research communications
of 5-{4′-[(2-{2-[2-(2-ammonioethoxy)ethoxy]ethoxy}ethyl)carbamoyl]-4-methoxy-[1,1′-biphenyl]-3-yl}-3-oxo-1,2,5-thiadiazolidin-2-ide 1,1-dioxide: a potential inhibitor of the enzyme protein tyrosine phosphatase 1B (PTP1B)
a125 Chemistry Bldg, University of Missouri Columbia, MO 65211, USA
*Correspondence e-mail: gatesk@missouri.edu
The title compound, C24H32N4O8S, (I), crystallizes as a zwitterion. The terminal amine N atom of the [(2-{2-[2-(2-ammonioethoxy)ethoxy]ethoxy}ethyl)carbamoyl] side chain is protonated, while the 1,2,5-thiadiazolidin-3-one 1,1-dioxide N atom is deprotonated. The side chain is turned over on itself with an intramolecular N—H⋯O hydrogen bond. The 1,2,5-thiadiazolidin-3-one 1,1-dioxide ring has an with the aryl-substituted N atom as the flap. Its mean plane is inclined by 62.87 (8)° to the aryl ring to which it is attached, while the aryl rings of the biphenyl unit are inclined to one another by 20.81 (8)°. In the crystal, molecules are linked by N—H⋯O and N—H⋯N hydrogen bonds, forming slabs lying parallel to (010). Within the slabs there are C—H⋯O and C—H⋯N hydrogen bonds and C—H⋯π interactions present.
Keywords: crystal structure; PTP1B; inhibitor; 1,2,5-thiadiazolidin-3-one 1,1-dioxide; hydrogen bonding.
CCDC reference: 1051176
1. Chemical context
A variety of 5-aryl-1,2,5-thiadiazolidin-3-one 1,1-dioxides have been developed as inhibitors of the enzyme protein tyrosine phosphatase 1B (PTP1B) (Combs, 2010). In this capacity, the 5-aryl-1,2,5-thiadiazolidin-3-one 1,1-dioxide core serves as a structural mimic of the phosphoryl tyrosine unit that is present in the endogenous substrates of the enzyme. The parent compound, 5-phenyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide 1 (Fig. 1), is a rather weak inhibitor of PTP1B, displaying a Ki value of approximately 2 mM (Black et al., 2005). predicted that this compound must bind to the enzyme active site in a conformation where the planes of the 1,2,5-thiadiazolidin-3-one 1,1-dioxide and aryl rings are twisted, rather than co-planar (Black et al., 2005). It was further anticipated that installation of substituents such as methyl or methoxy groups on the aryl ring at the position ortho to the 1,2,5-thiadiazolidin-3-one 1,1-dioxide substituent would bias the conformation of the free ligand toward the twisted form, thus serving to `pre-organize' the compounds for binding to the enzyme active site (Black et al., 2005). Indeed, compounds 2 and 3 (Ki values of 100 and 70 µM, respectively) display substantially higher affinities for PTP1B than does 1 (Black et al., 2005). X-ray analysis confirmed the twisted conformation of the 1,2,5-thiadiazolidin-3-one 1,1-dioxide and aryl ring systems in the protein–ligand structure of 4 bound to PTP1B (Black et al., 2005). The planes of these two rings are nearly perpendicular in the protein–ligand complex (dihedral angle of ca 88°, see: pdb code 2bgd). The ability of methyl and methoxy substituents to favor the twisted relationship between the 1,2,5-thiadiazolidin-3-one 1,1-dioxide and aryl rings in compounds like 2 and 3 has been studied computationally and the twisted relationship of these rings has been experimentally observed in the protein–ligand structure of 4 with the enzyme PTP1B. However, to the best of our knowledge no crystal structures of free 5-aryl-1,2,5-thiadiazolidin-3-one 1,1-dioxides have been published. Herein, we describe the of the title compound (I), shown in the scheme below, a derivative of compound 4.
