research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 71| Part 4| April 2015| Pages 336-338

Crystal structure 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)

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a125 Chemistry Bldg, University of Missouri Columbia, MO 65211, USA
*Correspondence e-mail: gatesk@missouri.edu

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 14 February 2015; accepted 24 February 2015; online 4 March 2015)

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 envelope conformation 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.

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[Combs, A. P. (2010). J. Med. Chem. 53, 2333-2344.]). 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[link]), is a rather weak inhibitor of PTP1B, displaying a Ki value of approximately 2 mM (Black et al., 2005[Black, E., Breed, J., Breeze, A. L., Embrey, K., Garcia, R., Gero, T. W., Godfrey, L., Kenny, P. W., Morley, A. D., Minshull, C. A., Pannifer, A. D., Read, J., Rees, A., Russell, D. J., Toader, D. & Tucker, J. (2005). Bioorg. Med. Chem. Lett. 15, 2503-2507.]). Docking studies 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[Black, E., Breed, J., Breeze, A. L., Embrey, K., Garcia, R., Gero, T. W., Godfrey, L., Kenny, P. W., Morley, A. D., Minshull, C. A., Pannifer, A. D., Read, J., Rees, A., Russell, D. J., Toader, D. & Tucker, J. (2005). Bioorg. Med. Chem. Lett. 15, 2503-2507.]). 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[Black, E., Breed, J., Breeze, A. L., Embrey, K., Garcia, R., Gero, T. W., Godfrey, L., Kenny, P. W., Morley, A. D., Minshull, C. A., Pannifer, A. D., Read, J., Rees, A., Russell, D. J., Toader, D. & Tucker, J. (2005). Bioorg. Med. Chem. Lett. 15, 2503-2507.]). 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[Black, E., Breed, J., Breeze, A. L., Embrey, K., Garcia, R., Gero, T. W., Godfrey, L., Kenny, P. W., Morley, A. D., Minshull, C. A., Pannifer, A. D., Read, J., Rees, A., Russell, D. J., Toader, D. & Tucker, J. (2005). Bioorg. Med. Chem. Lett. 15, 2503-2507.]). X-ray crystal structure analysis confirmed the twisted conformation of the 1,2,5-thia­diazo­lidin-3-one 1,1-dioxide and aryl ring systems in the protein–ligand co-crystal structure of 4 bound to PTP1B (Black et al., 2005[Black, E., Breed, J., Breeze, A. L., Embrey, K., Garcia, R., Gero, T. W., Godfrey, L., Kenny, P. W., Morley, A. D., Minshull, C. A., Pannifer, A. D., Read, J., Rees, A., Russell, D. J., Toader, D. & Tucker, J. (2005). Bioorg. Med. Chem. Lett. 15, 2503-2507.]). 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 co-crystal 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 crystal structure of the title compound (I)[link], shown in the scheme below, a derivative of compound 4.

[Scheme 1]
[Figure 1]
Figure 1
The parent compound 1 and related compounds.

2. Structural commentary

The title compound (I)[link], crystallized as a zwitterion (Fig. 2[link]). 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[link] and Fig. 2[link]). 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 envelope conformation 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 co-crystal structure of 4 bound to PTP1B (Black et al., 2005[Black, E., Breed, J., Breeze, A. L., Embrey, K., Garcia, R., Gero, T. W., Godfrey, L., Kenny, P. W., Morley, A. D., Minshull, C. A., Pannifer, A. D., Read, J., Rees, A., Russell, D. J., Toader, D. & Tucker, J. (2005). Bioorg. Med. Chem. Lett. 15, 2503-2507.]), where these two rings are nearly perpendicular to one another with a dihedral angle of ca 88° (see: Protein Data Bank entry: code 2bgd).

Table 1
Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the C3–C8 ring.

