Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2006 data_global _journal_name_full Org.Biomol.Chem. _journal_coden_Cambridge 0177 _publ_contact_author_name 'Francois Diederich' _publ_contact_author_address ; Laboratorium fur Organische Chemie ETH-Zurich Honggerberg HCI Z\"urich CH-8093 SWITZERLAND ; _publ_contact_author_email DIEDERICH@ORG.CHEM.ETHZ.CH _publ_section_title ; Multipolar Interactions in the D-Pocket of Thrombin: Large Differences between Tricyclic Imide and Lactam Inhibitors ; loop_ _publ_author_name 'Francois Diederich' 'David W. Banner' 'Anja Hoffman-Roder' 'Manfred Kansy' 'Ulrike Obst-Sander' ; J.Olsen ; 'Eliane Schweizer' 'Paul Seiler' 'Bjorn Wagner' data_anja10_D_04 _database_code_depnum_ccdc_archive 'CCDC 297366' _audit_creation_method SHELXL-97 _chemical_name_systematic ; ? ; _chemical_name_common ? _chemical_melting_point ? _chemical_formula_moiety 'C22 H22 Br F N2 O2' _chemical_formula_sum 'C22 H22 Br F N2 O2' _chemical_formula_weight 445.33 loop_ _atom_type_symbol _atom_type_description _atom_type_scat_dispersion_real _atom_type_scat_dispersion_imag _atom_type_scat_source C C 0.0033 0.0016 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' H H 0.0000 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' N N 0.0061 0.0033 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' O O 0.0106 0.0060 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' F F 0.0171 0.0103 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' Br Br -0.2901 2.4595 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' _symmetry_cell_setting Triclinic _symmetry_space_group_name_H-M ' P -1' loop_ _symmetry_equiv_pos_as_xyz 'x, y, z' '-x, -y, -z' _cell_length_a 9.4567(2) _cell_length_b 10.5163(2) _cell_length_c 10.6619(2) _cell_angle_alpha 78.900(1) _cell_angle_beta 89.899(1) _cell_angle_gamma 66.981(1) _cell_volume 954.45(3) _cell_formula_units_Z 2 _cell_measurement_temperature 173(2) _cell_measurement_reflns_used 3999 _cell_measurement_theta_min 3.76 _cell_measurement_theta_max 27.50 _exptl_crystal_description 'Cut fragment' _exptl_crystal_colour colorless _exptl_crystal_size_max 0.18 _exptl_crystal_size_mid 0.16 _exptl_crystal_size_min 0.15 _exptl_crystal_density_meas ? _exptl_crystal_density_diffrn 1.550 _exptl_crystal_density_method 'not measured' _exptl_crystal_F_000 456 _exptl_absorpt_coefficient_mu 2.184 _exptl_absorpt_correction_type none _exptl_absorpt_correction_T_min ? _exptl_absorpt_correction_T_max ? _exptl_absorpt_process_details ? _exptl_special_details ; ? ; _diffrn_ambient_temperature 