2. Structural commentary
The title compound (I), crystallized as a zwitterion (Fig. 2). The terminal amine N atom, N4, is protonated and the 1,2,5-thiadiazolidin-3-one 1,1-dioxide nitrogen atom, N1, is deprotonated. The [(2-{2-[2-(2-ammonioethoxy)ethoxy]ethoxy}ethyl)carbamoyl] side chain is folded over on itself with an intramolecular N—H⋯O hydrogen bond involving the ammonium group, N4, and an ether O atom, O7 (Table 1 and Fig. 2). The aryl rings of the biphenyl unit (C3–C8 and C9–C14) are inclined to one another by 20.81 (8)°. The 1,2,5-thiadiazolidin-3-one 1,1-dioxide ring (S1/N1/N2/C1/C2) has a shallow with nitrogen atom N2 as the flap. Its mean plane is inclined to the benzene ring to which it is attached (C3–C8) by 62.87 (8)°. This twisted relationship between the planes of the 1,2,5-thiadiazolidin-3-one 1,1-dioxide and aryl rings is substantially less than that seen in the protein–ligand structure of 4 bound to PTP1B (Black et al., 2005), where these two rings are nearly perpendicular to one another with a dihedral angle of ca 88° (see: Protein Data Bank entry: code 2bgd).
3. Supramolecular features
In the crystal of (I), molecules are linked by N—H⋯O and N—H⋯N hydrogen bonds, forming slabs lying parallel to the ac plane (Fig. 3 and Table 1). Within the slabs there are also C—H⋯O and C—H⋯N hydrogen bonds and C—H⋯π interactions present reinforcing the two-dimensional structure (Table 1).
4. Database survey
A search of the Cambridge Structural Database (Version 5.36; Groom & Allen, 2014) revealed no crystal structures of free 5-aryl-1,2,5-thiadiazolidin-3-one 1,1-dioxides. It did reveal the presence of five 1,2,5-thiadiazolidin-3-one 1,1-dioxide compounds substituted at the N atom in the 2-position. In the majority of these compounds, the five-membered 1,2,5-thiadiazolidine rings also have envelope conformations, with the N atom in the 5-position, as in compound (I), as the flap.
5. Synthesis and crystallization
The title compound was synthesized by amide bond formation between tert-butyl (2-{2-[2-(2-aminoethoxy)ethoxy]ethoxy}ethyl)carbamate and 3′-(1,1-dioxido-4-oxo-1,2,5-thiadiazolidin-2-yl)-4′-methoxy-[1,1′-biphenyl]-4-carboxylic acid via (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate. The precursors were synthesized according to published procedures (Black et al., 2005; Schwabacher et al., 1998). Full synthetic details will be published elsewhere. Single crystals of the title compound (I) were obtained by slow evaporation of a solution of (I) in methanol.
6. details
Crystal data, data collection and structure . The N-bound H atoms were located in a difference Fourier map and freely refined. The C-bound H atoms were included in calculated positions and treated as riding: C—H = 0.95–0.99 Å with Uiso(H) = 1.5Ueq(C) for methyl H atoms and = 1.2Ueq(C) for other H atoms.
