Crystal structure of (RS)-4-(3-carb-oxy-1-ethyl-6,8-di-fluoro-4-oxo-1,4-di-hydro-quinolin-7-yl)-2-methyl-piperazin-1-ium 3-carb-oxy-5-fluoro-benzoate.

In the title organic salt, C17H20F2N3O3 +·C8H4FO4 -, proton transfer leads to one protonated lomefloxacin mol-ecule (HLf+) and one 3-carb-oxy-5-fluoro-benzoate (5-F-Hip-) anion in the asymmetric unit. The HLf+ cation is bent, with a dihedral angle of 38.3 (1)° between the quinoline ring and the piperazinium moiety. In the crystal, two kinds of N-H⋯O and O-H⋯O hydrogen-bonded chains cross-link each other to produce a three-dimensional network structure that is additionally stabilized by weak C-H⋯O and C-H⋯F hydrogen bonds, as well as π-π inter-actions. The methyl group attached to the piperazinium ring is disordered over two sets of sites [refined ratio: 0.645 (5):0.335 (5)], indicating the presence of both enanti-omers of the cation in the structure.

Chemical context

Lomefloxacin [n class="Chemical">Lf; systematic name: (RS)-4-(3-carb­oxy-1-ethyl-6,8-di­fluoro-4-oxo-1,4-di­hydro­quinolin-7-yl)-2-methyl­piperazine] belongs to the fluoro­quinolones that represent an important family of highly effective broad-spectrum anti­bacterial agents (Ross & Riley, 1990 ▸; Reddy et al., 2011 ▸; Huang et al., 2013 ▸). Lomefloxacin is very useful for the treatment of a variety of infections, although its therapeutic action as a drug is limited due to poor aqueous solubility (1.03 mg ml−1, Ross & Riley, 1990 ▸). Using salts of lomefloxacin may overcome this problem. Several binary and ternary salts of lomefloxacin have been reported with supra­molecular arrangements of the cationic and anionic moieties, such as the terephthalate (Zhou et al., 2006 ▸), isophthalate (Zhang et al., 2015 ▸), picrate (Jasinski et al., 2011 ▸) or hydro­chloride (Holstein et al., 2012 ▸). However, the number of compounds related to solubility improvement is rather limited (Zhang et al., 2015 ▸).

In this context, we have used 3-carb­oxy-5-fluoro­benzoic acid (5-F-H2ip) for a proton-transfer reaction, and report here synthesis and crystal structure of the produced n class="Chemical">salt (HLf)+·(5-F-Hip−), (I).

Structural commentary

The structures of the mol­ecular entities of (I) are displayed in Fig. 1 ▸. Unlike other lomefloxacin salts (Zhang et al., 2015 ▸), the title compound reveals no guest solvents residing in the crystal structure. In the asymmetric unit, there is one n class="Gene">HLf+ cation and one 5-F-Hip− anion, i.e. only one proton has been transferred from the free acid. Within the HLf+ moiety, a non-planar conformation of the mol­ecule is formed with a dihedral angle of 38.3 (1)° between the aromatic ring plane and the piperazinium ring (the latter exhibits a chair conformation). An intra­molecular S(6) hydrogen-bonding pattern (Etter et al., 1990 ▸) is found between the carb­oxy­lic group and the carbonyl O atom (O2—H2⋯O1; Table 1 ▸). The 5-F-Hip− anion is nearly planar (r.m.s. deviation = 0.132 Å), with the highest deviation of 0.2645 (13) Å for the carboxyl­ate O6 atom.

Figure 1

Mol­ecular structures of the cation and anion in the title salt. Displacement ellipsoids are drawn at the 30% probability level.

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O5—H5⋯O7i	0.82	1.75	2.557 (2)	167
O2—H2⋯O1	0.82	1.78	2.535 (3)	153
N1—H1B⋯O7ii	0.89	2.48	3.046 (2)	122
N1—H1B⋯O6ii	0.89	1.91	2.790 (2)	170
N1—H1A⋯O3iii	0.89	1.94	2.811 (2)	165
C21—H21⋯O4iv	0.93	2.61	3.534 (3)	173
C17—H17C⋯F1	0.96	2.45	2.985 (3)	115
C17—H17B⋯F3v	0.96	2.53	3.380 (3)	148
C16—H16B⋯F1v	0.97	2.48	3.394 (3)	157
C16—H16B⋯F1	0.97	2.16	2.682 (2)	112
C16—H16A⋯O6vi	0.97	2.35	3.287 (3)	162
C14—H14⋯O6vi	0.93	2.59	3.448 (3)	154
C4—H4A⋯O4v	0.97	2.60	3.274 (3)	127
C2—H2B⋯F2	0.97	2.30	2.883 (2)	118
C2—H2A⋯F3	0.97	2.57	3.078 (2)	113

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) .

