Zwitterionic versus neutral mol­ecules of fluoro­quinolones: crystal structure of danofloxacin dihydrate

The crystal structure of danofloxacin (DFX) as a zwitterionic dihydrate [sys­tematic name: (1S,4S)-5-(3-carboxylato-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinolin-7-yl)-2-methyl-2,5-diazabicyclo[2.2.1]heptan-2-ium dihydrate], C₁₉H₂₀FN₃O₃·2H₂O, has been determined for the first time. The stability of the crystal structure is ensured by N—H...O and O—H...O hydrogen bonds, some of which are assisted by charge. The zwitterionic mol­ecules of DFX are packed in stacks and this structural motif can be defined as a basic one from a supra­molecular and energetic point of view. Hirshfeld surface analysis was used for an additional inter­pretation of the close contacts. The nature of the inter­molecular inter­actions was evaluated in a pairwise manner. Destabilizing inter­actions were also discussed. In the context of our study on danofloxacin, we addressed the question: how common is a zwitterionic form for fluoro­quinolones (FQ) in the crystalline state? A survey of the Cambridge Structural Database limited to anhydrous/hydrated/solvated forms of the most typical FQs revealed that neutral mol­ecules are preferred, while zwitterions are less common.

Computing details

For both structures, data collection: CrysAlis PRO (Rigaku OD, 2017); cell refinement: CrysAlis PRO (Rigaku OD, 2017); data reduction: CrysAlis PRO (Rigaku OD, 2017); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: Mercury (Macrae et al., 2020); software used to prepare material for publication: publCIF (Westrip, 2010).

(1S,4S)-5-(3-Carboxylato-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinolin-7-yl)-2-methyl-2,5-diazabicyclo[2.2.1]heptan-2-ium dihydrate (DFX-Mo)

Crystal data

C19H20FN3O3·2H2O	Dx = 1.455 Mg m^−3
Mr = 393.41	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121	Cell parameters from 3993 reflections
a = 7.1687 (4) Å	θ = 3.5–28.2°
b = 10.6689 (7) Å	µ = 0.11 mm^−1
c = 23.4887 (15) Å	T = 100 K
V = 1796.47 (19) Å^3	Needle(x)2610, colourless
Z = 4	0.26 × 0.11 × 0.06 mm
F(000) = 832

Data collection

XtaLAB Synergy, Dualflex, HyPix diffractometer	4050 independent reflections
Radiation source: micro-focus sealed X-ray tube, PhotonJet (Mo) X-ray Source	3470 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.040
ω scans	θmax = 28.3°, θmin = 3.4°
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2017)	h = −9→8
Tmin = 0.155, Tmax = 1.000	k = −11→14
9878 measured reflections	l = −30→30

Refinement

Refinement on F^2	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.043	w = 1/[σ^2(Fo^2) + (0.0731P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.108	(Δ/σ)max < 0.001
S = 1.01	Δρmax = 0.44 e Å^−3
4050 reflections	Δρmin = −0.25 e Å^−3
274 parameters	Absolute structure: Flack x determined using 1169 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
2 restraints	Absolute structure parameter: 0.1 (5)
Primary atom site location: difference Fourier map