details are summarized in Table 2
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Supporting information
CCDC reference: 1051176
10.1107/S2056989015003850/su5087sup1.cif
contains datablocks I, Global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S2056989015003850/su5087Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989015003850/su5087Isup3.cml
Data collection: APEX2 (Bruker, 2008); cell
SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL2013 (Sheldrick, 2015).C24H32N4O8S | Z = 2 |
Mr = 536.59 | F(000) = 568 |
Triclinic, P1 | Dx = 1.446 Mg m−3 |
a = 7.3483 (2) Å | Cu Kα radiation, λ = 1.54178 Å |
b = 12.2233 (3) Å | Cell parameters from 8971 reflections |
c = 13.9847 (4) Å | θ = 3.2–71.7° |
α = 95.323 (1)° | µ = 1.67 mm−1 |
β = 90.281 (2)° | T = 100 K |
γ = 99.802 (1)° | Plate, colourless |
V = 1232.16 (6) Å3 | 0.15 × 0.15 × 0.02 mm |
Bruker APEXII CCD area-detector diffractometer | 4292 reflections with I > 2σ(I) |
Radiation source: Incoatec microfocus Cu tube | Rint = 0.017 |
ω and phi scans | θmax = 72.1°, θmin = 3.2° |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | h = −8→7 |
Tmin = 0.89, Tmax = 0.97 | k = −15→15 |
15014 measured reflections | l = −16→16 |
4539 independent reflections |
Refinement on F2 | 0 restraints |
Least-squares matrix: full | Hydrogen site location: mixed |
R[F2 > 2σ(F2)] = 0.039 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.111 | w = 1/[σ2(Fo2) + (0.0647P)2 + 0.8661P] where P = (Fo2 + 2Fc2)/3 |
S = 1.03 | (Δ/σ)max < 0.001 |
4539 reflections | Δρmax = 0.56 e Å−3 |
351 parameters | Δρmin = −0.33 e Å−3 |
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. |
Refinement. Maximum electron density of 0.56 e is in the vicinity of C21 in the extended chain and may represent very minor disorder. |
x | y | z | Uiso*/Ueq | ||
S1 | 0.52151 (5) | 0.68948 (3) | 0.09933 (3) | 0.01945 (13) | |
O1 | 0.65998 (19) | 0.61868 (11) | 0.09811 (10) | 0.0305 (3) | |
O2 | 0.35802 (18) | 0.64660 (11) | 0.14874 (10) | 0.0317 (3) | |
O3 | 0.52042 (18) | 0.86988 (10) | −0.09372 (9) | 0.0266 (3) | |
O4 | 0.97456 (17) | 0.88464 (10) | 0.17601 (9) | 0.0242 (3) | |
O5 | −0.07338 (17) | 0.81837 (11) | 0.69084 (9) | 0.0296 (3) | |
O6 | −0.04449 (18) | 0.63027 (11) | 0.85611 (9) | 0.0279 (3) | |
O7 | 0.16486 (19) | 0.49974 (10) | 0.73225 (10) | 0.0305 (3) | |
O8 | 0.5123 (2) | 0.49283 (11) | 0.63370 (10) | 0.0359 (3) | |
N1 | 0.4761 (2) | 0.71885 (12) | −0.00657 (10) | 0.0239 (3) | |
N2 | 0.6032 (2) | 0.81729 (11) | 0.14491 (10) | 0.0221 (3) | |
N3 | 0.1468 (2) | 0.84118 (12) | 0.80862 (11) | 0.0232 (3) | |