Supra­molecular features

In the crystal structure, N1—H1A⋯O3iii inter­actions between the amino function of the piperazinium moiety and the non-protonated O atom of the carb­oxy­lic group of a neighboring n class="Gene">HLf+ cation result in a head-to-tail chain motif with descriptor C(13). Adjacent 5-F-Hip− moieties also form a head-to-tail chain, based on a C(8) pattern, involving O5—H5⋯O7i bonds between the carb­oxy­lic acid function and the carboxyl­ate function. The two kinds of chains inter­link with each other through N1—H1B⋯O6ii inter­actions between the second H atom of the amino group of the cation and one of the carboxyl­ate O atoms of the anion to form a three-dimensional network structure. Within this array (Fig. 2 ▸), additional weak C—H⋯O and C—H⋯F inter­actions are present (Table 1 ▸) as additional stabilization forces, along with π–π inter­actions between fluoro­quinolone benzene rings of the cations and and phenyl rings of the anions with a centroid-to-centroid separation of 3.7895 (12) Å.

Figure 2

A perspective view of (I) showing the N—H⋯O and O—H⋯O hydrogen-bonding inter­actions (dotted lines) between the two kinds of chains. ‘Acidic’ chains, i.e. chains involving only the anion, are shown in red for clarity.

Database survey

Two crystal structures (Zhang et al., 2015 ▸) based on lomefloxacin and n class="Chemical">isophthalic acid have been reported in the CSD (Verson 5.39; Groom et al., 2016 ▸) viz. CURKAD [4-(3-carb­oxy-1-ethyl-6,8-di­fluoro-4-oxo-1,4-di­hydro­quinolin-7-yl)-2-methyl­piperazin-1-ium 3-carb­oxy­benzoate hydrate] and CURKIL [4-(3-carb­oxy-1-ethyl-6,8-di­fluoro-4-oxo-1,4-di­hydro­quinolin-7-yl)-2-methyl­piperazin-1-ium 2,6-dioxo-1,2,3,6-tetra­hydro­pyrimidin-4-olate isophthalic acid methanol solvate monohydrate]. Both CURKAD and the title compound are proton-transfer compounds from isophthalic acids to the piperazine NH groups. In the structure of CURKIL, the isophthalic acid moiety remains protonated, and co-crystallized barbituric acid is the proton donor in this case. With respect to the supra­molecular networks in these structures, the contribution of the extra fluorine atom in (I) leads to additional hydrogen bonds of the type C—H⋯F.

Synthesis and crystallization

A methanol solution (6 ml) of 5-fluoro­n class="Chemical">isophthalic acid (5-F-H2ip; 20 mg, 0.1 mmol) was mixed with a slurry of lomefloxacin (Lf) (35 mg, 0.1 mmol) in 5 ml water under stirring. The mixture was exposed to ultrasound for ca 20 min, and was then filtered and left to slowly evaporate. Colourless block-like single crystals suitable for X-ray analysis were obtained after several weeks. Yield: 65% (35 mg, based on Lf). Analysis calculated for C25H24F3N3O7: C, 56.08; H, 4.52; N, 7.85%. Found: C, 56.06; H, 4.50; N, 7.82%. FT–IR (KBr pellet, cm−1): 3431b, 3070 (w), 2475 (w), 1718 (s), 1620 (vs, 1539 (m), 1456 (s), 1371 (m), 1275 (s), 1090 (m), 959 (m), 901 (w), 766 (m), 689 (m), 521 (w).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. H atoms bonded to C were placed geometrically and refined in a riding model: C—H = 0.96–0.98 Å; U iso(H) = 1.2U eq(C) or 1.5U eq(C-meth­yl). All O-bound and N-bound n class="Disease">H atoms were initially found in difference electron-density maps, and then refined using a riding model [O—H = 0.82 Å and N—H = 0.89 Å; U iso(H) = 1.2U eq(N) and 1.5U eq(O)]. The methyl group bound to the piperazinium ring is disordered over two positions with occupancies of 0.645 (5) and 0.355 (5).