Special details

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. Single-crystal X-ray diffraction data of DFX·2H₂O were measured using a Rigaku XtaLAB Synergy diffractometer at 100 K with Mo Kα radiation; crystal data, data collection and structure refinement details are summarized in Table 1.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	0.6256 (3)	0.53197 (17)	0.51228 (8)	0.0141 (4)
C2	0.6177 (3)	0.5699 (2)	0.56708 (10)	0.0151 (5)
H2	0.599788	0.656652	0.574276	0.018*
C3	0.6337 (3)	0.4915 (2)	0.61290 (9)	0.0142 (5)
C4	0.6546 (3)	0.3590 (2)	0.60383 (10)	0.0144 (5)
C5	0.6499 (3)	0.3189 (2)	0.54486 (9)	0.0126 (5)
C6	0.6597 (3)	0.1904 (2)	0.53131 (10)	0.0142 (5)
H6	0.659635	0.129618	0.560868	0.017*
C7	0.6690 (3)	0.1536 (2)	0.47649 (10)	0.0149 (5)
C8	0.6752 (3)	0.2385 (2)	0.42980 (9)	0.0134 (5)
C9	0.6590 (3)	0.3655 (2)	0.44321 (9)	0.0138 (5)
H9	0.657696	0.425771	0.413432	0.017*
C10	0.6449 (3)	0.4054 (2)	0.49949 (9)	0.0131 (5)
C11	0.6155 (4)	0.6208 (2)	0.46494 (10)	0.0156 (5)
H11	0.728748	0.624920	0.440161	0.019*
C12	0.5106 (4)	0.7403 (2)	0.47132 (11)	0.0233 (6)
H12A	0.560422	0.815493	0.451842	0.028*
H12B	0.449367	0.756900	0.508334	0.028*
C13	0.4327 (4)	0.6367 (2)	0.43489 (11)	0.0212 (5)
H13A	0.323952	0.589593	0.449588	0.025*
H13B	0.435057	0.648213	0.393071	0.025*
N14	0.7093 (3)	0.19730 (18)	0.37566 (8)	0.0141 (4)
C15	0.7345 (3)	0.2851 (2)	0.32804 (9)	0.0140 (5)
H15	0.822428	0.355648	0.336022	0.017*
C16	0.7983 (3)	0.1962 (2)	0.28103 (9)	0.0149 (5)
H16A	0.804532	0.236739	0.243158	0.018*
H16B	0.917492	0.153580	0.289865	0.018*
C17	0.6292 (3)	0.1116 (2)	0.28805 (10)	0.0144 (5)
H17	0.625929	0.038087	0.261672	0.017*
C18	0.6375 (3)	0.0777 (2)	0.35133 (9)	0.0143 (5)
H18A	0.512575	0.056574	0.366538	0.017*
H18B	0.724078	0.007168	0.358492	0.017*
C19	0.5439 (3)	0.3258 (2)	0.30579 (10)	0.0146 (5)
H19A	0.555589	0.391756	0.276379	0.018*
H19B	0.462960	0.356468	0.336962	0.018*
N20	0.4696 (3)	0.20346 (19)	0.28052 (8)	0.0144 (4)
C21	0.4088 (4)	0.2173 (2)	0.22052 (10)	0.0194 (5)
H21A	0.513152	0.248092	0.197491	0.029*
H21B	0.305277	0.277177	0.218524	0.029*
H21C	0.367629	0.135857	0.205893	0.029*
F22	0.6839 (2)	0.02933 (12)	0.46436 (6)	0.0203 (3)
C23	0.6265 (3)	0.5457 (2)	0.67236 (9)	0.0147 (5)
O24	0.5013 (2)	0.62526 (18)	0.68248 (7)	0.0224 (4)
O25	0.7419 (3)	0.50616 (17)	0.70775 (7)	0.0237 (4)
O26	0.6782 (2)	0.28076 (16)	0.64340 (6)	0.0156 (4)
O27	0.6183 (3)	0.05595 (17)	0.70254 (8)	0.0236 (4)
O28	0.4588 (3)	0.8631 (3)	0.63048 (9)	0.0341 (5)
H20	0.372 (4)	0.179 (2)	0.3029 (11)	0.008 (6)*
H27A	0.621 (6)	0.122 (2)	0.6835 (14)	0.060 (13)*
H27B	0.571 (4)	0.071 (3)	0.7344 (8)	0.018 (7)*
H28A	0.475 (6)	0.798 (5)	0.6509 (17)	0.055 (12)*
H28B	0.503 (5)	0.918 (4)	0.6505 (16)	0.039 (11)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0159 (10)	0.0101 (9)	0.0164 (9)	0.0004 (8)	0.0008 (8)	0.0011 (7)
C2	0.0122 (11)	0.0129 (10)	0.0201 (11)	−0.0004 (9)	0.0006 (9)	−0.0019 (9)
C3	0.0101 (11)	0.0144 (10)	0.0181 (11)	0.0003 (9)	0.0002 (9)	−0.0031 (9)
C4	0.0087 (11)	0.0156 (11)	0.0188 (11)	−0.0003 (9)	−0.0002 (9)	−0.0005 (9)
C5	0.0103 (11)	0.0109 (10)	0.0165 (11)	0.0001 (9)	−0.0006 (8)	0.0007 (8)
C6	0.0128 (11)	0.0122 (10)	0.0177 (10)	−0.0010 (9)	−0.0006 (9)	0.0033 (9)
C7	0.0164 (12)	0.0081 (10)	0.0204 (11)	0.0005 (9)	−0.0017 (9)	−0.0011 (9)
C8	0.0095 (11)	0.0140 (10)	0.0168 (10)	−0.0005 (9)	0.0002 (8)	−0.0015 (9)
C9	0.0127 (11)	0.0120 (10)	0.0168 (10)	0.0003 (9)	0.0000 (9)	0.0016 (9)
C10	0.0108 (11)	0.0109 (10)	0.0176 (11)	0.0002 (9)	0.0006 (9)	−0.0003 (8)
C11	0.0217 (12)	0.0099 (10)	0.0153 (10)	−0.0005 (10)	0.0011 (9)	0.0022 (9)
C12	0.0284 (15)	0.0142 (11)	0.0273 (13)	0.0053 (11)	0.0026 (11)	0.0021 (10)
C13	0.0229 (13)	0.0172 (12)	0.0234 (12)	0.0000 (10)	−0.0029 (10)	0.0061 (10)
N14	0.0159 (10)	0.0096 (8)	0.0169 (9)	−0.0006 (8)	0.0001 (8)	0.0000 (8)
C15	0.0136 (11)	0.0117 (10)	0.0169 (11)	−0.0014 (9)	0.0023 (9)	0.0006 (9)
C16	0.0127 (11)	0.0145 (10)	0.0176 (11)	−0.0013 (10)	0.0015 (9)	−0.0009 (9)
C17	0.0133 (11)	0.0131 (10)	0.0168 (10)	0.0034 (9)	0.0006 (9)	−0.0017 (9)
C18	0.0154 (11)	0.0101 (10)	0.0175 (11)	0.0004 (9)	0.0006 (9)	−0.0025 (8)
C19	0.0158 (12)	0.0095 (10)	0.0185 (11)	−0.0009 (9)	0.0005 (9)	−0.0013 (8)
N20	0.0126 (10)	0.0133 (9)	0.0172 (9)	−0.0008 (8)	0.0015 (8)	−0.0005 (8)
C21	0.0190 (13)	0.0215 (12)	0.0176 (11)	0.0001 (10)	−0.0023 (9)	0.0008 (10)
F22	0.0325 (9)	0.0083 (6)	0.0202 (7)	0.0020 (6)	−0.0012 (6)	−0.0009 (5)
C23	0.0173 (12)	0.0113 (10)	0.0156 (10)	−0.0037 (10)	0.0009 (9)	−0.0006 (8)
O24	0.0201 (10)	0.0218 (9)	0.0252 (9)	0.0074 (8)	−0.0034 (7)	−0.0073 (7)
O25	0.0270 (10)	0.0214 (9)	0.0226 (9)	0.0056 (8)	−0.0065 (8)	−0.0032 (8)
O26	0.0160 (9)	0.0149 (8)	0.0158 (8)	0.0002 (7)	−0.0015 (6)	0.0007 (6)
O27	0.0215 (10)	0.0213 (9)	0.0281 (10)	0.0031 (8)	0.0039 (8)	0.0084 (8)
O28	0.0358 (12)	0.0338 (12)	0.0326 (11)	−0.0035 (10)	−0.0083 (10)	0.0065 (11)