H1N3 | 0.256 (3) | 0.8427 (18) | 0.8228 (16) | 0.027 (6)* | |
N4 | 0.5520 (3) | 0.58747 (14) | 0.82658 (12) | 0.0291 (3) | |
H1N4 | 0.474 (4) | 0.520 (3) | 0.812 (2) | 0.052 (8)* | |
H2N4 | 0.510 (3) | 0.621 (2) | 0.8909 (19) | 0.041 (6)* | |
H3N4 | 0.685 (5) | 0.585 (2) | 0.831 (2) | 0.058 (8)* | |
C1 | 0.5371 (2) | 0.82684 (14) | −0.01819 (12) | 0.0206 (3) | |
C2 | 0.6324 (2) | 0.89346 (13) | 0.07032 (11) | 0.0198 (3) | |
H2A | 0.7659 | 0.9167 | 0.0595 | 0.024* | |
H2B | 0.5769 | 0.9607 | 0.0878 | 0.024* | |
C3 | 0.6802 (2) | 0.83838 (13) | 0.23985 (12) | 0.0187 (3) | |
C4 | 0.8705 (2) | 0.87285 (13) | 0.25612 (12) | 0.0204 (3) | |
C5 | 0.9381 (2) | 0.89174 (14) | 0.35051 (13) | 0.0229 (4) | |
H5 | 1.0668 | 0.9150 | 0.3628 | 0.028* | |
C6 | 0.8188 (2) | 0.87689 (14) | 0.42708 (12) | 0.0224 (3) | |
H6 | 0.8679 | 0.8896 | 0.4909 | 0.027* | |
C7 | 0.6289 (2) | 0.84384 (13) | 0.41224 (12) | 0.0193 (3) | |
C8 | 0.5638 (2) | 0.82427 (13) | 0.31696 (12) | 0.0197 (3) | |
H8 | 0.4352 | 0.8005 | 0.3047 | 0.024* | |
C9 | 0.4964 (2) | 0.83521 (13) | 0.49259 (12) | 0.0195 (3) | |
C10 | 0.5441 (2) | 0.88953 (14) | 0.58384 (12) | 0.0223 (3) | |
H10 | 0.6661 | 0.9293 | 0.5958 | 0.027* | |
C11 | 0.4178 (2) | 0.88685 (14) | 0.65740 (12) | 0.0230 (4) | |
H11 | 0.4549 | 0.9235 | 0.7190 | 0.028* | |
C12 | 0.2375 (2) | 0.83098 (13) | 0.64171 (12) | 0.0204 (3) | |
C13 | 0.1889 (3) | 0.77461 (16) | 0.55146 (13) | 0.0282 (4) | |
H13 | 0.0665 | 0.7354 | 0.5396 | 0.034* | |
C14 | 0.3165 (3) | 0.77503 (16) | 0.47882 (13) | 0.0281 (4) | |
H14 | 0.2816 | 0.7338 | 0.4187 | 0.034* | |
C15 | 1.1677 (3) | 0.92460 (19) | 0.18946 (15) | 0.0334 (4) | |
H15A | 1.1870 | 0.9942 | 0.2319 | 0.050* | |
H15B | 1.2233 | 0.9383 | 0.1272 | 0.050* | |
H15C | 1.2255 | 0.8687 | 0.2185 | 0.050* | |
C16 | 0.0893 (2) | 0.82919 (14) | 0.71575 (13) | 0.0226 (4) | |
C17 | 0.0153 (3) | 0.82894 (15) | 0.88628 (13) | 0.0270 (4) | |
H17A | −0.1093 | 0.8332 | 0.8612 | 0.032* | |
H17B | 0.0500 | 0.8914 | 0.9369 | 0.032* | |
C18 | 0.0089 (3) | 0.71993 (16) | 0.92983 (13) | 0.0273 (4) | |
H18A | 0.1319 | 0.7157 | 0.9570 | 0.033* | |
H18B | −0.0813 | 0.7146 | 0.9822 | 0.033* | |
C19 | 0.0108 (3) | 0.52875 (16) | 0.87786 (14) | 0.0294 (4) | |
H19A | −0.0770 | 0.4912 | 0.9229 | 0.035* | |
H19B | 0.1350 | 0.5449 | 0.9090 | 0.035* | |
C20 | 0.0145 (3) | 0.45443 (15) | 0.78734 (15) | 0.0303 (4) | |
H20A | 0.0284 | 0.3787 | 0.8026 | 0.036* | |
H20B | −0.1026 | 0.4487 | 0.7505 | 0.036* | |
C21 | 0.1833 (3) | 0.42988 (19) | 0.64803 (17) | 0.0431 (5) | |
H21A | 0.0660 | 0.4151 | 0.6101 | 0.052* | |
H21B | 0.2117 | 0.3577 | 0.6651 | 0.052* | |
C22 | 0.3357 (4) | 0.4859 (2) | 0.58984 (17) | 0.0510 (6) | |