D—H⋯A D—H H⋯A DA 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—H21BCg1ii 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.
[Figure 2]
Figure 2
A view of the mol­ecular structure of the title compound (I)[link], showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level. The intra­molecular N—H⋯O hydrogen bond is shown as a dashed line (see Table 1[link] for details) and C-bound H atoms have been omitted for clarity.

3. Supra­molecular features

In the crystal of (I)[link], mol­ecules are linked by N—H⋯O and N—H⋯N hydrogen bonds, forming slabs lying parallel to the ac plane (Fig. 3[link] and Table 1[link]). 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[link]).

[Figure 3]
Figure 3
A view along the c axis of the crystal packing of the title compound. The N—H⋯O and N—H⋯O hydrogen bonds are shown as dashed lines (see Table 1[link] for details) and C-bound H atoms have been omitted for clarity.

4. Database survey

A search of the Cambridge Structural Database (Version 5.36; Groom & Allen, 2014[Groom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. 53, 662-671.]) 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)[link], 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[Black, E., Breed, J., Breeze, A. L., Embrey, K., Garcia, R., Gero, T. W., Godfrey, L., Kenny, P. W., Morley, A. D., Minshull, C. A., Pannifer, A. D., Read, J., Rees, A., Russell, D. J., Toader, D. & Tucker, J. (2005). Bioorg. Med. Chem. Lett. 15, 2503-2507.]; Schwabacher et al., 1998[Schwabacher, A. W., Lane, J. W., Schiesher, M. W., Leigh, K. M. & Johnson, C. W. (1998). J. Org. Chem. 63, 1727-1729.]). Full synthetic details will be published elsewhere. Single crystals of the title compound (I)[link] were obtained by slow evaporation of a solution of (I)[link] in methanol.

6. Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. 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.

Table 2
Experimental details

Crystal data
Chemical formula C24H32N4O8S
Mr 536.59
Crystal system, space group Triclinic, P[\overline{1}]
Temperature (K) 100
a, b, c (Å) 7.3483 (2), 12.2233 (3), 13.9847 (4)
α, β, γ (°) 95.323 (1), 90.281 (2), 99.802 (1)
V3) 1232.16 (6)
Z 2
Radiation type Cu Kα
μ (mm−1) 1.67
Crystal size (mm) 0.15 × 0.15 × 0.02
 
Data collection
Diffractometer Bruker APEXII CCD area detector
Absorption correction Multi-scan (SADABS; Bruker, 2008[Bruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.89, 0.97
No. of measured, independent and observed [I > 2σ(I)] reflections 15014, 4539, 4292
Rint 0.017
(sin θ/λ)max−1) 0.617
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.039, 0.111, 1.03
No. of reflections 4539
No. of parameters 351
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.56, −0.33
Computer programs: APEX2 and SAINT (Bruker, 2008[Bruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS2013 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2013 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]) and Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]).

Supporting information


Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: 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).