Geometric parameters (Å, º)

N1—C2	1.350 (3)	N14—C15	1.470 (3)
N1—C10	1.391 (3)	N14—C18	1.490 (3)
N1—C11	1.463 (3)	C15—C19	1.526 (3)
C2—C3	1.367 (3)	C15—C16	1.525 (3)
C2—H2	0.9500	C15—H15	1.0000
C3—C4	1.437 (3)	C16—C17	1.520 (3)
C3—C23	1.512 (3)	C16—H16A	0.9900
C4—O26	1.261 (3)	C16—H16B	0.9900
C4—C5	1.450 (3)	C17—N20	1.516 (3)
C5—C10	1.410 (3)	C17—C18	1.531 (3)
C5—C6	1.410 (3)	C17—H17	1.0000
C6—C7	1.348 (3)	C18—H18A	0.9900
C6—H6	0.9500	C18—H18B	0.9900
C7—F22	1.360 (2)	C19—N20	1.529 (3)
C7—C8	1.423 (3)	C19—H19A	0.9900
C8—N14	1.368 (3)	C19—H19B	0.9900
C8—C9	1.396 (3)	N20—C21	1.483 (3)
C9—C10	1.392 (3)	N20—H20	0.92 (3)
C9—H9	0.9500	C21—H21A	0.9800
C11—C12	1.488 (3)	C21—H21B	0.9800
C11—C13	1.498 (4)	C21—H21C	0.9800
C11—H11	1.0000	C23—O25	1.246 (3)
C12—C13	1.505 (4)	C23—O24	1.259 (3)
C12—H12A	0.9900	O27—H27A	0.837 (13)
C12—H12B	0.9900	O27—H27B	0.838 (12)
C13—H13A	0.9900	O28—H28A	0.85 (5)
C13—H13B	0.9900	O28—H28B	0.81 (4)
C2—N1—C10	120.05 (18)	C8—N14—C18	124.76 (19)
C2—N1—C11	121.92 (19)	C15—N14—C18	107.22 (17)
C10—N1—C11	118.03 (19)	N14—C15—C19	109.39 (18)
N1—C2—C3	124.3 (2)	N14—C15—C16	101.07 (18)
N1—C2—H2	117.8	C19—C15—C16	101.39 (18)
C3—C2—H2	117.8	N14—C15—H15	114.5
C2—C3—C4	119.5 (2)	C19—C15—H15	114.5
C2—C3—C23	119.4 (2)	C16—C15—H15	114.5
C4—C3—C23	121.1 (2)	C17—C16—C15	92.93 (17)
O26—C4—C3	123.8 (2)	C17—C16—H16A	113.1
O26—C4—C5	120.8 (2)	C15—C16—H16A	113.1
C3—C4—C5	115.43 (19)	C17—C16—H16B	113.1
C10—C5—C6	117.8 (2)	C15—C16—H16B	113.1
C10—C5—C4	122.0 (2)	H16A—C16—H16B	110.5
C6—C5—C4	120.1 (2)	N20—C17—C16	101.84 (18)
C7—C6—C5	120.1 (2)	N20—C17—C18	107.18 (17)
C7—C6—H6	119.9	C16—C17—C18	102.40 (18)
C5—C6—H6	119.9	N20—C17—H17	114.6
C6—C7—F22	119.2 (2)	C16—C17—H17	114.6
C6—C7—C8	123.5 (2)	C18—C17—H17	114.6
F22—C7—C8	117.2 (2)	N14—C18—C17	100.57 (17)
N14—C8—C9	122.4 (2)	N14—C18—H18A	111.7
N14—C8—C7	121.2 (2)	C17—C18—H18A	111.7
C9—C8—C7	116.2 (2)	N14—C18—H18B	111.7
C10—C9—C8	121.1 (2)	C17—C18—H18B	111.7
C10—C9—H9	119.4	H18A—C18—H18B	109.4
C8—C9—H9	119.4	C15—C19—N20	101.64 (17)
N1—C10—C9	120.6 (2)	C15—C19—H19A	111.4
N1—C10—C5	118.3 (2)	N20—C19—H19A	111.4
C9—C10—C5	121.1 (2)	C15—C19—H19B	111.4
N1—C11—C12	120.2 (2)	N20—C19—H19B	111.4
N1—C11—C13	118.4 (2)	H19A—C19—H19B	109.3
C12—C11—C13	60.55 (17)	C21—N20—C17	113.41 (18)
N1—C11—H11	115.5	C21—N20—C19	112.72 (19)
C12—C11—H11	115.5	C17—N20—C19	104.10 (17)
C13—C11—H11	115.5	C21—N20—H20	110.3 (16)
C11—C12—C13	60.05 (16)	C17—N20—H20	109.0 (17)