H22A | 0.3335 | 0.4440 | 0.5256 | 0.061* | |
H22B | 0.3141 | 0.5621 | 0.5807 | 0.061* | |
C23 | 0.6108 (3) | 0.60309 (16) | 0.65657 (15) | 0.0344 (4) | |
H23A | 0.5972 | 0.6482 | 0.6026 | 0.041* | |
H23B | 0.7437 | 0.6005 | 0.6651 | 0.041* | |
C24 | 0.5416 (3) | 0.65799 (15) | 0.74680 (14) | 0.0297 (4) | |
H24A | 0.6178 | 0.7324 | 0.7631 | 0.036* | |
H24B | 0.4123 | 0.6680 | 0.7366 | 0.036* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1 | 0.0198 (2) | 0.0170 (2) | 0.0207 (2) | −0.00143 (15) | −0.00151 (15) | 0.00555 (14) |
O1 | 0.0350 (8) | 0.0252 (6) | 0.0340 (7) | 0.0097 (5) | 0.0005 (6) | 0.0085 (5) |
O2 | 0.0250 (7) | 0.0316 (7) | 0.0353 (7) | −0.0080 (5) | 0.0031 (6) | 0.0098 (6) |
O3 | 0.0334 (7) | 0.0249 (6) | 0.0221 (6) | 0.0042 (5) | −0.0041 (5) | 0.0077 (5) |
O4 | 0.0183 (6) | 0.0312 (6) | 0.0231 (6) | 0.0026 (5) | 0.0036 (5) | 0.0060 (5) |
O5 | 0.0197 (7) | 0.0391 (7) | 0.0312 (7) | 0.0057 (5) | 0.0018 (5) | 0.0076 (6) |
O6 | 0.0264 (7) | 0.0275 (6) | 0.0308 (7) | 0.0055 (5) | 0.0002 (5) | 0.0065 (5) |
O7 | 0.0299 (7) | 0.0246 (6) | 0.0351 (7) | 0.0004 (5) | 0.0045 (6) | 0.0007 (5) |
O8 | 0.0422 (8) | 0.0267 (7) | 0.0368 (7) | 0.0029 (6) | 0.0066 (6) | −0.0014 (6) |
N1 | 0.0289 (8) | 0.0204 (7) | 0.0217 (7) | 0.0008 (6) | −0.0043 (6) | 0.0044 (6) |
N2 | 0.0275 (8) | 0.0182 (7) | 0.0188 (7) | −0.0036 (5) | −0.0031 (6) | 0.0064 (5) |
N3 | 0.0194 (8) | 0.0262 (8) | 0.0237 (7) | 0.0021 (6) | 0.0040 (6) | 0.0032 (6) |
N4 | 0.0342 (10) | 0.0243 (8) | 0.0300 (8) | 0.0068 (7) | −0.0004 (7) | 0.0049 (6) |
C1 | 0.0199 (8) | 0.0219 (8) | 0.0206 (8) | 0.0042 (6) | −0.0002 (6) | 0.0039 (6) |
C2 | 0.0218 (8) | 0.0176 (7) | 0.0201 (8) | 0.0006 (6) | −0.0006 (6) | 0.0069 (6) |
C3 | 0.0212 (8) | 0.0158 (7) | 0.0188 (8) | 0.0015 (6) | −0.0018 (6) | 0.0042 (6) |
C4 | 0.0214 (9) | 0.0180 (7) | 0.0226 (8) | 0.0035 (6) | 0.0029 (7) | 0.0049 (6) |
C5 | 0.0166 (8) | 0.0252 (8) | 0.0263 (9) | 0.0009 (6) | −0.0020 (7) | 0.0035 (7) |
C6 | 0.0219 (9) | 0.0237 (8) | 0.0212 (8) | 0.0023 (6) | −0.0033 (7) | 0.0026 (6) |
C7 | 0.0206 (9) | 0.0174 (7) | 0.0205 (8) | 0.0031 (6) | 0.0002 (6) | 0.0050 (6) |
C8 | 0.0176 (8) | 0.0189 (8) | 0.0225 (8) | 0.0015 (6) | −0.0012 (6) | 0.0051 (6) |
C9 | 0.0202 (9) | 0.0188 (8) | 0.0207 (8) | 0.0039 (6) | −0.0003 (6) | 0.0065 (6) |
C10 | 0.0200 (9) | 0.0226 (8) | 0.0230 (8) | −0.0006 (6) | −0.0004 (7) | 0.0031 (6) |
C11 | 0.0266 (9) | 0.0205 (8) | 0.0210 (8) | 0.0014 (6) | 0.0001 (7) | 0.0019 (6) |
C12 | 0.0216 (9) | 0.0201 (8) | 0.0212 (8) | 0.0052 (6) | 0.0012 (6) | 0.0072 (6) |
C13 | 0.0204 (9) | 0.0373 (10) | 0.0251 (9) | −0.0017 (7) | −0.0024 (7) | 0.0052 (7) |
C14 | 0.0251 (10) | 0.0365 (10) | 0.0202 (8) | −0.0020 (7) | −0.0017 (7) | 0.0019 (7) |