Table 2

Experimental details

Crystal data
Chemical formula	C17H20F2N3O3 +·C8H4FO4 −
M r	535.47
Crystal system, space group	Monoclinic, P21/n
Temperature (K)	296
a, b, c (Å)	10.4324 (12), 16.5656 (19), 14.0448 (17)
β (°)	100.707 (3)
V (Å3)	2384.9 (5)
Z	4
Radiation type	Mo Kα
μ (mm−1)	0.13
Crystal size (mm)	0.22 × 0.20 × 0.16
Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2010 ▸)
T min, T max	0.970, 0.980
No. of measured, independent and observed [I > 2σ(I)] reflections	16570, 6292, 4335
R int	0.035
(sin θ/λ)max (Å−1)	0.711
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.054, 0.161, 0.98
No. of reflections	6292
No. of parameters	358
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.29, −0.28

Computer programs: APEX2 and SAINT (Bruker, 2010 ▸), SHELXS97 and SHELXTL (Sheldrick, 2008 ▸), SHELXL2014 (Sheldrick, 2015 ▸) and publCIF (Westrip, 2010 ▸).

Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989018016961/wm5472sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989018016961/wm5472Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989018016961/wm5472Isup3.cml

CCDC reference: 1025160

Additional supporting information: crystallographic information; 3D view; checkCIF report

C17H20F2N3O3+·C8H4FO4−	F(000) = 1112
Mr = 535.47	Dx = 1.491 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 10.4324 (12) Å	Cell parameters from 5522 reflections
b = 16.5656 (19) Å	θ = 2.2–29.9°
c = 14.0448 (17) Å	µ = 0.13 mm−1
β = 100.707 (3)°	T = 296 K
V = 2384.9 (5) Å3	Block, colorless
Z = 4	0.22 × 0.20 × 0.16 mm

Bruker APEXII CCD diffractometer	4335 reflections with I > 2σ(I)
φ and ω scans	Rint = 0.035
Absorption correction: multi-scan (SADABS; Bruker, 2010)	θmax = 30.4°, θmin = 1.9°
Tmin = 0.970, Tmax = 0.980	h = −14→14
16570 measured reflections	k = −23→21
6292 independent reflections	l = −19→13

Refinement on F2	0 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.054	H-atom parameters constrained
wR(F2) = 0.161	w = 1/[σ2(Fo2) + (0.085P)2 + 0.686P] where P = (Fo2 + 2Fc2)/3
S = 0.98	(Δ/σ)max < 0.001
6292 reflections	Δρmax = 0.29 e Å−3
358 parameters	Δρmin = −0.28 e Å−3

Geometry. 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.