C11—C12—H12A	117.8	C19—N20—H20	106.9 (16)
C13—C12—H12A	117.8	N20—C21—H21A	109.5
C11—C12—H12B	117.8	N20—C21—H21B	109.5
C13—C12—H12B	117.8	H21A—C21—H21B	109.5
H12A—C12—H12B	114.9	N20—C21—H21C	109.5
C11—C13—C12	59.40 (16)	H21A—C21—H21C	109.5
C11—C13—H13A	117.8	H21B—C21—H21C	109.5
C12—C13—H13A	117.8	O25—C23—O24	125.2 (2)
C11—C13—H13B	117.8	O25—C23—C3	117.7 (2)
C12—C13—H13B	117.8	O24—C23—C3	117.2 (2)
H13A—C13—H13B	115.0	H27A—O27—H27B	109 (3)
C8—N14—C15	121.66 (19)	H28A—O28—H28B	102 (4)
C10—N1—C2—C3	2.3 (4)	C10—N1—C11—C12	151.1 (2)
C11—N1—C2—C3	−177.3 (2)	C2—N1—C11—C13	−99.8 (3)
N1—C2—C3—C4	−2.1 (4)	C10—N1—C11—C13	80.5 (3)
N1—C2—C3—C23	178.7 (2)	N1—C11—C12—C13	−107.6 (2)
C2—C3—C4—O26	176.9 (2)	N1—C11—C13—C12	110.6 (2)
C23—C3—C4—O26	−4.0 (4)	C9—C8—N14—C15	1.1 (4)
C2—C3—C4—C5	−2.2 (3)	C7—C8—N14—C15	−173.8 (2)
C23—C3—C4—C5	177.0 (2)	C9—C8—N14—C18	−147.3 (2)
O26—C4—C5—C10	−172.7 (2)	C7—C8—N14—C18	37.8 (3)
C3—C4—C5—C10	6.4 (3)	C8—N14—C15—C19	−82.3 (3)
O26—C4—C5—C6	4.1 (3)	C18—N14—C15—C19	70.9 (2)
C3—C4—C5—C6	−176.8 (2)	C8—N14—C15—C16	171.3 (2)
C10—C5—C6—C7	1.8 (3)	C18—N14—C15—C16	−35.5 (2)
C4—C5—C6—C7	−175.2 (2)	N14—C15—C16—C17	54.55 (19)
C5—C6—C7—F22	178.1 (2)	C19—C15—C16—C17	−58.06 (19)
C5—C6—C7—C8	1.9 (4)	C15—C16—C17—N20	55.49 (18)
C6—C7—C8—N14	171.3 (2)	C15—C16—C17—C18	−55.30 (19)
F22—C7—C8—N14	−5.0 (3)	C8—N14—C18—C17	152.3 (2)
C6—C7—C8—C9	−3.9 (4)	C15—N14—C18—C17	0.2 (2)
F22—C7—C8—C9	179.8 (2)	N20—C17—C18—N14	−71.2 (2)
N14—C8—C9—C10	−172.8 (2)	C16—C17—C18—N14	35.5 (2)
C7—C8—C9—C10	2.3 (4)	N14—C15—C19—N20	−67.2 (2)
C2—N1—C10—C9	−178.0 (2)	C16—C15—C19—N20	39.0 (2)
C11—N1—C10—C9	1.7 (3)	C16—C17—N20—C21	89.4 (2)
C2—N1—C10—C5	1.9 (3)	C18—C17—N20—C21	−163.5 (2)
C11—N1—C10—C5	−178.4 (2)	C16—C17—N20—C19	−33.5 (2)
C8—C9—C10—N1	−178.9 (2)	C18—C17—N20—C19	73.7 (2)
C8—C9—C10—C5	1.2 (4)	C15—C19—N20—C21	−126.7 (2)
C6—C5—C10—N1	176.8 (2)	C15—C19—N20—C17	−3.3 (2)
C4—C5—C10—N1	−6.3 (3)	C2—C3—C23—O25	−136.5 (2)
C6—C5—C10—C9	−3.3 (3)	C4—C3—C23—O25	44.4 (3)
C4—C5—C10—C9	173.6 (2)	C2—C3—C23—O24	45.1 (3)
C2—N1—C11—C12	−29.2 (3)	C4—C3—C23—O24	−134.1 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N20—H20···O26^i	0.92 (3)	1.92 (3)	2.754 (3)	150 (2)
N20—H20···O25^i	0.92 (3)	2.20 (2)	2.782 (3)	121 (2)
O27—H27A···O26	0.84 (1)	1.98 (2)	2.805 (2)	169 (4)
O27—H27B···O24^ii	0.84 (1)	2.10 (1)	2.929 (3)	170 (3)
O28—H28A···O24	0.85 (5)	1.99 (5)	2.832 (3)	167 (4)
O28—H28B···O27^iii	0.81 (4)	2.09 (4)	2.900 (3)	179 (4)