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 top
Crystal data top
C24H32N4O8SZ = 2
Mr = 536.59F(000) = 568
Triclinic, P1Dx = 1.446 Mg m3
a = 7.3483 (2) ÅCu Kα radiation, λ = 1.54178 Å
b = 12.2233 (3) ÅCell parameters from 8971 reflections
c = 13.9847 (4) Åθ = 3.2–71.7°
α = 95.323 (1)°µ = 1.67 mm1
β = 90.281 (2)°T = 100 K
γ = 99.802 (1)°Plate, colourless
V = 1232.16 (6) Å30.15 × 0.15 × 0.02 mm
Data collection top
Bruker APEXII CCD area-detector
diffractometer
4292 reflections with I > 2σ(I)
Radiation source: Incoatec microfocus Cu tubeRint = 0.017
ω and phi scansθmax = 72.1°, θmin = 3.2°
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
h = 87
Tmin = 0.89, Tmax = 0.97k = 1515
15014 measured reflectionsl = 1616
4539 independent reflections
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.039H 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 reflectionsΔρmax = 0.56 e Å3
351 parametersΔρmin = 0.33 e Å3
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S10.52151 (5)0.68948 (3)0.09933 (3)0.01945 (13)
O10.65998 (19)0.61868 (11)0.09811 (10)0.0305 (3)
O20.35802 (18)0.64660 (11)0.14874 (10)0.0317 (3)
O30.52042 (18)0.86988 (10)0.09372 (9)0.0266 (3)
O40.97456 (17)0.88464 (10)0.17601 (9)0.0242 (3)
O50.07338 (17)0.81837 (11)0.69084 (9)0.0296 (3)
O60.04449 (18)0.63027 (11)0.85611 (9)0.0279 (3)
O70.16486 (19)0.49974 (10)0.73225 (10)0.0305 (3)
O80.5123 (2)0.49283 (11)0.63370 (10)0.0359 (3)
N10.4761 (2)0.71885 (12)0.00657 (10)0.0239 (3)
N20.6032 (2)0.81729 (11)0.14491 (10)0.0221 (3)
N30.1468 (2)0.84118 (12)0.80862 (11)0.0232 (3)
H1N30.256 (3)0.8427 (18)0.8228 (16)0.027 (6)*
N40.5520 (3)0.58747 (14)0.82658 (12)0.0291 (3)
H1N40.474 (4)0.520 (3)0.812 (2)0.052 (8)*
H2N40.510 (3)0.621 (2)0.8909 (19)0.041 (6)*
H3N40.685 (5)0.585 (2)0.831 (2)0.058 (8)*
C10.5371 (2)0.82684 (14)0.01819 (12)0.0206 (3)
C20.6324 (2)0.89346 (13)0.07032 (11)0.0198 (3)
H2A0.76590.91670.05950.024*
H2B0.57690.96070.08780.024*
C30.6802 (2)0.83838 (13)0.23985 (12)0.0187 (3)
C40.8705 (2)0.87285 (13)0.25612 (12)0.0204 (3)
C50.9381 (2)0.89174 (14)0.35051 (13)0.0229 (4)
H51.06680.91500.36280.028*
C60.8188 (2)0.87689 (14)0.42708 (12)0.0224 (3)
H60.86790.88960.49090.027*
C70.6289 (2)0.84384 (13)0.41224 (12)0.0193 (3)
C80.5638 (2)0.82427 (13)0.31696 (12)0.0197 (3)
H80.43520.80050.30470.024*
C90.4964 (2)0.83521 (13)0.49259 (12)0.0195 (3)