173(2) _diffrn_radiation_wavelength 0.7107 _diffrn_radiation_type MoK\a _diffrn_radiation_source 'fine-focus sealed tube' _diffrn_radiation_monochromator graphite _diffrn_measurement_device_type 'Kappa CCD' _diffrn_measurement_method CCD _diffrn_detector_area_resol_mean ? _diffrn_standards_number ? _diffrn_standards_interval_count ? _diffrn_standards_interval_time ? _diffrn_reflns_number 7417 _diffrn_reflns_av_R_equivalents 0.0162 _diffrn_reflns_av_sigmaI/netI 0.0347 _diffrn_reflns_limit_h_min -12 _diffrn_reflns_limit_h_max 11 _diffrn_reflns_limit_k_min -13 _diffrn_reflns_limit_k_max 13 _diffrn_reflns_limit_l_min -13 _diffrn_reflns_limit_l_max 13 _diffrn_reflns_theta_min 3.76 _diffrn_reflns_theta_max 27.50 _reflns_number_total 4368 _reflns_number_gt 3942 _reflns_threshold_expression >2sigma(I) _computing_data_collection 'Kappa CCD' _computing_cell_refinement 'HKL Scalepack (Otwinowski & Minor 1997)' _computing_data_reduction 'Denzo + Scalepak (Otwinowski & Minor, 1997)' _computing_structure_solution 'SIR97 (Altomare et Al., 1997)' _computing_structure_refinement 'SHELXL97 (Sheldrick, 1997)' _computing_molecular_graphics 'ORTEP (Johnson,1976)' _computing_publication_material SHELXL97 _refine_special_details ; Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ > 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ; _refine_ls_structure_factor_coef Fsqd _refine_ls_matrix_type full _refine_ls_weighting_scheme calc _refine_ls_weighting_details 'calc w=1/[\s^2^(Fo^2^)+(0.0122P)^2^+0.6461P] where P=(Fo^2^+2Fc^2^)/3' _atom_sites_solution_primary direct _atom_sites_solution_secondary difmap _atom_sites_solution_hydrogens geom _refine_ls_hydrogen_treatment riding _refine_ls_extinction_method SHELXL97 _refine_ls_extinction_coef 0.0103(12) _refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^ _refine_ls_number_reflns 4368 _refine_ls_number_parameters 276 _refine_ls_number_restraints 0 _refine_ls_R_factor_all 0.0342 _refine_ls_R_factor_gt 0.0289 _refine_ls_wR_factor_ref 0.0666 _refine_ls_wR_factor_gt 0.0637 _refine_ls_goodness_of_fit_ref 1.033 _refine_ls_restrained_S_all 1.033 _refine_ls_shift/su_max 0.001 _refine_ls_shift/su_mean 0.000 loop_ _atom_site_label _atom_site_type_symbol _atom_site_fract_x _atom_site_fract_y _atom_site_fract_z _atom_site_U_iso_or_equiv _atom_site_adp_type _atom_site_occupancy _atom_site_calc_flag _atom_site_refinement_flags _atom_site_disorder_assembly _atom_site_disorder_group C1 C 0.4416(2) 0.94499(19) 0.76657(18) 0.0317(4) Uani 1 d . . . H1A H 0.3505 1.0375 0.7454 0.023(5) Uiso 