Symmetry codes: (i) x−1/2, −y+1/2, −z+1; (ii) −x+1, y−1/2, −z+3/2; (iii) x, y+1, z.

(1S,4S)-5-(3-Carboxylato-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinolin-7-yl)-2-methyl-2,5-diazabicyclo[2.2.1]heptan-2-ium dihydrate (DFX-Cu)

Crystal data

C19H20FN3O3·2H2O	Dx = 1.449 Mg m^−3
Mr = 393.41	Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, P212121	Cell parameters from 5102 reflections
a = 7.1815 (2) Å	θ = 3.7–75.0°
b = 10.6840 (3) Å	µ = 0.95 mm^−1
c = 23.5104 (7) Å	T = 100 K
V = 1803.89 (9) Å^3	Needle, colourless
Z = 4	0.26 × 0.11 × 0.06 mm
F(000) = 832

Data collection

XtaLAB Synergy, Dualflex, HyPix diffractometer	3329 reflections with I > 2σ(I)
Radiation source: micro-focus sealed X-ray tube, PhotonJet (Cu) X-ray Source	Rint = 0.045
ω scans	θmax = 77.3°, θmin = 3.8°
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2017)	h = −8→9
Tmin = 0.503, Tmax = 1.000	k = −12→10
10288 measured reflections	l = −21→29
3612 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.046	w = 1/[σ^2(Fo^2) + (0.0787P)^2 + 0.459P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.131	(Δ/σ)max < 0.001
S = 1.10	Δρmax = 0.24 e Å^−3
3612 reflections	Δρmin = −0.34 e Å^−3
274 parameters	Absolute structure: Flack x determined using 1277 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
0 restraints	Absolute structure parameter: 0.05 (14)
Primary atom site location: difference Fourier map