	x	y	z	Uiso*/Ueq	Occ. (<1)
C2	0.2703 (2)	0.12846 (10)	0.77391 (12)	0.0390 (4)
H2A	0.1793	0.1429	0.7531	0.047*
H2B	0.3232	0.1710	0.7536	0.047*
C3	0.21645 (19)	−0.01366 (11)	0.75432 (12)	0.0385 (4)
H3A	0.2383	−0.0636	0.7249	0.046*
H3B	0.1251	−0.0021	0.7299	0.046*
C4	0.23908 (19)	−0.02326 (11)	0.86352 (12)	0.0391 (4)
H4A	0.1800	−0.0637	0.8804	0.047*
H4B	0.3277	−0.0416	0.8868	0.047*
C1	0.30073 (19)	0.12083 (11)	0.88315 (12)	0.0398 (4)	0.645 (5)
H1	0.3925	0.1055	0.9030	0.048*	0.645 (5)
C5	0.2784 (4)	0.1988 (2)	0.9320 (2)	0.0587 (11)	0.645 (5)
H5A	0.2890	0.1903	1.0006	0.088*	0.645 (5)
H5B	0.1915	0.2177	0.9074	0.088*	0.645 (5)
H5C	0.3403	0.2383	0.9191	0.088*	0.645 (5)
C1'	0.30073 (19)	0.12083 (11)	0.88315 (12)	0.0398 (4)	0.355 (5)
H1'	0.2728	0.1712	0.9098	0.048*	0.355 (5)
C5'	0.4401 (7)	0.1112 (5)	0.9223 (4)	0.064 (2)	0.355 (5)
H5'1	0.4858	0.1593	0.9101	0.096*	0.355 (5)
H5'2	0.4734	0.0660	0.8917	0.096*	0.355 (5)
H5'3	0.4525	0.1020	0.9909	0.096*	0.355 (5)
C6	0.32692 (16)	0.05742 (10)	0.63571 (11)	0.0314 (3)
C7	0.25702 (16)	0.02250 (11)	0.55222 (12)	0.0348 (4)
C8	0.29167 (16)	0.02851 (11)	0.46031 (11)	0.0360 (4)
C9	0.39760 (17)	0.07840 (11)	0.45220 (12)	0.0375 (4)
C10	0.46920 (18)	0.11506 (11)	0.53468 (13)	0.0378 (4)
H10	0.5396	0.1481	0.5295	0.045*
C11	0.43600 (17)	0.10242 (11)	0.62229 (12)	0.0354 (4)
C12	0.4354 (2)	0.09342 (13)	0.35878 (13)	0.0468 (5)
C13	0.3573 (2)	0.05467 (14)	0.27828 (13)	0.0511 (5)
C14	0.2580 (2)	0.00583 (15)	0.29119 (13)	0.0533 (6)
H14	0.2103	−0.0191	0.2366	0.064*
C15	0.3820 (3)	0.06630 (18)	0.17808 (15)	0.0690 (8)
C16	0.12118 (19)	−0.07161 (18)	0.37829 (15)	0.0621 (7)
H16A	0.0763	−0.0816	0.3124	0.075*
H16B	0.0576	−0.0514	0.4148	0.075*
C17	0.1759 (2)	−0.14920 (18)	0.4221 (2)	0.0711 (8)
H17A	0.2399	−0.1692	0.3869	0.107*
H17B	0.1070	−0.1880	0.4192	0.107*
H17C	0.2161	−0.1403	0.4885	0.107*
C18	0.15025 (16)	0.22254 (10)	0.33449 (12)	0.0331 (4)
C19	0.25938 (16)	0.27147 (10)	0.33760 (12)	0.0331 (4)
H19	0.2883	0.2841	0.2806	0.040*
C20	0.32544 (16)	0.30154 (10)	0.42577 (11)	0.0325 (3)
C21	0.28309 (17)	0.28192 (11)	0.51078 (12)	0.0352 (4)
H21	0.3271	0.3008	0.5703	0.042*
C22	0.17472 (17)	0.23394 (12)	0.50507 (12)	0.0389 (4)
C23	0.10696 (17)	0.20350 (11)	0.41930 (12)	0.0374 (4)
H23	0.0340	0.1710	0.4182	0.045*
C24	0.07378 (18)	0.18979 (11)	0.24192 (13)	0.0398 (4)
C25	0.44349 (18)	0.35535 (11)	0.43029 (12)	0.0390 (4)
F1	0.14586 (10)	−0.01682 (8)	0.56051 (8)	0.0542 (3)
F2	0.51182 (11)	0.13417 (7)	0.70199 (8)	0.0502 (3)
F3	0.13353 (12)	0.21463 (9)	0.58853 (8)	0.0600 (4)
N1	0.21749 (14)	0.05481 (9)	0.91112 (10)	0.0366 (3)
H1A	0.2354	0.0485	0.9751	0.044*
H1B	0.1339	0.0688	0.8945	0.044*
N2	0.29693 (15)	0.05198 (8)	0.72827 (10)	0.0349 (3)
N3	0.22256 (15)	−0.00954 (12)	0.37700 (10)	0.0466 (4)
O1	0.52996 (17)	0.13801 (11)	0.35126 (11)	0.0634 (4)
O2	0.4753 (2)	0.11777 (15)	0.16934 (12)	0.0864 (6)
H2	0.5061	0.1367	0.2226	0.130*
O3	0.3194 (2)	0.03032 (14)	0.10876 (11)	0.0906 (7)
O4	−0.03217 (17)	0.16034 (13)	0.23770 (11)	0.0770 (6)
O5	0.13137 (13)	0.19749 (9)	0.16727 (9)	0.0483 (3)
H5	0.0852	0.1778	0.1192	0.073*
O6	0.46630 (13)	0.38375 (9)	0.35255 (9)	0.0500 (4)
O7	0.51218 (16)	0.36907 (10)	0.51142 (10)	0.0619 (4)