C100.5441 (2)0.88953 (14)0.58384 (12)0.0223 (3)
H100.66610.92930.59580.027*
C110.4178 (2)0.88685 (14)0.65740 (12)0.0230 (4)
H110.45490.92350.71900.028*
C120.2375 (2)0.83098 (13)0.64171 (12)0.0204 (3)
C130.1889 (3)0.77461 (16)0.55146 (13)0.0282 (4)
H130.06650.73540.53960.034*
C140.3165 (3)0.77503 (16)0.47882 (13)0.0281 (4)
H140.28160.73380.41870.034*
C151.1677 (3)0.92460 (19)0.18946 (15)0.0334 (4)
H15A1.18700.99420.23190.050*
H15B1.22330.93830.12720.050*
H15C1.22550.86870.21850.050*
C160.0893 (2)0.82919 (14)0.71575 (13)0.0226 (4)
C170.0153 (3)0.82894 (15)0.88628 (13)0.0270 (4)
H17A0.10930.83320.86120.032*
H17B0.05000.89140.93690.032*
C180.0089 (3)0.71993 (16)0.92983 (13)0.0273 (4)
H18A0.13190.71570.95700.033*
H18B0.08130.71460.98220.033*
C190.0108 (3)0.52875 (16)0.87786 (14)0.0294 (4)
H19A0.07700.49120.92290.035*
H19B0.13500.54490.90900.035*
C200.0145 (3)0.45443 (15)0.78734 (15)0.0303 (4)
H20A0.02840.37870.80260.036*
H20B0.10260.44870.75050.036*
C210.1833 (3)0.42988 (19)0.64803 (17)0.0431 (5)
H21A0.06600.41510.61010.052*
H21B0.21170.35770.66510.052*
C220.3357 (4)0.4859 (2)0.58984 (17)0.0510 (6)
H22A0.33350.44400.52560.061*
H22B0.31410.56210.58070.061*
C230.6108 (3)0.60309 (16)0.65657 (15)0.0344 (4)
H23A0.59720.64820.60260.041*
H23B0.74370.60050.66510.041*
C240.5416 (3)0.65799 (15)0.74680 (14)0.0297 (4)
H24A0.61780.73240.76310.036*
H24B0.41230.66800.73660.036*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0198 (2)0.0170 (2)0.0207 (2)0.00143 (15)0.00151 (15)0.00555 (14)
O10.0350 (8)0.0252 (6)0.0340 (7)0.0097 (5)0.0005 (6)0.0085 (5)
O20.0250 (7)0.0316 (7)0.0353 (7)0.0080 (5)0.0031 (6)0.0098 (6)
O30.0334 (7)0.0249 (6)0.0221 (6)0.0042 (5)0.0041 (5)0.0077 (5)
O40.0183 (6)0.0312 (6)0.0231 (6)0.0026 (5)0.0036 (5)0.0060 (5)
O50.0197 (7)0.0391 (7)0.0312 (7)0.0057 (5)0.0018 (5)0.0076 (6)
O60.0264 (7)0.0275 (6)0.0308 (7)0.0055 (5)0.0002 (5)0.0065 (5)
O70.0299 (7)0.0246 (6)0.0351 (7)0.0004 (5)0.0045 (6)0.0007 (5)
O80.0422 (8)0.0267 (7)0.0368 (7)0.0029 (6)0.0066 (6)0.0014 (6)
N10.0289 (8)0.0204 (7)0.0217 (7)0.0008 (6)0.0043 (6)0.0044 (6)
N20.0275 (8)0.0182 (7)0.0188 (7)0.0036 (5)0.0031 (6)0.0064 (5)
N30.0194 (8)0.0262 (8)0.0237 (7)0.0021 (6)0.0040 (6)0.0032 (6)
N40.0342 (10)0.0243 (8)0.0300 (8)0.0068 (7)0.0004 (7)0.0049 (6)
C10.0199 (8)0.0219 (8)0.0206 (8)0.0042 (6)0.0002 (6)0.0039 (6)