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	0.6254 (4)	0.5318 (2)	0.51230 (11)	0.0243 (5)
C2	0.6177 (4)	0.5694 (3)	0.56713 (13)	0.0254 (6)
H2	0.599820	0.656095	0.574361	0.030*
C3	0.6339 (4)	0.4914 (3)	0.61277 (12)	0.0244 (6)
C4	0.6553 (4)	0.3589 (3)	0.60377 (13)	0.0232 (6)
C5	0.6499 (4)	0.3189 (3)	0.54485 (12)	0.0228 (6)
C6	0.6598 (4)	0.1907 (3)	0.53110 (13)	0.0244 (6)
H6	0.659942	0.129849	0.560557	0.029*
C7	0.6691 (4)	0.1543 (3)	0.47643 (13)	0.0240 (6)
C8	0.6756 (4)	0.2382 (3)	0.42988 (13)	0.0226 (6)
C9	0.6594 (4)	0.3655 (3)	0.44314 (13)	0.0252 (6)
H9	0.658102	0.425605	0.413382	0.030*
C10	0.6450 (4)	0.4051 (3)	0.49961 (13)	0.0226 (6)
C11	0.6153 (5)	0.6206 (3)	0.46479 (14)	0.0268 (6)
H11	0.728499	0.624941	0.440109	0.032*
C12	0.5106 (5)	0.7397 (3)	0.47131 (15)	0.0332 (7)
H12A	0.560349	0.814993	0.451982	0.040*
H12B	0.449241	0.755999	0.508276	0.040*
C13	0.4334 (5)	0.6367 (3)	0.43477 (16)	0.0327 (7)
H13A	0.324828	0.589415	0.449329	0.039*
H13B	0.435975	0.648430	0.393015	0.039*
N14	0.7094 (4)	0.1973 (2)	0.37574 (11)	0.0238 (5)
C15	0.7342 (4)	0.2848 (3)	0.32816 (12)	0.0237 (6)
H15	0.821823	0.355452	0.336088	0.028*
C16	0.7977 (4)	0.1963 (3)	0.28103 (13)	0.0254 (6)
H16A	0.803297	0.236896	0.243224	0.030*
H16B	0.917056	0.153966	0.289689	0.030*
C17	0.6297 (4)	0.1113 (3)	0.28811 (13)	0.0245 (6)
H17	0.626496	0.037881	0.261759	0.029*
C18	0.6375 (4)	0.0781 (3)	0.35086 (13)	0.0249 (6)
H18A	0.512655	0.057052	0.365913	0.030*
H18B	0.723614	0.007506	0.358047	0.030*
C19	0.5441 (4)	0.3249 (3)	0.30600 (14)	0.0255 (6)
H19A	0.463229	0.355204	0.337206	0.031*
H19B	0.555539	0.391210	0.276776	0.031*
N20	0.4701 (4)	0.2039 (3)	0.28055 (11)	0.0247 (6)
C21	0.4083 (5)	0.2175 (3)	0.22046 (13)	0.0304 (7)
H21A	0.513645	0.244480	0.196981	0.046*
H21B	0.308762	0.280087	0.218309	0.046*
H21C	0.361719	0.136925	0.206512	0.046*
F22	0.6839 (3)	0.02949 (16)	0.46437 (8)	0.0302 (4)
C23	0.6265 (4)	0.5458 (3)	0.67241 (13)	0.0246 (6)
O24	0.5012 (3)	0.6257 (2)	0.68254 (9)	0.0316 (5)
O25	0.7421 (3)	0.5062 (2)	0.70767 (10)	0.0334 (5)
O26	0.6781 (3)	0.2808 (2)	0.64333 (9)	0.0257 (5)
O27	0.6183 (3)	0.0560 (2)	0.70265 (11)	0.0332 (5)
O28	0.4593 (4)	0.8630 (3)	0.63032 (12)	0.0425 (6)
H20	0.364 (6)	0.179 (4)	0.3010 (16)	0.028 (9)*
H27A	0.627 (8)	0.135 (6)	0.683 (2)	0.070 (17)*
H27B	0.565 (6)	0.071 (4)	0.7371 (19)	0.038 (11)*
H28A	0.480 (7)	0.797 (6)	0.652 (2)	0.057 (15)*
H28B	0.517 (7)	0.917 (5)	0.654 (2)	0.047 (13)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0284 (12)	0.0184 (13)	0.0261 (12)	0.0002 (11)	0.0010 (10)	0.0010 (10)
C2	0.0262 (14)	0.0222 (15)	0.0277 (14)	−0.0002 (12)	0.0003 (12)	−0.0015 (12)
C3	0.0257 (14)	0.0197 (14)	0.0277 (14)	0.0003 (12)	0.0019 (12)	−0.0022 (11)
C4	0.0203 (13)	0.0205 (14)	0.0287 (14)	−0.0012 (12)	−0.0014 (11)	0.0013 (12)
C5	0.0242 (14)	0.0190 (14)	0.0252 (14)	−0.0005 (12)	−0.0014 (11)	0.0002 (11)
C6	0.0250 (14)	0.0196 (14)	0.0285 (14)	0.0002 (12)	−0.0007 (12)	0.0016 (12)
C7	0.0268 (14)	0.0131 (13)	0.0322 (15)	0.0018 (11)	−0.0030 (12)	−0.0006 (11)
C8	0.0205 (13)	0.0204 (14)	0.0269 (14)	0.0009 (11)	−0.0008 (11)	0.0024 (11)
C9	0.0231 (14)	0.0232 (15)	0.0294 (15)	−0.0002 (12)	−0.0005 (11)	0.0003 (12)
C10	0.0226 (13)	0.0181 (14)	0.0270 (15)	−0.0010 (11)	−0.0001 (11)	−0.0008 (11)
C11	0.0349 (16)	0.0192 (15)	0.0264 (14)	−0.0006 (13)	0.0009 (13)	0.0026 (12)
C12	0.0402 (18)	0.0250 (17)	0.0344 (16)	0.0053 (14)	0.0022 (15)	0.0014 (13)
C13	0.0347 (17)	0.0246 (17)	0.0387 (17)	−0.0009 (14)	−0.0034 (14)	0.0056 (14)
N14	0.0287 (13)	0.0188 (12)	0.0241 (12)	−0.0013 (10)	−0.0005 (10)	−0.0002 (10)
C15	0.0263 (14)	0.0203 (14)	0.0244 (14)	−0.0022 (12)	0.0006 (11)	−0.0003 (12)
C16	0.0252 (14)	0.0237 (15)	0.0273 (15)	0.0004 (12)	0.0008 (11)	−0.0002 (12)
C17	0.0237 (14)	0.0188 (14)	0.0310 (15)	0.0014 (12)	0.0025 (12)	−0.0035 (12)
C18	0.0262 (13)	0.0176 (15)	0.0308 (15)	−0.0006 (12)	−0.0014 (12)	−0.0028 (11)
C19	0.0273 (15)	0.0195 (15)	0.0299 (15)	0.0015 (12)	0.0030 (12)	−0.0013 (11)
N20	0.0245 (13)	0.0216 (13)	0.0280 (13)	−0.0005 (11)	0.0002 (10)	−0.0015 (10)
C21	0.0335 (17)	0.0288 (17)	0.0290 (16)	−0.0004 (14)	0.0002 (13)	−0.0006 (13)
F22	0.0451 (11)	0.0149 (9)	0.0307 (9)	0.0024 (8)	−0.0015 (8)	−0.0023 (7)
C23	0.0263 (14)	0.0196 (14)	0.0279 (14)	−0.0024 (12)	0.0000 (12)	−0.0010 (12)
O24	0.0325 (12)	0.0295 (12)	0.0327 (11)	0.0074 (10)	−0.0017 (9)	−0.0066 (9)
O25	0.0401 (13)	0.0294 (12)	0.0307 (11)	0.0069 (10)	−0.0064 (10)	−0.0032 (10)
O26	0.0281 (11)	0.0226 (11)	0.0263 (10)	−0.0005 (9)	−0.0015 (8)	0.0007 (8)
O27	0.0344 (12)	0.0291 (12)	0.0360 (13)	0.0034 (10)	0.0023 (10)	0.0065 (10)
O28	0.0469 (15)	0.0411 (15)	0.0395 (14)	−0.0020 (13)	−0.0086 (12)	0.0056 (13)