	U11	U22	U33	U12	U13	U23
C2	0.0599 (11)	0.0327 (9)	0.0257 (8)	0.0003 (8)	0.0111 (8)	−0.0032 (7)
C3	0.0511 (10)	0.0366 (9)	0.0280 (8)	−0.0052 (8)	0.0074 (7)	−0.0045 (7)
C4	0.0526 (10)	0.0355 (9)	0.0297 (8)	0.0002 (8)	0.0089 (7)	0.0023 (7)
C1	0.0533 (10)	0.0421 (10)	0.0244 (8)	−0.0045 (8)	0.0079 (7)	−0.0076 (7)
C5	0.087 (3)	0.052 (2)	0.0429 (18)	−0.0161 (17)	0.0286 (17)	−0.0244 (15)
C1'	0.0533 (10)	0.0421 (10)	0.0244 (8)	−0.0045 (8)	0.0079 (7)	−0.0076 (7)
C5'	0.066 (4)	0.091 (5)	0.033 (3)	−0.029 (4)	0.006 (3)	0.000 (3)
C6	0.0390 (8)	0.0346 (8)	0.0204 (7)	0.0060 (7)	0.0047 (6)	−0.0019 (6)
C7	0.0321 (8)	0.0470 (10)	0.0252 (8)	0.0041 (7)	0.0050 (6)	−0.0063 (7)
C8	0.0358 (8)	0.0502 (10)	0.0201 (7)	0.0152 (7)	0.0005 (6)	−0.0052 (7)
C9	0.0411 (9)	0.0482 (10)	0.0240 (8)	0.0183 (8)	0.0084 (7)	0.0030 (7)
C10	0.0411 (9)	0.0401 (9)	0.0337 (9)	0.0066 (7)	0.0111 (7)	0.0017 (7)
C11	0.0418 (9)	0.0362 (9)	0.0262 (8)	0.0040 (7)	0.0011 (7)	−0.0031 (7)
C12	0.0539 (11)	0.0578 (12)	0.0312 (9)	0.0269 (10)	0.0143 (8)	0.0094 (8)
C13	0.0613 (12)	0.0703 (14)	0.0233 (8)	0.0313 (11)	0.0119 (8)	0.0059 (8)
C14	0.0551 (12)	0.0824 (15)	0.0194 (8)	0.0299 (11)	−0.0009 (8)	−0.0088 (9)
C15	0.0890 (18)	0.0935 (19)	0.0263 (10)	0.0476 (16)	0.0155 (11)	0.0118 (11)
C16	0.0340 (10)	0.113 (2)	0.0366 (10)	0.0000 (11)	0.0000 (8)	−0.0361 (12)
C17	0.0545 (13)	0.0898 (19)	0.0727 (16)	−0.0240 (13)	0.0213 (12)	−0.0368 (15)
C18	0.0350 (8)	0.0344 (8)	0.0284 (8)	0.0011 (7)	0.0014 (7)	0.0012 (6)
C19	0.0377 (8)	0.0372 (9)	0.0236 (7)	0.0006 (7)	0.0036 (6)	0.0052 (6)
C20	0.0367 (8)	0.0331 (8)	0.0262 (8)	0.0031 (7)	0.0016 (6)	0.0046 (6)
C21	0.0406 (9)	0.0405 (9)	0.0225 (7)	0.0050 (7)	0.0010 (6)	0.0017 (6)
C22	0.0399 (9)	0.0517 (11)	0.0261 (8)	0.0057 (8)	0.0091 (7)	0.0082 (7)
C23	0.0345 (8)	0.0428 (10)	0.0344 (9)	0.0006 (7)	0.0054 (7)	0.0068 (7)
C24	0.0452 (10)	0.0417 (10)	0.0307 (8)	−0.0073 (8)	0.0023 (7)	0.0016 (7)
C25	0.0415 (9)	0.0446 (10)	0.0271 (8)	−0.0048 (8)	−0.0038 (7)	0.0082 (7)
F1	0.0424 (6)	0.0885 (9)	0.0324 (6)	−0.0148 (6)	0.0091 (5)	−0.0211 (6)
F2	0.0567 (7)	0.0588 (7)	0.0332 (6)	−0.0169 (5)	0.0034 (5)	−0.0103 (5)
F3	0.0566 (7)	0.0962 (10)	0.0305 (6)	−0.0063 (7)	0.0170 (5)	0.0108 (6)
N1	0.0432 (8)	0.0460 (8)	0.0210 (6)	0.0023 (6)	0.0072 (6)	−0.0016 (6)
N2	0.0506 (8)	0.0330 (7)	0.0219 (6)	−0.0036 (6)	0.0087 (6)	−0.0057 (5)
N3	0.0396 (8)	0.0754 (12)	0.0227 (7)	0.0143 (8)	0.0002 (6)	−0.0126 (7)
O1	0.0681 (10)	0.0823 (11)	0.0460 (8)	0.0089 (9)	0.0270 (8)	0.0126 (8)
O2	0.1021 (15)	0.1232 (18)	0.0419 (9)	0.0267 (13)	0.0340 (10)	0.0196 (10)
O3	0.1254 (16)	0.1244 (17)	0.0205 (7)	0.0381 (14)	0.0098 (9)	0.0027 (9)
O4	0.0699 (10)	0.1159 (15)	0.0427 (8)	−0.0525 (11)	0.0038 (8)	−0.0062 (9)
O5	0.0497 (8)	0.0640 (9)	0.0298 (6)	−0.0099 (6)	0.0036 (6)	−0.0103 (6)
O6	0.0497 (8)	0.0677 (9)	0.0292 (6)	−0.0176 (7)	−0.0014 (6)	0.0136 (6)
O7	0.0681 (9)	0.0778 (11)	0.0312 (7)	−0.0309 (8)	−0.0134 (7)	0.0147 (7)