C20.0218 (8)0.0176 (7)0.0201 (8)0.0006 (6)0.0006 (6)0.0069 (6)
C30.0212 (8)0.0158 (7)0.0188 (8)0.0015 (6)0.0018 (6)0.0042 (6)
C40.0214 (9)0.0180 (7)0.0226 (8)0.0035 (6)0.0029 (7)0.0049 (6)
C50.0166 (8)0.0252 (8)0.0263 (9)0.0009 (6)0.0020 (7)0.0035 (7)
C60.0219 (9)0.0237 (8)0.0212 (8)0.0023 (6)0.0033 (7)0.0026 (6)
C70.0206 (9)0.0174 (7)0.0205 (8)0.0031 (6)0.0002 (6)0.0050 (6)
C80.0176 (8)0.0189 (8)0.0225 (8)0.0015 (6)0.0012 (6)0.0051 (6)
C90.0202 (9)0.0188 (8)0.0207 (8)0.0039 (6)0.0003 (6)0.0065 (6)
C100.0200 (9)0.0226 (8)0.0230 (8)0.0006 (6)0.0004 (7)0.0031 (6)
C110.0266 (9)0.0205 (8)0.0210 (8)0.0014 (6)0.0001 (7)0.0019 (6)
C120.0216 (9)0.0201 (8)0.0212 (8)0.0052 (6)0.0012 (6)0.0072 (6)
C130.0204 (9)0.0373 (10)0.0251 (9)0.0017 (7)0.0024 (7)0.0052 (7)
C140.0251 (10)0.0365 (10)0.0202 (8)0.0020 (7)0.0017 (7)0.0019 (7)
C150.0175 (9)0.0517 (12)0.0328 (10)0.0062 (8)0.0031 (8)0.0133 (9)
C160.0229 (10)0.0196 (8)0.0258 (9)0.0033 (6)0.0030 (7)0.0053 (6)
C170.0255 (9)0.0293 (9)0.0252 (9)0.0032 (7)0.0081 (7)0.0006 (7)
C180.0241 (9)0.0340 (10)0.0231 (8)0.0022 (7)0.0040 (7)0.0038 (7)
C190.0231 (9)0.0292 (9)0.0367 (10)0.0016 (7)0.0006 (8)0.0131 (8)
C200.0226 (9)0.0249 (9)0.0438 (11)0.0018 (7)0.0007 (8)0.0094 (8)
C210.0386 (12)0.0417 (12)0.0427 (12)0.0026 (9)0.0010 (10)0.0108 (10)
C220.0471 (14)0.0703 (17)0.0295 (11)0.0007 (12)0.0019 (10)0.0079 (10)
C230.0421 (12)0.0263 (9)0.0336 (10)0.0014 (8)0.0054 (9)0.0049 (8)
C240.0369 (11)0.0225 (9)0.0296 (9)0.0024 (7)0.0016 (8)0.0065 (7)
Geometric parameters (Å, º) top
S1—O21.4341 (13)C8—H80.9500
S1—O11.4429 (13)C9—C101.397 (2)
S1—N11.6025 (14)C9—C141.402 (3)
S1—N21.6429 (14)C10—C111.388 (2)
O3—C11.237 (2)C10—H100.9500
O4—C41.365 (2)C11—C121.390 (2)
O4—C151.425 (2)C11—H110.9500
O5—C161.226 (2)C12—C131.395 (3)
O6—C191.428 (2)C12—C161.505 (2)
O6—C181.435 (2)C13—C141.386 (3)
O7—C211.410 (2)C13—H130.9500
O7—C201.414 (2)C14—H140.9500
O8—C221.419 (3)C15—H15A0.9800
O8—C231.424 (2)C15—H15B0.9800
N1—C11.345 (2)C15—H15C0.9800
N2—C31.425 (2)C17—C181.509 (3)
N2—C21.454 (2)C17—H17A0.9900
N3—C161.351 (2)C17—H17B0.9900
N3—C171.459 (2)C18—H18A0.9900
N3—H1N30.82 (2)C18—H18B0.9900
N4—C241.481 (2)C19—C201.491 (3)
N4—H1N40.93 (3)C19—H19A0.9900
N4—H2N41.03 (3)C19—H19B0.9900
N4—H3N40.98 (3)C20—H20A0.9900
C1—C21.515 (2)C20—H20B0.9900
C2—H2A0.9900C21—C221.496 (3)
C2—H2B0.9900C21—H21A0.9900
C3—C81.385 (2)C21—H21B0.9900