Geometric parameters (Å, º)

N1—C2	1.352 (4)	N14—C15	1.469 (4)
N1—C10	1.393 (4)	N14—C18	1.493 (4)
N1—C11	1.468 (4)	C15—C19	1.523 (4)
C2—C3	1.364 (4)	C15—C16	1.526 (4)
C2—H2	0.9500	C15—H15	1.0000
C3—C4	1.440 (4)	C16—C17	1.519 (4)
C3—C23	1.519 (4)	C16—H16A	0.9900
C4—O26	1.260 (4)	C16—H16B	0.9900
C4—C5	1.450 (4)	C17—C18	1.518 (4)
C5—C10	1.407 (4)	C17—N20	1.524 (4)
C5—C6	1.409 (4)	C17—H17	1.0000
C6—C7	1.345 (4)	C18—H18A	0.9900
C6—H6	0.9500	C18—H18B	0.9900
C7—F22	1.367 (3)	C19—N20	1.521 (4)
C7—C8	1.416 (4)	C19—H19A	0.9900
C8—N14	1.368 (4)	C19—H19B	0.9900
C8—C9	1.399 (4)	N20—C21	1.488 (4)
C9—C10	1.397 (4)	N20—H20	0.94 (4)
C9—H9	0.9500	C21—H21A	0.9800
C11—C12	1.486 (5)	C21—H21B	0.9800
C11—C13	1.494 (5)	C21—H21C	0.9800
C11—H11	1.0000	C23—O25	1.247 (4)
C12—C13	1.503 (5)	C23—O24	1.263 (4)
C12—H12A	0.9900	O27—H27A	0.96 (6)
C12—H12B	0.9900	O27—H27B	0.91 (5)
C13—H13A	0.9900	O28—H28A	0.87 (6)
C13—H13B	0.9900	O28—H28B	0.91 (6)
C2—N1—C10	119.9 (3)	C8—N14—C18	125.2 (3)
C2—N1—C11	122.1 (3)	C15—N14—C18	106.6 (2)
C10—N1—C11	118.1 (3)	N14—C15—C19	109.3 (2)
N1—C2—C3	124.4 (3)	N14—C15—C16	101.2 (2)
N1—C2—H2	117.8	C19—C15—C16	101.2 (2)
C3—C2—H2	117.8	N14—C15—H15	114.5
C2—C3—C4	119.6 (3)	C19—C15—H15	114.5
C2—C3—C23	119.3 (3)	C16—C15—H15	114.5
C4—C3—C23	121.0 (3)	C17—C16—C15	93.1 (2)
O26—C4—C3	123.8 (3)	C17—C16—H16A	113.1
O26—C4—C5	120.9 (3)	C15—C16—H16A	113.1
C3—C4—C5	115.3 (3)	C17—C16—H16B	113.1
C10—C5—C6	117.6 (3)	C15—C16—H16B	113.1
C10—C5—C4	122.0 (3)	H16A—C16—H16B	110.5
C6—C5—C4	120.2 (3)	C18—C17—C16	102.5 (2)
C7—C6—C5	120.2 (3)	C18—C17—N20	107.0 (2)
C7—C6—H6	119.9	C16—C17—N20	101.4 (2)
C5—C6—H6	119.9	C18—C17—H17	114.8
C6—C7—F22	119.0 (3)	C16—C17—H17	114.8
C6—C7—C8	123.8 (3)	N20—C17—H17	114.8
F22—C7—C8	117.1 (3)	N14—C18—C17	101.2 (2)
N14—C8—C9	122.2 (3)	N14—C18—H18A	111.5
N14—C8—C7	121.5 (3)	C17—C18—H18A	111.5
C9—C8—C7	116.1 (3)	N14—C18—H18B	111.5
C10—C9—C8	120.8 (3)	C17—C18—H18B	111.5
C10—C9—H9	119.6	H18A—C18—H18B	109.3
C8—C9—H9	119.6	N20—C19—C15	102.0 (2)
N1—C10—C9	120.4 (3)	N20—C19—H19A	111.4
N1—C10—C5	118.4 (3)	C15—C19—H19A	111.4
C9—C10—C5	121.2 (3)	N20—C19—H19B	111.4
N1—C11—C12	120.0 (3)	C15—C19—H19B	111.4
N1—C11—C13	118.5 (3)	H19A—C19—H19B	109.2
C12—C11—C13	60.6 (2)	C21—N20—C19	113.2 (3)
N1—C11—H11	115.5	C21—N20—C17	113.5 (2)
C12—C11—H11	115.5	C19—N20—C17	104.1 (2)
C13—C11—H11	115.5	C21—N20—H20	106 (2)
C11—C12—C13	60.0 (2)	C19—N20—H20	109 (2)
C11—C12—H12A	117.8	C17—N20—H20	111 (2)
C13—C12—H12A	117.8	N20—C21—H21A	109.5