C2—N2	1.469 (2)	C12—O1	1.252 (3)
C2—C1	1.513 (2)	C12—C13	1.419 (3)
C2—C1'	1.513 (2)	C13—C14	1.353 (3)
C2—H2A	0.9700	C13—C15	1.490 (3)
C2—H2B	0.9700	C14—N3	1.349 (2)
C3—N2	1.461 (2)	C14—H14	0.9300
C3—C4	1.516 (2)	C15—O3	1.222 (4)
C3—H3A	0.9700	C15—O2	1.317 (4)
C3—H3B	0.9700	C16—N3	1.478 (3)
C4—N1	1.492 (2)	C16—C17	1.492 (4)
C4—H4A	0.9700	C16—H16A	0.9700
C4—H4B	0.9700	C16—H16B	0.9700
C1—N1	1.494 (2)	C17—H17A	0.9600
C1—C5	1.501 (3)	C17—H17B	0.9600
C1—H1	0.9800	C17—H17C	0.9600
C5—H5A	0.9600	C18—C23	1.386 (2)
C5—H5B	0.9600	C18—C19	1.392 (2)
C5—H5C	0.9600	C18—C24	1.495 (2)
C1'—C5'	1.465 (7)	C19—C20	1.393 (2)
C1'—N1	1.494 (2)	C19—H19	0.9300
C1'—H1'	0.9800	C20—C21	1.386 (2)
C5'—H5'1	0.9600	C20—C25	1.512 (2)
C5'—H5'2	0.9600	C21—C22	1.372 (3)
C5'—H5'3	0.9600	C21—H21	0.9300
C6—C7	1.387 (2)	C22—F3	1.3594 (19)
C6—N2	1.395 (2)	C22—C23	1.374 (3)
C6—C11	1.402 (2)	C23—H23	0.9300
C7—F1	1.354 (2)	C24—O4	1.200 (2)
C7—C8	1.407 (2)	C24—O5	1.308 (2)
C8—C9	1.402 (3)	C25—O7	1.249 (2)
C8—N3	1.405 (2)	C25—O6	1.252 (2)
C9—C10	1.395 (3)	N1—H1A	0.8900
C9—C12	1.460 (2)	N1—H1B	0.8900
C10—C11	1.355 (2)	O2—H2	0.8200
C10—H10	0.9300	O5—H5	0.8200
C11—F2	1.351 (2)
N2—C2—C1	110.44 (14)	O1—C12—C9	121.66 (19)
N2—C2—C1'	110.44 (14)	C13—C12—C9	115.34 (19)
N2—C2—H2A	109.6	C14—C13—C12	120.31 (17)
C1—C2—H2A	109.6	C14—C13—C15	118.4 (2)
N2—C2—H2B	109.6	C12—C13—C15	121.3 (2)
C1—C2—H2B	109.6	N3—C14—C13	125.18 (19)
H2A—C2—H2B	108.1	N3—C14—H14	117.4
N2—C3—C4	110.04 (14)	C13—C14—H14	117.4
N2—C3—H3A	109.7	O3—C15—O2	122.4 (2)
C4—C3—H3A	109.7	O3—C15—C13	122.0 (3)
N2—C3—H3B	109.7	O2—C15—C13	115.6 (2)
C4—C3—H3B	109.7	N3—C16—C17	112.61 (17)
H3A—C3—H3B	108.2	N3—C16—H16A	109.1
N1—C4—C3	110.75 (14)	C17—C16—H16A	109.1
N1—C4—H4A	109.5	N3—C16—H16B	109.1
C3—C4—H4A	109.5	C17—C16—H16B	109.1
N1—C4—H4B	109.5	H16A—C16—H16B	107.8
C3—C4—H4B	109.5	C16—C17—H17A	109.5
H4A—C4—H4B	108.1	C16—C17—H17B	109.5
N1—C1—C5	111.26 (18)	H17A—C17—H17B	109.5
N1—C1—C2	107.76 (14)	C16—C17—H17C	109.5
C5—C1—C2	111.7 (2)	H17A—C17—H17C	109.5
N1—C1—H1	108.7	H17B—C17—H17C	109.5
C5—C1—H1	108.7	C23—C18—C19	120.05 (15)
C2—C1—H1	108.7	C23—C18—C24	117.27 (15)
