.0110
_cell_measurement_theta_min      2.8950
_cell_volume                     2715.65(8)
_computing_cell_refinement       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      150(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.1417
_diffrn_detector_type            Ruby
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.939
_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    -25.00  58.00   1.00   25.00    --   17.44 -99.00-180.00   83
  2  \w     35.00 106.00   1.00   25.00    --   17.44 178.00 -30.00   71
  3  \w     -7.00  92.00   1.00   25.00    --   17.44  38.00  90.00   99
  4  \w    -63.00  58.00   1.00   25.00    --   17.44 -19.00 -90.00  121
  5  \w     35.00 106.00   1.00   25.00    --   17.44 178.00  30.00   71
  6  \w    -25.00  23.00   1.00   25.00    --  -18.38 -99.00 -90.00   48
  7  \w    -25.00  23.00   1.00   25.00    --  -18.38 -99.00  60.00   48
  8  \w    -57.00  42.00   1.00   25.00    --   17.44 -38.00  30.00   99
  9  \w     -7.00  92.00   1.00   25.00    --   17.44  38.00-120.00   99
 10  \w    -11.00  91.00   1.00   25.00    --   17.44  57.00 -30.00  102
 11  \w    -25.00  23.00   1.00   25.00    --  -18.38 -99.00 150.00   48
 12  \w    -67.00  -8.00   1.00   25.00    --  -18.38 112.00 145.00   59
 13  \w   -106.00 -53.00   1.00   25.00    --  -18.38 178.00 -60.00   53
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Ruby, Gemini'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0754817000
_diffrn_orient_matrix_UB_12      0.0129233000
_diffrn_orient_matrix_UB_13      0.0051627000
_diffrn_orient_matrix_UB_21      -0.0082959000
_diffrn_orient_matrix_UB_22      -0.0022264000
_diffrn_orient_matrix_UB_23      -0.0375938000
_diffrn_orient_matrix_UB_31      0.0026643000
_diffrn_orient_matrix_UB_32      -0.0452979000
_diffrn_orient_matrix_UB_33      0.0079598000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0404
_diffrn_reflns_av_unetI/netI     0.0347
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.939
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       23
_diffrn_reflns_limit_k_min       -23
_diffrn_reflns_limit_l_max       27
_diffrn_reflns_limit_l_min       -27
_diffrn_reflns_number            83915
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.939
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         32.441
_diffrn_reflns_theta_min         2.430
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    5.043
_exptl_absorpt_correction_T_max  0.721
_exptl_absorpt_correction_T_min  0.083
_exptl_absorpt_correction_type   analytical
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.41 (Rigaku Oxford Diffraction, 2015)
Analytical numeric absorption correction using a multifaceted crystal
			model based on expressions derived by R.C. Clark & J.S. Reid.
(Clark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887-897)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            brown
_exptl_crystal_colour_primary    brown
_exptl_crystal_density_diffrn    1.672
_exptl_crystal_description       block
_exptl_crystal_F_000             1350
_exptl_crystal_size_max          0.5
_exptl_crystal_size_mid          0.13
_exptl_crystal_size_min          0.038
_refine_diff_density_max         4.285
_refine_diff_density_min         -2.400
_refine_diff_density_rms         0.128
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.033
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     798
_refine_ls_number_reflns         18356
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.033
_refine_ls_R_factor_all          0.0479
_refine_ls_R_factor_gt           0.0330
_refine_ls_shift/su_max          0.002
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0272P)^2^+5.4758P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0687
_refine_ls_wR_factor_ref         0.0751
_reflns_Friedel_coverage         0.000
_reflns_number_gt                14877
_reflns_number_total             18356
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jm8b00906_si_004.cif
_cod_data_source_block           fc10
_cod_original_cell_volume        2715.64(8)
_cod_original_formula_sum        'C29.20 H31.80 Cl Ir N5 O0.20'
_cod_database_code               1553262
_chemical_oxdiff_formula         'C30 H38 N8 O Cl2 Ir2'
_reflns_odcompleteness_completeness 99.80
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     26.32
_olex2_refinement_description
;

In molecule C101 to C132, the aniline was modeled over two positions related by 
a small shift in the bond to N107. The occupancy was linked to a free variable 
which refined to 56:44. C106 and C6 had nearly identical positions and 
their thermal parameters were linked with an EADP instruction.