C3—C41.401 (2)C22—H22A0.9900
C4—C51.393 (2)C22—H22B0.9900
C5—C61.393 (2)C23—C241.505 (3)
C5—H50.9500C23—H23A0.9900
C6—C71.394 (2)C23—H23B0.9900
C6—H60.9500C24—H24A0.9900
C7—C81.399 (2)C24—H24B0.9900
C7—C91.490 (2)
O2—S1—O1113.21 (8)C14—C13—H13119.5
O2—S1—N1112.24 (8)C12—C13—H13119.5
O1—S1—N1111.49 (8)C13—C14—C9121.12 (17)
O2—S1—N2109.69 (8)C13—C14—H14119.4
O1—S1—N2111.90 (8)C9—C14—H14119.4
N1—S1—N297.26 (7)O4—C15—H15A109.5
C4—O4—C15117.63 (14)O4—C15—H15B109.5
C19—O6—C18112.83 (14)H15A—C15—H15B109.5
C21—O7—C20111.72 (15)O4—C15—H15C109.5
C22—O8—C23115.10 (18)H15A—C15—H15C109.5
C1—N1—S1111.85 (12)H15B—C15—H15C109.5
C3—N2—C2125.75 (13)O5—C16—N3123.27 (16)
C3—N2—S1120.81 (11)O5—C16—C12120.31 (16)
C2—N2—S1111.22 (11)N3—C16—C12116.41 (16)
C16—N3—C17121.27 (16)N3—C17—C18112.19 (15)
C16—N3—H1N3120.7 (16)N3—C17—H17A109.2
C17—N3—H1N3116.9 (15)C18—C17—H17A109.2
C24—N4—H1N4108.5 (17)N3—C17—H17B109.2
C24—N4—H2N4113.3 (14)C18—C17—H17B109.2
H1N4—N4—H2N4107 (2)H17A—C17—H17B107.9
C24—N4—H3N4102.2 (17)O6—C18—C17108.55 (14)
H1N4—N4—H3N4117 (2)O6—C18—H18A110.0
H2N4—N4—H3N4109 (2)C17—C18—H18A110.0
O3—C1—N1124.30 (16)O6—C18—H18B110.0
O3—C1—C2121.76 (15)C17—C18—H18B110.0
N1—C1—C2113.94 (14)H18A—C18—H18B108.4
N2—C2—C1104.42 (13)O6—C19—C20109.31 (15)
N2—C2—H2A110.9O6—C19—H19A109.8
C1—C2—H2A110.9C20—C19—H19A109.8
N2—C2—H2B110.9O6—C19—H19B109.8
C1—C2—H2B110.9C20—C19—H19B109.8
H2A—C2—H2B108.9H19A—C19—H19B108.3
C8—C3—C4119.87 (15)O7—C20—C19108.74 (15)
C8—C3—N2118.94 (15)O7—C20—H20A109.9
C4—C3—N2121.19 (15)C19—C20—H20A109.9
O4—C4—C5125.49 (16)O7—C20—H20B109.9
O4—C4—C3115.86 (15)C19—C20—H20B109.9
C5—C4—C3118.65 (15)H20A—C20—H20B108.3
C6—C5—C4120.62 (16)O7—C21—C22109.08 (18)
C6—C5—H5119.7O7—C21—H21A109.9
C4—C5—H5119.7C22—C21—H21A109.9
C5—C6—C7121.50 (16)O7—C21—H21B109.9
C5—C6—H6119.3C22—C21—H21B109.9
C7—C6—H6119.3H21A—C21—H21B108.3
C6—C7—C8117.06 (15)O8—C22—C21112.5 (2)
C6—C7—C9122.74 (15)O8—C22—H22A109.1
C8—C7—C9120.11 (15)C21—C22—H22A109.1
C3—C8—C7122.29 (16)O8—C22—H22B109.1
C3—C8—H8118.9C21—C22—H22B109.1
C7—C8—H8118.9H22A—C22—H22B107.8
C10—C9—C14117.26 (16)O8—C23—C24111.71 (16)
C10—C9—C7121.45 (15)O8—C23—H23A109.3
C14—C9—C7121.26 (15)C24—C23—H23A109.3
C11—C10—C9121.63 (16)O8—C23—H23B109.3
C11—C10—H10119.2C24—C23—H23B109.3
C9—C10—H10119.2H23A—C23—H23B107.9
C10—C11—C12120.59 (16)N4—C24—C23109.41 (16)
C10—C11—H11119.7N4—C24—H24A109.8