C1—C5—H5A	109.5	C19—C18—C24	122.67 (15)
C1—C5—H5B	109.5	C18—C19—C20	120.20 (15)
H5A—C5—H5B	109.5	C18—C19—H19	119.9
C1—C5—H5C	109.5	C20—C19—H19	119.9
H5A—C5—H5C	109.5	C21—C20—C19	119.84 (16)
H5B—C5—H5C	109.5	C21—C20—C25	119.31 (15)
C5'—C1'—N1	114.0 (3)	C19—C20—C25	120.85 (14)
C5'—C1'—C2	113.4 (3)	C22—C21—C20	118.46 (16)
N1—C1'—C2	107.76 (14)	C22—C21—H21	120.8
C5'—C1'—H1'	107.1	C20—C21—H21	120.8
N1—C1'—H1'	107.1	F3—C22—C21	118.36 (16)
C2—C1'—H1'	107.1	F3—C22—C23	118.42 (16)
C1'—C5'—H5'1	109.5	C21—C22—C23	123.22 (15)
C1'—C5'—H5'2	109.5	C22—C23—C18	118.23 (16)
H5'1—C5'—H5'2	109.5	C22—C23—H23	120.9
C1'—C5'—H5'3	109.5	C18—C23—H23	120.9
H5'1—C5'—H5'3	109.5	O4—C24—O5	123.81 (17)
H5'2—C5'—H5'3	109.5	O4—C24—C18	121.90 (17)
C7—C6—N2	125.94 (15)	O5—C24—C18	114.29 (15)
C7—C6—C11	114.87 (14)	O7—C25—O6	123.89 (17)
N2—C6—C11	119.18 (14)	O7—C25—C20	118.06 (15)
F1—C7—C6	116.89 (14)	O6—C25—C20	118.06 (15)
F1—C7—C8	118.88 (15)	C4—N1—C1'	111.92 (13)
C6—C7—C8	124.17 (16)	C4—N1—C1	111.92 (13)
C9—C8—N3	119.17 (15)	C4—N1—H1A	109.2
C9—C8—C7	117.20 (15)	C1—N1—H1A	109.2
N3—C8—C7	123.56 (17)	C4—N1—H1B	109.2
C10—C9—C8	119.86 (15)	C1—N1—H1B	109.2
C10—C9—C12	118.66 (18)	H1A—N1—H1B	107.9
C8—C9—C12	121.49 (17)	C6—N2—C3	121.34 (13)
C11—C10—C9	119.92 (17)	C6—N2—C2	116.36 (13)
C11—C10—H10	120.0	C3—N2—C2	111.61 (13)
C9—C10—H10	120.0	C14—N3—C8	118.45 (18)
F2—C11—C10	118.87 (16)	C14—N3—C16	117.24 (17)
F2—C11—C6	117.42 (14)	C8—N3—C16	124.05 (16)
C10—C11—C6	123.71 (16)	C15—O2—H2	109.5
O1—C12—C13	123.00 (18)	C24—O5—H5	109.5
N2—C3—C4—N1	54.3 (2)	C18—C19—C20—C25	−179.48 (16)
N2—C2—C1—N1	−59.2 (2)	C19—C20—C21—C22	−1.1 (3)
N2—C2—C1—C5	178.3 (2)	C25—C20—C21—C22	179.11 (16)
N2—C2—C1'—C5'	67.9 (4)	C20—C21—C22—F3	179.86 (15)
N2—C2—C1'—N1	−59.2 (2)	C20—C21—C22—C23	0.8 (3)
N2—C6—C7—F1	3.7 (3)	F3—C22—C23—C18	−179.23 (16)
C11—C6—C7—F1	−175.55 (15)	C21—C22—C23—C18	−0.2 (3)
N2—C6—C7—C8	−179.07 (16)	C19—C18—C23—C22	−0.2 (3)
C11—C6—C7—C8	1.7 (3)	C24—C18—C23—C22	−179.07 (16)
F1—C7—C8—C9	171.85 (15)	C23—C18—C24—O4	12.6 (3)
C6—C7—C8—C9	−5.3 (3)	C19—C18—C24—O4	−166.2 (2)