1 calc R . . N2 N 0.44530(18) 0.86615(15) 0.66752(14) 0.0281(3) Uani 1 d . . . C3 C 0.5740(2) 0.83263(17) 0.60349(16) 0.0274(4) Uani 1 d . . . C4 C 0.6863(2) 0.87696(17) 0.66563(16) 0.0254(4) Uani 1 d . . . H4A H 0.7287 0.9302 0.5990 0.031(5) Uiso 1 calc R . . C5 C 0.5909(2) 0.97331(18) 0.75393(16) 0.0273(4) Uani 1 d . . . H5A H 0.5673 1.0750 0.7171 0.031(5) Uiso 1 calc R . . C6 C 0.8200(2) 0.75477(18) 0.75629(15) 0.0237(3) Uani 1 d . . . H6A H 0.9139 0.7766 0.7483 0.030(5) Uiso 1 calc R . . N7 N 0.76854(16) 0.76753(15) 0.88682(13) 0.0238(3) Uani 1 d . . . C8 C 0.6901(2) 0.92203(18) 0.87998(16) 0.0262(4) Uani 1 d . . . H8A H 0.6233 0.9405 0.9528 0.022(5) Uiso 1 calc R . . C9 C 0.8185(2) 0.9739(2) 0.89126(19) 0.0350(4) Uani 1 d . . . H9A H 0.7824 1.0599 0.9279 0.045(6) Uiso 1 calc R . . H9B H 0.8573 0.9945 0.8067 0.049(7) Uiso 1 calc R . . C10 C 0.9430(3) 0.8488(2) 0.9824(2) 0.0447(5) Uani 1 d . . . H10A H 0.9428 0.8680 1.0698 0.067(8) Uiso 1 calc R . . H10B H 1.0464 0.8313 0.9514 0.089(10) Uiso 1 calc R . . C11 C 0.9017(2) 0.7202(2) 0.98313(17) 0.0330(4) Uani 1 d . . . H11A H 0.9904 0.6416 0.9604 0.047(6) Uiso 1 calc R . . H11B H 0.8740 0.6870 1.0692 0.051(7) Uiso 1 calc R . . C12 C 0.86268(19) 0.60750(17) 0.73230(15) 0.0225(3) Uani 1 d . . . C13 C 0.7655(2) 0.53558(18) 0.75857(16) 0.0256(4) Uani 1 d . . . H13A H 0.6733 0.5768 0.7984 0.029(5) Uiso 1 calc R . . C14 C 0.8018(2) 0.40497(19) 0.72729(17) 0.0278(4) Uani 1 d . . . H14A H 0.7353 0.3567 0.7450 0.035(5) Uiso 1 calc R . . C15 C 0.9373(2) 0.34622(18) 0.66960(16) 0.0255(3) Uani 1 d . . . C16 C 1.0385(2) 0.41158(18) 0.64641(16) 0.0266(4) Uani 1 d . . . H16A H 1.1324 0.3682 0.6096 0.034(5) Uiso 1 calc R . . C17 C 0.9997(2) 0.54291(18) 0.67838(16) 0.0254(3) Uani 1 d . . . H17A H 1.0683 0.5892 0.6630 0.030(5) Uiso 1 calc R . . Br18 Br 0.98301(2) 0.172403(19) 0.616548(19) 0.03651(8) Uani 1 d . . . O19 O 0.59366(17) 0.77763(14) 0.50988(12) 0.0354(3) Uani 1 d . . . O20 O 0.42827(18) 0.87099(18) 0.88791(14) 0.0434(4) Uani 1 d . . . H20A H 0.5152 0.8091 0.9183 0.080(11) Uiso 1 calc R . . C21 C 0.3163(2) 0.82971(19) 0.63757(19) 0.0333(4) Uani 1 d . . . H21A H 0.2987 0.8461 0.5432 0.043(6) Uiso 1 calc R . . H21B H 0.2220 0.8939 0.6692 0.044(6) Uiso 1 calc R . . C22 C 0.34088(19) 0.67837(18) 0.69511(17) 0.0266(4) Uani 1 d . . . C23 C 0.37498(19) 0.57965(19) 0.61787(17) 0.0263(4) Uani 1 d . . . H23A H 0.3829 0.6080 0.5289 0.028(5) Uiso 1 calc R . . C24 C 0.3979(2) 0.44003(19) 0.66778(17) 0.0281(4) Uani 1 d . . . H24A H 0.4213 0.3728 0.6145 0.037(6) Uiso 1 calc R . . C25 C 0.3854(2) 0.40287(19) 0.79650(18) 0.0304(4) Uani 1 d . . . C26 C 0.3492(2) 0.4967(2) 0.87687(18) 0.0359(4) Uani 1 d . . . H26A H 0.3395 0.4676 0.9653 0.044(6) Uiso 1 calc R . . C27 C 0.3272(2) 0.6354(2) 0.82512(18) 0.0328(4) Uani 1 d . . . H27A H 0.3025 0.7020 0.8790 0.043(6) Uiso 1 calc R . . F28 F 0.40661(16) 0.26630(12) 0.84684(12) 0.0459(3) Uani 1 d . . . loop_ _atom_site_aniso_label _atom_site_aniso_U_11 _atom_site_aniso_U_22 _atom_site_aniso_U_33 _atom_site_aniso_U_23 _atom_site_aniso_U_13 _atom_site_aniso_U_12 C1 0.0308(9) 0.0263(9) 0.0352(10) -0.0138(8) -0.0030(7) -0.0052(8) N2 0.0326(8) 0.0220(7) 0.0288(7) -0.0071(6) -0.0062(6) -0.0090(6) C3 0.0378(10) 0.0175(8) 0.0221(8) 0.0003(6) -0.0063(7) -0.0081(7) C4 0.0347(9) 0.0209(8) 0.0206(8) -0.0028(6) -0.0002(7) -0.0119(7) C5 0.0352(10) 0.0183(8) 0.0271(9) -0.0062(7) -0.0029(7) -0.0088(7) C6 0.0270(9) 0.0248(8) 0.0216(8) -0.0052(6) 0.0030(6) -0.0125(7) N7 0.0270(7) 0.0249(7) 0.0187(7) -0.0046(5) 0.0002(5) -0.0096(6) C8 0.0321(9) 0.0251(8) 0.0244(8) -0.0095(7) 0.0015(7) -0.0125(7) C9 0.0428(11) 0.0393(11) 0.0345(10) -0.0148(8) 0.0049(8) -0.0251(9) C10 0.0387(12) 0.0479(13) 0.0523(13) -0.0176(10) -0.0073(9) -0.0191(10) C11 0.0334(10) 0.0400(10) 0.0251(9) -0.0054(8) -0.0050(7) -0.0146(9) C12 0.0235(8) 0.0228(8) 0.0197(7) -0.0027(6) -0.0001(6) -0.0083(7) C13 0.0223(8) 0.0246(8) 0.0268(8) -0.0037(7) 0.0030(6) -0.0069(7) C14 0.0244(8) 0.0254(9) 0.0320(9) -0.0017(7) -0.0008(7) -0.0102(7) C15 0.0275(9) 0.0199(8) 0.0243(8) -0.0030(6) -0.0034(6) -0.0051(7) C16 0.0232(8) 0.0276(9) 0.0245(8) -0.0050(7) 0.0013(6) -0.0055(7) C17 0.0249(8) 0.0283(9) 0.0228(8) -0.0034(7) 0.0010(6) -0.0112(7) Br18 0.03997(12) 0.02284(11) 0.04286(12) -0.00958(8) 0.00099(8) -0.00715(8) O19 0.0511(8) 0.0318(7) 0.0228(6) -0.0085(5) -0.0038(6) -0.0147(6) O20 0.0440(9) 0.0641(10) 0.0367(8) -0.0234(7) 0.0109(6) -0.0309(8) C21 0.0317(10) 0.0252(9) 0.0387(10) -0.0064(8) -0.0116(8) -0.0069(8) C22 0.0214(8) 0.0250(8) 0.0319(9) -0.0090(7) -0.0015(7) -0.0062(7) C23 0.0247(8) 0.0310(9) 0.0257(8) -0.0082(7) 0.0040(6) -0.0126(7) C24 0.0265(9) 0.0289(9) 0.0336(9) -0.0142(7) 0.0086(7) -0.0125(7) C25 0.0290(9) 0.0264(9) 0.0361(10) -0.0057(7) 0.0058(7) -0.0116(7) C26 0.0420(11) 0.0418(11) 0.0259(9) -0.0090(8) 0.0056(8) -0.0179(9) C27 0.0348(10) 0.0342(10) 0.0320(9) -0.0169(8) 0.0043(8) -0.0116(8) F28 0.0610(8) 0.0301(6) 0.0466(7) -0.0041(5) 0.0129(6) -0.0198(6) _geom_special_details ; All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. ; loop_ _geom_bond_atom_site_label_1 _geom_bond_atom_site_label_2 _geom_bond_distance _geom_bond_site_symmetry_2 _geom_bond_publ_flag C1 O20 1.408(2) . ? C1 N2 1.455(2) . ? C1 C5 1.553(3) . ? N2 C3 1.351(2) . ? N2 C21 1.467(2) . ? C3 O19 1.226(2) . ? C3 C4 1.515(2) . ? C4 C5 1.542(2) . ? C4 C6 1.562(2) . ? C5 C8 1.519(2) . ? C6 N7 1.487(2) . ? C6 C12 1.513(2) . ? N7 C11 1.485(2) . ? N7 C8 1.486(2) . ? C8 C9 1.527(3) . ? C9 C10 1.537(3) . ? C10 C11 1.547(3) . ? C12 C17 1.389(2) . ? C12 C13 1.398(2) . ? C13 C14 1.387(2) . ? C14 C15 1.388(2) . ? C15 C16 1.378(3) . ? C15 Br18 1.9046(17) . ? C16 C17 1.394(2) . ? C21 C22 1.516(3) . ? C22 C23 1.388(2) . ? C22 C27 1.395(3) . ? C23 C24 1.392(2) . ? C24 C25 1.371(3) . ? C25 F28 1.367(2) . ? C25 C26 1.373(3) . ? C26 C27 1.389(3) . ? loop_ _geom_angle_atom_site_label_1 _geom_angle_atom_site_label_2 _geom_angle_atom_site_label_3 _geom_angle _geom_angle_site_symmetry_1 _geom_angle_site_symmetry_3 _geom_angle_publ_flag O20 C1 N2 111.27(15) . . ? O20 C1 C5 115.17(15) . . ? N2 C1 C5 104.07(14) . . ? C3 N2 C1 115.15(15) . . ? C3 N2 C21 122.77(15) . . ? C1 N2 C21 122.06(16) . . ? O19 C3 N2 125.10(17) . . ? O19 C3 C4 126.50(18) . . ? N2 C3 C4 108.39(14) . . ? C3 C4 C5 105.08(15) . . ? C3 C4 C6 115.20(14) . . ? C5 C4 C6 104.98(13) . . ? C8 C5 C4 104.79(14) . . ? C8 C5 C1 112.13(15) . . ? C4 C5 C1 104.89(14) . . ? N7 C6 C12 112.61(13) . . ? N7 C6 C4 103.74(13) . . ? C12 C6 C4 116.64(13) . . ? C11 N7 C8 104.36(13) . . ? C11 N7 C6 111.41(14) . . ? C8 N7 C6 104.72(12) . . ? N7 C8 C5 102.58(13) . . ? N7 C8 C9 105.87(15) . . ? C5 C8 C9 117.83(15) . . ? C8 C9 C10 103.04(16) . . ? C9 C10 C11 105.85(16) . . ? N7 C11 C10 106.94(15) . . ? C17 C12 C13 118.53(16) . . ? C17 C12 C6 119.47(15) . . ? C13 C12 C6 121.96(15) . . ? C14 C13 C12 120.95(16) . . ? C13 C14 C15 118.69(16) . . ? C16 C15 C14 122.00(16) . . ? C16 C15 Br18 118.68(13) . . ? C14 C15 Br18 119.31(13) . . ? C15 C16 C17 118.35(16) . . ? C12 C17 C16 121.41(16) . . ? N2 C21 C22 114.04(14) . . ? C23 C22 C27 118.48(17) . . ? C23 C22 C21 120.15(16) . . ? C27 C22 C21 121.36(16) . . ? C22 C23 C24 121.50(16) . . ? C25 C24 C23 117.65(17) . . ? F28 C25 C24 118.35(17) . . ? F28 C25 C26 118.35(17) . . ? C24 C25 C26 123.28(18) . . ? C25 C26 C27 118.11(18) . . ? C26 C27 C22 120.96(17) . . ? loop_ _geom_torsion_atom_site_label_1 _geom_torsion_atom_site_label_2 _geom_torsion_atom_site_label_3 _geom_torsion_atom_site_label_4 _geom_torsion _geom_torsion_site_symmetry_1 _geom_torsion_site_symmetry_2 _geom_torsion_site_symmetry_3 _geom_torsion_site_symmetry_4 _geom_torsion_publ_flag O20 C1 N2 C3 -120.07(17) . . . . ? C5 C1 N2 C3 4.55(19) . . . . ? O20 C1 N2 C21 61.6(2) . . . . ? C5 C1 N2 C21 -173.79(15) . . . . ? C1 N2 C3 O19 -173.37(16) . . . . ? C21 N2 C3 O19 5.0(3) . . . . ? C1 N2 C3 C4 5.6(2) . . . . ? C21 N2 C3 C4 -176.06(14) . . . . ? O19 C3 C4 C5 165.62(16) . . . . ? N2 C3 C4 C5 -13.35(18) . . . . ? O19 C3 C4 C6 -79.4(2) . . . . ? N2 C3 C4 C6 101.66(16) . . . . ? C3 C4 C5 C8 133.77(14) . . . . ? C6 C4 C5 C8 11.86(18) . . . . ? C3 C4 C5 C1 15.52(17) . . . . ? C6 C4 C5 C1 -106.39(15) . . . . ? O20 C1 C5 C8 -3.5(2) . . . . ? N2 C1 C5 C8 -125.55(15) . . . . ? O20 C1 C5 C4 109.68(16) . . . . ? N2 C1 C5 C4 -12.39(17) . . . . ? C3 C4 C6 N7 -100.21(16) . . . . ? C5 C4 C6 N7 14.85(17) . . . . ? C3 C4 C6 C12 24.2(2) . . . . ? C5 C4 C6 C12 139.28(15) . . . . ? C12 C6 N7 C11 83.77(17) . . . . ? C4 C6 N7 C11 -149.23(14) . . . . ? C12 C6 N7 C8 -163.99(13) . . . . ? C4 C6 N7 C8 -36.99(16) . . . . ? C11 N7 C8 C5 162.09(14) . . . . ? C6 N7 C8 C5 44.91(16) . . . . ? C11 N7 C8 C9 37.98(17) . . . . ? C6 N7 C8 C9 -79.20(16) . . . . ? C4 C5 C8 N7 -34.27(17) . . . . ? C1 C5 C8 N7 78.95(16) . . . . ? C4 C5 C8 C9 81.49(19) . . . . ? C1 C5 C8 C9 -165.29(15) . . . . ? N7 C8 C9 C10 -34.09(19) . . . . ? C5 C8 C9 C10 -148.05(16) . . . . ? C8 C9 C10 C11 17.2(2) . . . . ? C8 N7 C11 C10 -26.31(19) . . . . ? C6 N7 C11 C10 86.15(18) . . . . ? C9 C10 C11 N7 5.2(2) . . . . ? N7 C6 C12 C17 -132.77(16) . . . . ? C4 C6 C12 C17 107.44(18) . . . . ? N7 C6 C12 C13 49.6(2) . . . . ? C4 C6 C12 C13 -70.2(2) . . . . ? C17 C12 C13 C14 -2.4(2) . . . . ? C6 C12 C13 C14 175.32(15) . . . . ? C12 C13 C14 C15 0.3(3) . . . . ? C13 C14 C15 C16 2.1(3) . . . . ? C13 C14 C15 Br18 -176.25(13) . . . . ? C14 C15 C16 C17 -2.2(3) . . . . ? Br18 C15 C16 C17 176.14(12) . . . . ? C13 C12 C17 C16 2.3(2) . . . . ? C6 C12 C17 C16 -175.50(15) . . . . ? C15 C16 C17 C12 0.0(2) . . . . ? C3 N2 C21 C22 80.6(2) . . . . ? C1 N2 C21 C22 -101.2(2) . . . . ? N2 C21 C22 C23 -105.29(19) . . . . ? N2 C21 C22 C27 75.9(2) . . . . ? C27 C22 C23 C24 -1.0(3) . . . . ? C21 C22 C23 C24 -179.87(16) . . . . ? C22 C23 C24 C25 0.1(3) . . . . ? C23 C24 C25 F28 179.59(16) . . . . ? C23 C24 C25 C26 1.2(3) . . . . ? F28 C25 C26 C27 -179.73(17) . . . . ? C24 C25 C26 C27 -1.3(3) . . . . ? C25 C26 C27 C22 0.2(3) . . . . ? C23 C22 C27 C26 0.9(3) . . . . ? C21 C22 C27 C26 179.70(18) . . . . ? _diffrn_measured_fraction_theta_max 0.994 _diffrn_reflns_theta_full 27.50 _diffrn_measured_fraction_theta_full 0.994 _refine_diff_density_max 0.316 _refine_diff_density_min -0.426 _refine_diff_density_rms 0.051