C11—C12—H12B	117.8	N20—C21—H21B	109.5
C13—C12—H12B	117.8	H21A—C21—H21B	109.5
H12A—C12—H12B	114.9	N20—C21—H21C	109.5
C11—C13—C12	59.4 (2)	H21A—C21—H21C	109.5
C11—C13—H13A	117.8	H21B—C21—H21C	109.5
C12—C13—H13A	117.8	O25—C23—O24	125.3 (3)
C11—C13—H13B	117.8	O25—C23—C3	117.4 (3)
C12—C13—H13B	117.8	O24—C23—C3	117.2 (3)
H13A—C13—H13B	115.0	H27A—O27—H27B	107 (4)
C8—N14—C15	121.8 (2)	H28A—O28—H28B	95 (5)
C10—N1—C2—C3	2.2 (5)	C10—N1—C11—C12	151.3 (3)
C11—N1—C2—C3	−177.3 (3)	C2—N1—C11—C13	−99.8 (4)
N1—C2—C3—C4	−1.9 (5)	C10—N1—C11—C13	80.7 (4)
N1—C2—C3—C23	178.8 (3)	N1—C11—C12—C13	−107.8 (3)
C2—C3—C4—O26	177.2 (3)	N1—C11—C13—C12	110.4 (3)
C23—C3—C4—O26	−3.5 (5)	C9—C8—N14—C15	1.1 (4)
C2—C3—C4—C5	−2.5 (4)	C7—C8—N14—C15	−174.0 (3)
C23—C3—C4—C5	176.7 (3)	C9—C8—N14—C18	−147.0 (3)
O26—C4—C5—C10	−172.9 (3)	C7—C8—N14—C18	37.9 (4)
C3—C4—C5—C10	6.8 (4)	C8—N14—C15—C19	−82.5 (3)
O26—C4—C5—C6	3.5 (4)	C18—N14—C15—C19	70.7 (3)
C3—C4—C5—C6	−176.7 (3)	C8—N14—C15—C16	171.3 (3)
C10—C5—C6—C7	1.7 (4)	C18—N14—C15—C16	−35.5 (3)
C4—C5—C6—C7	−174.9 (3)	N14—C15—C16—C17	54.4 (2)
C5—C6—C7—F22	178.2 (3)	C19—C15—C16—C17	−58.2 (3)
C5—C6—C7—C8	2.1 (5)	C15—C16—C17—C18	−54.9 (3)
C6—C7—C8—N14	171.3 (3)	C15—C16—C17—N20	55.6 (2)
F22—C7—C8—N14	−4.8 (4)	C8—N14—C18—C17	152.5 (3)
C6—C7—C8—C9	−4.1 (4)	C15—N14—C18—C17	0.4 (3)
F22—C7—C8—C9	179.8 (3)	C16—C17—C18—N14	35.1 (3)
N14—C8—C9—C10	−173.0 (3)	N20—C17—C18—N14	−71.1 (3)
C7—C8—C9—C10	2.4 (4)	N14—C15—C19—N20	−67.5 (3)
C2—N1—C10—C9	−177.9 (3)	C16—C15—C19—N20	38.7 (3)
C11—N1—C10—C9	1.6 (4)	C15—C19—N20—C21	−126.7 (3)
C2—N1—C10—C5	2.2 (4)	C15—C19—N20—C17	−3.1 (3)
C11—N1—C10—C5	−178.3 (3)	C18—C17—N20—C21	−163.3 (3)
C8—C9—C10—N1	−178.8 (3)	C16—C17—N20—C21	89.7 (3)
C8—C9—C10—C5	1.2 (5)	C18—C17—N20—C19	73.2 (3)
C6—C5—C10—N1	176.7 (3)	C16—C17—N20—C19	−33.8 (3)
C4—C5—C10—N1	−6.8 (4)	C2—C3—C23—O25	−136.5 (3)
C6—C5—C10—C9	−3.3 (4)	C4—C3—C23—O25	44.2 (4)
C4—C5—C10—C9	173.3 (3)	C2—C3—C23—O24	44.9 (4)
C2—N1—C11—C12	−29.2 (4)	C4—C3—C23—O24	−134.3 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N20—H20···O26^i	0.94 (4)	1.92 (4)	2.761 (3)	148 (3)
N20—H20···O25^i	0.94 (4)	2.17 (4)	2.792 (4)	123 (3)
O27—H27A···O26	0.96 (6)	1.86 (6)	2.811 (3)	172 (5)
O27—H27B···O24^ii	0.91 (5)	2.03 (5)	2.929 (4)	168 (4)
O28—H28A···O24	0.87 (6)	1.98 (7)	2.833 (4)	165 (5)
O28—H28B···O27^iii	0.91 (6)	2.00 (6)	2.906 (4)	172 (4)

Symmetry codes: (i) x−1/2, −y+1/2, −z+1; (ii) −x+1, y−1/2, −z+3/2; (iii) x, y+1, z.