In complex C201 to C232, the biphenyl group was modeled over two positions. 
This was originally linked to a free variable but fixed at 50:50 at later 
stages of the refinement. Several AFIX 66 restraints were used on the 
disordered benzene rings.
A small amount of electron density was modeled as a partially occupied methanol 
and fitted into a PART 2 instruction so not to have a steric clash with some 
of the fragments in the PART 1 instruction of the biphenyl and a symmetry 
related biphenyl.  
Several of the NHs were located in a difference map but they and the OH were 
placed at calculated positions for the refinement. 

1. Fixed Uiso
 At 1.2 times of:
  All C(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
2. Restrained distances
 H01-H11A_$1
 -2.3 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
Uanis(C106) = Uanis(C6)
4. Others
 Sof(H10A)=Sof(C6)=Sof(C5)=Sof(H5)=Sof(C4)=Sof(H4)=Sof(C3)=Sof(H3)=Sof(C2)=
 Sof(H2)=Sof(C1)=Sof(H1)=1-FVAR(1)
 Sof(H107)=Sof(C106)=Sof(C101)=Sof(H101)=Sof(C102)=Sof(H102)=Sof(C103)=
 Sof(H103)=Sof(C104)=Sof(H104)=Sof(C105)=Sof(H105)=FVAR(1)
 Fixed Sof: C217(0.5) C212(0.5) H212(0.5) C213(0.5) H213(0.5) C214(0.5)
 H214(0.5) C215(0.5) H215(0.5) C216(0.5) H216(0.5) C31A(0.5) H31A(0.5)
 C29A(0.5) H29A(0.5) C218(0.5) C219(0.5) H219(0.5) C220(0.5) H220(0.5)
 C221(0.5) C222(0.5) H222(0.5) C223(0.5) H223(0.5) C28A(0.5) H28A(0.5)
 C32A(0.5) H32A(0.5) C30A(0.5) C27A(0.5) C23A(0.5) H23J(0.5) C22A(0.5)
 H22D(0.5) C26A(0.5) C21A(0.5) H21C(0.5) C25A(0.5) H25A(0.5) C24A(0.5)
 H24A(0.5) O01(0.4) H01(0.4) C02(0.4) H02A(0.4) H02B(0.4) H02C(0.4)
5.a Aromatic/amide H refined with riding coordinates:
 N211(H211), N108(H108), N208(H208), N111(H111), N207(H207), N107(H107),
 N107(H10A), C116(H116), C205(H205), C201(H201), C120(H120), C123(H123),
 C204(H204), C115(H115), C119(H119), C112(H112), C122(H122), C202(H202),
 C203(H203), C101(H101), C5(H5), C4(H4), C3(H3), C2(H2), C1(H1), C114(H114),
 C113(H113), C102(H102), C103(H103), C212(H212), C213(H213), C214(H214),
 C215(H215), C216(H216), C31A(H31A), C29A(H29A), C219(H219), C220(H220),
 C222(H222), C223(H223), C28A(H28A), C32A(H32A), C104(H104), C105(H105),
 C23A(H23J), C22A(H22D), C21A(H21C), C25A(H25A), C24A(H24A)
5.b Fitted hexagon refined as free rotating group:
 C6(C5,C4,C3,C2,C1), C217(C212,C213,C214,C215,C216), C218(C219,C220,C221,C222,
 C223)
5.c X=CH2 refined with riding coordinates:
 N210(H21A,H21B), N110(H11A,H11B)
5.d Idealised Me refined as rotating group:
 C129(H12A,H12B,H12C), C132(H13A,H13B,H13C), C229(H22A,H22B,H22C), C230(H23A,
 H23B,H23C), C232(H23D,H23E,H23F), C231(H23G,H23H,H23I), C131(H13D,H13E,H13F),
 C130(H13G,H13H,H13I), C02(H02A,H02B,H02C)
5.e Idealised tetrahedral OH refined as rotating group:
 O01(H01)
;
_shelx_shelxl_version_number     2014/7
_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 1.333
_oxdiff_exptl_absorpt_empirical_full_min 0.579