C12—C11—H11119.7C23—C24—H24A109.8
C11—C12—C13118.37 (16)N4—C24—H24B109.8
C11—C12—C16123.98 (16)C23—C24—H24B109.8
C13—C12—C16117.63 (16)H24A—C24—H24B108.2
C14—C13—C12120.93 (17)
O2—S1—N1—C1121.10 (13)C9—C7—C8—C3175.66 (14)
O1—S1—N1—C1110.68 (13)C6—C7—C9—C1019.1 (2)
N2—S1—N1—C16.33 (14)C8—C7—C9—C10157.39 (16)
O2—S1—N2—C368.27 (15)C6—C7—C9—C14162.95 (16)
O1—S1—N2—C358.24 (15)C8—C7—C9—C1420.6 (2)
N1—S1—N2—C3174.93 (14)C14—C9—C10—C111.7 (3)
O2—S1—N2—C2127.73 (12)C7—C9—C10—C11176.34 (15)
O1—S1—N2—C2105.76 (13)C9—C10—C11—C121.1 (3)
N1—S1—N2—C210.94 (13)C10—C11—C12—C132.2 (2)
S1—N1—C1—O3179.31 (14)C10—C11—C12—C16176.56 (15)
S1—N1—C1—C20.00 (19)C11—C12—C13—C140.6 (3)
C3—N2—C2—C1174.45 (15)C16—C12—C13—C14178.28 (17)
S1—N2—C2—C111.42 (16)C12—C13—C14—C92.3 (3)
O3—C1—C2—N2173.35 (16)C10—C9—C14—C133.4 (3)
N1—C1—C2—N27.3 (2)C7—C9—C14—C13174.70 (17)
C2—N2—C3—C8127.60 (17)C17—N3—C16—O57.3 (3)
S1—N2—C3—C870.86 (19)C17—N3—C16—C12173.40 (14)
C2—N2—C3—C452.4 (2)C11—C12—C16—O5151.68 (17)
S1—N2—C3—C4109.13 (16)C13—C12—C16—O527.1 (2)
C15—O4—C4—C53.1 (2)C11—C12—C16—N327.6 (2)
C15—O4—C4—C3177.13 (15)C13—C12—C16—N3153.56 (16)
C8—C3—C4—O4179.96 (14)C16—N3—C17—C18105.25 (19)
N2—C3—C4—O40.1 (2)C19—O6—C18—C17157.75 (15)
C8—C3—C4—C50.3 (2)N3—C17—C18—O659.8 (2)
N2—C3—C4—C5179.71 (15)C18—O6—C19—C20159.42 (15)
O4—C4—C5—C6179.90 (15)C21—O7—C20—C19176.42 (17)
C3—C4—C5—C60.2 (2)O6—C19—C20—O770.69 (19)
C4—C5—C6—C70.6 (3)C20—O7—C21—C22176.10 (19)
C5—C6—C7—C81.1 (2)C23—O8—C22—C21119.2 (2)
C5—C6—C7—C9175.45 (15)O7—C21—C22—O869.3 (3)
C4—C3—C8—C70.3 (2)C22—O8—C23—C2478.5 (2)
N2—C3—C8—C7179.69 (14)O8—C23—C24—N455.8 (2)
C6—C7—C8—C31.0 (2)
Hydrogen-bond geometry (Å, º) top
Cg1 is the centroid of the C3–C8 ring.
D—H···AD—HH···AD···AD—H···A
N3—H1N3···O3i0.82 (2)2.22 (3)3.012 (2)161 (2)
N4—H1N4···O1ii0.93 (3)2.29 (3)3.010 (2)133 (2)
N4—H1N4···O70.93 (3)2.49 (3)3.106 (2)124 (2)
N4—H2N4···N1i1.03 (3)1.82 (3)2.821 (2)163 (2)
N4—H3N4···O6iii0.98 (3)1.99 (3)2.942 (2)162 (3)
C2—H2B···O3iv0.992.303.267 (2)166
C18—H18A···N1i0.992.573.545 (2)168
C22—H22A···O8ii0.992.633.343 (3)129
C24—H24A···O5iii0.992.583.298 (2)129
C21—H21B···Cg1ii0.992.703.555 (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.

References

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Volume 71| Part 4| April 2015| Pages 336-338
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