C15 | 0.0175 (9) | 0.0517 (12) | 0.0328 (10) | 0.0062 (8) | 0.0031 (8) | 0.0133 (9) |
C16 | 0.0229 (10) | 0.0196 (8) | 0.0258 (9) | 0.0033 (6) | 0.0030 (7) | 0.0053 (6) |
C17 | 0.0255 (9) | 0.0293 (9) | 0.0252 (9) | 0.0032 (7) | 0.0081 (7) | 0.0006 (7) |
C18 | 0.0241 (9) | 0.0340 (10) | 0.0231 (8) | 0.0022 (7) | 0.0040 (7) | 0.0038 (7) |
C19 | 0.0231 (9) | 0.0292 (9) | 0.0367 (10) | 0.0016 (7) | −0.0006 (8) | 0.0131 (8) |
C20 | 0.0226 (9) | 0.0249 (9) | 0.0438 (11) | 0.0018 (7) | 0.0007 (8) | 0.0094 (8) |
C21 | 0.0386 (12) | 0.0417 (12) | 0.0427 (12) | −0.0026 (9) | 0.0010 (10) | −0.0108 (10) |
C22 | 0.0471 (14) | 0.0703 (17) | 0.0295 (11) | −0.0007 (12) | 0.0019 (10) | −0.0079 (10) |
C23 | 0.0421 (12) | 0.0263 (9) | 0.0336 (10) | 0.0014 (8) | 0.0054 (9) | 0.0049 (8) |
C24 | 0.0369 (11) | 0.0225 (9) | 0.0296 (9) | 0.0024 (7) | 0.0016 (8) | 0.0065 (7) |
S1—O2 | 1.4341 (13) | C8—H8 | 0.9500 |
S1—O1 | 1.4429 (13) | C9—C10 | 1.397 (2) |
S1—N1 | 1.6025 (14) | C9—C14 | 1.402 (3) |
S1—N2 | 1.6429 (14) | C10—C11 | 1.388 (2) |
O3—C1 | 1.237 (2) | C10—H10 | 0.9500 |
O4—C4 | 1.365 (2) | C11—C12 | 1.390 (2) |
O4—C15 | 1.425 (2) | C11—H11 | 0.9500 |
O5—C16 | 1.226 (2) | C12—C13 | 1.395 (3) |
O6—C19 | 1.428 (2) | C12—C16 | 1.505 (2) |
O6—C18 | 1.435 (2) | C13—C14 | 1.386 (3) |
O7—C21 | 1.410 (2) | C13—H13 | 0.9500 |
O7—C20 | 1.414 (2) | C14—H14 | 0.9500 |
O8—C22 | 1.419 (3) | C15—H15A | 0.9800 |
O8—C23 | 1.424 (2) | C15—H15B | 0.9800 |
N1—C1 | 1.345 (2) | C15—H15C | 0.9800 |
N2—C3 | 1.425 (2) | C17—C18 | 1.509 (3) |
N2—C2 | 1.454 (2) | C17—H17A | 0.9900 |
N3—C16 | 1.351 (2) | C17—H17B | 0.9900 |
N3—C17 | 1.459 (2) | C18—H18A | 0.9900 |
N3—H1N3 | 0.82 (2) | C18—H18B | 0.9900 |
N4—C24 | 1.481 (2) | C19—C20 | 1.491 (3) |
N4—H1N4 | 0.93 (3) | C19—H19A | 0.9900 |
N4—H2N4 | 1.03 (3) | C19—H19B | 0.9900 |
N4—H3N4 | 0.98 (3) | C20—H20A | 0.9900 |
C1—C2 | 1.515 (2) | C20—H20B | 0.9900 |
C2—H2A | 0.9900 | C21—C22 | 1.496 (3) |
C2—H2B | 0.9900 | C21—H21A | 0.9900 |
C3—C8 | 1.385 (2) | C21—H21B | 0.9900 |
C3—C4 | 1.401 (2) | C22—H22A | 0.9900 |
C4—C5 | 1.393 (2) | C22—H22B | 0.9900 |
C5—C6 | 1.393 (2) | C23—C24 | 1.505 (3) |
C5—H5 | 0.9500 | C23—H23A | 0.9900 |
C6—C7 | 1.394 (2) | C23—H23B | 0.9900 |
C6—H6 | 0.9500 | C24—H24A | 0.9900 |
C7—C8 | 1.399 (2) | C24—H24B | 0.9900 |
C7—C9 | 1.490 (2) | ||
O2—S1—O1 | 113.21 (8) | C14—C13—H13 | 119.5 |
O2—S1—N1 | 112.24 (8) | C12—C13—H13 | 119.5 |
O1—S1—N1 | 111.49 (8) | C13—C14—C9 | 121.12 (17) |
O2—S1—N2 | 109.69 (8) | C13—C14—H14 | 119.4 |
O1—S1—N2 | 111.90 (8) | C9—C14—H14 | 119.4 |
N1—S1—N2 | 97.26 (7) | O4—C15—H15A | 109.5 |
C4—O4—C15 | 117.63 (14) | O4—C15—H15B | 109.5 |