F1—C7—C8—N3	−5.2 (3)	C23—C18—C24—O5	−168.50 (16)
C6—C7—C8—N3	177.68 (16)	C19—C18—C24—O5	12.6 (3)
N3—C8—C9—C10	−178.45 (15)	C21—C20—C25—O7	12.1 (3)
C7—C8—C9—C10	4.4 (2)	C19—C20—C25—O7	−167.74 (18)
N3—C8—C9—C12	1.7 (2)	C21—C20—C25—O6	−167.64 (17)
C7—C8—C9—C12	−175.47 (15)	C19—C20—C25—O6	12.5 (3)
C8—C9—C10—C11	−0.1 (3)	C3—C4—N1—C1'	−55.9 (2)
C12—C9—C10—C11	179.77 (16)	C3—C4—N1—C1	−55.9 (2)
C9—C10—C11—F2	175.67 (15)	C5'—C1'—N1—C4	−69.3 (3)
C9—C10—C11—C6	−3.9 (3)	C2—C1'—N1—C4	57.47 (19)
C7—C6—C11—F2	−176.49 (15)	C5—C1—N1—C4	−179.7 (2)
N2—C6—C11—F2	4.2 (2)	C2—C1—N1—C4	57.47 (19)
C7—C6—C11—C10	3.1 (3)	C7—C6—N2—C3	22.2 (3)
N2—C6—C11—C10	−176.24 (16)	C11—C6—N2—C3	−158.57 (16)
C10—C9—C12—O1	0.1 (3)	C7—C6—N2—C2	−119.34 (19)
C8—C9—C12—O1	179.95 (17)	C11—C6—N2—C2	59.9 (2)
C10—C9—C12—C13	−179.44 (16)	C4—C3—N2—C6	159.44 (15)
C8—C9—C12—C13	0.4 (2)	C4—C3—N2—C2	−57.40 (19)
O1—C12—C13—C14	178.65 (19)	C1—C2—N2—C6	−153.88 (15)
C9—C12—C13—C14	−1.8 (3)	C1'—C2—N2—C6	−153.88 (15)
O1—C12—C13—C15	−1.3 (3)	C1—C2—N2—C3	61.0 (2)
C9—C12—C13—C15	178.26 (17)	C1'—C2—N2—C3	61.0 (2)
C12—C13—C14—N3	1.2 (3)	C13—C14—N3—C8	1.0 (3)
C15—C13—C14—N3	−178.91 (19)	C13—C14—N3—C16	−173.3 (2)
C14—C13—C15—O3	−3.4 (3)	C9—C8—N3—C14	−2.4 (2)
C12—C13—C15—O3	176.5 (2)	C7—C8—N3—C14	174.54 (17)
C14—C13—C15—O2	176.5 (2)	C9—C8—N3—C16	171.48 (18)
C12—C13—C15—O2	−3.6 (3)	C7—C8—N3—C16	−11.6 (3)
C23—C18—C19—C20	−0.1 (3)	C17—C16—N3—C14	104.7 (2)
C24—C18—C19—C20	178.77 (16)	C17—C16—N3—C8	−69.3 (2)
C18—C19—C20—C21	0.7 (3)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5···O7i	0.82	1.75	2.557 (2)	167
O2—H2···O1	0.82	1.78	2.535 (3)	153
N1—H1B···O7ii	0.89	2.48	3.046 (2)	122
N1—H1B···O6ii	0.89	1.91	2.790 (2)	170
N1—H1A···O3iii	0.89	1.94	2.811 (2)	165
C21—H21···O4iv	0.93	2.61	3.534 (3)	173
C17—H17C···F1	0.96	2.45	2.985 (3)	115
C17—H17B···F3v	0.96	2.53	3.380 (3)	148
C16—H16B···F1v	0.97	2.48	3.394 (3)	157
C16—H16B···F1	0.97	2.16	2.682 (2)	112
C16—H16A···O6vi	0.97	2.35	3.287 (3)	162
C14—H14···O6vi	0.93	2.59	3.448 (3)	154
C4—H4A···O4v	0.97	2.60	3.274 (3)	127
C2—H2B···F2	0.97	2.30	2.883 (2)	118
C2—H2A···F3	0.97	2.57	3.078 (2)	113