C19—O6—C18 | 112.83 (14) | H15A—C15—H15B | 109.5 |
C21—O7—C20 | 111.72 (15) | O4—C15—H15C | 109.5 |
C22—O8—C23 | 115.10 (18) | H15A—C15—H15C | 109.5 |
C1—N1—S1 | 111.85 (12) | H15B—C15—H15C | 109.5 |
C3—N2—C2 | 125.75 (13) | O5—C16—N3 | 123.27 (16) |
C3—N2—S1 | 120.81 (11) | O5—C16—C12 | 120.31 (16) |
C2—N2—S1 | 111.22 (11) | N3—C16—C12 | 116.41 (16) |
C16—N3—C17 | 121.27 (16) | N3—C17—C18 | 112.19 (15) |
C16—N3—H1N3 | 120.7 (16) | N3—C17—H17A | 109.2 |
C17—N3—H1N3 | 116.9 (15) | C18—C17—H17A | 109.2 |
C24—N4—H1N4 | 108.5 (17) | N3—C17—H17B | 109.2 |
C24—N4—H2N4 | 113.3 (14) | C18—C17—H17B | 109.2 |
H1N4—N4—H2N4 | 107 (2) | H17A—C17—H17B | 107.9 |
C24—N4—H3N4 | 102.2 (17) | O6—C18—C17 | 108.55 (14) |
H1N4—N4—H3N4 | 117 (2) | O6—C18—H18A | 110.0 |
H2N4—N4—H3N4 | 109 (2) | C17—C18—H18A | 110.0 |
O3—C1—N1 | 124.30 (16) | O6—C18—H18B | 110.0 |
O3—C1—C2 | 121.76 (15) | C17—C18—H18B | 110.0 |
N1—C1—C2 | 113.94 (14) | H18A—C18—H18B | 108.4 |
N2—C2—C1 | 104.42 (13) | O6—C19—C20 | 109.31 (15) |
N2—C2—H2A | 110.9 | O6—C19—H19A | 109.8 |
C1—C2—H2A | 110.9 | C20—C19—H19A | 109.8 |
N2—C2—H2B | 110.9 | O6—C19—H19B | 109.8 |
C1—C2—H2B | 110.9 | C20—C19—H19B | 109.8 |
H2A—C2—H2B | 108.9 | H19A—C19—H19B | 108.3 |
C8—C3—C4 | 119.87 (15) | O7—C20—C19 | 108.74 (15) |
C8—C3—N2 | 118.94 (15) | O7—C20—H20A | 109.9 |
C4—C3—N2 | 121.19 (15) | C19—C20—H20A | 109.9 |
O4—C4—C5 | 125.49 (16) | O7—C20—H20B | 109.9 |
O4—C4—C3 | 115.86 (15) | C19—C20—H20B | 109.9 |
C5—C4—C3 | 118.65 (15) | H20A—C20—H20B | 108.3 |
C6—C5—C4 | 120.62 (16) | O7—C21—C22 | 109.08 (18) |
C6—C5—H5 | 119.7 | O7—C21—H21A | 109.9 |
C4—C5—H5 | 119.7 | C22—C21—H21A | 109.9 |
C5—C6—C7 | 121.50 (16) | O7—C21—H21B | 109.9 |
C5—C6—H6 | 119.3 | C22—C21—H21B | 109.9 |
C7—C6—H6 | 119.3 | H21A—C21—H21B | 108.3 |
C6—C7—C8 | 117.06 (15) | O8—C22—C21 | 112.5 (2) |
C6—C7—C9 | 122.74 (15) | O8—C22—H22A | 109.1 |
C8—C7—C9 | 120.11 (15) | C21—C22—H22A | 109.1 |
C3—C8—C7 | 122.29 (16) | O8—C22—H22B | 109.1 |
C3—C8—H8 | 118.9 | C21—C22—H22B | 109.1 |
C7—C8—H8 | 118.9 | H22A—C22—H22B | 107.8 |
C10—C9—C14 | 117.26 (16) | O8—C23—C24 | 111.71 (16) |
C10—C9—C7 | 121.45 (15) | O8—C23—H23A | 109.3 |
C14—C9—C7 | 121.26 (15) | C24—C23—H23A | 109.3 |
C11—C10—C9 | 121.63 (16) | O8—C23—H23B | 109.3 |
C11—C10—H10 | 119.2 | C24—C23—H23B | 109.3 |
C9—C10—H10 | 119.2 | H23A—C23—H23B | 107.9 |
C10—C11—C12 | 120.59 (16) | N4—C24—C23 | 109.41 (16) |
C10—C11—H11 | 119.7 | N4—C24—H24A | 109.8 |
C12—C11—H11 | 119.7 | C23—C24—H24A | 109.8 |
C11—C12—C13 | 118.37 (16) | N4—C24—H24B | 109.8 |
C11—C12—C16 | 123.98 (16) | C23—C24—H24B | 109.8 |
C13—C12—C16 | 117.63 (16) | H24A—C24—H24B | 108.2 |
C14—C13—C12 | 120.93 (17) | ||
O2—S1—N1—C1 | 121.10 (13) | C9—C7—C8—C3 | 175.66 (14) |
O1—S1—N1—C1 | −110.68 (13) | C6—C7—C9—C10 | 19.1 (2) |
N2—S1—N1—C1 | 6.33 (14) | C8—C7—C9—C10 | −157.39 (16) |
O2—S1—N2—C3 | 68.27 (15) | C6—C7—C9—C14 | −162.95 (16) |
O1—S1—N2—C3 | −58.24 (15) | C8—C7—C9—C14 | 20.6 (2) |
N1—S1—N2—C3 | −174.93 (14) | C14—C9—C10—C11 | −1.7 (3) |
O2—S1—N2—C2 | −127.73 (12) | C7—C9—C10—C11 | 176.34 (15) |
O1—S1—N2—C2 | 105.76 (13) | C9—C10—C11—C12 | −1.1 (3) |
N1—S1—N2—C2 | −10.94 (13) | C10—C11—C12—C13 | 2.2 (2) |
S1—N1—C1—O3 | 179.31 (14) | C10—C11—C12—C16 | −176.56 (15) |
S1—N1—C1—C2 | 0.00 (19) | C11—C12—C13—C14 | −0.6 (3) |
C3—N2—C2—C1 | 174.45 (15) | C16—C12—C13—C14 | 178.28 (17) |
S1—N2—C2—C1 | 11.42 (16) | C12—C13—C14—C9 | −2.3 (3) |
O3—C1—C2—N2 | 173.35 (16) | C10—C9—C14—C13 | 3.4 (3) |
N1—C1—C2—N2 | −7.3 (2) | C7—C9—C14—C13 | −174.70 (17) |
C2—N2—C3—C8 | 127.60 (17) | C17—N3—C16—O5 | 7.3 (3) |
S1—N2—C3—C8 | −70.86 (19) | C17—N3—C16—C12 | −173.40 (14) |
C2—N2—C3—C4 | −52.4 (2) | C11—C12—C16—O5 | 151.68 (17) |
S1—N2—C3—C4 | 109.13 (16) | C13—C12—C16—O5 | −27.1 (2) |
C15—O4—C4—C5 | −3.1 (2) | C11—C12—C16—N3 | −27.6 (2) |
C15—O4—C4—C3 | 177.13 (15) | C13—C12—C16—N3 | 153.56 (16) |
C8—C3—C4—O4 | −179.96 (14) | C16—N3—C17—C18 | 105.25 (19) |
N2—C3—C4—O4 | 0.1 (2) | C19—O6—C18—C17 | 157.75 (15) |
C8—C3—C4—C5 | 0.3 (2) | N3—C17—C18—O6 | −59.8 (2) |
N2—C3—C4—C5 | −179.71 (15) | C18—O6—C19—C20 | −159.42 (15) |
O4—C4—C5—C6 | −179.90 (15) | C21—O7—C20—C19 | 176.42 (17) |
C3—C4—C5—C6 | −0.2 (2) | O6—C19—C20—O7 | 70.69 (19) |
C4—C5—C6—C7 | −0.6 (3) | C20—O7—C21—C22 | 176.10 (19) |
C5—C6—C7—C8 | 1.1 (2) | C23—O8—C22—C21 | −119.2 (2) |
C5—C6—C7—C9 | −175.45 (15) | O7—C21—C22—O8 | 69.3 (3) |
C4—C3—C8—C7 | 0.3 (2) | C22—O8—C23—C24 | 78.5 (2) |
N2—C3—C8—C7 | −179.69 (14) | O8—C23—C24—N4 | 55.8 (2) |
C6—C7—C8—C3 | −1.0 (2) |
Cg1 is the centroid of the C3–C8 ring. |
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H1N3···O3i | 0.82 (2) | 2.22 (3) | 3.012 (2) | 161 (2) |
N4—H1N4···O1ii | 0.93 (3) | 2.29 (3) | 3.010 (2) | 133 (2) |
N4—H1N4···O7 | 0.93 (3) | 2.49 (3) | 3.106 (2) | 124 (2) |
N4—H2N4···N1i | 1.03 (3) | 1.82 (3) | 2.821 (2) | 163 (2) |
N4—H3N4···O6iii | 0.98 (3) | 1.99 (3) | 2.942 (2) | 162 (3) |
C2—H2B···O3iv | 0.99 | 2.30 | 3.267 (2) | 166 |
C18—H18A···N1i | 0.99 | 2.57 | 3.545 (2) | 168 |
C22—H22A···O8ii | 0.99 | 2.63 | 3.343 (3) | 129 |
C24—H24A···O5iii | 0.99 | 2.58 | 3.298 (2) | 129 |
C21—H21B···Cg1ii | 0.99 | 2.70 | 3.555 (2) | 165 |
Symmetry codes: (i) x, y, z+1; (ii) −x+1, −y+1, −z+1; (iii) x+1, y, z; (iv) −x+1, −y+2, −z. |
Acknowledgements
We are grateful to the National Institutes of Health (CA 100757) for partial support of this work.
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